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Sample records for differentiated neuroendocrine carcinoma

  1. The Genetic Landscape of Breast Carcinomas with Neuroendocrine Differentiation

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    Marchiò, Caterina; Geyer, Felipe C; Ng, Charlotte KY; Piscuoglio, Salvatore; De Filippo, Maria R; Cupo, Marco; Schultheis, Anne M; Lim, Raymond S; Burke, Kathleen A; Guerini-Rocco, Elena; Papotti, Mauro; Norton, Larry; Sapino, Anna; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Neuroendocrine breast carcinomas (NBCs) account for 2–5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal 'intrinsic' subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair. Their mutational repertoire was compared to that of ER+/HER2- (n=240), PAM50-defined luminal breast cancers (n=209 luminal A; n=111 luminal B) and invasive lobular carcinomas (n=127) from The Cancer Genome Atlas. NBCs were found to harbour a median of 4.5 (range 1-11) somatic mutations, similar to that of luminal B breast cancers (median=3, range 0-17) but significantly higher than that of luminal A breast cancers (median=3, range 0-18, p=0.02). The most frequently mutated genes were GATA3, FOXA1, TBX3, ARID1A (3/18, 17%), and PIK3CA, AKT1, CDH1 (2/18, 11%). NBCs less frequently harboured PIK3CA mutations than common forms of ER+/HER2, luminal A and invasive lobular carcinomas (pcancers. No TP53 somatic mutations were detected in NBCs. Compared to common forms of luminal breast cancers, NBCs display a distinctive repertoire of somatic mutations featuring lower frequency of TP53 and PIK3CA mutations, and enrichment for FOXA1, TBX3 mutations, and akin to neuroendocrine tumours from other sites, ARID1A mutations. PMID:27925203

  2. Chromophobe renal cell carcinoma with neuroendocrine differentiation/morphology: A clinicopathological and genetic study of three cases

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    Chisato Ohe, MD

    2014-09-01

    Full Text Available Chromophobe renal cell carcinoma (ChRCC with neuroendocrine differentiation/morphology (NED/NEM is exceedingly rare. We present three cases of ChRCC with NED/NEM, two of which showed positivity for neuroendocrine markers on immunohistochemical analysis. Patients ranged in age from 49 to 79 years (mean: 64.3 years. One of the three patients died of metastatic disease to multiple organs. Of the remaining two patients, one is currently alive without disease and the other is alive with disease. Histologically, all three tumors were composed of conventional ChRCC and NEM showed glandular and rosette formation. Immunohistochemically, tumor cells were positive for CK7, KAI1, E-cadherin, and c-kit in both ChRCC and neuroendocrine areas in three cases. CD56 and synaptophysin immunoreactivity were detected in two cases; in only the neuroendocrine area in one case and in both components in the other. Neuroendocrine granules were ultrastructurally observed at both neuroendocrine and conventional areas of ChRCC. Array comparative genomic hybridization (CGH study indicated losses of chromosomes 1, 2, 6, 10, 17, 21, and Y in both conventional ChRCC and NED in one case. In addition, losses of chromosomes 1, 2, 4, 6, 9, 10, 13, 16p, 17, and 21 were observed in both components of the remaining one tumor. Furthermore, loss of chromosome 5 was identified only in the neuroendocrine area in this case. We concluded that the neuroendocrine area may reflect dedifferentiation within ChRCC. It is possible that losses of chromosomes 4, 5, and 16p may be involved in the neuroendocrine differentiation or progression of ChRCC.

  3. High-Dose Lanreotide in the Treatment of Poorly Differentiated Pancreatic Neuroendocrine Carcinoma: A Case Report

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    Frank Van Fraeyenhove

    2014-03-01

    Full Text Available Pancreatic neuroendocrine tumors (NETs, including poorly differentiated carcinomas (NECs, are rarely encountered. The majority of these tumors do not secrete excess hormones, but functioning NETs produce large amounts of vasoactive peptides and may cause carcinoid syndrome. Synthetic somatostatin analogs (SSAs have been widely used in NETs for control of hormonal syndromes. Here, we present a case of poorly differentiated, grade 3 pancreatic NEC associated with carcinoid syndrome, for which adequate symptom control was achieved for 2 years and 4 months using the long-acting SSA lanreotide Autogel®. In February 2009, a 55-year-old woman presented with episodes of flushing, diarrhea and epigastric pain. Imaging techniques revealed the presence of a metabolically active mass expressing somatostatin receptors in the hilar area of the liver. Histopathological examination confirmed the malignant nature of the mass, which was identified as a poorly differentiated grade 3 pancreatic NEC (TNM staging: T4NxM0. Therapeutic options were limited for the patient because of the extent of the primary mass involving the celiac axis, severe gastrointestinal toxicity experienced as a side effect of chemotherapy with cisplatin-etoposide and, later in the course of the disease, extensive liver metastases and carcinoid heart syndrome. Along with a palliative debulking surgery and right portal vein embolization, biotherapy with a high dose of lanreotide Autogel (120 mg/14 days contributed to alleviation of symptoms caused by hormone overproduction, even after the development of liver metastases. These results suggest that patients with poorly differentiated NECs who exhibit signs of carcinoid syndrome can benefit from treatment with somatostatin analogs.

  4. Dermatomyositis Associated with Lung Neuroendocrine Carcinoma

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    Takashima, Reina; Takamatsu, Kazufumi; Shinkawa, Yutaka; Yagita, Masato; Fukui, Motonari; Fujita, Masaaki

    2017-01-01

    Dermatomyositis is associated with various types of malignancy. However, the association of dermatomyositis with lung neuroendocrine carcinoma is rare. We herein report a case of dermatomyositis with lung neuroendocrine carcinoma. PMID:28321077

  5. Dermatomyositis Associated with Lung Neuroendocrine Carcinoma

    OpenAIRE

    Takashima, Reina; Takamatsu, Kazufumi; Shinkawa, Yutaka; Yagita, Masato; Fukui, Motonari; Fujita, Masaaki

    2017-01-01

    Dermatomyositis is associated with various types of malignancy. However, the association of dermatomyositis with lung neuroendocrine carcinoma is rare. We herein report a case of dermatomyositis with lung neuroendocrine carcinoma.

  6. Chromophobe renal cell carcinoma of the kidney with neuroendocrine differentiation: A case report with review of literature

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    Ghadeer A Mokhtar

    2015-01-01

    Full Text Available Chromophobe renal cell carcinoma (chRCC is a distinctive type of malignant kidney tumor characterized by large cells with defined cell membrane. Primary renal neuroendocrine tumors (NET are rare with morphology similar to NET at other sites. There are few case reports describing the coexistence of these 2 neoplasms within the same tumor mass. We describe a case of chRCC with neuroendocrine features in a 70-year-old male patient who presented with hematuria and right flank pain. The histological and immunohistochemical features of both components were characteristic with no overlapping features. The neuroendocrine element was associated with nodal metastasis.

  7. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

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    Ciuffreda Libero

    2009-11-01

    Full Text Available Abstract Background Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU infusion plus long-acting release (LAR octreotide in patients with neuroendocrine carcinoma. Methods Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily plus LAR octreotide (20 mg monthly. Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Results Assessment by Response Evaluation Criteria in Solid Tumors (RECIST criteria showed partial response in 7 (24.1%, stable disease in 20 (69.0%, and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A response was observed in 12/25 assessable patients (48.0%; symptom relief was obtained in 9/15 symptomatic patients (60.0%. There was non significant decrease in circulating vascular epithelial growth factor (VEGF over time. Median time to progression was 22.6 months (range, 2.7-68.5; median overall survival was not reached yet. Toxicity was mild and manageable. Conclusion Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. Trial registration NCT00953394

  8. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

    International Nuclear Information System (INIS)

    Brizzi, Maria P; Ferretti, Benedetta; Alabiso, Oscar; Ciuffreda, Libero; Bertetto, Oscar; Papotti, Mauro; Dogliotti, Luigi; Berruti, Alfredo; Ferrero, Anna; Milanesi, Enrica; Volante, Marco; Castiglione, Federico; Birocco, Nadia; Bombaci, Sebastiano; Perroni, Davide

    2009-01-01

    Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma. Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m 2 daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable. Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. NCT00953394

  9. Roles for miR-375 in Neuroendocrine Differentiation and Tumor Suppression via Notch Pathway Suppression in Merkel Cell Carcinoma.

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    Abraham, Karan J; Zhang, Xiao; Vidal, Ricardo; Paré, Geneviève C; Feilotter, Harriet E; Tron, Victor A

    2016-04-01

    Dysfunction of key miRNA pathways regulating basic cellular processes is a common driver of many cancers. However, the biological roles and/or clinical applications of such pathways in Merkel cell carcinoma (MCC), a rare but lethal cutaneous neuroendocrine (NE) malignancy, have yet to be determined. Previous work has established that miR-375 is highly expressed in MCC tumors, but its biological role in MCC remains unknown. Herein, we show that elevated miR-375 expression is a specific feature of well-differentiated MCC cell lines that express NE markers. In contrast, miR-375 is strikingly down-regulated in highly aggressive, undifferentiated MCC cell lines. Enforced miR-375 expression in these cells induced NE differentiation, and opposed cancer cell viability, migration, invasion, and survival, pointing to tumor-suppressive roles for miR-375. Mechanistically, miR-375-driven phenotypes were caused by the direct post-transcriptional repression of multiple Notch pathway proteins (Notch2 and RBPJ) linked to cancer and regulation of cell fate. Thus, we detail a novel molecular axis linking tumor-suppressive miR-375 and Notch with NE differentiation and cancer cell behavior in MCC. Our findings identify miR-375 as a putative regulator of NE differentiation, provide insight into the cell of origin of MCC, and suggest that miR-375 silencing may promote aggressive cancer cell behavior through Notch disinhibition. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Neuroendocrine Carcinoma: Immunohistochemistry Department Of Cancer Institute 1996 - 2000

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    Yazdani F

    2003-07-01

    Full Text Available Dispersed neuroendocrine system (D.N.S consists of a wide variety of cells that are present in the central and peripheral nervous system and in many classic endocrine organs and different tissues such as respiratory and gastrointestinal tracts, skin, prostate, breast and also their neoplasm show neuroendocrine differentiation by electron microscopy, immunohistochemistry or biochemical techniques:"nMaterials and Methods: The present study has been carried out by case-series method in order to evaluating the characteristics of all types of neuroendocrine carcinoma: different anatomical locations during 5 years period in immunohistochemistry department of cancer institute."nResults: The diagnosis of 109 cases of neuroendocrine carcinoma consisting of neuroendocrine carcinoma, small cell carcinoma, medullary carcinoma of thyroid, carcinoid tumor and merkel cell carcinoma are confirmed that among them the most common diagnosis was related to neuroendocrine carcinoma (50.5 percent. The most prevalent age group was 40-49 years and male to female distribution were 56 percent and 44 percent respectively. Anatomical distribution of tumor show that about 30 percent of cases were metastatic carcinoma, 30 percent in thyroid, respiratory tract and head and neck region and remainder in a variety of tissues. In over 50 percent of cases one of endocrinoid patterns as trabecular, organoid or mixed of them were seen."nConclusion: Immunohistochemically N.S.E (Neuron Specific Enolase show high sensitivity with 96 percent positive reaction and more specific endocrine markers as chromogranin A in 80 percent and synaptophysin only in 24 percent because of lesser application of the latter. Also epithelial markers such as cytokeratin and E.M.A."n(Epithelial Membrane Antigen were positive in 69 percent and 74 percent respectively. Mean survival rate of all neuroendocrine carcinoma reached to 4.8 years with lowest survival of 4.3 years among small cell carcinoma and

  11. [Laryngeal neuroendocrine carcinoma: a case report].

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    Hallaoui, Y; El Kohen, A; Sefiani, S; Benchekroun, L; Jazouli, N; Kzadri, M

    2004-01-01

    Laryngeal neuroendocrine carcinomas are uncommon and not well known tumors. Three histological subtypes, each of them with a different prognosis and treatment, can be identified. We report a case of a large cell laryngeal neuroendocrine carcinoma in 32 old-year boy who presented a right glotto-subglottic tumoral process. The patient was treated by total laryngectomy associated with bilateral functional neck dissection but without postoperative chemotherapy. A disease recurrence occured three months after surgery consisting on a massive involvment of laterocervical and sus clavicular lymph nodes. The authors discussed the clinical features, the histological and immunohistochemical characteristics, the treatment and the prognosis of laryngeal neuroendocrine carcinoma, according to literature. (full article translated in English available on www.ent-review.com).

  12. Neuroendocrine carcinoma of the prostate gland.

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    Hoof, Pamela; Tsai-Nguyen, Ginger; Paulson, Scott; Syed, Almas; Mora, Adam

    2016-01-01

    Small cell prostate carcinoma (SCPC) has a clinical course and prognosis that is markedly different from that of common adenocarcinoma of the prostate. The patient in this case presented with fever of unknown origin, dyspnea, and near spinal cord compression. He was subsequently found to have widely metastatic high-grade neuroendocrine carcinoma of prostatic origin. This case emphasizes that despite the commonality of prostate cancer, there are rare presentations of this common disease.

  13. Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

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    Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

    2017-12-01

    Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Basal cell carcinoma with progression to metastatic neuroendocrine carcinoma: Case report and review of the literature

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    Volkan Adsay

    2010-03-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Merkel cell carcinoma (MCC or primary cutaneous neuroendocrine carcinoma is a malignant tumor considered to demonstrate differentiation towards Merkel cells that are present at the base of the epidermis or around the apical end of some hair follicles and are thought to play an yet uncertain role in sensory transduction. Here we present the case of a 54-year-old female with a basal cell carcinoma (BCC of the skin with neuroendocrine features (positivity for chromogranin that has evolved during multiple recurrences and radiotherapy into a high-grade neuroendocrine carcinoma with morphologic and immunohistochemical features of MCC (trabecular and nesting arrangement, positivity for chromogranin, cytokeratin 20, neuron specific enolase, and also neurosecretory granules on electron microscopy. The progression from a chromogranin positive basal cell carcinoma of the skin, to a high grade neuroendocrine carcinoma demonstrates the potential for cross differentiation among skin tumors.

  15. Large cell neuroendocrine carcinoma of the ampulla of Vater.

    LENUS (Irish Health Repository)

    Beggs, Rachel E

    2012-09-01

    Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution.

  16. Large-Cell Neuroendocrine Carcinoma of the Esophagus: A Case from Saudi Arabia

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    Hadi Kuriry

    2015-10-01

    Full Text Available Neuroendocrine carcinomas of the esophagus are very rare, and the majority are high grade (poorly differentiated. They occur most frequently in males in their sixth and seventh decades of life. There have been no concrete data published on clinical features or on prognosis. We report a case of large-cell neuroendocrine carcinoma of the esophagus in a 66-year-old Saudi female with progressive dysphagia and weight loss. Upper endoscopy revealed an esophageal ulcerated mass.

  17. Breast carcinoma with neuroendocrine features: a brief review

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    Petra Jurčić

    2016-06-01

    Full Text Available Breast carcinoma with neuroendocrine features (BCNF is a rare entity that is defined by a neuroendocrine (NE architecture and cytomorphology combined with an immunohistochemical expression of chromogranin A or B and/or synaptophysin. According to the 2012 World Health Organization (WHO classification, they are classified into three subtypes: invasive breast carcinoma with NE differentiation, well-differentiated NE tumor, and poorly differentiated small cell carcinoma. BCNF are typically positive for the estrogen and progesterone receptor and negative for Her-2/ neu protein. The clinical features are not sufficiently specific to distinguish BCNF from other breast carcinomas. BCNF can mimic benign lesions on mammography, so the additional use of ultrasound or MRI can improve detection. Other imaging tests are useful to detect or rule out metastatic disease. Although standardized treatment guidelines have not yet been established, the mainstay of treatment for early BCNFs is surgery. Adjuvant treatment decisions should be individualized and should take into consideration the prognostic and predictive factors, clinical evidence and the patient’s overall health treatment preferences. Therapeutic options in the metastatic setting include surgery, chemotherapy, peptide receptor radionuclide therapy and molecular-targeted agents. These options are not mutually exclusive and are interchangeable.

  18. A neuroendocrine carcinoma of undetermined origin in a dog.

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    Kuwata, Kazunori; Shibutani, Makoto; Kemmochi, Yusuke; Taniai, Eriko; Morita, Reiko; Ogawa, Bunichiro; Mitsumori, Kunitoshi

    2010-09-01

    In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-like structures. Scattered small necrotic foci and invasion to fibrous septa were typically observed. Neoplastic cells showed round to oval-shaped nuclei with prominent nucleoli and abundant eosinophilic cytoplasm that were positive for Grimelius' silver impregnation staining and immunostaining with cytokeratin, synaptophysin, vasoactive intestinal peptide and chromogranin A, indicative of the development of a neuroendocrine carcinoma. However, judging from the distribution of tumors lacking the portion suggestive of the primary site in any organ examined, as well as no further indication of differentiation potential of neoplastic cells, this tumor has so far been diagnosed as neuroendocrine carcinoma of undetermined origin.

  19. Neuroendocrine Carcinomas of the Gastroenteropancreatic System

    DEFF Research Database (Denmark)

    Ilett, Emma Elizabeth; Langer, Seppo W; Olsen, Ingrid Holst

    2015-01-01

    To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type....... Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4-16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning...... detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation...

  20. Colonic neuroendocrine carcinoma in a child

    International Nuclear Information System (INIS)

    Sasi, Omai Al; Rifai, Ayman; Hugosson, Claes; Sathiapalan, Rajeev; Kofide, Amani; Tulbah, Asthma Mahmoud Mohamed; Al-Mehaidib, Ali

    2005-01-01

    A 10-year-old boy with congenital immunodeficiency (X-linked agammaglobulinaemia) presented with loss of appetite and weight, right-sided abdominal pain, diarrhoea and low-grade fever. Radiological investigations with barium follow-through, CT, PET and octreotide scans revealed a primary caecal/ascending proximal colonic mass with liver and bony metastases. Urine screen for 5HIAA was positive. Percutaneous liver biopsy confirmed the diagnosis of neuroendocrine carcinoma. The radiological work-up and the usefulness of various imaging modalities in the diagnosis of this rare paediatric tumour are discussed. The PET scan demonstrated the primary tumour and the metastatic locations more vividly than the octreotide scan, which is currently considered to be the most specific imaging modality for neuroendocrine masses. (orig.)

  1. Cutaneous Metastasis of Neuroendocrine Carcinoma with Unknown Primary Site: Case Report and Review of the Literature.

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    Amorim, Gustavo Moreira; Quintella, Danielle; Cuzzi, Tullia; Rodrigues, Rosangela; Ramos-E-Silva, Marcia

    2015-01-01

    We report a new case of neuroendocrine carcinoma for which it was not possible to find the primary site until now. The recent medical literature about skin metastasis of neuroendocrine carcinoma (neuroendocrine tumor) is discussed.

  2. Cutaneous Metastasis of Neuroendocrine Carcinoma with Unknown Primary Site: Case Report and Review of the Literature

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    Gustavo Moreira Amorim

    2015-10-01

    Full Text Available We report a new case of neuroendocrine carcinoma for which it was not possible to find the primary site until now. The recent medical literature about skin metastasis of neuroendocrine carcinoma (neuroendocrine tumor is discussed.

  3. Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

    African Journals Online (AJOL)

    neuroendocrine carcinoma (NEC) of the breast as having more than 50% neoplastic tumor cells expressing neuroendocrine. (NE) markers.[2] These tumors are usually seen in elderly women around sixth or seventh decade of life as reported in literatures.[1,3] Herein we report a case of primary NCE of breast in a middle ...

  4. Neuroendocrine small cell carcinoma of the uterine cervix.

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    Reig Castillejo, Anna; Membrive Conejo, Ismael; Foro Arnalot, Palmira; Rodríguez de Dios, Nuria; Algara López, Manuel

    2010-07-01

    Neuroendocrine small cell carcinoma of the uterine cervix (SCC) is a rare disease that mixes clinical and biological characteristics of both cervical neoplasms and neuroendocrine small cell cancer. The prognosis is poor and the optimal treatment has not yet been clarified. Multimodality treatment, with surgery and concurrent chemoradiation has recently been shown to improve local control and survival rates.

  5. Targeting Neuroendocrine Differentiation for Prostate Cancer Radiosensitization

    Science.gov (United States)

    2014-10-01

    doses when ACREB was expressed (Fig. 6A). Because clonogenic assay assesses the reproductive ability of cells after a single exposure, which is...29] Slovin SF. Neuroendocrine differentiation in prostate cancer: a sheep in wolf’s clothing? Nat Clin Pract Urol. 2006;3:138-144. [30] Lilleby W

  6. Neuroendocrine differentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois

    2008-01-01

    Roč. 102, č. 5 (2008), s. 393 ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků. Konference Sigma-Aldrich /8./. 10.06.2008-13.06.2008, Devět skal - Žďárské vrchy] R&D Projects: GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * prostate cancer * neuroendocrine-like cells Subject RIV: BO - Biophysics

  7. Primary Neuroendocrine Carcinoma of Ocular Adnexa

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    Daisuke Yamanouchi

    2013-01-01

    Full Text Available We present our findings in a case of primary neuroendocrine carcinoma (NEC of the lacrimal gland and a case of primary Merkel cell carcinoma (MCC of the eyelid. An 86-year-old man noticed a swelling of the left upper eyelid three months earlier. We performed excision biopsy and histopathological examination indicated that he had a primary NEC of the left lacrimal gland. He underwent chemotherapy followed by excision including the clinically visible margins and 50 Gy radiotherapy of the surgical margins. He had neither recurrence nor metastasis for 6 months since the last radiotherapy. An 80-year-old man noticed a nodule in the right upper eyelid and was referred to our hospital because the size was increasing rapidly. A complete surgical excision of the margins of the tumor was performed with histopathological confirmation of negative margins. The final diagnosis was a primary MCC of the right upper eyelid. After surgery, he underwent 50 Gy radiotherapy on the neck to prevent metastasis. No recurrence or metastasis was found for two years. Although primary NEC of the ocular adnexa is extremely rare, the tumor has high malignancy and readily metastasizes. Thus, combined therapy including surgery, radiotherapy, and/or chemotherapy is needed for complete management of NEC.

  8. Primary small cell neuroendocrine carcinoma of the breast: a report of two cases and review of the literature

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    Spinelli C

    2013-09-01

    Full Text Available Primary neuroendocrine carcinomas of the breast are extremely rare. Neuroendocrine tumors mainly occur in the broncopolmonary system and gastrointestinal tract. The diagnosis of small cell neuroendocrine carcinoma (SCNC of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. We are going to describe two cases and to discuss their clinical, radiological and pathological manifestations. Introduction: Neuroendocrine tumors are rare and slow-growing neoplasias derived from neuroendocrine cells. We describe two cases of small cell neuroendocrine carcinoma of the breast and discuss their clinical, radiological and pathological manifestations. Case report: Our patients are two Italian females (38 and 36 year-old with no family history of breast disease. In both cases the diagnosis was confirmed after surgery, when immunohistochemistry revealed a neuroendocrine differentiation of the tumor. The patients are alive and disease free after more than ten years of follow-up. Conclusion: Primary neuroendocrine carcinomas of the breast are extremely rare. The diagnosis of SCNC of the breast can only be made if a non mammary site is excluded or if an in situ component can be found. After surgery, a strict follow-up including octreotide scan should be performed and this doesn’t differ from the one of the usual breast carcinoma.

  9. Immunohistochemical Analysis of Neuroendocrine (NE) Differentiation in Testicular Germ Cell Tumors (GCTs): Use of Confocal Laser Scanning Microscopy (CLSM) to Demonstrate Direct NE Differentiation from GCTs

    International Nuclear Information System (INIS)

    Kumaki, Nobue; Umemura, Shinobu; Kajiwara, Hiroshi; Itoh, Johbu; Itoh, Yoshiko; Osamura, R.Yoshiyuki

    2007-01-01

    Neuroendocrine (NE) differentiation is infrequent in testicular tumors and its histogenesis is not well understood. The present study is aimed at elucidating the pathway of neuroendocrine differentiation in germ cell tumors (GCTs) of the testis. In the analysis of 46 germ cell tumor components from 23 testicular tumors, we focused on GCTs with neuroendocrine differentiation, 7 teratoma, 1 embryonal carcinoma and 1 neuroendocrine carcinoma by immunohistochemical study and confocal laser scanning microscopy (CLSM) analysis. NE marker positive cells were noted in the tumor with collision of teratoma and embryonal carcinoma (E&T tumor), in the immature columnar cells of transitional form of embryonal carcinoma to teratoma (E-T cells) and neuroendocrine carcinoma cells, in addition to the well known mature intestinal mucosa in teratoma. Double staining for a NE marker (CGA) and a germ cell marker (PLAP) demonstrated the localization of both proteins in the same E-T cells confirmed by CLSM. Another finding, indicating the intimate relation between embryonal carcinoma and neuroendcrine differentiation, is that neuroendocrine carcinoma expressed a marker of embryonal carcinoma, CD30. The present results indicated that the NE cells might be differentiated from embryonal carcinoma, a view that has not been proposed before, but that is made in the present study using CLSM

  10. Metastatic primary neuroendocrine carcinoma of the breast (NECB

    Directory of Open Access Journals (Sweden)

    Tsung-Hsien Tsai

    2018-03-01

    Full Text Available Neuroendocrine carcinoma of the breast (NECB is a subtype of breast cancer. The diagnostic criteria of primary NECB were established in 2003 and updated in 2012. It is a rare entity, and few studies have reported the histogenesis, immunohistochemistry for a pathological diagnosis, clinical behavior, therapeutic strategies, and the prognostic factors. Because of the rarity of this disease, consistent diagnostic criteria will remind physicians of this disease when making a differential diagnosis to enable a timely diagnosis and prompt treatment. Herein, we report a case of primary NECB who presented with a history of right hip pain arising from an osteolytic lesion in the right acetabulum and ischium. The course of investigation started with metastasis in the right hip and concluded with a diagnosis of NECB. In addition to the case report, we also conducted a literature review.

  11. Primary giant hepatic neuroendocrine carcinoma: a case report.

    Science.gov (United States)

    Rocca, Aldo; Calise, Fulvio; Marino, Giuseppina; Montagnani, Stefania; Cinelli, Mariapia; Amato, Bruno; Guerra, Germano

    2014-01-01

    Carcinoid tumours arise from neuroendocrine cells and may develop in almost any organ. These type of tumours actually are correctly termed neuroendocrine tumours. Hepatic neuroendocrine carcinomas rarely arise as primary tumour; in fact on 100 cases reported in literature just a few of these are of primary nature. We report the case of a giant hepatic neuroendocrine carcinoma in a 55-year-old man. The symptoms were only recurrent hypoglycemia and an abdominal mass. Diagnosis was performed by blood analysis, ultrasonography, TC scan and In111-DTPA-octreotide scan. Surgical treatment occurred by an en bloc removal of the mass and a wide resection with free margins. Histological examination confirmed diagnosis. Clinical and instrumental diagnostic follow-up show the patient still alive, in very good conditions and disease free two years after surgery. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  12. Large Cell Neuroendocrine Carcinoma of the Rectum Presenting with Extensive Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Vinay Minocha

    2014-01-01

    Full Text Available Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.

  13. Radiosensitivity related to neuroendocrine and endodermal differentation in lung carcinoma lines

    International Nuclear Information System (INIS)

    Duchesne, G.; Casoni, A.; Pera, M.

    1988-01-01

    A panel of human lung carcinoma lines was studied with respect to hormone production and intermediate filament expression to distinguish between endodermal and neuroendocrine differentation. An index of the degree of neuroendocrine differentiation of each line was derived from the presence or absence of hormone production, cytokeratins, neurofilaments and an embryonic endodermal cell marker, which allowed identification of three groups showing high, intermediate or low neuroendocrine expression. This grouping correlated well with the in vitro radiosensitivity of the lines, those expressing pure neuroendocrine features being significantly more radiosensitive than those with an endodermal phenotype, with the intermediate group having intermediate sensitivity. Use of such an index might predict those patients likely to benefit from the use of radiotherapy in their management. 30 refs.; 3 figs.; 3 tabs

  14. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Paolo Aiello

    2014-01-01

    Full Text Available The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

  15. Pulmonary neuroendocrine carcinoma mimicking neurocysticercosis: a case report.

    Science.gov (United States)

    Lam, John C; Robinson, Stephen R; Schell, Andrew; Vaughan, Stephen

    2016-06-02

    Neurocysticercosis occurs when the eggs of the pork tapeworm (Taenia solium) migrate and hatch into larvae within the central nervous system. Neurocysticercosis is the most common cause of seizures in the developing world and is characterized on brain imaging by cysts in different stages of evolution. In Canada, cases of neurocysticercosis are rare and most of these patients acquire the disease outside of Canada. We report the case of a patient with multiple intracranial lesions whose history and diagnostic imaging were consistent with neurocysticercosis. Pathological investigations ultimately demonstrated that her brain lesions were secondary to malignancy. Brain metastases are considered to be the most common cause of intracranial cystic lesions. We present the case of a 60-year-old Canadian-born Caucasian woman with a subacute history of ataxia, lower extremity hyper-reflexia, and otalgia who resided near a pig farm for most of her childhood. Computed tomography and magnetic resonance imaging showed that she had multiple heterogeneous intracranial cysts, suggestive of neurocysticercosis. Despite a heavy burden of disease, serological tests for cysticercosis were negative. This result and a lack of the central scolices on neuroimaging that are pathognomonic of neurocysticercosis prompted whole-body computed tomography imaging to identify another etiology. The whole-body computed tomography revealed right hilar lymphadenopathy associated with soft tissue nodules in her chest wall and abdomen. A biopsy of an anterior chest wall nodule demonstrated high-grade poorly differentiated carcinoma with necrosis, which stained strongly positive for thyroid transcription factor-1 and synaptophysin on immunohistochemistry. A diagnosis of stage 4 metastatic small cell neuroendocrine carcinoma was made and our patient was referred for oncological palliative treatment. This case illustrates the importance of the diagnostic approach to intracranial lesions. Our patient

  16. Primary neuroendocrine carcinoma of breast: a rare case report ...

    African Journals Online (AJOL)

    Primary neuroendocrine carcinoma (PNEC) of breast was an unknown pathologic entity till recently due its rare incidence and lack of definitive criteria for diagnosis. We present a case of PNEC of breast in a middle aged lady. A 34 years lady presented with a breast lump since 1 month, who underwent modified radical ...

  17. Mixed acinar-neuroendocrine carcinoma of the pancreas

    DEFF Research Database (Denmark)

    Jakobsen, Mark; Klöppel, Günter; Detlefsen, Sönke

    2016-01-01

    cells in the cystic areas were reminiscent of acinar cells, and the majority was arranged in a solid growth pattern. Immunohistochemistry revealed >30% positivity for chymotrypsin, chromogranin A, synaptophysin, and CD56. The diagnosis of a mixed acinar-neuroendocrine carcinoma (MAEC) was made. Review...

  18. Primary neuroendocrine carcinoma of thymus: A rare cause of Cushing′s syndrome

    Directory of Open Access Journals (Sweden)

    Arora Raman

    2010-01-01

    Full Text Available Thymomas constitute majority of the thymic neoplasms. In contrast, neuroendocrine tumors (carcinoid and neuroendocrine carcinoma of thymus are extremely rare. Thymic carcinoids may present rarely with Cushing′s syndrome due to the ectopic production of adrenocorticotropic hormone (ACTH. Recognition of this association is imperative for appropriate management of patients. We describe three cases of rare atypical carcinoid tumor (neuroendocrine carcinoma of the thymus. Case 1, of a 26-year-old man presenting with Cushing′s syndrome, case 2 - a 23-year-old female with Cushingoid features, and Case 3 - a 39-year-old man complaining of progressively worsening dyspnea. Computed tomography (CT scans of chest in all three patients revealed anterior mediastinal mass. Excision of tumors and histological examination of the three tumors showed a carcinoid tumor with nuclear pleomorphism, increased mitotic activity and focal necrosis. The features suggested a diagnosis of atypical carcinoid tumor in all the three cases. The tumor cells in Cases 1 and 2 showed focal immunohistochemical staining for ACTH. Atypical carcinoid (neuroendocrine carcinoma, well-differentiated and moderately-differentiated of the thymus is a rare thymic tumor which carries a worse prognosis compared to thymoma and requires aggressive therapy. Hence, an accurate diagnosis is essential.

  19. Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Kim, Ji Hoon; Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2015-05-01

    To identify the CT features in differentiating grade 3 neuroendocrine carcinomas from grade 1/2 neuroendocrine tumours. This study included 161 patients with surgically confirmed pancreatic neuroendocrine neoplasms. Pathology slides were reviewed to determine the tumour grade. CT image analysis included size, pattern, calcification, margin, pancreatic duct dilatation, bile duct dilatation, vascular invasion, arterial enhancement ratio, and portal enhancement ratio. We used 2 cm, 3 cm, and 4 cm as cutoff values of tumour size and 0.9 and 1.1 of enhancement ratio to determine the sensitivity and specificity. Pathology analysis identified 167 lesions in 161 patients. 154 lesions (92 %) were grade 1/2 and 13 (8 %) were grade 3. Portal enhancement ratio (< 1.1) showed high sensitivity and specificity 92.3 % and 80.5 %, respectively in differentiating grade 3 from grade 1/2. It showed the highest odds ratio (49.60), followed by poorly defined margin, size (> 3 cm), bile duct dilatation, and vascular invasion. When at least two of these five criteria were used in combination, the sensitivity and specificity for diagnosing grade 3 were 92.3 % (12/13) and 87.7 % (135/154), respectively. By using specific CT findings, grade 3 can be differentiated from grade 1/2 with a high diagnostic accuracy leading to an appropriate imaging staging. (orig.)

  20. Chemotherapy for pulmonary large cell neuroendocrine carcinomas : Does the regimen matter?

    NARCIS (Netherlands)

    Derks, Jules L.; van Suylen, Robert Jan; Thunnissen, Erik; den Bakker, Michael A.; Groen, Harry J.; Smit, Egbert F.; Damhuis, Ronald A.; van den Broek, Esther C.; Speel, Ernst-Jan M.; Dingemans, Anne-Marie C.

    Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC. The Netherlands Cancer

  1. Gastric Collision Tumor Consisting of Mucinous Carcinoma and Large Cell Neuroendocrine Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Su Min; Lee, Ye Ri; Han, Eun Mee; Yeon, Jae Woo; Yoo, Jin Young; Choi, Jong Mun; Sim, Ji Ye [Bundang Jesaeng General Hospital, Seongnam (Korea, Republic of)

    2010-06-15

    The concurrence of two different pathological tumors of the stomach is infrequent. Even rarer is a gastric collision tumor of both tumor types. Although there have been a few reported cases of gastric collision tumors that consisted of an adenocarcinoma and neuroendocrine carcinoma, to the best of our knowledge, there is no documented case report of a gastric collision tumor consisting of a mucinous carcinoma and large cell neuroendocrine carcinoma. We report a case of gastric collision tumor, consisting of a mucinous carcinoma and large cell neuroendocrine carcinoma that presented as abdominal discomfort in a 64-year-old man. This finding draws attention to the related findings from previous studies on gastric collision tumors

  2. Secretagogin is a novel marker for neuroendocrine differentiation

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Wagner, Ludwig; Sørensen, Flemming Brandt

    2005-01-01

    tumors. Western blotting, immunohistochemistry, immunofluorescence microscopy and ELISA were applied. Western blot analysis detected a 32-kDa secretagogin band in samples from normal mucosa. Immunohistochemical analyses on tissue specimens showed that secretagogin is exclusively expressed...... in neuroendocrine cells and nerve cells in normal mucosa of the digestive tract. Tissues adjacent to benign hyperplasic polyps and adenomas showed a decreased number of secretagogin-expressing neuroendocrine cells. Secretagogin co-localized with neuroendocrine markers (chromogranin A, neuron-specific enolase......, synaptophysin) in neuroendocrine cells in crypts of normal mucosa, and in tumor cells of carcinoids. Secretagogin was strongly expressed in the cytosol and the nucleus of 19 well-differentiated neuroendocrine carcinoids and carcinoid metastases, as well as in neuroendocrine tumors from the lung, pancreas...

  3. Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmed M Ragab Shalaby

    2016-01-01

    Full Text Available Background: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. Materials and Methods: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. Results: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3–20% in 1 patient and neuroendocrine carcinoma (MIB-1: ≥21% in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. Conclusion: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis.

  4. A Neuroendocrine Carcinoma of Undetermined Origin in a Dog

    OpenAIRE

    Kuwata, Kazunori; Shibutani, Makoto; Kemmochi, Yusuke; Taniai, Eriko; Morita, Reiko; Ogawa, Bunichiro; Mitsumori, Kunitoshi

    2010-01-01

    In this report, we describe a case of neuroendocrine carcinoma of undetermined origin in a dog. Necropsy revealed scattered small neoplastic nodules in the bilateral lungs and a small nodule in the parapancreatic lymph node. Histopathologically, both pulmonary and lymph nodal nodules showed a similar histologic pattern, with neoplastic cells being arranged in diffusely proliferating sheet-like cellular nests separated by variable amounts of fibrous septa, sometimes forming rosettes and duct-l...

  5. Neuroendocrine carcinoma of the mammary gland in a dog.

    Science.gov (United States)

    Nakahira, R; Michishita, M; Yoshimura, H; Hatakeyama, H; Takahashi, K

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  7. Temozolomide as second or third line treatment of patients with neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Sørensen, Jens B; Federspiel, Birgitte

    2012-01-01

    Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results.......Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results....

  8. Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.

    Science.gov (United States)

    Claimon, Apichaya; Chuthapisith, Suebwong; Samarnthai, Norasate; Pusuwan, Pawana

    2015-08-01

    The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor

  9. Targeting neuroendocrine differentiation for prostate cancer radiosensitization

    Science.gov (United States)

    2017-12-01

    progression. Prostate, 2007. 67(7): p. 764-73. 17. Deeble, P.D., et al., Interleukin-6- and cyclic AMP -mediated signaling potentiates neuroendocrine...intracellular cyclic AMP . Proc Natl Acad Sci U S A, 1994. 91(12): p. 5330-4. 25. Amorino, G.P. and S.J. Parsons, Neuroendocrine cells in prostate cancer...Aggarwal S, Kim SW, Ryu SH, Chung WC and Koo JS. Growth suppression of lung cancer cells by targeting cyclic AMP response ele- ment-binding protein

  10. FOXA2 is a sensitive and specific marker for small cell neuroendocrine carcinoma of the prostate.

    Science.gov (United States)

    Park, Jung Wook; Lee, John K; Witte, Owen N; Huang, Jiaoti

    2017-09-01

    The median survival of patients with small cell neuroendocrine carcinoma is significantly shorter than that of patients with classic acinar-type adenocarcinoma. Small cell neuroendocrine carcinoma is traditionally diagnosed based on histologic features because expression of current immunohistochemical markers is inconsistent. This is a challenging diagnosis even for expert pathologists and particularly so for pathologists who do not specialize in prostate cancer. New biomarkers to aid in the diagnosis of small cell neuroendocrine carcinoma are therefore urgently needed. We discovered that FOXA2, a pioneer transcription factor, is frequently and specifically expressed in small cell neuroendocrine carcinoma compared with prostate adenocarcinoma from published mRNA-sequencing data of a wide range of human prostate cancers. We verified the expression of FOXA2 in human prostate cancer cell lines and xenografts, patient biopsy specimens, tissue microarrays of prostate cancers with lymph node metastasis, primary small cell neuroendocrine carcinoma, and metastatic treatment-related small cell neuroendocrine carcinoma and cases from a rapid autopsy program. FOXA2 expression was present in NCI-H660 and PC3 neuroendocrine cell lines, but not in LNCAP and CWR22 adenocarcinoma cell lines. Of the human prostate cancer specimens, 20 of 235 specimens (8.5%) showed diagnostic histologic features of small cell neuroendocrine carcinoma as judged histologically. Fifteen of 20 small cell neuroendocrine carcinoma tissues (75%) showed strong expression of FOXA2 (staining intensity 2 or 3). FOXA2 expression was also detected in 9 of 215 prostate cancer tissues (4.2%) that were histologically defined as adenocarcinoma. Our findings demonstrate that FOXA2 is a sensitive and specific molecular marker that may be extremely valuable in the pathologic diagnosis of small cell neuroendocrine carcinoma.

  11. Poorly-differentiated colorectal neuroendocrine tumour: CT differentiation from well-differentiated neuroendocrine tumour and poorly-differentiated adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ji Hee [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Se Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2017-09-15

    The differentiation of poorly-differentiated neuroendocrine tumours (PD-NETs), well-differentiated NETs (WD-NETs), and adenocarcinomas (ADCs) is important due to different management options and prognoses. This study is to find the differential CT features of colorectal PD-NETs from WD-NETs and ADCs. CT features of 25 colorectal WD-NETs, 36 PD-NETs, and 36 ADCs were retrospectively reviewed. Significant variables were assessed using univariate and multivariate analyses. Receiver operating characteristics analysis determined the optimal cut-off value of tumour and lymph node (LN) size. Large size, rectum location, ulceroinfiltrative morphology without intact overlying mucosa, heterogeneous attenuation with necrosis, presence of ≥3 enlarged LNs, and metastasis were significant variables to differentiate PD-NETs from WD-NETs (P < 0.05). High attenuation on arterial phase, persistently high enhancement pattern, presence of ≥6 enlarged LNs, large LN size, and wash-in/wash-out enhancement pattern of liver metastasis were significant variables to differentiate PD-NETs from ADCs (P < 0.05). Compared to WD-NETs, colorectal PD-NETs are usually large, heterogeneous, and ulceroinfiltrative mass without intact overlying mucosa involving enlarged LNs and metastasis. High attenuation on arterial phase, presence of enlarged LNs with larger size and greater number, and wash-in/wash-out enhancement pattern of liver metastasis can be useful CT discriminators of PD-NETs from ADCs. (orig.)

  12. Sexual differentiation and the neuroendocrine hypothesis of autism.

    Science.gov (United States)

    Aiello, Timothy P; Whitaker-Azmitia, Patricia M

    2011-10-01

    The phenotypic expression of autism spectrum disorders varies widely in severity and characteristics and it is, therefore, likely that a number of etiological factors are involved. However, one finding which has been found consistently is that there is a greater incidence of autism in boys than girls. Recently, attention has been given to the extreme male hypothesis-that is that autism behaviors are an extreme form of typical male behaviors, including lack of empathy and language deficits but an increase in so-called systemizing behaviors, such as attention to detail and collecting. This points to the possibility that an alteration during sexual differentiation of the brain may occur in autism. During sexual differentiation of the brain, two brain regions are highly sexually dimorphic-the amygdala and the hypothalamus. Both of these regions are also implicated in the neuroendocrine hypothesis of autism, wherein a balance between oxytocin and cortisol may contribute to the disorder. We are thus proposing that the extreme male hypothesis and the neuroendocrine hypothesis are in fact compatible in that sexual differentiation of the brain towards an extreme male phenotype would result in the neuroendocrine changes proposed in autism. We have preliminary data, treating developing rat pups with the differentiating hormone 17-β estradiol during a critical time and showing changes in social behaviors and oxytocin, to support this hypothesis. Further studies should be undertaken to confirm the role of extremes of normal sexual differentiation in producing the neuroendocrine changes associated with autism. Copyright © 2011 Wiley-Liss, Inc.

  13. Neuroendocrine Carcinomas of the Gastroenteropancreatic System: A Comprehensive Review

    Science.gov (United States)

    Ilett, Emma Elizabeth; Langer, Seppo W.; Olsen, Ingrid Holst; Federspiel, Birgitte; Kjær, Andreas; Knigge, Ulrich

    2015-01-01

    To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type. Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4–16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning surgery are often undecided and second-line chemotherapy is not yet established. After an analysis of over 2600 articles, we can conclude that there is indeed more empirical literature concerning GEP-NECs available than previously assumed. This unique review is based on 333 selected articles and contains detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation, diagnosis, treatment and survival are presented. Finally, key points are discussed with directions for future research priorities. PMID:26854147

  14. A Novel Case of Functional Gastric Neuroendocrine Carcinoma Occurred after Endoscopic Submucosal Dissection

    Directory of Open Access Journals (Sweden)

    Yoshiaki Shibata

    2013-01-01

    Full Text Available In Japan, endoscopic submucosal dissection (ESD is becoming a standard treatment for intramucosal differentiated gastric cancer. Although ESD is associated with a high cure rate for patients with early gastric cancer, tumors may recur, albeit rarely. We performed ESD on an 80-year-old man with a small depressed type of gastric cancer of the posterior wall of the cardia, found to be locally invasive on histology. Thirty months later, local recurrence and multiple liver metastases were detected, accompanied by frequent severe hypoglycemia. Despite chemotherapy, the patient died 6 months after relapse. On autopsy, the recurrent gastric lesion and liver metastases were examined immunohistochemically. Several characteristic tumor cells were positive for chromogranin A, cluster of differentiation (CD 56, Ki-67, and insulin-like growth factor (IGF-II. Western blot analysis of the patient’s serum obtained during a hypoglycemic attack showed the high molecular weight form of IGF-II or “big” IGF-II. The patient was diagnosed with non-islet cell tumor hypoglycemia (NICTH, with “big” IGF-II being produced by the gastric neuroendocrine carcinoma. This is the novel case of a functional gastric neuroendocrine carcinoma that occurred after ESD and induced a hypoglycemic attack associated with NICTH.

  15. Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Galleberg, R. B.; Knigge, U; Tiensuu Janson, E.

    2017-01-01

    Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce....

  16. Segregation of neuronal and neuroendocrine differentiation in the sympathoadrenal lineage.

    Science.gov (United States)

    Huber, Katrin

    2015-01-01

    Neuronal and neuroendocrine cells possess the capacity for Ca(2+)-regulated discharge of messenger molecules, which they release into synapses or the blood stream, respectively. The neural-crest-derived sympathoadrenal lineage gives rise to the sympathetic neurons of the autonomic nervous system and the neuroendocrine chromaffin cells of the adrenal medulla. These cells provide an excellent model system for studying common and distinct developmental mechanisms underlying the acquisition of neuroendocrine and neuronal properties. As catecholaminergic cells, they possess common markers related to noradrenaline synthesis, storage and release, but they also display diverging gene expression patterns and are morphologically and functionally different. The precise mechanisms that underlie the diversification of sympathoadrenal cells into neurons and neuroendocrine cells are not fully understood. However, in the past we could show that the establishment of a chromaffin phenotype does not depend on signals from the adrenal cortex and that chromaffin cells and sympathetic neurons apparently differ from the onset of their catecholaminergic differentiation. Nevertheless, the cues that specifically induce neuroendocrine features remain elusive. The early development of the progenitors of chromaffin cells and sympathetic neurons depends on a common set of transcription factors with overlapping but distinct influences on their development. In addition to the well-defined role of transcription factors as developmental regulators, our understanding of post-transcriptional gene regulation by microRNAs has substantially increased within the last few decades. This review highlights the major similarities and differences between chromaffin cells and sympathetic neurons, summarizes our current knowledge of the roles of selected transcription factors, microRNAs and environmental signals for the neuroendocrine differentiation of sympathoadrenal cells, and draws comparisons with the

  17. Neuroendocrine Tumors of the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Fisseler-Eckhoff, Annette, E-mail: Annette.Fisseler-Eckhoff@hsk-wiesbaden.de; Demes, Melanie [Department of Pathology und Cytology, Dr. Horst-Schmidt-Kliniken (HSK), Wiesbaden 65199 (Germany)

    2012-07-31

    Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1–G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

  18. Small cell neuroendocrine carcinoma of the endometrium, a rare aggressive tumor

    International Nuclear Information System (INIS)

    Rajab, Khalil E.; Sandhu, Amarjit K.; Rajeswari, Mangla S.; Malik, A.

    2005-01-01

    This is a report of a young infertile woman with a history of 8 years amenorrhea, who presented with history of vaginal bleeding of 2 months duration. Investigations revealed a small cell neuroendocrine carcinoma of the endometrium, which penetrated half of the thickness of uterine wall. We have described the clinical progress and management of this rare and highly malignant cancer. A review of the pathological types and behavior of clear cell neuroendocrine carcinoma is presented. (author)

  19. CT differentiation of poorly-differentiated gastric neuroendocrine tumours from well-differentiated neuroendocrine tumours and gastric adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Ho; Kim, Se Hyung; Shin, Cheong-il; Han, Joon Koo; Choi, Byung Ihn [Seoul National University Hospital, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Jongno-gu, Seoul (Korea, Republic of); Kim, Min-A [Seoul National University Hospital, Department of Pathology, Jongno-gu, Seoul (Korea, Republic of)

    2015-07-15

    To evaluate the differential CT features of gastric poorly-differentiated neuroendocrine tumours (PD-NETs) from well-differentiated NETs (WD-NETs) and gastric adenocarcinomas (ADCs) and to suggest differential features of hepatic metastases from gastric NETs and ADCs. Our study population was comprised of 36 patients with gastric NETs (18 WD-NETs, 18 PD-NETs) and 38 patients with gastric ADCs who served as our control group. Multiple CT features were assessed to identify significant differential CT findings of PD-NETs from WD-NETs and ADCs. In addition, CT features of hepatic metastases including the metastasis-to-liver ratio were analyzed to differentiate metastatic NETs from ADCs. The presence of metastatic lymph nodes was the sole differentiator of PD-NETs from WD-NETs (P =.001, odds ratio = 56.67), while the presence of intact overlying mucosa with mucosal tenting was the sole significant CT feature differentiating PD-NETs from ADCs (P =.047, odds ratio = 15.3) For hepatic metastases, metastases from NETs were more hyper-attenuated than those from ADCs. The presence of metastatic LNs and intact overlying mucosa with mucosal tenting are useful CT discriminators of PD-NETs from WD-NETs and ADCs, respectively. In addition, a higher metastasis-to-liver ratio may help differentiate hepatic metastases of gastric NETs from those of gastric ADCs with high accuracy. (orig.)

  20. Differentiated nasosinusal epidermoid carcinoma

    International Nuclear Information System (INIS)

    Palomo Luna, Jorge; Bestard Hartman, Isel de la Caridad; Fe Soca, Andres Manuel de la

    2012-01-01

    Two case reports of young patients, who were treated in the Otolaryngology Department from 'Dr. Joaquin Castillo Duany' Teaching Clinical Surgical Hospital in Santiago de Cuba are presented. One of the cases presented nasal obstruction, rhinorrhoea and facial pain, for 7 months; the other one presented an increase of volume in the right ocular globe. In both, the results of the biopsy confirmed the diagnosis of differentiated nasosinusal epidermoid carcinoma

  1. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

    Directory of Open Access Journals (Sweden)

    Andreas Krieg

    Full Text Available Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN according to their proliferation index into G1- or G2-neuroendocrine tumors (NET and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC. Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1 or lymph node metastases (NEC-DUE2 from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

  2. Neuro-endocrine tumours of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Soussi, A.C.; Benghiat, A.; Holgate, C.S.; Majumdar, B. (Derbyshire Royal Infirmary, Derby (UK))

    1990-06-01

    The authors report on two types of neuroendocrine carcinoma of the heat and neck, small cell carcinoma of the ethmoid and large cell carcinoma of the larynx, demonstrating a differential response to radiotherapy. (author).

  3. Primary Neuroendocrine Breast Carcinoma in a 13-Year-Old Girl: Ultrasonography and Pathology Findings

    Directory of Open Access Journals (Sweden)

    Mazamaesso Tchaou

    2017-01-01

    Full Text Available Neuroendocrine carcinoma (NEC of the breast is a rare disease and has been scarcely reported by African authors. The authors report a case of breast NEC in a 13-year-old African girl initially diagnosed as an atypical adenofibroma by ultrasonography. Ultrasound-guided biopsy and conventional histological examination indicated two potential diagnoses: primary malignant non-Hodgkin’s lymphoma and undifferentiated carcinoma. According to immunohistochemistry performed on paraffin blocks in France, infiltrating ductal carcinoma with a strong neuroendocrine component was confirmed by CD56, CD57, and chromogranin A markers.

  4. A Rare Case of Primary Infiltrating Neuroendocrine Carcinoma of the Breast

    International Nuclear Information System (INIS)

    Nawawi, Ouzreiah; Ying Goh, Keat; Rahmat, Kartini

    2012-01-01

    Primary neuroendocrine carcinoma of the breast is a very rare malignant tumor. There are not many cases reported in the English literature since it was first documented in 1983. Reports on the imaging features, in particular the ultrasonographic features of this rare tumor are scarce. Herein, we report a case of aggressive primary infiltrating neuroendocrine carcinoma of the breast, masquerading as an inflammatory breast condition in a 22-year-old young lady, perhaps the youngest case ever reported in the English literature. We discuss the imaging features and highlight the Doppler ultrasonographic findings of this rare breast carcinoma. This is the first documentation on Doppler ultrasonographic findings of primary neuroendocrine carcinoma of the breast in the literature

  5. INSM1 is a Sensitive and Specific Marker of Neuroendocrine Differentiation in Head and Neck Tumors.

    Science.gov (United States)

    Rooper, Lisa M; Bishop, Justin A; Westra, William H

    2018-05-01

    The head and neck is the site of a wide and sometimes bewildering array of neuroendocrine (NE) tumors. Although recognition of NE differentiation may be necessary for appropriate tumor classification and treatment, traditional NE markers such as synaptophysin, chromogranin, and CD56 are not always sufficiently sensitive or specific to make this distinction. Insulinoma-associated protein 1 (INSM1) is a novel transcription factor that has recently demonstrated excellent sensitivity and specificity for NE differentiation in various anatomic sites, but has not yet been extensively evaluated in tumors of the head and neck. We performed INSM1 immunohistochemistry on NE tumors (n=97) and non-NE tumors (n=626) across all histologic grades and anatomic subsites of the head and neck. INSM1 was positive in all types of head and neck NE tumors evaluated here (99.0% sensitivity), including middle ear adenoma, pituitary adenoma, paraganglioma, medullary thyroid carcinoma, olfactory neuroblastoma, small cell carcinoma, large cell NE carcinoma, and sinonasal teratocarcinosarcoma. Notably, it was positive in the vast majority of high-grade NE malignancies (95.8% sensitivity). INSM1 also was negative in almost all non-NE tumors (97.6% specificity) with the highest rates of reactivity in alveolar rhabdomyosarcoma and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily B, member 1 (SMARCB1)-deficient sinonasal carcinoma. These findings confirm that INSM1 may be used as a standalone first-line marker of NE differentiation for tumors of the head and neck.

  6. Primary neuroendocrine carcinoma of the thymus | Gaude | Nigerian ...

    African Journals Online (AJOL)

    Primary neuroendocrine tumors of the thymus, previously known as carcinoid tumors of the thymus, are unusual and rare tumors, and prognosis for these patients has been difficult to predict. We hereby report a case of primary neuroendocrine tumor of the thymus that had an aggressive and fatal course in spite of surgical ...

  7. Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation.

    Science.gov (United States)

    Papa, Anselmo; Rossi, Luigi; Verrico, Monica; Di Cristofano, Claudio; Moretti, Valentina; Strudel, Martina; Zoratto, Federica; Minozzi, Marina; Tomao, Silverio

    2017-09-01

    The lung large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensity to metastasize and very poor prognosis. We report an atypical presentation of lung LCNEC was diagnosed from a metastatic nodule on the breast. Our patient is a 59-years-old woman that presented in March 2014 nonproductive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment. © 2015 John Wiley & Sons Ltd.

  8. Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

    Directory of Open Access Journals (Sweden)

    Christopher Williams

    2005-01-01

    Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

  9. Tissue microarray analysis as a screening tool for neuroendocrine carcinoma of the breast

    DEFF Research Database (Denmark)

    Brask, Julie Benedicte; Talman, Maj-Lis Møller; Wielenga, Vera Timmermans

    2014-01-01

    Neuroendocrine carcinoma of the breast (NCB) is a fairly recent diagnostic entity added by WHO in 2003. Since then, studies have indicated that NCB potentially displays a worse prognosis than invasive ductal carcinoma. However, due to a lack of standard use of immunohistochemical staining...... for neuroendocrine markers and the fact that NCB may only show slight neuroendocrine morphology that can easily be overlooked, NCB is often underdiagnosed. Consequently, there is a need for fast and reliable detection method for NCB. Here, we take a first step toward finding an easy way of identifying NCB...... by investigating the usefulness of tissue microarray (TMA) analysis as a screening tool. We present our findings with regard to sensitivity and specificity compared with whole-mount sections. The material consists of 240 cases of breast cancer divided into 20 TMA blocks that were all immunohistochemically stained...

  10. MR imaging features and staging of neuroendocrine carcinomas of the uterine cervix with pathological correlations

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Xiaohui; Zhang, Xiang; Hu, Huijun; Li, Guozhao; Wang, Dongye; Zhang, Fang; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou (China); Ban, Xiaohua [Sun Yat-Sen University, Medical Imaging and Minimally Invasive Interventional Center and State Key Laboratory of Oncology in Southern China, Cancer Center, Guangzhou, Guangdong (China); Wang, Charles Qian [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou (China); University of New South Wales, JMO, Westmead Hospital, Sydney (Australia)

    2016-12-15

    To determine MR imaging features and staging accuracy of neuroendocrine carcinomas (NECs) of the uterine cervix with pathological correlations. Twenty-six patients with histologically proven NECs, 60 patients with squamous cell carcinomas (SCCs), and 30 patients with adenocarcinomas of the uterine cervix were included. The clinical data, pathological findings, and MRI findings were reviewed retrospectively. MRI features of cervical NECs, SCCs, and adenocarcinomas were compared, and MRI staging of cervical NECs was compared with the pathological staging. Cervical NECs showed a higher tendency toward a homogeneous signal intensity on T2-weighted imaging and a homogeneous enhancement pattern, as well as a lower ADC value of tumour and a higher incidence of lymphadenopathy, compared with SCCs and adenocarcinomas (P < 0.05). An ADC value cutoff of 0.90 x 10{sup -3} mm{sup 2}/s was robust for differentiation between cervical NECs and other cervical cancers, with a sensitivity of 63.3 % and a specificity of 95 %. In 21 patients who underwent radical hysterectomy and lymphadenectomy, the overall accuracy of tumour staging by MR imaging was 85.7 % with reference to pathology staging. Homogeneous lesion texture and low ADC value are likely suggestive features of cervical NECs and MR imaging is reliable for the staging of cervical NECs. (orig.)

  11. Gene expression signatures of neuroendocrine prostate cancer and primary small cell prostatic carcinoma.

    Science.gov (United States)

    Tsai, Harrison K; Lehrer, Jonathan; Alshalalfa, Mohammed; Erho, Nicholas; Davicioni, Elai; Lotan, Tamara L

    2017-11-13

    Neuroendocrine prostate cancer (NEPC) may be rising in prevalence as patients with advanced prostate cancer potentially develop resistance to contemporary anti-androgen treatment through a neuroendocrine phenotype. While prior studies comparing NEPC and prostatic adenocarcinoma have identified important candidates for targeted therapy, most have relied on few NEPC patients due to disease rarity, resulting in thousands of differentially expressed genes collectively and offering an opportunity for meta-analysis. Moreover, past studies have focused on prototypical NEPC samples with classic immunohistochemistry profiles, whereas there is increasing recognition of atypical phenotypes. In the primary setting, small cell prostatic carcinoma (SCPC) is frequently admixed with adenocarcinomas that may be clonally related, and a minority of SCPCs express markers typical of prostatic adenocarcinoma while rare cases do not express neuroendocrine markers. We derived a meta-signature of prototypical high-grade NEPC, then applied it to develop a classifier of primary SCPC incorporating disease heterogeneity. Prototypical NEPC samples from 15 patients across 6 frozen tissue microarray datasets were assessed for genes with consistent outlier expression relative to adenocarcinomas. Resulting genes were used to determine subgroups of primary SCPCs (N=16) and high-grade adenocarcinomas (N=16) profiled by exon arrays using formalin-fixed paraffin-embedded (FFPE) material from our institutional archives. A subgroup classifier was developed using differential expression for feature selection, and applied to radical prostatectomy cohorts. Sixty nine and 375 genes demonstrated consistent outlier expression in at least 80% and 60% of NEPC patients, with close resemblance in expression between NEPC and small cell lung cancer. Clustering by these genes generated 3 subgroups among primary samples from our institution. Nearest centroid classification based on the predominant phenotype from each

  12. Outcome and CT differentiation of gallbladder neuroendocrine tumours from adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae-Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Se Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital and Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Lee, Kyoung Boon [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of)

    2017-02-15

    To retrospectively investigate clinical outcome and differential CT features of gallbladder (GB) neuroendocrine tumours (NETs) from adenocarcinomas (ADCs). Nineteen patients with poorly-differentiated (PD) NETs and 19 patients with PD ADCs were enrolled. Clinical outcome was compared by the Kaplan-Meier method. We assessed qualitative and quantitative CT features to identify significant differential CT features of PD NETs from ADCs using univariate and multivariate analyses. Receiver operating characteristic (ROC) analysis was used for quantitative CT features. PD NETs showed poorer prognosis with significantly shorter median survival days than ADCs (363 vs. 590 days, P = 0.03). On univariate analysis, NETs more frequently manifested as GB-replacing type and showed well-defined margins accompanied with intact overlying mucosa. On multivariate analysis, well-defined margin was the sole significant CT differentiator (odds ratio = 27.817, P = 0.045). Maximum size of hepatic and lymph node (LN) metastases was significantly larger in NETs (11.0 cm and 4.62 cm) than ADCs (2.40 cm and 2.41 cm). Areas under ROC curves for tumour-to-mucosa ratio, maximum size of hepatic and LN metastasis were 0.772, 0.932 and 0.919, respectively (P < 0.05). GB PD NETs show poorer prognosis than ADCs. Well-defined margin, larger hepatic and LN metastases are useful CT differentiators of GB NETs from ADCs. (orig.)

  13. Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of Bladder Neuroendocrine Carcinoma.

    Science.gov (United States)

    Zhou, Hui-Hui; Liu, Li-Yan; Yu, Guo-Hua; Qu, Gui-Mei; Gong, Pei-You; Yu, Xiao; Yang, Ping

    2017-08-01

    Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis. The clinicopathological data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650 days) were analyzed retrospectively based on immunohistochemical staining. Survival analyses were carried out using the Kaplan-Meier method and tested with the log-rank method. Multivariate Cox regression analysis was adopted to screen independent risk factors affecting patients' survival. In these 39 cases of BNEC, there were 26 cases of male patients, 13 female, with the proportion of male to female being 2:1. The ages of onset ranged from 44 to 86, with the median age being 62 and the average age 61.97 years, respectively. Histologically, referring to the WHO standard of neuroendocrine lung tumor classification, there were 7 cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas and 12 large-cell carcinomas. In these cases there were 11 cases of featured urothelium carcinomas and 9 cases of adenocarcinomas. Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive expression for the neuroendocrinic markers, including neural cell adhesion molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and 8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common antigen (LCA) were all negatively expressed. During the follow-up period, 12 patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%, 74

  14. Primary small cell neuroendocrine carcinoma of the breast: The histogenetic diatribe

    Directory of Open Access Journals (Sweden)

    Cabibi D

    2013-12-01

    Full Text Available The article entitled “Primary small cell neuroendocrine carcinoma of the breast: a report of two cases and review of the literature” by Spinelli et al. [1]. The authors stated that “the histogenesis is still unclear because the presence of neuroendocrine cells in normal breast has not been proved conclusively”. Moreover they reported two histogenetic hypotheses, the first one stating that “small cell neuroendocrine carcinoma (SCNC is a variant of metaplastic carcinoma arising from a lobular or ductal carcinoma”, the second one claiming that “it is a distinct type of breast carcinoma different from the usual type”. We appreciate this case report and we agree with the authors on the histogenetic diatribe of this rare type of breast neoplasia. In this background, we would highlight our previous case report about a solid variant of mammary adenoid cystic carcinoma merging with "small cell carcinoma" [2] in which we found positivity for CD10 and S100 and negativity for estrogen receptors, both in sbACC and in SCC, in keeping with a myoepithelial origin of both neoplastic areas [3] supporting the hypothesis that the “two components share the same histogenetic myoepithelial origin and represent an example of dedifferentiation along neuroendocrine phenotype lines occurring in a multipotential neoplastic stem line, already committed towards a myoepithelial phenotype”. These findings are in keeping with the first hypothesis about the metaplastic, divergent histogenetic nature of SNSC and we think that this rare SNSC, albeit arising from a different tumor, could be introduced in this case review of the literature, also for its contribute to the histogenetic diatribe.

  15. Androgen-deprivation therapy-induced aggressive prostate cancer with neuroendocrine differentiation

    Directory of Open Access Journals (Sweden)

    Julia Lipianskaya

    2014-08-01

    Full Text Available Most prostate cancers (PCas are classified as acinar type (conventional adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor (AR and prostate-specific antigen (PSA. There are also scattered neuroendocrine (NE cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.

  16. Interplay of CREB and ATF2 in Ionizing Radiation-Induced Neuroendocrine Differentiation of Prostate Cancer Cells

    Science.gov (United States)

    2011-06-01

    cancer cells to transdifferentiate into neuroendocrine-like (NE-like) cells, a process also known as neuroendocrine differentiation (NED) that is associated with disease progression and...by which prostate cancer cells survive the treatment and contribute to

  17. An Eustachian Tube Neuroendocrine Carcinoma: A Previously Undescribed Entity and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Gavin J. le Nobel

    2016-01-01

    Full Text Available Primary sinonasal and middle ear neuroendocrine carcinomas are rare malignancies of the head and neck. Owing to the rarity of these tumors, the clinical behavior and optimal management of these tumors are not well defined. We present a case of an incidentally discovered sinonasal neuroendocrine carcinoma that was found to originate from the Eustachian tube, which has not previously been described in the literature. This patient was treated with primary surgical resection using a combination of transnasal and transaural approaches and achieved an incomplete resection. Follow-up imaging demonstrated continued tumor growth in the Eustachian tube as well as a new growth in the ipsilateral cerebellopontine angle and findings suspicious of perineural invasion. However, the tumor exhibited a benign growth pattern and despite continued growth the patient did not receive additional treatment and he remains asymptomatic 35 months following his original surgery.

  18. Topotecan Monotherapy in Heavily Pretreated Patients with Progressive Advanced Stage Neuroendocrine Carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Knigge, Ulrich; Federspiel, Birgitte

    2014-01-01

    BACKGROUND: Neuroendocrine carcinomas (WHO grade 3) are highly aggressive tumors with an immense tendency to metastasize and with a poor prognosis. In advanced disease, there is no standard treatment beyond first-line platin/etoposide-based chemotherapy. Topotecan is widely used as second...... neuroendocrine carcinomas (Ki67>20%, G3) successively treated with oral topotecan 2.3 mg/m(2) d1-5 every 3 weeks. All patients had previously received treatment with carboplatin/etoposide. Demographic, clinical and pathological features were recorded. CT-evaluations according to RECIST 1.1 were performed after...... patients were evaluable for response: Five achieved stable disease (SD) and 17 progressed (PD). The median overall survival for the 22 patients was 3.2 months and the median progression-free survival was 2.1 months. The one-year survival was 18%. There were no treatment related deaths. The treatment...

  19. Evaluation of somatostatin receptors in large cell pulmonary neuroendocrine carcinoma with 99mTc-EDDA/HYNIC-TOC scintigraphy.

    Science.gov (United States)

    Nocuń, Anna; Chrapko, Beata; Gołębiewska, Renata; Stefaniak, Bogusław; Czekajska-Chehab, Elżbieta

    2011-06-01

    Large cell pulmonary neuroendocrine carcinoma (LCNEC) is a poorly differentiated and high-grade neoplasm. It is positioned between an atypical carcinoid and small cell neuroendocrine carcinoma of the lung in a distinct family of pulmonary neuroendocrine tumors. The aim of our study was to detect somatostatin receptors in this uncommon malignancy and to evaluate the sensitivity of somatostatin receptor scintigraphy (SRS) in LCNEC staging. We analyzed data of 26 patients (mean age: 61.5±7.9 years) with histologically confirmed diagnosis of LCNEC, including 18 cases not treated surgically and eight patients after the resection of the primary tumor. SRS was carried out with technetium-99m ethylene diamine-diacetic acid/hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC). A visual analysis of scintigraphic images was done with reference to conventional imaging modalities (computed tomography and bone sicintigraphy). SRS sensitivity for the detection of primary lesions, supradiaphragmatic metastases, and infradiaphragmatic metastases was 100, 83.3%, and 0%, respectively. Five out of 13 metastases to the liver appeared on SRS as photopenic foci, visible on the background of physiological hepatic activity. Only one of the nine metastases to the skeletal system was found by SRS with sensitivity as low as 11.1%. The overall SRS sensitivity for the detection of secondary lesions and of all lesions was 54.8 and 62.2%, respectively. Within a rather large series of LCNEC, the primary tumor showed an uptake of Tc-TOC in all cases, whereas some metastases did show Tc-TOC uptake and some others did not.

  20. Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

    African Journals Online (AJOL)

    whole body computed tomography and magnetic resonance imaging revealed no extra mammary primary tumor. Hence the diagnosis of PNEC of breast was confirmed. Patient received chemo and hormonal therapy and doing well after 6 months of follow up. Keywords: Breast carcinoma, Immunohistochemistry, ...

  1. Neuroendocrine carcinoma of the breast - a pilot study of a Danish population of 240 breast cancer patients

    DEFF Research Database (Denmark)

    Brask, Julie Benedicte; Talman, Maj-Lis Møller; Wielenga, Vera Timmermans

    2014-01-01

    Neuroendocrine carcinoma of the breast - a very recent diagnosis, which was not recognized by WHO until 2003 - has lately been the subject of increasing attention. It is defined as a primary breast cancer with morphologic features similar to other types of neuroendocrine tumors of the lung......, apparent limitations of the WHO definition appear to influence diagnosis. Here, we present our own results obtained from 13 cases and furthermore review previous reports with particular reference to incidence, clinical, histological, and prognostic features....

  2. [Neuroendocrine carcinoma of the urinary bladder. A case report].

    Science.gov (United States)

    Aragón-Tovar, Anel Rogelio; Pineda-Rodríguez, Marco Elí; Puente-Gallegos, Francisco Edgardo; Zavala-Pompa, Angel

    2014-01-01

    Small cell carcinoma of the urinary bladder is an infrequent lesion. We present the case of a 68-year-old male who arrived at the emergency room with a history of 24-h gross hematuria. Imaging studies show a urinary bladder tumor with a 218 cc volume that during a 20-day period increased to 426 cc. Histopathological images with hematoxylin-eosin show an infiltrating solid mass with uneven borders. It is composed of neoplastic cells with evident nuclei predominance and scant cytoplasm (small cells). Chromogranin immunohistochemical staining shows a diffusely positive cytoplasmic granular pattern on neoplastic cells. High molecular weight cytokeratin staining shows a negative pattern on neoplastic cells along with a positive pattern on reporsurrounding normal urothelium. Tumoral mass is positive for synaptophysin and CD-56 and negative for CK-7 and CK-20. Patient therapy was based on radiation plus chemotherapy. Small cell carcinoma of the urinary bladder represents 0.35-0.70% of urinary bladder tumors. Histological and immunohistochemical identification are key elements in the diagnosis. Treatment approach is based on cisplatin-based chemotherapy plus radical cystectomy, except when metastatic disease is present.

  3. Neuroendocrine differentiation in a case of cervical cancer | Rashed ...

    African Journals Online (AJOL)

    Neuroendocrine neoplasms may occur in the uterine cervix, although rarely; it accounts for 0.5-1% of all malignant tumors of the uterine cervix. A case report of an Ethiopian female presented at the Gynecology Out-Patient Clinic at Jimma University Hospital, complaining from irregular vaginal bleeding over the previous ...

  4. End-Stage Renal Disease From Cast Nephropathy in a Teenager With Neuroendocrine Carcinoma.

    Science.gov (United States)

    Butani, Lavjay; Ducore, Jonathan

    2016-07-01

    Cast nephropathy is the most common manifestation of renal injury in patients with multiple myeloma but is rarely reported in other conditions. We are reporting our experience in caring for a teenager with a metastatic neuroendocrine carcinoma who developed rapidly progressive kidney injury that advanced to end-stage renal disease. On renal biopsy extensive tubular necrosis and intratubular eosinophilic casts were noted. This previously unreported finding should prompt oncologists to closely monitor for such a complication in patients with secretory tumors. Whether early plasmapheresis could be of benefit, as has been tried in multiple myeloma, remains to be determined.

  5. Cutaneous Neuroendocrine Carcinoma of the External Auditory Canal: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yi-Ke Li

    2012-01-01

    Full Text Available Cutaneous neuroendocrine carcinoma (cNEC is rarely seen in the external ear. In this paper, we newly describe a patient with cNEC in his right external auditory canal, followed by a further discussion on the clinical features, diagnosis, and treatments of cNEC of the external ear. A review of the literature showed that cNEC of the external auditory canal generally presents as asymptomatic and that pathology yields the most confirmative diagnosis. A wide resection with adjuvant radiotherapy and chemotherapy is recommended. The overall prognosis of this condition is poor.

  6. Large-cell neuroendocrine carcinoma of the uterine cervix- a ...

    African Journals Online (AJOL)

    On histopathological examination, all 5 tumours showed features of a high-grade poorly differentiated malignant neoplasm with ulceration and extensive tumour necrosis including trabecular and organoid growth patterns. All 5 neoplasms also showed strong immunoreactivity for MNF116, while their endocrine nature was ...

  7. Vascular thrombosis as a cause of abdominal pain in a patient with neuroendocrine carcinoma of pancreas: Findings on 68Ga-DOTANOC PET/CT

    International Nuclear Information System (INIS)

    Naswa, Niraj; Kumar, Rakesh; Bal, Chandrasekhar; Malhotra, Arun

    2012-01-01

    Neuroendocrine tumors of pancreas are relatively rare neoplasms and are classified as either functioning or non-functioning tumors. A 55-year-old female diagnosed with a large, well-differentiated, non-functional neuroendocrine carcinoma of pancreas, presented with abdominal pain of increasing severity. A contrast-enhanced examination of the abdomen was performed to reveal a large, diffuse, enhancing pancreatic mass with multiple filling defects within the mesenteric vasculature. We present findings on 68 Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI 3 -Octreotide, positron emission tomography-computed tomography ( 68 Ga-DOTANOC PET/CT) and the importance of somatostatin receptor-based PET imaging in such patients

  8. Primary Small Cell Neuroendocrine Carcinoma of the Nasal Cavity After Successful Curative Therapy of Nasopharyngeal Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Chien-Heng Lin

    2009-03-01

    Full Text Available Patients with head and neck cancer have a greater risk of developing second primary malignant neoplasms than patients with any other type of malignancy. Small cell neuroendocrine carcinoma (SNEC mainly occurs in the lung, and is rarely found in the head and neck region. Only a few cases of sinonasal SNEC have been reported in the English literature. A woman aged 53 years, who had undergone successful curative radiotherapy for nasopharyngeal carcinoma 10 years earlier, presented with a history of bleeding from the left nostril for several weeks. A computed tomography scan of the head and neck showed a mass in the left nasal cavity with extension into the maxillary sinus. A biopsy specimen was taken and pathology revealed SNEC. The patient underwent a full course of concurrent chemoradiotherapy. No local recurrence or distant metastasis was noted during the 12 months of follow-up.

  9. Primary large cell neuroendocrine carcinoma of the breast, a case report with an unusual clinical course.

    Science.gov (United States)

    Janosky, Maxwell; Bian, Jessica; Dhage, Shubhada; Levine, Jamie; Silverman, Joshua; Jors, Kathryn; Moy, Linda; Cangiarella, Joan; Muggia, Franco; Adams, Sylvia

    2015-01-01

    Large cell neuroendocrine carcinoma of the breast (NECB) is an extremely rare type of breast cancer; little is known about effective chemotherapies, and data on pathologic response to treatment are unavailable. We report the case of a 34-years-old woman with large cell NECB with initial clinical and pathologic evidence of treatment response to anthracycline-containing neo-adjuvant therapy. Histologic reassessment early during anthracycline chemotherapy revealed cell death with necrosis of 50% of the tumor cells seen in the biopsy specimen. After completing neo-adjuvant chemotherapy, the patient underwent breast-conserving surgery. Pathologic evaluation of the surgical specimen showed a partial response but margins were positive for residual carcinoma. Despite repeated neo-adjuvant chemotherapy, radiotherapy, and surgical resection, the tumor grew rapidly between surgeries and recurred systemically. Therefore, we review the literature on large cell NECB and its treatment options. © 2015 Wiley Periodicals, Inc.

  10. Anti-N-methyl-D-aspartate receptor encephalitis associated with hepatic neuroendocrine carcinoma: A case report.

    Science.gov (United States)

    Lim, Ee Wei; Yip, Chun Wai

    2017-07-01

    Anti-N-methyl-D-aspartate receptor (Anti-NMDAR) encephalitis can present with and without tumor. Tumor associations are less common in older patients. We report a 65-year-old gentleman who presented with one week history of cough, chills, rigor and altered behavior, followed by florid visual and auditory hallucinations. Mini mental status examination score was 16/30. Both cerebrospinal fluid and plasma anti-NMDA receptor antibodies were detected. A course of intravenous methylprednisolone was given with partial symptom improvement. A hepatic neuroendocrine carcinoma was detected and confirmed on biopsy. Unfortunately, he developed several medical complications: non-ST elevation myocardial infarction, infected foot gangrene and peripheral vascular disease, which made him unsuitable for both surgery and chemotherapy. He passed away 6months later due to the progression of the malignancy. This case illustrated that NMDAR encephalitis may be associated with an uncommon hepatic neuroendocrine carcinoma in an older person, which is responsive to early treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Small-cell neuroendocrine carcinoma of the esophagus: an autopsy case report

    Directory of Open Access Journals (Sweden)

    Mariana Bellaguarda de Castro Sepulvida

    2014-03-01

    Full Text Available Small-cell neuroendocrine carcinoma is a well-known aggressive neoplasia, which is usually associated with a poor prognosis. The lung is the most common primary site, but other organs may be involved, especially those of the digestive tract. The authors report the case of a 71-year-old Caucasian, male patient who was admitted because of congestive heart failure and loss of vision accompanied by right proptosis. Skull and sinuses computed tomography showed a tumoral mass involving the posterior region of the right eye, local bones, and paranasal sinuses. Because of severe hemodynamic instability, the patient died and no diagnostic investigation could be performed. Autopsy findings revealed small-cell neuroendocrine carcinoma of the esophagus and metastases to the posterior region of the right ocular globe, which affected the sinuses, the muscles of the ocular region, the orbit bones, the skull, the meninges and the brain, plus the liver, adrenal glands, and the pericardium. This case called the author’s attention to the extent of the metastatic disease in a patient who was firstly interpreted as presenting solely with congestive heart failure. The autopsy findings substantially aid the understanding of the immediate cause of death.

  12. Pancreatic neuroendocrine tumor - incidental finding during a follow-up CT for primary ovarian carcinoma

    International Nuclear Information System (INIS)

    Ivanova, D.; Balev, B.

    2013-01-01

    Pancreatic neuroendocrine tumors (PNET) are primary, usually we 11-differentiated pancreatic tumors. Their origin is not fully understood, but they are thought to develop from the pluripotent cells in the exocrine part of the pancreas. PNET are a heterogeneous group with different malignant potential. In some of the patients with sporadical forms of PNET there is association with other malignancies such as ovarian cancer, breast cancer, bladder and prostate cancers. We present a case of 50-year-old woman, with incidentally found pancreatic neoplasm, during a follow-up CT for ovarian cancer. Laparotomy and pancreatic biopsy are performed. Histological diagnosis confirms a well- differentiated endocrine tumor of the pancreas. (authors)

  13. West Nile Virus Encephalitis in a Patient with Neuroendocrine Carcinoma

    Directory of Open Access Journals (Sweden)

    Romina Deldar

    2016-01-01

    Full Text Available Importance. Oftentimes, when patients with metastatic cancer present with acute encephalopathy, it is suspected to be secondary to their underlying malignancy. However, there are multiple causes of delirium such as central nervous system (CNS infections, electrolyte abnormalities, and drug adverse reactions. Because West Nile Virus (WNV neuroinvasive disease has a high mortality rate in immunosuppressed patients, a high index of suspicion is required in patients who present with fever, altered mental status, and other neurological symptoms. Observations. Our case report details a single patient with brain metastases who presented with unexplained fever, encephalopathy, and new-onset tremors. Initially, it was assumed that his symptoms were due to his underlying malignancy or seizures. However, because his unexplained fevers persisted, lumbar puncture was pursued. Cerebrospinal fluid analysis included WNV polymerase chain reaction and serologies were ordered which eventually led to diagnosis of WNV encephalitis. Conclusions and Relevance. Patients with metastatic cancer who present with encephalopathy are often evaluated with assumption that malignancy is the underlying etiology. This can lead to delays in diagnosis and possible mistreatment. Our case highlights the importance of maintaining a broad differential diagnosis and an important diagnostic consideration of WNV encephalitis in patients with cancer.

  14. ACTH-secreting pancreatic neuroendocrine carcinoma with ovarian and pelvic metastases causing Cushing's syndrome: a case report.

    Science.gov (United States)

    Yao, Wen-Qing; Wu, Xia; Li, Gan-Di; Wu, Wei-Lu; Wang, Wei-Ya

    2015-01-01

    Adrenocorticotropin hormone (ACTH)-secreting pancreatic neuroendocrine carcinoma (NEC) with ovarian and pelvic metastases causing Cushing's syndrome is very rare and might be misdiagnosed. We describe a case of ACTH-secreting pancreatic poorly differentiated NEC developing bilateral ovarian and pelvic metastases. A 27-year-old woman presented with thirst, polydipsia, fatigue and poorly controlled hyperglycemia. Laboratory and imaging investigations revealed hypokalemia, hyperglycaemia, ACTH-dependent hypercortisolemia and a 12-cm mass at the junction of body and tail of the pancreas with ovarian and pelvic nodules. The patient underwent partial pancreatectomy and splenectomy, uterectomy, bilateral oophorectomy, and excision of peritoneal nodules. Tumors in pancreas, ovaries and pelvis were diagnosed as poor-differentiated NEC. After 19-month chemotherapy, she developed pelvic metastasis. The tumor in our case is a large, poorly differentiated NEC secreting ACTH and causing CS, with ovarian metastases. To our knowledge, this new additional case of ACTH-secreting pancreatic NEC with ovarian metastases would add to the better understanding of this tumor.

  15. Vulvar mucinous adenocarcinoma with neuroendocrine differentiation: A case report and review of the literature

    NARCIS (Netherlands)

    Rosmalen, M.H. Van; Reijnen, C.; Boll, D.; Pijnenborg, J.M.A.; Wurff, A.A. van der; Piek, J.M.

    2016-01-01

    BACKGROUND: There are limited cases in literature of patients with mucinous adenocarcinoma of the vulva with neuroendocrine differentiation have. With this new case, we aim to provide an overview of the existing literature and present a tool with relevant markers for the pathologist in the

  16. Aberrant expression of cystatin C in prostate cancer is associated with neuroendocrine differentiation.

    Science.gov (United States)

    Jiborn, Thomas; Abrahamson, Magnus; Gadaleanu, Virgil; Lundwall, Ake; Bjartell, Anders

    2006-07-01

    To investigate the expression of cystatin C and the relationship with neuroendocrine differentiation and proliferation in benign and malignant prostatic tissues, as cystatin C, the most important inhibitor of human lysosomal cysteine proteases, is considered to be a major regulator of pathological protein degradation in inflammatory and neoplastic diseases. Immunoreactivity for cystatin C, prostate-specific antigen, Ki-67 and the neuroendocrine marker chromogranin A was examined in whole-mount radical prostatectomy specimens and using tissue microarrays. Cystatin C in tissue homogenates was analysed by Western blotting and enzyme-linked immunosorbent assay (ELISA). The expression and relative levels of cystatin C mRNA were assessed by in situ hybridization and quantitative real-time polymerase chain reaction (QRT-PCR). The intensity of cystatin C immunostaining in Gleason grade 2 and 3 prostate cancer was significantly higher than in benign prostatic tissues, but decreased significantly with increasing Gleason grades. There was strong expression of cystatin C in neuroendocrine-like cells, which increased significantly with increasing Gleason grades. The Ki-67 immunoreactivity also increased significantly during de-differentiation. In situ hybridization showed staining patterns in concordance with the immunohistochemical results. ELISA showed high concentrations of cystatin C in benign and malignant tissue extracts and QRT-PCR further corroborated that the cystatin C gene is highly expressed in both benign and malignant prostatic tissues. There was a significant decrease in the immunohistochemical expression of cystatin C in non-neuroendocrine prostate cancer cells, concomitant with increasing Gleason grades. That there were more strongly cystatin C-positive neuroendocrine-like cells in prostate cancer than in benign prostatic tissue suggests a connection between cystatin C and neuroendocrine differentiation in prostate cancer progression.

  17. Irinotecan plus cisplatin followed by octreotide long-acting release maintenance treatment in advanced gastroenteropancreatic neuroendocrine carcinoma: IPO-NEC study.

    Science.gov (United States)

    Li, Jie; Lu, Ming; Lu, Zhihao; Li, Zhongwu; Liu, Yiqiang; Yang, Li; Li, Jian; Zhang, Xiaotian; Zhou, Jun; Wang, Xicheng; Gong, Jifang; Gao, Jing; Li, Yan; Shen, Lin

    2017-04-11

    There have been very few prospective studies of first-line chemotherapy on advanced gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC). This phase II study assessed the activity and safety of irinotecan plus cisplatin (IP) followed by octreotide long-acting release (LAR) maintenance treatment in advanced GEP-NEC. Forty patients were treated and eighteen patients (45.0%) had a partial response. The median progression-free survival (PFS) and overall survival (OS) were 5.7 months and 12.9 months, respectively. Because GEP-NECs are heterogeneous, a subgroup analysis was conducted by dividing all patients into a high proliferation neuroendocrine tumor (NET) group (well differentiated neuroendocrine neoplasms with a Ki-67 level between 20-60%) or a poorly differentiated NEC (PDNEC) group. Compared with the PDNEC group, the patients in high proliferation NET group had a lower response rate (0% versus 51.4%) but longer PFS (8.9 versus 5.7 months) and received more octreotide LAR treatment (median cycles, 7 versus 3). The most common toxicities included grade 3/4 leukopenia/neutropenia (60%), nausea/vomiting (17.5%) and diarrhea (12.5%). Therefore, IP is an active regimen in patients with advanced GEP-PDNEC and should probably not be given to patients with advanced high proliferative NET. The benefit of octreotide LAR maintenance therapy on high proliferation NETs requires further study.

  18. hGH and GHR expression in large cell neuroendocrine carcinoma of the colon and rectum.

    Science.gov (United States)

    Jukić, Zoran; Limani, Rinë; Luci, Lumturije Gashi; Nikić, Vivian; Mijić, August; Tomas, Davor; Krušlin, Božo

    2012-08-01

    Large cell neuroendocrine carcinoma (LCNEC) is an aggressive neoplasm with a low frequency of occurrence in the digestive tract. We present a series of eight patients diagnosed with LCNEC of the colon and rectum. Grossly, tumors were presented as endophytic/ulcerative, annular and polypoid masses, with a gray-white color and necrosis in most cases. Histologically, they were high-grade tumors composed of large cells of organoid, nesting, trabecular, rosette-like and palisading patterns, with a high mitotic rate. Tumors were immunoreactive for neuroendocrine markers, including chromogranin A (2/8), synaptophysin (7/8), and neuron-specific enolase (8/8). Moreover, we analyzed the expression of growth hormone (hGH) and growth hormone receptor (GHR) in colorectal LCNECs and six tumors were immunoreactive for hGH, while five tumors were immunoreactive for GHR. To our knowledge hGH and GHR expression has not been previously analyzed in colorectal LCNEC. Their overexpression suggests a role of hGH and GHR in the development of colorectal LCNEC.

  19. Genomic profiling of a combined large cell neuroendocrine carcinoma of the submandibular gland.

    Science.gov (United States)

    Andreasen, Simon; Persson, Marta; Kiss, Katalin; Homøe, Preben; Heegaard, Steffen; Stenman, Göran

    2016-04-01

    A 69-year-old female with no previous medical history presented with a rapidly growing submandibular mass. Fine needle aspiration cytology suggested a small-cell carcinoma and PET-CT showed increased 18-FDG uptake in the submandibular mass as well as in a lung mass. Submandibular resection and selective neck dissection was performed and histopathologic examination revealed a combined large-cell neuroendocrine carcinoma (LCNEC) with a squamous component and without lymph node metastases. Resection of the lung tumor revealed a papillary adenocarcinoma that was morphologically distinctly different from the LCNEC. The patient died of her lung cancer after 19 months without evidence of recurrence of the LCNEC. Genomic profiling of the salivary gland LCNEC revealed a hypodiploid genome predominated by losses of whole chromosomes or chromosome arms involving chromosomes 3p, 4, 7q, 10, 11, 13, 16q and gains of 3q and 16p. In addition, there was a segmental gain of 9p23-p22.3 including the NFIB oncogene. Continued studies of salivary gland LCNEC may provide new knowledge concerning potential diagnostic biomarkers and may ultimately also lead to the identification of new treatment targets for patients with these aggressive carcinomas.

  20. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.

    Science.gov (United States)

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan; Stigare, Jerker; Wikström, Johan; Boldt, Henning Bünsow; Kristensen, Bjarne Winther; Pontén, Fredrik; Trouillas, Jacqueline

    2017-09-01

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

  1. Neuroendocrine Cell Carcinoma of Unknown Primary Arising in Long Standing History of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stergios Boussios

    2015-01-01

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune disease that targets myelinated axons in the central nervous system (CNS. Cancer of unknown primary site (CUP is a well-recognised clinical disorder, accounting for 3–5% of all malignant epithelial tumors. CUP is clinically characterised as an aggressive disease with early dissemination. Studies of cancer risk in MS patients have shown inconsistent findings. An increased risk of malignancy in patients with MS has been suggested, but recently serious questions have been raised regarding this association. Use of disease-modifying therapies might contribute to an increased cancer risk in selected MS patients. The concurrence of MS and CUP is exceptionally rare. Here we describe the case of a neuroendocrine carcinoma of unknown primary diagnosed in a male patient with a nine-year history of MS. The discussion includes data from all available population-based register studies with estimates of certain malignancies in patients with MS.

  2. Surgical Treatment as a Principle for Patients with High-Grade Pancreatic Neuroendocrine Carcinoma

    DEFF Research Database (Denmark)

    Haugvik, Sven-Petter; Janson, Eva Tiensuu; Österlund, Pia

    2016-01-01

    BACKGROUND: This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery...... for patients undergoing resection of the primary tumor and resection/radiofrequency ablation of synchronous metastatic liver disease (n = 12), and 13 months for patients with synchronous metastatic disease given systemic chemotherapy alone (n = 78). The 3-year survival rate after surgery of the primary tumor....... Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment....

  3. Nasal neuroendocrine carcinoma in a free-living Japanese raccoon dog (Nyctereutes procyonoides viverrinus).

    Science.gov (United States)

    Kubo, M; Matsuo, Y; Okano, T; Sakai, H; Masegi, T; Asano, M; Uchida, K; Yanai, T

    2009-01-01

    Neuroendocrine carcinoma was diagnosed in the left nasal cavity of a free-living Japanese raccoon dog (Nyctereutes procyonoides viverrinus). Microscopically, the tumour consisted of sheets of anaplastic cells separated by narrow zones of fibrovascular stroma. The neoplastic cells had varying numbers of cytoplasmic granules stained by the Grimelius method. Immunohistochemically, the neoplastic cells were variably labelled for cytokeratin AE1/AE3, vimentin, chromogranin A and S-100. Ultrastructurally, some of the neoplastic cells had cytoplasmic membrane-bound dense-core granules of approximate diameter 140-240nm. The tumour had infiltrated the cerebrum and metastasized to the pituitary gland, mandibular and pulmonary lymph nodes, lungs, thyroid gland and adrenal glands.

  4. Neuroendocrine carcinoma as a rare cause of jejunal intussusception in an adult. Management and literature review.

    Science.gov (United States)

    Sahsamanis, Georgios; Mitsopoulos, Georgios; Deverakis, Titos; Terzoglou, Alexandra; Evangelidis, Paschalis; Dimitrakopoulos, Georgios

    2017-05-01

    Intussusception of the small bowel is an uncommon condition, with the majority of cases being observed during infancy. A number of points are responsible, with benign and malignant lesions of the small intestine being the most common. Herein, we present the case of a 75-year-old male patient with vague abdominal pain and black stool during defecation, who underwent surgery due to jejunal intussusception. Pathology report demonstrated a neuroendocrine carcinoma as the underlying cause for his condition, with no additional metastases during the initial diagnosis. Although a conservative approach for management of intussusception is viable, the possibility of gastric outlet obstruction and the presence of malignancy as the primary point usually lead to urgent surgery. In the case of malignancy, adjuvant chemotherapy or additional symptomatic therapy with close follow-up may be required depending on tumor's grade and aggressiveness.

  5. Thymic large cell neuroendocrine carcinoma: report of a resected case - a case report

    Directory of Open Access Journals (Sweden)

    Jiang Shi-Xu

    2010-11-01

    Full Text Available Abstract Thymic large cell neuroendocrine carcinomas (LCNECs are very rare. We here describe a case in which the tumor could be completely resected. A 55-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor found at a regular health check-up. The patient underwent an extended thymectomy of an invasive thymoma of Masaoka's stage II that had been suspected preoperatively. The tumor was located in the right lobe of the thymus and was completely resected. Final pathological diagnosis of the surgical specimen was thymic LCNEC. The patient underwent adjuvant chemotherapy with irinotecan and cisplatin in accordance with the diagnosis of a lung LCNEC, and is alive without recurrence or metastasis 16 months after surgery.

  6. (68)Ga-DOTATOC PET and gene expression profile in patients with neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid H; Langer, Seppo W; Federspiel, Birgitte H

    2016-01-01

    Somatostatin receptor expression on both protein and gene expression level was compared with in vivo (68)Ga-DOTATOC PET/CT in patients with neuroendocrine carcinomas (NEC). Twenty-one patients with verified NEC who underwent a (68)Ga-DOTATOC PET/CT between November 2012 and May 2014, were...... retrospectively included. By real-time polymerase chain reaction, we quantitatively determined the gene expression of several genes and compared with (68)Ga-DOTATOC PET uptake. By immunohistochemistry we qualitatively studied the expression of assorted proteins in NEC. The median age at diagnosis was 68 years...... (range 41-84) years. All patients had WHO performance status 0-1. Median Ki67 index was 50% (range 20-100%). Gene expression of somatostatin receptor subtype (SSTR) 2 and Ki67 were both positively correlated to the (68)Ga-DOTATOC uptake (r=0.89; p

  7. First-line chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma

    Directory of Open Access Journals (Sweden)

    Bongiovanni A

    2015-12-01

    Full Text Available Alberto Bongiovanni,1 Nada Riva,1 Marianna Ricci,1 Chiara Liverani,1 Federico La Manna,1 Alessandro De Vita,1 Flavia Foca,2 Laura Mercatali,1 Stefano Severi,3 Dino Amadori,4 Toni Ibrahim1 1Osteoncology and Rare Tumors Center, 2Unit of Biostatistics and Clinical Trials, 3Nuclear Medicine Unit, 4Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST IRCCS, Meldola, FC, Italy Background and aim: To investigate the efficacy of platinum-based chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma (mGEP-NEC and define predictive and prognostic factors. Methods: Twenty mGEP-NEC patients were treated with cisplatin or carboplatin/etoposide between April 2010 and October 2014. Both large-cell and small-cell histologies were included. Cisplatin 25 mg/m2 was administered on days 1–3 followed by etoposide 100 mg/m2 on days 1–3 every 21 days. Carboplatin 300 mg/m2 was administered on day 1 followed by etoposide 100 mg/m2 on days 1–3. Results: Of the 19 evaluable patients, 13 obtained a partial response, four showed stable disease, and two progressed. Median overall survival (mOS was 13.5 months and median progression-free survival (mPFS was 10.9 months. Gallium-68 positron emission tomography/computerizsed tomography-positive patients had a higher, albeit not significantly, OS than those with negative results (75% vs 34.3% at 18 months; P=0.06. mPFS was 19.3 and 6.3 months (P<0.01 in mGEP-NEC patients with Ki67 ≤55% or >55%, respectively. mOS was 8.1 months in the latter group but was not reached in the Ki67 ≤55% group (P-value =0.039. Patients with a lower body mass index (BMI had a better prognosis in terms of both OS and PFS. Patients with BMI ≥25 had a mOS of 11.7 months (P=0.0293 and a mPFS of 6.2 months (P=0.0057. Conclusion: Platinum-based chemotherapy showed good efficacy in mGEP-NEC patients. Those with Ki67 ≤55%, positive Gallium-68 positron emission

  8. Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma

    DEFF Research Database (Denmark)

    Ali, Abir Salwa; Grönberg, Malin; Federspiel, Birgitte

    2017-01-01

    of immunoreactive p53 protein in GEP-NEC. Materials and methods Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate...... and differentiation were re-evaluated. All specimens were immunostained for p53 protein using a commercially available monoclonal antibody. Kaplan-Meier curves and cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS). Results All tumor tissues were immunoreactive...... for either one or both neuroendocrine biomarkers (chromogranin A and synaptophysin) and Ki67 index was >20% in all cases. p53 immunoreactivity was only shown in 39% of the cases and was not found to be a prognostic marker for the whole cohort. However, p53 immunoreactivity was correlated with shorter PFS...

  9. Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2007-01-01

    Full Text Available Beckground/Aim. Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC. Methods. A clinical trial included 158 patients (74% males and 26% females, with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion or chemotherapy only in stage III (with pleural effusion and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion, the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. Results. A total of 53 patients (34% had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively. Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.5%, 34 (21.5% and 33 (20.1% patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (p < 0.001; a two - year survival time noted in 30% of the patients (p = 0

  10. Small cell neuroendocrine carcinoma of the endometrium with pulmonary metastasis: A clinicopathologic study of a case and a brief review of the literature

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    Antonio D'Antonio

    2016-02-01

    Full Text Available Neuroendocrine carcinomas (NEC of the female genital tract are aggressive and rare tumors that usually involve the cervix and ovary, and are seen rarely in the endometrium in perimenopausal or postmenopausal women. We presented a case of a73 year-old postmenopausal woman with vaginal bleeding and abdominal pain. A subsequent computerized tomography (CT scan of pelvis showed an enlarged uterus (20,0 × 12,0 cm with para-aortic and pelvic lymph node metastases. She underwent surgical debulking and staging of an endometrial tumor with omental metastasis and positive lymph nodes. The pathological diagnosis was primary small cell carcinoma (SCC combined with endometrioid carcinoma of uterine corpus. Her final FIGO stage was IVB. Three months after surgery CT-total body showed a metastasis to left lung of SCC. Because the small-cell component of endometrial tumor showed a strong positivity for TTF1 as pulmonary counterpart a differential diagnosis with a primary small cell carcinoma of the lung should be made. Identifying an appropriate therapeutic management for SCC of endometrium is challenging since these are extremely rare tumors. An optimal initial therapeutic approach to this rare disease, especially at an advanced stage, has not yet been clearly defined. However, in these a multidisciplinary therapy, including surgery, chemotherapy, and radiotherapy represent until this time the only therapeutic option.

  11. Basal cell carcinoma: CD56 and cytokeratin 5/6 staining patterns in the differential diagnosis with Merkel cell carcinoma.

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    Panse, Gauri; McNiff, Jennifer M; Ko, Christine J

    2017-06-01

    Basal cell carcinoma (BCC) can resemble Merkel cell carcinoma (MCC) on histopathological examination and while CK20 is a useful marker in this differential, it is occasionally negative in MCC. CD56, a sensitive marker of neuroendocrine differentiation, is sometimes used to identify MCC, but has been reportedly variably positive in BCC as well. In contrast, CK5/6 consistently labels BCC but is not expressed in neuroendocrine tumors. We evaluated 20 cases of BCC for the pattern of CD56 and cytokeratin 5/6 (CK5/6) staining, hypothesizing that these 2 stains could differentiate BCC from MCC in difficult cases. Seventeen cases of MCC previously stained with CD56 were also examined. All BCCs showed patchy expression of CD56 except for 2 cases, which showed staining of greater than 70% of tumor. CK5/6 was diffusely positive in all cases of BCC. Fifteen of 17 MCCs were diffusely positive for CD56. The difference in the pattern of CD56 expression between MCC and BCC (diffuse vs patchy, respectively) was statistically significant (P < .05). BCC typically shows patchy CD56 expression and diffuse CK5/6 positivity. These 2 markers can be used to distinguish between BCC and MCC in challenging cases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. [Primary Neuroendocrine Carcinoma of Thymus Caused Cushing Syndrome: Surgical Treatment and Prognosis Analysis].

    Science.gov (United States)

    Li, Li; Chen, Yeye; Li, Shanqing; Liu, Hongsheng; Huang, Cheng; Qin, Yingzhi

    2015-07-01

    Primary neuroendocrine carcinoma of thymus (pNECT) is a rare thymic neoplasm. Some pNECTs could produce an adrenocorticotropic hormone and cause Cushing syndrome (CS). The aim os this study is to discuss the diagnostic technique and surgical management of pNECT-caused CS and analyze prognosis factors to improve the clinical experience of the disease. The outcome of surgery and follow-up of 14 cases (eight males and six females) of pNECT-caused CS were retrospectively analyzed from November 1987 to June 2013. The median age of the patients was 29, and the median duration of the disease was four months (1 month-44 months). All cases exhibited clinical evidence for the diagnosis of CS, and thoracic computed tomography (CT) was used to detect thymic tumors. Surgical treatment significantly decreased the concentration of both serum cortisol and adrenocorticotropic hormone (Pdisease with aggressive characteristics and unclear prognosis. Early diagnosis and therapy is a challenge for clinicians. Thoracic CT is important for disease location and preoperative evaluation and should be routinely applied to all CS patients to allow early surgery and improved prognosis.

  13. Primary Neuroendocrine Carcinoma of Thymus Caused Cushing Syndrome: 
Surgical Treatment and Prognosis Analysis

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    Li LI

    2015-07-01

    Full Text Available Background and objective Primary neuroendocrine carcinoma of thymus (pNECT is a rare thymic neoplasm. Some pNECTs could produce an adrenocorticotropic hormone and cause Cushing syndrome (CS. The aim os this study is to discuss the diagnostic technique and surgical management of pNECT-caused CS and analyze prognosis factors to improve the clinical experience of the disease. Methods The outcome of surgery and follow-up of 14 cases (eight males and six females of pNECT-caused CS were retrospectively analyzed from November 1987 to June 2013. Result The median age of the patients was 29, and the median duration of the disease was four months (1 month-44 months. All cases exhibited clinical evidence for the diagnosis of CS, and thoracic computed tomography (CT was used to detect thymic tumors. Surgical treatment significantly decreased the concentration of both serum cortisol and adrenocorticotropic hormone (P<0.01 but caused one death in the perioperative period. With multidisciplinary therapy, the median survival was 38 months. Conclusion pNECT-caused CS is a rare disease with aggressive characteristics and unclear prognosis. Early diagnosis and therapy is a challenge for clinicians. Thoracic CT is important for disease location and preoperative evaluation and should be routinely applied to all CS patients to allow early surgery and improved prognosis.

  14. Ovarian Basaloid Carcinoma with Shadow Cell Differentiation

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    Michal Zamecnik

    2014-01-01

    Full Text Available So-called shadow cell differentiation (SCD is typical for pilomatrixoma and other skin lesions with follicular differentiation, but it was rarely described also in some visceral carcinomas. We report a case of ovarian basaloid carcinoma with SCD. The tumor presented as a 14 cm ovarian mass in a 45-year-old woman, and therefore the adnexectomy and hysterectomy were performed. The tumor was of high stage. Multiple metastases were found in the liver, retroperitoneal and mediastinal lymph nodes, and the lung. Histologically, the tumor showed a pattern of high-grade basaloid carcinoma with numerous shadow cells. Extensive histologic examination did not reveal any glandular or preexisting teratoma component. Immunohistochemically, the tumor expressed markers of squamous cell differentiation, such as p63, cytokeratin 5/6, and high-molecular-weight keratin. Cytokeratin 7 and CA125 were positive in scattered cells of the lesion. Estrogen and progesterone receptor, vimentin, and p53 were negative. Beta-catenin showed nuclear and cytoplasmic positivity, indicating possible tumor proliferation/differentiation via Wnt signaling pathway. To our knowledge, SCD in basaloid carcinoma of the ovary was not described before. In addition to the description of the case, we review the literature on SCD in visceral carcinomas.

  15. Treatment of well-differentiated thyroid carcinoma

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    Block, M.A.

    1981-01-01

    Improved selection of thyroid nodules for surgery and greater individualization of surgery for well-differentiated thyroid carcinoma are emphasized. Thyroid nodules are common but infrequently are manifestations of carcinoma. Needle biopsy permits better selection of patients with thyroid nodules for surgery by identifying those which are malignant or are likely to become malignant. Experience in performing diagnostic needle biopsies and in cytologic and histologic interpretation is essential. The majority of well-differentiated thyroid carcinomas are well-localized papillary carcinomas controlled by surgery, usually a lobectomy or partial thyroidectomy. Well-differentiated thyroid carcinomas include papillary and follicular types and their subsets. The extent of surgery should be individualized based on gross extent of disease, histologic variety, and age of the patient. The prognosis is reduced for patients more than 40 years of age. With appropriate early surgical treatment, the outlook is excellent. Metastatic disease can frequently also be controlled by large doses of thyroid hormone and the use of radioactive iodine

  16. Neuroendocrine breast cancer.

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    Graça, Susana; Esteves, Joana; Costa, Sílvia; Vale, Sílvio; Maciel, Jorge

    2012-08-13

    Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast lump. Physical examination, mammography and ultrasonography showed a 2.4 cm nodule, probably a benign lesion (BI-RADS 3). A fine needle aspiration biopsy was performed and revealed proliferative epithelial papillary lesion. She was submitted to excisional biopsy and histology showed endocrine breast cancer well differentiated (G1). Immunohistochemically, tumour cells were positive for synaptophysin. These breast cancers are characterised for their excellent prognosis and conservative treatment is almost always enough to obtain patient cure.

  17. Differentiated thyroid carcinoma : nuclear medicine studies

    NARCIS (Netherlands)

    Verkooijen, Ronald B.T.

    2009-01-01

    The therapy of choice in patients suffering from differentiated thyroid cancer (DTC), subdivided into papillary and follicular thyroid carcinoma, is (near-)total thyroidectomy. This is routinely followed by the administration of radioiodine (RaI)-131 (131I) to destroy any remaining benign or

  18. HPV genotyping in neuroendocrine carcinoma of the uterine cervix in northern Thailand.

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    Siriaunkgul, Sumalee; Utaipat, Utaiwan; Settakorn, Jongkolnee; Sukpan, Kornkanok; Srisomboon, Jatupol; Khunamornpong, Surapan

    2011-11-01

    To determine the distribution of HPV genotypes in cervical neuroendocrine carcinoma (NECA) in northern Thailand, and evaluate the correlation between HPV genotype and clinicopathologic features. Samples from 111 women treated for cervical NECA at Chiang Mai University Hospital between 1992 and 2009 were tested for HPV genotype. Samples were formaldehyde-fixed, paraffin-embedded, and tested via nested PCR and dot blot hybridization. Ninety-seven of the 111 samples were adequate for DNA analysis. HPV DNA was detected in 93 samples, of which 76 (81.7%) were single, 14 (15.1%) were multiple, and 3 (3.2%) were untyped infections. HPV18 was the most common subtype (70 cases, 75.3%), followed by HPV16 (28 cases, 30.1%). Other genotypes included HPV58 (3.2%), HPV52 (2.1%), and HPV33 (1.1%). Collectively, HPV16 and/or HPV18 were found in 83 cases (89.3%). Women with HPV18 infection were significantly younger (42.0years) than those with non-HPV18 infections (54.1years) (P=0.003). Associated adenocarcinoma in situ was more frequently seen among women with HPV18 infection (P=0.034). HPV18 infection was predominant in cervical NECA. Variations in HPV genotype may be related to the clinicopathologic features and pathogenetic pathways of NECA. Vaccination against HPV16 and HPV18 might provide protection against cervical NECA in almost 90% of cases. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Differentiated thyroid carcinoma and intestinal polyposis syndromes.

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    Triggiani, Vincenzo; Angelo Giagulli, Vito; Tafaro, Angela; Resta, Francesco; Sabba, Carlo; Licchelli, Brunella; Guastamacchia, Edoardo

    2012-12-01

    Familial Adenomatous Polyposis, Cowden's Syndrome, and Peutz-Jeghers Syndrome are well known as Intestinal Polyposis Syndromes, inherited conditions characterized by the development of polyps of the gastro-intestinal tract in association with extra-intestinal manifestations, in particular malignant tumors at different sites. Thyroid carcinoma is sometimes a part of the clinical picture of these syndromes. The aim of this paper is to review the literature dealing with the association between differentiated thyroid carcinomas and Intestinal Polyposis Syndromes in order to point out peculiar aspects, providing suggestions for the screening and the management of thyroid tumors in these patients.

  20. Pazopanib Hydrochloride in Treating Patients With Advanced Neuroendocrine Cancer

    Science.gov (United States)

    2015-10-15

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Multiple Endocrine Neoplasia Type 1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor

  1. Rapid development of thymic neuroendocrine carcinoma despite transcervical thymectomy in a patient with multiple endocrine neoplasia type 1

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    Dhalapathy Sadacharan

    2013-01-01

    Full Text Available Thymic neuroendocrine (NE tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1. They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT at the time of parathyroid surgery for primary hyperparathyroidism (PHPT in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting.

  2. Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system.

    Science.gov (United States)

    Yamaguchi, Tomohiro; Machida, Nozomu; Morizane, Chigusa; Kasuga, Akiyoshi; Takahashi, Hideaki; Sudo, Kentaro; Nishina, Tomohiro; Tobimatsu, Kazutoshi; Ishido, Kenji; Furuse, Junji; Boku, Narikazu; Okusaka, Takuji

    2014-09-01

    This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato-biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato-biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46-0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48-1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  3. Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.

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    Shashank J Patel

    Full Text Available Neuroendocrine (NE differentiation has gained increased attention as a prostate cancer (PC prognostic marker. The aim of this study is to determine whether host germline genetic variation influences tumor progression and metastasis in C57BL/6-Tg(TRAMP8247Ng/J (TRAMP mouse model of aggressive NEPC. TRAMP mice were crossed to the eight progenitor strains of the Collaborative Cross recombinant inbred panel to address this. Tumor growth and metastasis burden were quantified in heterozygous transgene positive F1 male mice at 30 weeks of age. Compared to wild-type C57BL/6J-Tg(TRAMP824Ng/J males, TRAMP x CAST/EiJ, TRAMP x NOD/ShiLtJ and TRAMP x NZO/HlLtJ F1 males displayed significant increases in tumor growth. Conversely, TRAMP x WSB/EiJ and TRAMP x PWK/PhJ F1 males displayed significant reductions in tumor growth. Interestingly, despite reduced tumor burden, TRAMP x WSB/EiJ males had an increased nodal metastasis burden. Patterns of distant pulmonary metastasis tended to follow the same patterns as that of local dissemination in each of the strains. All tumors and metastases displayed positive staining for NE markers, synaptophysin, and FOXA2. These experiments conclusively demonstrate that the introduction of germline variation by breeding modulates tumor growth, local metastasis burden, and distant metastasis frequency in this model of NEPC. These strains will be useful as model systems to facilitate the identification of germline modifier genes that promote the development of aggressive forms of PC.

  4. The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors.

    Science.gov (United States)

    Hindié, Elif

    2017-01-01

    Neuroendocrine tumors (NET) are often metastatic at the time of diagnosis. Metastatic well-differentiated (G1/G2) NET may display a wide range of behaviors, ranging from indolent to aggressive, even within apparently homogeneous categories. Thus, selecting the optimal treatment strategy is a challenging task. Somatostatin receptor imaging (SRI) is the standard molecular imaging technique for well-differentiated NET. When performed with 68 Ga-labeled somatostatin analogs (SRI-PET), it offers exquisite sensitivity for disease staging. SRI is also a prerequisite for using targeted radionuclide therapy (e.g. 177 Lu-DOTATATE). 18F-FDG imaging has traditionally been reserved for staging poorly-differentiated G3 neuroendocrine carcinomas. However, recent data showed that FDG imaging has prognostic value in patients with well-differentiated NET: high uptake was associated with an increased risk of early progression while low uptake suggested an indolent tumor. In this issue of the Journal, Chan and colleagues propose a grading system where the results from the combined reading of SRI-PET and FDG-PET are reported as a single parameter, the "NETPET" score. While the scoring system still needs validation, it is clear that time has come to think about FDG and SRI in metastatic NET not as competitors but as complementary imaging modalities. Dual-tracer imaging can be viewed as a way to characterize disease phenotype in the whole-body. Moving from the prognostic value of dual-tracer imaging to a tool that allows for individualized management would require prospective trials. This editorial will argue that dual-tracer FDG-PET and SRI-PET might influence management of patients with well-differentiated metastatic NET and help selecting between different therapy options.

  5. Well differentiated endocrine carcinomas of the pancreas

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    Čolović Radoje

    2011-01-01

    Full Text Available Introduction. For the difference from poorly differentiated, well differentiated endocrine carcinomas of the pancreas are the tumours in whom with aggressive surgery and chemotherapy fair results can be achieved. Objective. The aim of the study was to point out the importance of such treatment. Methods. Over a 6-year period eight patients (seven female and one male of average age 51 years (ranging from 23 to 71 years were operated on for well differentiated endocrine carcinoma: six of the head and two of the tail of the pancreas. There were two functional and six nonfunctional tumours. Pain in the upper part of the abdomen in seven, mild loss in weight in two, strong heartburn in two, obstructive jaundice in three, diarrhoea in one, sudden massive bleeding from gastric varicosities due to prehepatic portal hypertension caused by pancreatic head tumour in one, and bruise in one patient were registered preoperatively. US and CT in all, angiography in one, octreoscan in two and PET scan in one patient were performed. Whipple’s procedure was performed in six and distal pancreatectomy in two patients, as well as systemic lymphadenectomy in all and excision of liver secondary tumours in two patients. In the patient with massive gastric bleeding a total gastrectomy was performed first, followed by Whipple’s procedure a month later. Results. R0 resection was achieved in all patients. Lymph nodes metastases were found in six patients. Six patients were given chemotherapy. One patient died 3 years after surgery, seven are still alive, on average 2.5 years. A local recurrence after distal pancreatectomy that occurred 5 years after surgery was successfully reresected and the patient is on peptide-receptor radiotherapy. In other six patients there were no local recurence or distant metastases. Conclusion. With aggressive surgery and chemotherapy fair results can be achieved in well differentiated endocrine carcinomas of the pancreas.

  6. Hypervascular solid-appearing serous cystic neoplasms of the pancreas: Differential diagnosis with neuroendocrine tumours

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    Park, Hye Sun; Kim, So Yeon; Park, Seong Ho; Lee, Seung Soo; Byun, Jae Ho; Kim, Jin Hee; Kim, Hyoung Jung; Lee, Moon-Gyu [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Hong, Seung-Mo [University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, Seoul (Korea, Republic of)

    2016-05-15

    To describe imaging findings of arterial hypervascular solid-appearing serous cystic neoplasms (SCNs) of the pancreas on CT and MR and determine imaging features differentiating them from neuroendocrine tumours (NETs). We retrospectively identified 15 arterial hypervascular solid-appearing SCNs and randomly chose 30 size-matched pancreatic NETs. On CT, two radiologists in consensus assessed the size, morphology, and CT attenuation. On MR, predominant signal intensity and the amount of the cystic component on T2-weighted images and ADC maps were evaluated and compared using Fisher's exact and Student's t-test. The mean SCN size was 2.6 cm (range, 0.8-8.3). The CT findings were similar between the two tumours: location, shape, margin, and enhancement pattern. SCNs were significantly more hypodense on non-enhanced CT images than NETs (P =.03). They differed significantly on MR: bright signal intensity (P =.01) and more than a 10 % cystic component on T2-weighted images (P =.01) were more common in SCNs than in NETs. All SCNs showed a non-restrictive pattern on the ADC map, while NETs showed diffusion restriction (P <.01). Arterial hypervascular solid-appearing SCNs and NETs share similar imaging features. Non-enhanced CT and MR images with T2-weighted images and ADC maps can facilitate the differentiation. (orig.)

  7. Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258 and its Therapeutic Implications

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    Shalini S. Yadav

    2017-06-01

    Full Text Available Prostate cancer (PCa remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT; however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC. With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC. This, along with previous observations of an increase in the number of such NE cells in aggressive tumors, has been suggested as a mechanism of resistance development during prostate cancer progression. Dovitinib (TKI-258/CHIR-258 is a pan receptor tyrosine kinase (RTK inhibitor that targets VEGFR, FGFR, PDGFR, and KIT. It has shown efficacy in mouse-model of PCa bone metastasis, and is presently in clinical trials for several cancers. We observed that both androgen receptor (AR positive and AR-negative PCa cells differentiate into a NE phenotype upon treatment with Dovitinib. The NE differentiation was also observed when mice harboring PC3-xenografted tumors were systemically treated with Dovitinib. The mechanistic underpinnings of this differentiation are unclear, but seem to be supported through MAPK-, PI3K-, and Wnt-signaling pathways. Further elucidation of the differentiation process will enable the identification of alternative salvage or combination therapies to overcome the potential resistance development.

  8. Extensive multiarterial resection attending total duodenopancreatectomy and adrenalectomy for MEN-1-associated neuroendocrine carcinomas.

    Science.gov (United States)

    Egorov, Vyacheslav Ivanovich; Kharazov, Alexander Felixovich; Pavlovskaya, Alla Ivanovna; Petrov, Roman Valeryevich; Starostina, Natalia Sergeevna; Kondratiev, Eugeny Valerievich; Filippova, Ekaterina Mikhailovna

    2012-10-27

    Pancreatic neuroendocrine tumors (PNTs) are relatively uncommon although these neoplasms have been noted to grow in occurrence in recent decades. Surgical removal of locally advanced PNTs involving major vessels and adjacent organs is warranted by reason of an appreciably more favorable prognosis as compared to exocrine pancreas cancer. We are reporting a case of successful multi-organ resection combined with a wide excision of the superior mesenteric, common, proper, left and right hepatic arteries (in the presence of the hepatomesenteric trunk variant of aberrant arterial anatomy) for multifocal PNTs in the setting of multiple neuroendocrine neoplasia type 1 syndrome. The procedure resulted in pain abolition, a significant improvement in the patient's life quality and allowed her to return to work. Follow-up computed tomography at 15 mo post-surgery showed no evidence of disease recurrence.

  9. Periampullary mass--a rare presentation of poorly differentiated neuroendocrine cancer of duodenum in a young adult: a case report and review of literature.

    Science.gov (United States)

    Singh, Neha; Nayak, Hemanta K; Bagchi, Avishek; Kar, Premashis

    2012-10-09

    Poorly differentiated neuroendocrine tumour in the periampullary region of the duodenum is a rare entity. This entity usually present in old men. Here we report a periampullary poorly differentiated neuroendocrine cancer (PDEC) of duodenum presenting in a young man with subacute history of jaundice, abdominal pain, pancreatitis and constitutional symptoms. MRI localised the tumour and endoscopy-guided biopsy of the lesion proved the diagnosis. Although palliative surgery and chemotherapy were planned, the patient opted to leave against medical advice.

  10. Large cell neuroendocrine carcinoma originating from the uterine endometrium: a report on magnetic resonance features of 2 cases with very rare and aggressive tumor

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    Natsuko Makihara

    2012-06-01

    Full Text Available Neuroendocrine carcinomas (NEC of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.

  11. Differentiation between chalazion and sebaceous carcinoma by noninvasive meibography.

    Science.gov (United States)

    Nemoto, Yuji; Arita, Reiko; Mizota, Atsushi; Sasajima, Yuko

    2014-01-01

    Sebaceous carcinoma is notorious for masquerading clinically as other benign lesions such as chalazion. A tool to better differentiate between these two conditions would thus be desirable. To examine the potential application of noninvasive meibography in the differential diagnosis of chalazion and sebaceous carcinoma of the eyelid as a retrospective cross-sectional study. Five individuals with chalazion and three patients with sebaceous carcinoma were observed. Noninvasive meibography was performed to visualize the reflectivity and shape of the lesion in each subject. Noninvasive meibographic imaging revealed chalazion as a lesion of overall low reflectivity with small regions of higher reflectivity corresponding to lipid granules. On the other hand, the noninvasive meibography revealed sebaceous carcinoma as a poorly marginated lesion of high reflectivity in the eyelid. Noninvasive meibographic imaging may prove useful for the differential diagnosis of chalazion and sebaceous carcinoma. It may also be informative in definition of the resection area in carcinoma patients.

  12. A classification prognostic score to predict OS in stage IV well-differentiated neuroendocrine tumors.

    Science.gov (United States)

    Pusceddu, Sara; Barretta, Francesco; Trama, Annalisa; Botta, Laura; Milione, Massimo; Buzzoni, Roberto; de Braud, Filipppo; Mazzaferro, Vincenzo; Pastorino, Ugo; Seregni, Ettore; Mariani, Luigi; Gatta, Gemma; Di Bartolomeo, Maria; Femia, Daniela; Prinzi, Natalie; Coppa, Jorgelina; Panzuto, Francesco; Antonuzzo, Lorenzo; Bajetta, Emilio; Maria, Brizzi Pia; Campana, Davide; Catena, Laura; Comber, Harry; Dwane, Fiona; Fazio, Nicola; Faggiano, Antongiulio; Giuffrida, Dario; Henau, Kris; Ibrahim, Toni; Marconcini, Riccardo; Massironi, Sara; Žakelj, Maja Primic; Spada, Francesca; Tafuto, Salvatore; Van Eycken, Elizabeth; Van der Zwan, Jan Maaten; Žagar, Tina; Giacomelli, Luca; Miceli, Rosalba

    2018-03-20

    No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n=515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n=457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n=415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: I) Favorable-risk group: 10-year OS ≥70%; II) Intermediate-risk group: 30% ≤10-year OS OS <30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three 'field-practice' cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses.

  13. Neuroendocrine carcinoma arising in soft tissue: three case reports and literature review

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    McAleese Jonathan

    2007-07-01

    Full Text Available Abstract Background Neuroendocrine tumours (NET are tumours arising from neuroendocrine cells of neural crest origin. They are characterised by the presence of neurosecretory granules which react positively to silver stains and to specific markers including neuron specific enolase, synaptophysin and chromogranin. Metastasis to the skin occurs infrequently but primary soft tissue NET is excessively rare. Case presentation We report our experience with 3 such cases. In the first case, the NET originated in muscle and was treated with wide surgical excision and adjuvant radiotherapy. The second case presented as a subcutaneous mass in the foot and the tumour was positive on 123I mIBG scan. She has had prolonged recurrence-free survival following primary hypo-fractionated radiotherapy. In the third case, a cutaneous nodule proved to be a NET and at surgery, lymph node disease was present. He has remained disease-free after surgical excision without the need for external beam radiotherapy. Conclusion These tumours appear to have a good prognosis. Complete excision offers potentially curative treatment. Adjuvant radiotherapy may be helpful when the tumour margin is narrow. For patients with unresectable disease or where surgery would not be appropriate, radiotherapy appears to be an effective therapeutic option.

  14. Liver metastasis from neuroendocrine carcinoma after the use of the new direct-action antivirals against hepatitis C virus in a patient with past history of hepatocellular carcinoma

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    María Caldas

    Full Text Available The use of the new direct-action antivirals against hepatitis C virus provides very high viral eradication rates. However, various recently published articles recommend caution with their use after the appearance of some cases of de novo tumors (originated in hepatic and extra-hepatic locations and a possible shorter time period of recurrence of hepatocellular carcinomas previously treated with surgery or loco-regional therapies. The sudden drop of the number of natural killer cells secondary to the use of these new medicines has been suggested as one of the possible mechanisms responsible for this process. However, due to the controversy concerning this subject and the absence of long-term follow-up studies in clinical practice, caution is needed before definitive conclusions are settled. We present the case report of a patient diagnosed of chronic liver disease secondary to hepatitis C virus infection and a past history of hepatocellular carcinoma in complete remission after radiofrequency ablation. He was treated with the new direct-action antivirals reaching sustained viral response. Six months later, the patient was diagnosed with liver metastasis from a small-cell neuroendocrine tumor of unknown primary site.

  15. External Beam Radiation in Differentiated Thyroid Carcinoma

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    Salem Billan

    2016-01-01

    Full Text Available The treatment of differentiated thyroid carcinoma (DTC is surgery followed in some cases by adjuvant treatment, mostly with radioactive iodine (RAI. External beam radiotherapy (EBRT is less common and not a well-established treatment modality in DTC. The risk of recurrence depends on three major prognostic factors: extra-thyroid extension, patient’s age, and tumor with reduced iodine uptake. Increased risk for recurrence is a major factor in the decision whether to treat the patient with EBRT. Data about the use of EBRT in DTC are limited to small retrospective studies. Most series have demonstrated an increase in loco-regional control. The risk/benefit from giving EBRT requires careful patient selection. Different scoring systems have been proposed by different investigators and centers. The authors encourage clinicians treating DTC to become familiarized with those scoring systems and to use them in the management of different cases. The irradiated volume should include areas of risk for microscopic disease. Determining those areas in each case can be difficult and requires detailed knowledge of the surgery and pathological results, and also understanding of the disease-spreading pattern. Treatment with EBRT in DTC can be beneficial, and data support the use of EBRT in high-risk patients. Randomized controlled trials are needed for better confirmation of the role of EBRT.

  16. Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells

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    Diez Soraya

    2010-03-01

    Full Text Available Abstract Background Wnt-11 is a secreted protein that modulates cell growth, differentiation and morphogenesis during development. We previously reported that Wnt-11 expression is elevated in hormone-independent prostate cancer and that the progression of prostate cancer from androgen-dependent to androgen-independent proliferation correlates with a loss of mutual inhibition between Wnt-11- and androgen receptor-dependent signals. However, the prevalence of increased expression of Wnt-11 in patient tumours and the functions of Wnt-11 in prostate cancer cells were not known. Results Wnt-11 protein levels in prostate tumours were determined by immunohistochemical analysis of prostate tumour tissue arrays. Wnt-11 protein was elevated in 77/117 of tumours when compared with 27 benign prostatic hypertrophy specimens and was present in 4/4 bone metastases. In addition, there was a positive correlation between Wnt-11 expression and PSA levels above 10 ng/ml. Androgen-depleted LNCaP prostate cancer cells form neurites and express genes associated with neuroendocrine-like differentiation (NED, a feature of prostate tumours that have a poor prognosis. Since androgen-depletion increases expression of Wnt-11, we examined the role of Wnt-11 in NED. Ectopic expression of Wnt-11 induced expression of NSE and ASCL1, which are markers of NED, and this was prevented by inhibitors of cyclic AMP-dependent protein kinase, consistent with the known role of this kinase in NED. In contrast, Wnt-11 did not induce NSE expression in RWPE-1 cells, which are derived from benign prostate, suggesting that the role of Wnt-11 in NED is specific to prostate cancer. In addition, silencing of Wnt-11 expression in androgen-depleted LNCaP cells prevented NED and resulted in apoptosis. Silencing of Wnt-11 gene expression in androgen-independent PC3 cells also reduced expression of NSE and increased apoptosis. Finally, silencing of Wnt-11 reduced PC3 cell migration and ectopic

  17. Radioactive iodine treatment of differentiated thyroid carcinoma in teenager

    International Nuclear Information System (INIS)

    Chen Yonghui

    2008-01-01

    Incidence rate of differentiated thyroid carcinoma in teenager is not high. It has some different characteristics compared to adult differentiated thyroid carcinoma. Such as larger tumor at diagnosis; greater prevalence of neck lymph node and distant metastases at diagnosis; more sodium-iodide symporter expression; high recurrence rate but higher overall survival rate. 131 I administration to remove residual thyroid tissue and treat metastases is still one of the important approaches after surgery. (authors)

  18. Combined Chronic Lymphocytic Leukemia and Pancreatic Neuroendocrine Carcinoma: A Collision Tumor Variation

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    Kaijun Huang

    2016-01-01

    Full Text Available Chronic lymphocytic leukemia (CLL-induced immunodeficiency has been implicated in the occurrence of several secondary or concurrent malignancies. We hereby present the first case of combined CLL and pancreatic neuroendocrine tumor as collision neoplasms within metastatic periportal lymphadenopathy in a 62-year-old patient who presented with obstructive jaundice. An ovoid nodular mass was seen posterior to the head of the pancreas on magnetic resonance cholangiopancreatography and the patient subsequently underwent endoscopic retrograde cholangiopancreatography, with successful placement of two stents within the identified hilar stricture. Tn-111 pentetreotide scintigraphy with single-photon emission computed tomography (CT/CT disclosed two foci of somatostatin receptor positive tissue in the upper abdomen correlating to the previously seen porta hepatis and portacaval lymphadenopathy and the patient was treated with octreotide. Simultaneous onset of CLL and secondary malignancies that each has a different disease status is a rare phenomenon but is important to diagnose for establishing an appropriate treatment strategy, which in certain cases may involve the use of agents active in both types of malignancy to minimize toxicity.

  19. Combinatorial code of growth factors and neuropeptides define neuroendocrine differentiation in PC12 cells.

    NARCIS (Netherlands)

    Beaujean, D.; Rosenbaum, C.; Muller, H.W.; Willemsen, J.J.; Lenders, J.W.M.; Bornstein, S.R.

    2003-01-01

    Adrenal chromaffin cells constitute one of the first cell types to have been defined as a neuroendocrine cell type. Since they produce dopamine, these cells have been proposed for the treatment of neuronal deficits in human Parkinson's disease. However, the factors involved in the development of

  20. Opportunities for 2-[{sup 18}F] Fluoro-2-Deoxy-D-Glucose PET/CT in Cervical-Vaginal Neuroendocrine Carcinoma: Case Series and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yin; Lin, Wan Y.; Lu, Yu Y.; Wang, Hsin Y.; Tsai, Shih C. [Dept. Nuclear Medicine, Taichung Veterans General Hospital, Taichung (China); Liang, Ji A.; Kao, Chia H. [China Medical University Hospital, Taichung (China)

    2012-11-15

    Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[{sup 18}F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) scan for the detection of this rare malignancy. Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). Two cases (cases 1 and 4) were restaged after {sup 18}F-FDG PET/CT scan in the initial staging process. Post-treatment {sup 18}F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. {sup 18}F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the {sup 18}F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the {sup 18}F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation.

  1. CT differentiation of invasive thymoma and thymic carcinoma

    International Nuclear Information System (INIS)

    Lee, Eun Jung; Jung, Gyoo Sik; Kim, Seong Min; Huh, Jin Do; Joh, Young Duk; Shin, Mi Jung; Kim, Jung Sik; Suh, Soo Jhi

    1998-01-01

    In order to determine the differential points between them, we analyzed the CT findings of invasive thymoma and thymic carcinoma. We retrospectively reviewed the CT scans of 14 patients with invasive thymoma and 15 with thymic carcinoma, confirmed by surgery(n=3D19) or percutaneous needle aspiration(n=3D10) between 1988 and 1996. CT findings were evaluated in each group for intrathoracic spread(posterior, direct posterior, and anterolateral), obliteration of the fat plane between the mass and vascular structures, vessel encasement, invasion of adjacent mediastinal structures, pleural implants, mediastinal nodes and distant metastasis. Direct posterior spread was more common in thymic carcinoma than invasive thymoma;it was seen in one case (7%) of invasive thymoma and 12(80%) of thymic carcinoma(p=3D0.00). Posterior spread was seen in six cases (43%) of in vasive thymoma and nine (60%) of thymic carcinoma. Anterolateral spread was seen only in two cases (13%) of thymic carcinoma. Obliteration of the fat plane was seen in nine cases (64%) of invasive thymoma and 14 (93%) of thymic carcinoma, while vessel encasement was seen in two cases (14%) of invasive thymoma and 13(87%) of thymic carcinoma(p=3D0.00). Invasion of adjacent structures was seen in two cases (14%) of invasive thymoma and eight (53%) of thymic carcinoma. Pleural implants were more common in invasive thymoma than thymic carcinoma, being seen in six cases (43%) of the former and one (7%) of the latter(p=3D0.04). Mediastinal lymphadenopathy was seen in three cases (21%) of invasive thymoma and ten (67%) of thymic carcinoma. Distant metastases were observed only in six cases (40%) of thymic carcinoma(p=3D0.02). Although differentiation between invasive thymoma and thymic carcinoma is difficult on the basis of CT findings, there are certain differential points. Thymic carcinomas showed a higher rate of direct posterior intrathoracic spread, vessel encasement, mediastinal nodes and distant metastases than

  2. CT differentiation of invasive thymoma and thymic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Jung; Jung, Gyoo Sik; Kim, Seong Min; Huh, Jin Do; Joh, Young Duk [Kosin Medical College, Pusan (Korea, Republic of); Shin, Mi Jung [Wallace Memorial Baptist Hospital, Pusan (Korea, Republic of); Kim, Jung Sik; Suh, Soo Jhi [Keimyung Univ., Taegu (Korea, Republic of)

    1998-11-01

    In order to determine the differential points between them, we analyzed the CT findings of invasive thymoma and thymic carcinoma. We retrospectively reviewed the CT scans of 14 patients with invasive thymoma and 15 with thymic carcinoma, confirmed by surgery(n=3D19) or percutaneous needle aspiration(n=3D10) between 1988 and 1996. CT findings were evaluated in each group for intrathoracic spread(posterior, direct posterior, and anterolateral), obliteration of the fat plane between the mass and vascular structures, vessel encasement, invasion of adjacent mediastinal structures, pleural implants, mediastinal nodes and distant metastasis. Direct posterior spread was more common in thymic carcinoma than invasive thymoma;it was seen in one case (7%) of invasive thymoma and 12(80%) of thymic carcinoma(p=3D0.00). Posterior spread was seen in six cases (43%) of in vasive thymoma and nine (60%) of thymic carcinoma. Anterolateral spread was seen only in two cases (13%) of thymic carcinoma. Obliteration of the fat plane was seen in nine cases (64%) of invasive thymoma and 14 (93%) of thymic carcinoma, while vessel encasement was seen in two cases (14%) of invasive thymoma and 13(87%) of thymic carcinoma(p=3D0.00). Invasion of adjacent structures was seen in two cases (14%) of invasive thymoma and eight (53%) of thymic carcinoma. Pleural implants were more common in invasive thymoma than thymic carcinoma, being seen in six cases (43%) of the former and one (7%) of the latter(p=3D0.04). Mediastinal lymphadenopathy was seen in three cases (21%) of invasive thymoma and ten (67%) of thymic carcinoma. Distant metastases were observed only in six cases (40%) of thymic carcinoma(p=3D0.02). Although differentiation between invasive thymoma and thymic carcinoma is difficult on the basis of CT findings, there are certain differential points. Thymic carcinomas showed a higher rate of direct posterior intrathoracic spread, vessel encasement, mediastinal nodes and distant metastases than

  3. Differentiation between chalazion and sebaceous carcinoma by noninvasive meibography

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    Nemoto Y

    2014-09-01

    Full Text Available Yuji Nemoto,1 Reiko Arita,2,3 Atsushi Mizota,1 Yuko Sasajima4 1Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, 2Itoh Clinic, Saitama, 3Department of Ophthalmology, The University of Tokyo, Tokyo, 4Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan Background: Sebaceous carcinoma is notorious for masquerading clinically as other benign lesions such as chalazion. A tool to better differentiate between these two conditions would thus be desirable.Purpose: To examine the potential application of noninvasive meibography in the differential diagnosis of chalazion and sebaceous carcinoma of the eyelid as a retrospective cross-sectional study.Methods: Five individuals with chalazion and three patients with sebaceous carcinoma were observed. Noninvasive meibography was performed to visualize the reflectivity and shape of the lesion in each subject.Results: Noninvasive meibographic imaging revealed chalazion as a lesion of overall low reflectivity with small regions of higher reflectivity corresponding to lipid granules. On the other hand, the noninvasive meibography revealed sebaceous carcinoma as a poorly marginated lesion of high reflectivity in the eyelid.Conclusion: Noninvasive meibographic imaging may prove useful for the differential diagnosis of chalazion and sebaceous carcinoma. It may also be informative in definition of the resection area in carcinoma patients. Keywords: noninvasive meibography, sebaceous carcinoma, chalazion, eyelid 

  4. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

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    Thomas Gress

    2012-02-01

    Full Text Available Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-a, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  5. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rinke, Anja, E-mail: sprengea@staff.uni-marburg.de; Michl, Patrick; Gress, Thomas [Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, Marburg D-35043 (Germany)

    2012-02-08

    Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN) should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-α, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET) has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  6. Comparison of WHO 2000 and WHO 2010 classifications of gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Karakuş, Esra; Helvacı, Ayşe; Ekinci, Ozgür; Dursun, Ayşe

    2014-02-01

    Grading and staging are important in gastroenteropancreatic neuroendocrine tumors for directing treatment. In this study, we evaluated the histopathological parameters of gastroenteropancreatic neuroendocrine tumors and statistically analyzed the correlations of these parameters between the World Health Organization (WHO) 2000 and 2010 classifications. A total of 77 cases diagnosed as neuroendocrine tumors were included in the study. Cases were classified according to the WHO 2000 and WHO 2010 classification systems, and the differences and correlations between the two systems were discussed. Among the 50 cases that were diagnosed as well-differentiated neuroendocrine tumor according to WHO 2000, 45 were found to be Grade 1 and 5 were found to be Grade 2 according to the WHO 2010 classification. Among the 8 cases with well-differentiated neuroendocrine carcinoma according to WHO 2000; 5 and 3 were Grade 1 and Grade 2, respectively, according to the WHO 2010 classification. All of the 19 cases with poorly differentiated neuroendocrine carcinoma according to WHO 2000 were found to be Grade 3 according to the WHO 2010 classification. No differences were found between the classifications in the poorly differentiated group with a full correlation between the two classifications. Although WHO 2000 seems to be a better classification to predict prognosis, since it is based on various parameters, such as depth of invasion, angiolymphatic invasion, and presence of metastasis, it was concluded that there was no difference between the WHO 2000 and WHO 2010 classification, which is based on only the number of mitoses and Ki-67 proliferation index.

  7. The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells

    Science.gov (United States)

    Labrecque, Mark P.; Takhar, Mandeep K.; Nason, Rebecca; Santacruz, Stephanie; Tam, Kevin J.; Massah, Shabnam; Haegert, Anne; Bell, Robert H.; Altamirano-Dimas, Manuel; Collins, Colin C.; Lee, Frank J.S.; Prefontaine, Gratien G.; Cox, Michael E.; Beischlag, Timothy V.

    2016-01-01

    Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role Rb plays in mediating hypoxia-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that loss of Rb in conjunction with hypoxia leads to aberrant expression of hypoxia-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies. PMID:27015368

  8. Triple malignancy in a single patient including a cervical carcinoma, a basal cell carcinoma of the skin and a neuroendocrine carcinoma from an unknown primary site: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2011-09-01

    Full Text Available Abstract Introduction The occurrence of multiple primary cancers is rare. Only a few cases and patient reviews of an association of triple malignancy have been reported. Case presentation We report here a case of a 78-year-old Moroccan woman presenting initially with a synchronous double malignancy, the first in her cervix and the second in her skin. Our patient was treated with radiation therapy for both tumors and remained in good control for 17 years, when she developed a metastatic disease from a neuroendocrine carcinoma of an unknown primary site. Conclusions Although the association of multiple primary cancers can be considered a rare occurrence, improving survival in cancer patients has made this situation more frequent.

  9. Poorly Differentiated Squamous Cell Carcinoma Arising in Tattooed Skin

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    Deba P. Sarma

    2010-01-01

    Full Text Available Introduction. Tattoos have increasingly become accepted by mainstream Western society. As a result, the incidence of tattoo-associated dermatoses is on the rise. The presence of a poorly differentiated squamous cell carcinoma in an old tattooed skin is of interest as it has not been previously documented. Case Presentation. A 79-year-old white homeless man of European descent presented to the dermatology clinic with a painless raised nodule on his left forearm arising in a tattooed area. A biopsy of the lesion revealed a poorly differentiated squamous cell carcinoma infiltrating into a tattoo. The lesion was completely excised and the patient remains disease-free one year later. Conclusion. All previous reports of squamous cell carcinomas arising in tattoos have been well-differentiated low-grade type or keratoacanthoma-type and are considered to be coincidental rather than related to any carcinogenic effect of the tattoo pigments. Tattoo-associated poorly differentiated invasive carcinoma appears to be extremely rare.

  10. Small cell carcinoma of the vulva: case report

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    Ana Correia

    2017-04-01

    Full Text Available Neuroendocrine tumours are rare in the gynaecologic tract, comprising approximately 2% of all gynaecological tumours. They have an aggressive behaviour and are a diagnostic and clinical challenge, due to their rarity and the lack of standardized therapeutic approaches. There are a few case reports. It is defined as a high-grade carcinoma exhibiting neuroendocrine differentiation. The authors describe the case of a 70-year-old woman, with vulvar neuroendocrine small cell carcinoma after superficial vulvectomy. The patient was submitted to a surgery with wide local excision and adjuvant radiation therapy. A review of the literature on this topic is also presented.

  11. 68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT.

    Science.gov (United States)

    Kroiss, A; Putzer, D; Decristoforo, C; Uprimny, C; Warwitz, B; Nilica, B; Gabriel, M; Kendler, D; Waitz, D; Widmann, G; Virgolini, I J

    2013-04-01

    We wanted to establish the range of (68)Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 (68)Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUVmax (mean ± standard deviation) values of (68)Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (p TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUVmax can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUVmax, except in liver metastases of patients with NET.

  12. Radioactive Iodine Therapy of Differentiated Thyroid Carcinoma: Redesigning the Paradigm

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    Stanley J. Goldsmith

    2017-02-01

    Full Text Available Radioactive iodine therapy has evolved over the past 70 years from treatment of known metastatic thyroid carcinoma to include adjuvant use to decrease the incidence of recurrent disease and to ablation of normal remnant tissue following thyroidectomy, even for minimal tumor involvement. Advances in laboratory testing, development of drugs useful in radioiodine treatment, as well as advances in radiation detection and imaging instrumentation, have progressively improved the utility of radioiodine therapy of differentiated thyroid carcinoma. Guidelines have proliferated and they have become more detailed and complex. This trend is likely to continue as the science and technology involved increases in sophistication and efficacy.

  13. Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

    Science.gov (United States)

    Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. Copyright © 2016 Elsevier GmbH. All rights reserved.

  14. Cutaneous Sweat Gland Carcinomas with Basaloid Differentiation: An Update with Emphasis on Differential Diagnoses.

    Science.gov (United States)

    Flux, Katharina; Brenn, Thomas

    2017-09-01

    This article focuses on primary cutaneous sweat gland carcinomas with basaloid differentiation, including cribriform apocrine carcinoma, endocrine mucin-producing sweat gland carcinoma, mucinous carcinoma, adenoid cystic carcinoma, spiradenocarcinoma, and digital papillary adenocarcinoma. These tumors are rare and pose a significant diagnostic challenge. Their clinical presentation is nonspecific and there is significant overlap of their histologic features. Confident diagnosis is necessary because their clinical behavior ranges from indolent, nonrecurring, nonmetastasizing tumors to those with potential for disseminated disease and mortality. They should be separated from cutaneous metastases of primary visceral adenocarcinomas. Salient features of these rare entities are discussed with emphasis on distinguishing features and diagnostic clues. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Multicentricidade no carcinoma diferenciado da tireóide Multicentricity in the thyroid differentiated carcinoma

    Directory of Open Access Journals (Sweden)

    José Francisco Salles Chagas

    2009-02-01

    Full Text Available O tratamento cirúrgico de escolha no carcinoma diferenciado da tireóide sempre foi controverso. OBJETIVO: Analisar o acometimento tumoral do lobo contralateral da tireóide no carcinoma diferenciado, correlacionando risco e benefício com as complicações decorrentes da segunda intervenção. CASUÍSTICA E MÉTODO: Estudo retrospectivo, de 1998 a 2006, com 27 pacientes submetidos à tireoidectomia menos que total, sendo 21 lobectomias, cinco tireoidectomias subtotais e uma istmectomia. Foram analisados: gênero, idade, tipo de cirurgia, complicações, histopatológico do espécime cirúrgico e invasão do lobo contralateral. As idades variaram de 17 a 89 anos; o tipo histopatológico mais freqüente foi o carcinoma papilífero clássico (18 casos, seguido do carcinoma folicular (seis casos, do carcinoma papilífero variante folicular (dois casos e do carcinoma de células Hürthle (um caso. Vinte e um pacientes foram submetidos à totalização da tireoidectomia, 15 a 30 dias depois. RESULTADOS: A análise do lobo contralateral foi negativa para carcinoma em 16 (76,5% e positiva nos cinco restantes (23,8%. As complicações observadas foram: disfonia temporária (três casos e hipoparatireoidismo (dois casos, sendo um permanente. CONCLUSÃO: A totalização da tireoidectomia é um procedimento importante no tratamento do carcinoma bem diferenciado da tireóide pelo elevado acometimento contralateral (23,8%. A incidência de complicações é pequena.The treatment of choice for the well differentiated thyroid carcinoma has always been controversial. AIM: to analyze tumor invasion of the thyroid gland's contralateral lobe in cases of differentiated carcinoma, correlating risk/benefit with the complications of a second surgical approach. MATERIALS AND METHODS: Retrospective study, from 1998 to 2006, of 27 patients undergoing less than total thyroidectomy: lobectomy (21, subtotal thyroidectomy (5 or isthmusectomy (1. Gender, age, type of surgery

  16. [Neuroendocrine tumors: Peptide receptors radionuclide therapy (PRRT)].

    Science.gov (United States)

    Papamichail, Dimitris G; Exadaktylou, Paraskevi E; Chatzipavlidou, Vasiliki D

    2016-01-01

    Neuroendocrine tumors (neuroendocrine tumors-NET) are a heterogeneous group of neoplasms with a common embryological origin and diverse biological behavior, derived from cells of the neuroendocrine system, the system APUD (amine precursor uptake and decarboxylation). They are characterized by overexpression of all five somatostatin receptors (SSTR1-SSTR5), particularly type 2 (SST2). Surgical resection of the tumor is the treatment option, with a possibility of complete remission in patients with limited disease. Somatostatin analogs (octreotide and lanreotide) are the treatment of choice in patients with residual disease, particularly when it comes to NET non-pancreatic origin. Systemic chemotherapy is administered primarily to patients with poorly differentiated carcinomas. PRRT treatment is recommended in case of non-responsiveness of the disease. The ideal candidates for PRRT are patients with unresectable disease of high and intermediate differentiation. Somatostatine analogs radiolabelled with Indium-111 ((111)In), Yttrium-90 ((90)Y), Lutetium-177 ((177)Lu) and Bismuth-213 ((213)Bi), are selectively concentrated in the tumor cells, causing maximum tissue damage to tumors and with fewer effects on healthy tissue and the immune system. In the current review, it was demonstrated that patients with unresectable grade 1 or 2 disease showed increased PFS (progression free survival) and OS (overall survival), while quality of life was improved after PRRT treatment as compared to somatostatin analogs, chemotherapy and other targeted therapies.

  17. Dietary patterns as risk factors of differentiated thyroid carcinoma.

    Science.gov (United States)

    Przybylik-Mazurek, Elwira; Hubalewska-Dydejczyk, Alicja; Kuźniarz-Rymarz, Sylwia; Kieć-Klimczak, Małgorzata; Skalniak, Anna; Sowa-Staszczak, Anna; Gołkowski, Filip; Kostecka-Matyja, Marta; Pach, Dorota

    2012-01-10

    Nutritional factors are known to be important in the development of different metabolic diseases. The history of nodular or diffuse goiter is closely related to risk of thyroid carcinoma. On account of the function of the thyroid gland, many studies focus on iodine intake. The aim of the study was to assess whether dietary patterns could be risk factors of differentiated thyroid carcinoma. The case-control study was based on a questionnaire, which included information about dietary patterns and was carried out on 284 patients comprising 30 males (mean age 58.4±13.7 years), and 254 females (mean age 52.1±13.8 years), as well as 345 randomly selected controls: 58 males (mean age 60.2±12 years) and 287 females (mean age 53.4±14.3 years) randomly selected from the Population Register and adjusted by age and gender to the group of TC. The main groups of nutritional products, i.e. starchy foods, meat, dairy products, vegetables, fruits, and beverages, were analyzed. Consumption of vegetables, fruits, saltwater fish and cottage cheese was significantly lower in patients with differentiated thyroid carcinoma than in controls, quite the contrary to starchy foods, especially white bread. Dietary patterns appear to modify the risk of thyroid carcinoma. A diet rich in vegetables and fruit, as well as saltwater fish (a source of iodine) and low-fat meat, could be an important protective factor.

  18. "MONOCLONAL ANTIBODY HBME-1 USEFULNESS IN DIFFERENTIATION OF BENIGN NEOPLASM AND DIFFERENTIATED THYROID CARCINOMA"

    Directory of Open Access Journals (Sweden)

    M. Mokhtari

    2005-05-01

    Full Text Available HBME-l is an antimesothelial monoclonal antibody that recognizes an unknown antigen on microvilli of mesothelial cells. The antibody is only relatively specific for mesothelium and is used in the differential diagnosis of mesothelioma and adenocarcinoma within the context of an appropriate immuno-histochemical panel. HBME-l has also been reported to strongly and uniformly stain papillary and follicular carcinoma of the thyroid while benign disorders have been usually negative. We studied the immunoreactivity of HBME-l in 90 cases of benign and malignant thyroid lesions. We found strong positive staining in the majority of papillary carcinomas (28/31, in some of follicular carcinomas (4/6,and in a few follicular adenomas (2/17. Negative staining was found in oxyphilic cell adenoma (0/4, nodular goiter (0/13 and undifferentiated carcinoma. The results suggest that monoclonal antibody HBME-l is useful in differentiating papillary and follicular carcinoma of the thyroid from benign lesions, especially in more differentiated lesions. Strong and generalized immunoreactivity for HBME-l in a follicular lesion should raise the suspicion of malignancy, but negative staining specially in poorly differentiated lesion does not rule out malignancy.

  19. Invasive Carcinoma of Breast with Adnexal Differentiation of Trichoblastic Type

    Directory of Open Access Journals (Sweden)

    Sarala Ravindran

    2016-06-01

    Full Text Available We present a rare distinctive variant of invasive carcinoma of breast characterized by adnexal differentiation of tumor of trichoblastic type. The neoplasm was identified in a mastectomy specimen from an 83-year-old Chinese woman. Morphologically, the trichoblastic differentiation was characterized by the formation of solid sheets and nests of basaloid cells. The tumor cells were positive for cytokeratin 5/6, BER-EP4, bcl-2, and beta-catenin. Stromal cells were positive for CD10. The tumor cells exhibited a and ldquo;triple negative and rdquo; profile; the nuclei did not react with antibodies to estrogen and progesterone receptors but failed to show overexpression of the HER2/neu protein. The MIB-1 labeling index averaged 20%. It is hoped that this case increases awareness for this unique morphological variant of invasive ductal carcinoma. [J Interdiscipl Histopathol 2016; 4(2.000: 48-51

  20. Eccrine syringofibroadenoma associated with well-differentiated squamous cell carcinoma.

    Science.gov (United States)

    Kacerovska, Denisa; Nemcova, Jana; Michal, Michal; Kazakov, Dmitry V

    2008-12-01

    We report a case of an eccrine syringofibroadenoma (ESFA) associated with well-differentiated squamous cell carcinoma. The patient was an 85-year-old man, who had a 2.5x2.5-cm, brown-colored ulcerated nodule, with a fragile, flesh-colored bleeding surface located beyond the metacarpophalangeal joint of the second finger of his left hand. Histopathologically, there were areas of a well-differentiated squamous cell carcinoma, alternating with the typical area of ESFA characterized by anastomosing cords, strands, and columns of epithelial cells extending from the crusted epidermis into a thickened, edematous, myxoid vascular-rich dermis. Immunohistochemically, the areas with dysplastic epithelium were positive for p16, whereas the benign ESFA parts tested negative. Human papillomavirus was detected in the lesional tissue by polymerase chain reaction, and the subsequent sequencing analysis demonstrated that the virus was close to human papillomavirus type 107.

  1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin has both pro-carcinogenic and anti-carcinogenic effects on neuroendocrine prostate carcinoma formation in TRAMP mice

    International Nuclear Information System (INIS)

    Moore, Robert W.; Fritz, Wayne A.; Schneider, Andrew J.; Lin, Tien-Min; Branam, Amanda M.; Safe, Stephen; Peterson, Richard E.

    2016-01-01

    It is well established that the prototypical aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can both cause and protect against carcinogenesis in non-transgenic rodents. But because these animals almost never develop prostate cancer with old age or after carcinogen exposure, whether AHR activation can affect cancer of the prostate remained unknown. We used animals designed to develop this disease, Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, to investigate the potential role of AHR signaling in prostate cancer development. We previously reported that AHR itself has prostate tumor suppressive functions in TRAMP mice; i.e., TRAMP mice in which Ahr was knocked out developed neuroendocrine prostate carcinomas (NEPC) with much greater frequency than did those with both Ahr alleles. In the present study we investigated effects of AHR activation by three different xenobiotics. In utero and lactational TCDD exposure significantly increased NEPC tumor incidence in TRAMP males, while chronic TCDD treatment in adulthood had the opposite effect, a significant reduction in NEPC incidence. Chronic treatment of adult TRAMP mice with the low-toxicity selective AHR modulators indole-3-carbinol or 3,3′-diindolylmethane did not significantly protect against these tumors. Thus, we demonstrate, for the first time, that ligand-dependent activation of the AHR can alter prostate cancer incidence. The nature of the responses depended on the timing of AHR activation and ligand structures. - Highlights: • TRAMP mice model aggressive neuroendocrine prostate carcinomas in men • In utero/lactational TCDD exposure raised prostate cancer incidence in TRAMP mice. • TCDD treatment in adulthood lowered prostate cancer incidence in TRAMP mice. • No significant protection was seen in TRAMP mice given I3C or DIM in adulthood. • This is the first report that TCDD alters prostate cancer incidence in lab animals.

  2. Differentiation between chalazion and sebaceous carcinoma by noninvasive meibography

    OpenAIRE

    Nemoto Y; Arita R; Mizota A; Sasajima Y

    2014-01-01

    Yuji Nemoto,1 Reiko Arita,2,3 Atsushi Mizota,1 Yuko Sasajima4 1Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, 2Itoh Clinic, Saitama, 3Department of Ophthalmology, The University of Tokyo, Tokyo, 4Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan Background: Sebaceous carcinoma is notorious for masquerading clinically as other benign lesions such as chalazion. A tool to better differentiate between these two conditions would thus be desira...

  3. Function of PTP1B in Neuroendocrine Differentiation of Prostate Cancer

    National Research Council Canada - National Science Library

    Huang, Jiaoti

    2008-01-01

    ... differentiation of prostate cancer cells, particularly the relationship of PTP1B to IL-8 signaling through its receptors CXCR1 and CXCR2, to IGF-1 receptor signaling through PI3 kinase/AKT/mTOR pathway...

  4. {sup 68}Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kroiss, A.; Putzer, D.; Decristoforo, C.; Uprimny, C.; Warwitz, B.; Nilica, B.; Gabriel, M.; Kendler, D.; Waitz, D.; Virgolini, I.J. [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Widmann, G. [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria)

    2013-04-15

    We wanted to establish the range of {sup 68}Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 {sup 68}Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUV{sub max} (mean {+-} standard deviation) values of {sup 68}Ga-DOTA-TOC were 29.8 {+-} 16.5 in 162 liver metastases, 19.8 {+-} 18.8 in 89 bone metastases and 34.6 {+-} 17.1 in 43 pancreatic NET (33.6 {+-} 14.3 in 30 tumours of the uncinate process and 36.3 {+-} 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUV{sub max} (p < 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUV{sub max} between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUV{sub max} for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p < 0.0001). {sup 68}Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUV{sub max} can offer important clinical

  5. Well-differentiated thyroid carcinoma in Martinique

    International Nuclear Information System (INIS)

    Azaloux, H.; Dieye, M.; Draganescu, C.; Istrate, M.; Dorival, M.J.; Baudin-Veronique, J.; Escarmant, P.; Amar, A.; Francois, H.

    2002-01-01

    The thyroid neoplasm is easily entered in the accounts in Martinique with the Tumor Registry created in 1981. This is not a frequent cancer but its frequency grew since 1981 till 1995. The treatment of the well differentiated thyroid cancer is well standardized with a total thyroidectomy generally followed by a metabolic thyroidectomy with 131 I. The follow-up is composed by clinical exam, TSH and thyroglobulin measurements. The results are very good and we mean to continue this strategy refining it for the little papillary tumors and using the recombinant TSH. The Tchernobyl event in 1986 generated new epidemiological considerations and has been the object of multiples studies.The studies realized in such a very distant site like Martinique permitted the realization of comparisons with the Tumor Registry of the 'Bas Rhin' in France a geographical area that could have been concerned by the disaster. The result of this study fends a growth of the incidence of the thyroid neoplasm almost identical with that registered in the mainland with a net increase for the papillary neoplasms. We may then conclude that the growth percentage since 1981 till 1995 due to the availability and more frequent using of many new diagnostic means less operator-dependent than before. By this descriptive study we may purport that the incidence of the thyroid cancer is low (4,45 per 100000 population for women and 0,9 per 100000 population for men). Treatment is consensual and thanks to the lifelong administration of exogenous thyroid hormone the quality of life of these patients is maintained along with a sure recovery in most of the cases. The mortality due to the thyroid cancer is very low in the orthoplasic form (less than 1 % of all types of cancer). The precocious screening of the thyroid neoplasm has to enter then in the guidelines in medical education. It consists in the systematical exploring of a thyroid nodule by clinical exam and by ultrasonography, radioisotope scanning with Tc

  6. Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.

    Science.gov (United States)

    Fazio, Nicola; Buzzoni, Roberto; Delle Fave, Gianfranco; Tesselaar, Margot E; Wolin, Edward; Van Cutsem, Eric; Tomassetti, Paola; Strosberg, Jonathan; Voi, Maurizio; Bubuteishvili-Pacaud, Lida; Ridolfi, Antonia; Herbst, Fabian; Tomasek, Jiri; Singh, Simron; Pavel, Marianne; Kulke, Matthew H; Valle, Juan W; Yao, James C

    2018-01-01

    In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma

    Science.gov (United States)

    Na’ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv

    2016-01-01

    Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC. PMID:26886954

  8. Dietary patterns as risk factors of differentiated thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Elwira Przybylik-Mazurek

    2012-01-01

    Full Text Available Nutritional factors are known to be important in the development of different metabolic diseases. The history of nodular or diffuse goiter is closely related to risk of thyroid carcinoma. On account of the function of the thyroid gland, many studies focus on iodine intake.The aim of the study was to assess whether dietary patterns could be risk factors of differentiated thyroid carcinoma.Material/Methods:The case-control study was based on a questionnaire, which included information about dietary patterns and was carried out on 284 patients comprising 30 males (mean age 58.4±13.7 years, and 254 females (mean age 52.1±13.8 years, as well as 345 randomly selected controls: 58 males (mean age 60.2±12 years and 287 females (mean age 53.4±14.3 years randomly selected from the Population Register and adjusted by age and gender to the group of TC. The main groups of nutritional products, i.e. starchy foods, meat, dairy products, vegetables, fruits, and beverages, were analyzed.Results:Consumption of vegetables, fruits, saltwater fish and cottage cheese was significantly lower in patients with differentiated thyroid carcinoma than in controls, quite the contrary to starchy foods, especially white bread.Conclusions:Dietary patterns appear to modify the risk of thyroid carcinoma. A diet rich in vegetables and fruit, as well as saltwater fish (a source of iodine and low-fat meat, could be an important protective factor.

  9. A Calcitonin Non-producing Neuroendocrine Tumor of the Thyroid Gland.

    Science.gov (United States)

    Kasajima, Atsuko; Cameselle-Teijeiro, José; Loidi, Lourdes; Takahashi, Yoshio; Nakashima, Noriaki; Sato, Satoko; Fujishima, Fumiyoshi; Watanabe, Mika; Nakazawa, Tadao; Naganuma, Hiroshi; Kondo, Tetsuo; Kato, Ryohei; Sasano, Hironobu

    2016-12-01

    Neuroendocrine tumors of the thyroid gland are generally considered to derive from parafollicular endocrine cells (C cells) and are generally referred to as medullary thyroid carcinomas (MTC). Calcitonin secretion is almost always detected in MTC and a prerequisite for both clinical and pathological diagnosis. Thyroid neuroendocrine tumors without any apparent calcitonin secretion reflect a diagnostic dilemma because non-calcitonin-producing MTCs have virtually not been characterized. Here, we report a case of primary thyroid neuroendocrine tumors lacking calcitonin secretion or expression. The tumor cells expressed cytokeratins, chromogranin A, and synaptophysin, all of which were consistent with epithelial and neuroendocrine differentiation. Thyroid transcription factor-1 paired box gene 8, and carcinoembryonic antigen were also immunohistochemically detected, consistent with its thyroid origin. However, the tumor was negative for calcitonin both by immunohistochemistry and in situ hybridization, hence, not meeting the definition of MTC. Despite the loss of calcitonin expression, immunoreactivity for the calcitonin-gene-related peptide was detected in the tumor. Somatic gene mutations of RET, H-RAS, K-RAS, or BRAF were not detected in this case. A limited number of calcitonin non-producing thyroid neuroendocrine tumors are available in the scientific literature available in English, and its etiology and clinical manifestations remain largely unknown. Our case, along with the rare, previously reported cases, suggests that calcitonin non-producing neuroendocrine tumors of the thyroid gland are most likely derived from C cells, but should be differentiated from ordinary MTCs.

  10. Neuroendocrine Tumor, diagnostic difficulties

    Directory of Open Access Journals (Sweden)

    Pedro Oliveira

    2017-06-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH secretion is a rare disease. A 51 years old woman, with a Cushing syndrome secondary to ectopic ACTH secretion, diagnosed in 2009, with mediastinal lymphadenopathy, whose biopsy was compatible with lung small cell carcinoma, staged as IIIB using TNM classification. No other lesions were found in patient study. The patient was submitted to chemotherapy, associated to ketoconazole 200 mg twice daily, with partial remission of both conditions. Three years later was admitted with an aggravation of Cushing syndrome. There was no evidence of progression of pulmonary disease. A cystic lesion in the pancreatic uncinated process was found by abdominal CT scan and with avid uptake by DOTANOC PET discreet in anterior mediastinal lymphadenopathy. Biopsy of pancreatic mass revealed a neuroendocrine tumor. Pulmonary masses were biopsied again and was in favor of neuroendocrine tumor. It was assumed the diagnosis of pancreatic neuroendocrine tumor with mediastinal metastasis. The patient initiated lanreotid (120 mg, monthly, subcutaneous in association with ketoconazole. After 5 months of therapy, patient died with sepsis secondary to pneumonia. Neuroendocrine tumours are rare, difficult to diagnose and with poor prognosis when associated with ectopic ACTH secreting Cushing syndrome.

  11. Poorly Differentiated Thyroid Carcinoma Arising in Struma Ovarii

    Directory of Open Access Journals (Sweden)

    Surapan Khunamornpong

    2015-01-01

    Full Text Available Struma ovarii is an uncommon type of ovarian mature teratoma with a predominant thyroid component. The morphological spectrum of the thyroid tissue ranges from that of normal thyroid to proliferative adenoma-like lesions and thyroid-type carcinomas (malignant transformation. The histologic features of ovarian strumal lesions sometimes cause diagnostic problems due to the confusion with other types of ovarian neoplasms and the difficulty in the prediction of their clinical behavior. We report an extremely rare case of poorly differentiated thyroid carcinoma arising in struma ovarii. A 22-year-old woman presented with a 15 cm right ovarian mass. The tumor showed a predominantly tubular pattern which raised a differential diagnosis between endometrioid adenocarcinoma and Sertoli cell tumor. A review of the gross specimen with additional tissue sampling helped identify the teratomatous and strumal nature, with a support by immunohistochemical staining. Despite FIGO stage IA by optimal staging procedure and the absence of identifiable lymphovascular invasion, the patient developed pulmonary metastasis 15 months after surgery and died from the progression of the disease 7 years after the diagnosis. This case emphasizes the importance of macroscopic examination of the specimen and the awareness of this uncommon tumor in the differential diagnosis of ovarian neoplasms.

  12. Endocrine Mucin-Producing Sweat Gland Carcinoma, a Histological Challenge

    OpenAIRE

    Brett, Mary Anne; Salama, Samih; Gohla, Gabriella; Alowami, Salem

    2017-01-01

    Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare adnexal tumor of the skin with low-grade cytological features and neuroendocrine differentiation. It has a predilection for the skin of the eyelid, but has also been reported in the face and rarely extra-facial locations. The tumor is seen more frequently in women and on average affects the elderly. It is histologically and immunohistochemically analogous to solid papillary carcinoma of the breast/endocrine ductal carcinoma in...

  13. Induction of differentiation of murine embryonal carcinoma cells by ouabain

    International Nuclear Information System (INIS)

    Zimmerman, B.T.

    1986-01-01

    Embryonal carcinoma (EC) cells can be induced to differentiate by ouabain at concentrations which inhibit Na + , K + -ATPase activity as measured by inhibition of 86 Rb + uptake. Since the pharmacologic action of ouabain is thought to be specific, the authors investigated the role of Na + , K + -ATPase inhibition and specific metabolic consequences of this inhibition in the induction of EC differentiation, and explored whether this might be a common mode of action for a variety of structurally diverse inducers. The Na + , K + -ATPase maintains ionic gradients in cells. However, results of studies utilizing specific ionophores, channel blockers, and media deficient in specific components failed to demonstrate a consistent role for ion flux or concentration in the differentiation process. The Na + , K + -ATPase is a major consumer of ATP. They therefore examined the effect of Na + , K + -ATPase inhibition on the adenylate energy charge as measured by high performance liquid chromatography of adenylate nucleotides. Ouabain was found to significantly decrease the energy charge in sensitive cells suggesting a role for suppression of ATP turnover is triggering differentiation. However, direct inhibition of glycolysis also induced differentiation without decreasing the energy charge, suggesting that reduction of the energy charge is not a common mechanism for induction of differentiation of EC

  14. [Small cell neuroendocrine tumour of the bladder: with reference to a case and bibliographical revision].

    Science.gov (United States)

    Lahoz Tornos, A; Marrón Penón, Maria C; Pardo López, Maria L; Nogueras Gimeno, M A; Pujol Obis, E; Del Villar Sordo, V

    2006-09-01

    The small cell neuroendocrine tumour is an infrecuent neoplasia, with inmunohistochemistry being the key to diagnosis. We present a new case making reference to treatment and its evolution there after. The clinic, diagnosis and treatment of this tumour is described. Bibliographical revision follours. The neuroendocrine tumour of small cell is an infrecuent neoplasia, in which the inmunohistochemistry study is key in the diagnosis. The differential diagnosis includes the high degree diferentiation transitionals cells carcinoma and primary and secondary linfoma. The standard treatment is based on chemotherapy plus surgery.

  15. Members of the crustacean hyperglycemic hormone (CHH) peptide family are differentially distributed both between and within the neuroendocrine organs of Cancer crabs: implications for differential release and pleiotropic function.

    Science.gov (United States)

    Hsu, Yun-Wei A; Messinger, Daniel I; Chung, J Sook; Webster, Simon G; de la Iglesia, Horacio O; Christie, Andrew E

    2006-08-01

    The crustacean hyperglycemic hormone (CHH) family of peptides includes CHH, moult-inhibiting hormone (MIH) and mandibular organ-inhibiting hormone (MOIH). In the crab Cancer pagurus, isoforms of these peptides, as well as CHH precursor-related peptide (CPRP), have been identified in the X-organ-sinus gland (XO-SG) system. Using peptides isolated from the C. pagurus SG, antibodies to each family member and CPRP were generated. These sera were then used to map the distributions and co-localization patterns of these peptides in the neuroendocrine organs of seven Cancer species: Cancer antennarius, Cancer anthonyi, Cancer borealis, Cancer gracilis, Cancer irroratus, Cancer magister and Cancer productus. In addition to the XO-SG, the pericardial organ (PO) and two other neuroendocrine sites contained within the stomatogastric nervous system, the anterior cardiac plexus (ACP) and the anterior commissural organ (ACO), were studied. In all species, the peptides were found to be differentially distributed between the neuroendocrine sites in conserved patterns: i.e. CHH, CPRP, MIH and MOIH in the XO-SG, CHH, CPRP and MOIH in the PO, and MOIH in the ACP (no immunolabeling was found in the ACO). Moreover, in C. productus (and probably in all species), the peptides present in the XO-SG and PO were differentially distributed between the neurons within each of these neuroendocrine organs (e.g. CHH and CPRP in one set of XO somata with MIH and MOIH co-localized in a different set of cell bodies). Taken collectively, the differential distributions of CHH family members and CPRP both between and within the neuroendocrine organs of crabs of the genus Cancer suggests that each of these peptides may be released into the circulatory system in response to varied, tissue-specific cues and that the PO- and/or ACP-derived isoforms may possess functions distinct from those classically ascribed to their release from the SG.

  16. Variable CT Findings of Epithelial Origin Ovarian Carcinoma According to the Degree of Histologic Differentiation

    International Nuclear Information System (INIS)

    Jang, Yun Jin; Kim, Jeong Kon; Park, Sung Bin; Cho, Kyoung Sik

    2007-01-01

    We wanted to evaluate the CT findings of epithelial origin ovarian carcinoma according to the degree of histologic differentiation. This study enrolled 124 patients with 31 well differentiated, 44 moderately differentiated and 95 poorly differentiated carcinomas with epithelial origin. The CT images were retrospectively evaluated with regard to bilateral ovarian involvement, the tumor's nature, lymphadenopathy, adjacent organ invasion, peritoneal tumor seeding, a large amount of ascites and distant metastasis. In cystic, predominantly cystic and mixed tumors, the tumor wall, septa, papillary projection and necrosis in the solid portion were assessed. Bilateral ovarian involvement was more common in the poorly (48%) and moderately (42%) differentiated carcinomas than in the well differentiated carcinomas (7%) (p < 0.05). The frequency of a predominantly solid or solid nature was greater in the moderately and poorly differentiated carcinomas than in the well differentiated carcinomas (p < 0.0001). In the 87 tumors with a cystic, predominantly cystic or mixed nature, septa greater than 3 mm, papillary projection and necrosis in the solid portion were more common in the poorly differentiated carcinoma (91%, 91% and 77%, respectively) than in the moderately (64%, 68% and 34%, respectively) and well differentiated carcinomas (63%, 47% and 27%, respectively) (p < 0.05). Lymphadenopathy, organ invasion, tumor seeding and a large amount of ascites were more common in the poorly differentiated carcinomas (38%, 27%, 73% and 69%, respectively) than in the moderately (13%, 10%, 48% and 45%, respectively) and well differentiated carcinomas (3%, 0%, 10% and 17%, respectively) (p < 0.05). Epithelial origin ovarian carcinoma shows different CT findings according to the degree of histologic differentiation

  17. The effect of transforming growth factor beta on human neuroendocrine tumor BON cell proliferation and differentiation is mediated through somatostatin signaling.

    Science.gov (United States)

    Leu, Frank P; Nandi, Minesh; Niu, Congrong

    2008-06-01

    The dual effect of the ubiquitous inflammatory cytokine transforming growth factor beta1 (TGF beta) on cellular proliferation and tumor metastasis is intriguing but complex. In epithelial cell- and neural cell-derived tumors, TGF beta serves as a growth inhibitor at the beginning of tumor development but later becomes a growth accelerator for transformed tumors. The somatostatin (SST) signaling pathway is a well-established antiproliferation signal, and in this report, we explore the interplay between the SST and TGF beta signaling pathways in the human neuroendocrine tumor cell line BON. We defined the SST signaling pathway as a determinant for neuroendocrine tumor BON cells in responding to TGF beta as a growth inhibitor. We also determined that TGF beta induces the production of SST and potentially activates the negative growth autocrine loop of SST, which leads to the downstream induction of multiple growth inhibitory effectors: protein tyrosine phosphatases (i.e., SHPTP1 and SHPTP2), p21(Waf1/Cip1), and p27(Kip1). Concurrently, TGF beta down-regulates the growth accelerator c-Myc protein and, collectively, they establish a firm antiproliferation effect on BON cells. Additionally, any disruption in the activation of either the TGF beta or SST signaling pathway in BON leads to "reversible" neuroendocrine-mesenchymal transition, which is characterized by the loss of neuroendocrine markers (i.e., chromogranin A and PGP 9.5), as well as the altered expression of mesenchymal proteins (i.e., elevated vimentin and Twist and decreased E-cadherin), which has previously been associated with elevated metastatic potential. In summary, TGF beta-dependent growth inhibition and differentiation is mediated by the SST signaling pathway. Therefore, any disruption of this TGF beta-SST connection allows BON cells to respond to TGF beta as a growth accelerator instead of a growth suppressor. This model can potentially apply to other cell types that exhibit a similar interaction of

  18. Sarcomatoid differentiation in renal cell carcinoma: prognostic implications

    Directory of Open Access Journals (Sweden)

    Marcos F. Dall'Oglio

    2005-02-01

    Full Text Available INTRODUCTION: Renal cell carcinoma with sarcomatoid differentiation is a tumor with aggressive behavior that is poorly responsive to immunotherapy. The objective of this study is to report our experience in the treatment of 15 patients with this tumor. MATERIALS AND METHODS: We retrospectively analyzed 15 consecutive cases of renal cell carcinoma with sarcomatoid differentiation diagnosed between 1991 and 2003. The clinical presentation and the pathological stage were assessed, as were the tumor's pathological features, use of adjuvant immunotherapy and survival. The study's primary end-point was to assess survival of these individuals. RESULTS: The sample included 8 women and 7 men with mean age of 63 years (44 - 80; follow-up ranged from 1 to 100 months (mean 34. Upon presentation, 87% were symptomatic and 4 individuals had metastatic disease. Mean tumor size was 9.5 cm (4 - 24 with the following pathological stages: 7% pT1, 7% pT2, 33% pT3, and 53% pT4. The pathological features showed high-grade tumors with tumoral necrosis in 87% of the lesions and 80% of intratumoral microvascular invasion. Disease-free and cancer-specific survival rates were 40 and 46% respectively, with 2 cases responding to adjuvant immunotherapy. CONCLUSIONS: Patients with sarcomatoid tumors of the kidney have a low life expectancy, and sometimes surgical resection associated with immunotherapy can lead to a long-lasting therapeutic response.

  19. Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma.

    Science.gov (United States)

    Zhang, Leilei; Huang, Xiaolin; Zhu, Xiaowei; Ge, Shengfang; Gilson, Eric; Jia, Renbing; Ye, Jing; Fan, Xianqun

    2016-03-15

    Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC. © 2015 UICC.

  20. Surgery and staging of pancreatic neuroendocrine tumors: a 14-year experience.

    Science.gov (United States)

    Ito, Hiromichi; Abramson, Michael; Ito, Kaori; Swanson, Edward; Cho, Nancy; Ruan, Daniel T; Swanson, Richard S; Whang, Edward E

    2010-05-01

    The aims of this study were to evaluate contemporary outcomes associated with the surgical management of pancreatic neuroendocrine tumors (PNETs) and to assess the prognostic value of the World Health Organization (WHO) classification and TNM staging for PNETs. The medical records of 73 consecutive patients with PNETs treated at a single institution from January 1992 through September 2006 were reviewed. Survival was analyzed with the Kaplan-Meier method (median follow-up: 43 months). Median patient age was 52 years (range, 19-83 years), and 36 (49%) patients were male. Thirty-three patients had a well-differentiated neuroendocrine tumor (WDT), 26 had a well-differentiated neuroendocrine carcinoma (WDCa), and 14 had a poorly differentiated neuroendocrine carcinoma (PDCa). Fifty (68%) patients underwent potentially curative resection, and the 5-year disease-specific survival (DSS) rate for the entire cohort was 62%. WHO classification and TNM staging system provided good prognostic stratification of patients; 5-year DSS rates were 100% for WDT, 57% for WDCa, 8% for PDCa, respectively, by WHO classification (p < 0.001), and 100% for stage 1, 90% for stage 2, 57% for stage 3, and 8% for stage 4, respectively, by TNM stage (p < 0.001). Among the patients who underwent potentially curative resection, nodal status, distant metastasis, and tumor grade were significant prognostic factors. WHO classification and TNM staging are useful for prognostic stratification among patients with PNETs.

  1. Difficulty in Differentiating Breast Fibroadenoma from Carcinoma : A Case Report and Review of Literature

    OpenAIRE

    我喜屋, 亮; 山下, 雅知; 大城, 直人; 慶田, 喜信; 比嘉, 司; 当山, 勝徳; 武島, 正則; 平安山, 英義; 仲間, 健; 新垣, 京子; Gakiya, Akira; Yamashita, Masatomo; Ohshiro, Naoto; Keida, Yoshinobu; Higa, Tsukasa

    1993-01-01

    Fibroadenoma is a commonly found benign tumor of the breast; however carcinoma in a fibroadenoma is rarely encountered. In this paper we described a case of fibroadenoma difficult to differentiate from carcinoma. A 17-year-old woman visited our hospital complaining of a left breast lump. Ultrasonography showed a well-defined and hypoechoic ovoid mass. Excisional biopsy was done and diagnosed as fibroadenoma; however it was difficult to differentiate histologically from carcinoma. The features...

  2. Quality and Timing of Stressors Differentially Impact on Brain Plasticity and Neuroendocrine-Immune Function in Mice

    Directory of Open Access Journals (Sweden)

    Sara Capoccia

    2013-01-01

    Full Text Available A growing body of evidence suggests that psychological stress is a major risk factor for psychiatric disorders. The basic mechanisms are still under investigation but involve changes in neuroendocrine-immune interactions, ultimately affecting brain plasticity. In this study we characterized central and peripheral effects of different stressors, applied for different time lengths, in adult male C57BL/6J mice. We compared the effects of repeated (7 versus 21 days restraint stress (RS and chronic disruption of social hierarchy (SS on neuroendocrine (corticosterone and immune function (cytokines and splenic apoptosis and on a marker of brain plasticity (brain-derived neurotrophic factor, BDNF . Neuroendocrine activation did not differ between SS and control subjects; by contrast, the RS group showed a strong neuroendocrine response characterized by a specific time-dependent profile. Immune function and hippocampal BDNF levels were inversely related to hypothalamic-pituitary-adrenal axis activation. These data show a fine modulation of the crosstalk between central and peripheral pathways of adaptation and plasticity and suggest that the length of stress exposure is crucial to determine its final outcome on health or disease.

  3. Influence of abiraterone acetate on neuroendocrine differentiation in chemotherapy-naive metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Dong, Baijun; Fan, Liancheng; Wang, Yanqing; Chi, Chenfei; Ma, Xiaowei; Wang, Rui; Cai, Wen; Shao, Xiaoguang; Pan, Jiahua; Zhu, Yinjie; Shangguan, Xun; Xin, Zhixiang; Hu, Jianian; Xie, Shaowei; Kang, Xiaonan; Zhou, Lixin; Xue, Wei

    2017-05-01

    To determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). We conducted an analysis in 115 chemotherapy-naïve mCRPC patients who would be treated with chemotherapy. The serum levels of chromogranin A (CgA), neurone-specific enolase (NSE) were measured in 67 mCRPC patients without AA treatment and 48 patients after the failure of AA treatment, in which these markers were also measured in 34 patients before and after 6 months of AA treatment. Comparative t-test was used to evaluate the serial changes of serum NED markers during AA treatment and univariate and multivariate analyses were performed to test the influence of AA treatment on NED. Serum CgA were NSE were evaluated to be above the upper limit of normal (ULN) in 56 (48.7%) and 29 (25.2%) patients before chemotherapy. In 34 patients with serial evaluation, serum CgA level of 14 patients and NSE of 14 patients increased after the failure of AA treatment. There was no significant difference of NED markers (CgA or NSE variation (P = 0.243) between at baseline and after the failure of AA treatment. Compared with the CgA elevation group in the first 6 months of AA treatment and baseline supranormal CgA group, the CgA decline group, and baseline normal CgA group has a much longer median PSA PFS (14.34 vs 10.00 months, P < 0.001, and 14.23 vs 10.30 months, P = 0.02) and rPFS, respectively (18.33 vs 11.37 months, P < 0.001, and 17.10 vs 12.07 months, P = 0.03). In logistic univariate analysis, AA treatment and its duration were not independent factors influencing NED. We hypothesized that AA might not significantly lead to progression of NED of mCRPC in general. Furthermore, we found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment. Serial CgA and NSE evaluation might help clinicians guide clinical treatment of m

  4. High glucose induces N-linked glycosylation-mediated functional upregulation and overexpression of Cav3.2 T-type calcium channels in neuroendocrine-like differentiated human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Kazuki Fukami

    2017-01-01

    Full Text Available Given that Cav3.2 T-type Ca2+ channels were functionally regulated by asparagine (N-linked glycosylation, we examined effects of high glucose on the function of Cav3.2, known to regulate secretory function, in neuroendocrine-like differentiated prostate cancer LNCaP cells. High glucose accelerated the increased channel function and overexpression of Cav3.2 during neuroendocrine differentiation, the former prevented by enzymatic inhibition of N-glycosylation and cleavage of N-glycans. Hyperglycemia thus appears to induce N-linked glycosylation-mediated functional upregulation and overexpression of Cav3.2 in neuroendocrine-like differentiated prostate cancer cells.

  5. Differentiation in neuroblastoma: diffusion-limited hypoxia induces neuro-endocrine secretory protein 55 and other markers of a chromaffin phenotype.

    Directory of Open Access Journals (Sweden)

    Fredrik Hedborg

    2010-09-01

    Full Text Available Neuroblastoma is a childhood malignancy of sympathetic embryonal origin. A high potential for differentiation is a hallmark of neuroblastoma cells. We have previously presented data to suggest that in situ differentiation in tumors frequently proceeds along the chromaffin lineage and that decreased oxygen (hypoxia plays a role in this. Here we explore the utility of Neuro-Endocrine Secretory Protein 55 (NESP55, a novel member of the chromogranin family, as a marker for this process.Immunohistochemical analyses and in situ hybridizations were performed on human fetal tissues, mouse xenografts of human neuroblastoma cell lines, and on specimens of human neuroblastoma/ganglioneuroma. Effects of anaerobic exposure on gene expression by cultured neuroblastoma cells was analyzed with quantitative real-time PCR. Fetal sympathetic nervous system expression of NESP55 was shown to be specific for chromaffin cell types. In experimental and clinical neuroblastoma NESP55 immunoreactivity was specific for regions of chronic hypoxia. NESP55 expression also correlated strikingly with morphological evidence of differentiation and with other chromaffin-specific patterns of gene expression, including IGF2 and HIF2α. Anaerobic culture of five neuroblastoma cell lines resulted in an 18.9-fold mean up-regulation of NESP55.The data confirms that chronic tumor hypoxia is a key microenvironmental factor for neuroblastoma cell differentiation, causing induction of chromaffin features and NESP55 provides a reliable marker for this neuronal to neuroendocrine transition. The hypoxia-induced phenotype is the predominant form of differentiation in stroma-poor tumors, while in stroma-rich tumors the chromaffin phenotype coexists with ganglion cell-like differentiation. The findings provide new insights into the biological diversity which is a striking feature of this group of tumors.

  6. THE ASSOCIATION OF WELL-DIFFERENTIATED THYROID-CARCINOMA WITH INSULAR OR ANAPLASTIC THYROID-CARCINOMA - EVIDENCE FOR DEDIFFERENTIATION IN TUMOR PROGRESSION

    NARCIS (Netherlands)

    van der Laan, Bernard F.A.M.; FREEMAN, JL; TSANG, RW; ASA, SL

    1993-01-01

    The sequence of tumorigenesis in the thyroid is unclear. It has been proposed that anaplastic carcinomas of the thyroid develop by dedifferentiation in pre-existing differentiated carcinomas. We reviewed all anaplastic and insular (poorly differentiated) thyroid carcinomas in a consultation practice

  7. Whole body diffusion for metastatic disease assessment in neuroendocrine carcinomas: comparison with OctreoScan® in two cases

    Directory of Open Access Journals (Sweden)

    Cossetti Rachel Jorge D

    2012-05-01

    Full Text Available Abstract Neuroendocrine tumor (NET patients must be adequately staged in order to improve a multidisciplinary approach and optimal management for metastatic disease. Currently available imaging studies include somatostatin receptor scintigraphy, like OctreoScan®, computed tomography (CT, scans and magnetic resonance imaging (MRI, which analyze vascular concentration and intravenous contrast enhancement for anatomic tumor localization. However, these techniques require high degree of expertise for interpretation and are limited by their availability, cost, reproducibility, and follow-up imaging comparisons. NETs significantly reduce water diffusion as compared to normal tissue. Diffusion-weighted imaging (DWI in MRI has an advantageous contrast difference: the tumor is represented with high signal over a black normal surrounding background. The whole-body diffusion (WBD technique has been suggested to be a useful test for detecting metastasis from various anatomic sites. In this article we report the use of DWI in MRI and WBD in two cases of metastatic pulmonary NET staging in comparison with OctreoScan® in order to illustrate the potential advantage of DWI and WBD in staging NETs.

  8. Recurrent endocrine mucin-producing sweat gland carcinoma.

    Science.gov (United States)

    Emanuel, Patrick O; de Vinck, David; Waldorf, Heidi A; Phelps, Robert G

    2007-12-01

    Endocrine mucin-producing sweat gland carcinoma is a rare skin tumor that most commonly involves the eyelid of elderly women. Morphologically and immunohistochemically, it is analogous to endocrine ductal carcinoma in situ of the breast and mammary solid papillary carcinoma; also, like the analogous breast lesion, there is an often associated invasive mucinous carcinoma with neuroendocrine differentiation. We describe the case of a 65-year-old woman with endocrine mucin-producing sweat gland carcinoma of the eyelid that recurred 3 years after an apparently complete excision.

  9. Peritoneal and mediastinal highly differentiated follicular carcinoma of ovarian origin

    International Nuclear Information System (INIS)

    Carey, Kathleen; Jain, Manoj; Krishna, Murli; Accurso, Joseph

    2014-01-01

    A 70-year-old female patient presented to her primary care doctor with persistent elevated alkaline phosphatase of suspected metastatic etiology. Computed tomography demonstrated epicardial and peritoneal nodules. Biopsy of one of the peritoneal nodules revealed thyroid tissue and extraovarian struma ovarii was considered. The patient had a history of remote total abdominal hysterectomy and bilateral salpingo-oophorectomy 31 years prior for endometriosis with no available pathology from that surgery. The patient recalls being told that she had a left ovarian cyst. A thyroid ultrasound was performed that demonstrated multiple nodules without concerning features; however, due to high clinical suspicion, a total thyroidectomy was performed. Upon full histological evaluation a 0.5 cm papillary microcarcinoma was found. Given the rarity of metastatic papillary cancer to the peritoneum and the small size and grade of the tumor, a diagnosis of highly differentiated follicular carcinoma of ovarian origin was favored. The patient was subsequently treated with radioiodine therapy

  10. Prognostic factors in well-differentiated carcinoma of the thyroid

    International Nuclear Information System (INIS)

    Rao, R.S.; Parikh, H.K.

    1999-01-01

    The choice of treatment for a well-differentiated carcinoma (WDC) of the thyroid has remained controversial for several decades. This is unfortunate because WDC occurs in the young, particularly in women, and is compatible with several years of survival. A retrospective analysis of 417 cases of WDC of the thyroid treated by definitive surgery at the Tata Memorial Hospital for the 15-year period (1970 to 1985) form the basis of the conclusion drawn in the present report. These include cases that were referred primarily and those who underwent revision or completion thyroidectomy at the hospital after being treated elsewhere. All relevant data of the cases with WDC, including histopathology slides, were reviewed by an experienced pathologist

  11. Basal cell carcinoma of the prostate: a case report.

    Science.gov (United States)

    Stearns, Gillian; Cheng, Jed-Sian; Shapiro, Oleg; Nsouli, Imad

    2012-06-01

    A 69-year-old man presented with gross hematuria and irritative urinary symptoms. He underwent transurethral resection of his prostate. The prostate chips revealed 70% poorly differentiated carcinoma with neuroendocrine features, initially read as small cell carcinoma, later as basal cell carcinoma. PSA at this time was 0.3. He received 4 cycles of etoposide and cisplatin. After which, rebiopsy of the prostate showed tumor consistent with poorly differentiated basal cell carcinoma. Given progression on chemotherapy, decision was made to proceed with radical prostatectomy. Metastatic workup was negative. Gross extraprostatic invasion was noted but lymph nodes were free of metastatic disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Design and Validation of the GI-NEC Score to Prognosticate Overall Survival in Patients With High-Grade Gastrointestinal Neuroendocrine Carcinomas.

    Science.gov (United States)

    Lamarca, Angela; Walter, Thomas; Pavel, Marianne; Borbath, Ivan; Freis, Patricia; Nuñez, Barbara; Childs, Alexa; McNamara, Mairéad G; Hubner, Richard A; Garcia-Carbonero, Rocio; Meyer, Tim; Valle, Juan W; Barriuso, Jorge

    2017-01-01

    Prognostic markers for risk stratification of patients with gastrointestinal high-grade neuroendocrine carcinomas (GI-NECs) are lacking; we designed and validated a prognostic score for overall survival (OS). Consecutive patients diagnosed in five neuroendocrine specialist European centers were included. Patients were divided into three cohorts: a training cohort (TC), an external validation cohort (EVC), and a prospective validation cohort (PVC). Prognostic factors were identified by log-rank test, Cox-regression, and logistic regression analyses. The derived score was internally and externally validated. All statistical tests were two-sided. Of 395 patients screened, 313 were eligible (TC = 109 patients, EVC = 184 patients, and PVC = 20 patients). The derived prognostic score included five variables: presence of liver metastases, alkaline phosphatase (ALK), lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group performance status (ECOG PS), and Ki67. In multivariable analysis, the score was prognostic for OS (hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.47 to 2.35, P EVC and PVC, in which our score was able to prognosticate for OS when adjusted for other prognostic variables in the multivariable analysis (HR = 1.85, 95% CI = 1.27 to 2.71, P = .001; and HR = 4.51, 95% CI = 1.87 to 10.87, P = .001, respectively). The score classified patients into two groups with incremental risk of death: group A (0-2 points, 181 patients [63.9%], median OS = 19.4 months, 95% CI = 16.1 to 25.1) and group B (3-6 points, 102 patients [36.1%], median OS = 5.2 months, 95% CI = 3.6 to 6.9). The GI-NEC score identifies two distinct patient cohorts; it provides a tool for clinicians when making treatment decisions and may be used as a stratification factor in future clinical trials. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Report of a case of acinar cell carcinoma with its differential diagnosis on endoscopic ultrasound-guided fine-needle aspiration cytology

    Directory of Open Access Journals (Sweden)

    Misao Yoneda

    2014-01-01

    Full Text Available Acinar cell carcinomas (ACCs of the pancreas are a rare tumor accounting for only about 2% of all pancreas tumors. We report herein on this case and discuss how to distinguish ACCs from neuroendocrine tumors (NETs and solid pseudo-papillary tumor (SPTs morphologically and immunohistochemically. In cytological findings, the nuclear-cytoplasmic ratio was high, and the cytoplasm was granular, but zymogen granules were not evident. The nucleus was biased in location, assuming small circular and irregular forms. Chromatin was fine granular in shape and distributed nonuniformly, accompanied by evident nucleoli. Immunohistochemically was positive for β-catenin (cell membrane and part of nuclei, synaptophysin (focal, chromogranin A (focal and chymotrypsin were all positive. Although the cytological distinction of ACCs from NETs and SPTs is difficult, the nuclear chromatin pattern and nuclear inclusion bodies, pseudopapillary arrangement and hyaline globules seem to play an important role in the cytological differential diagnosis. Furthermore, not only enzymatic and neuroendocrine markers, but also antibodies to β-catenin, vimentin and so on seem to be useful in the differential diagnosis.

  14. Reclassifying bronchial-pulmonary carcinoma: Differentiating histological type in biopsies by immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Lina Carvalho

    2009-11-01

    Full Text Available The current state of molecular knowledge on lung cancer demands a histological classification which goes beyond small-cell and non-small-cell carcinoma to provide support for tailored therapy in aiding in understanding of the drugs currently available.As diagnosis and follow-up in the vast majority of lung cancer cases is based on biopsies and cytology samples, Immunohistochemical Bronchial Pulmonary Carcinoma Classification (IBPCC is necessary to reveal the raft of characteristics available. This provides morphological support for the WHO's 1999/2004 classification, in addition to an understanding of carcinogenesis.The immunohistochemical panel clarifies the main morphology and cytology characteristics to maintain the leading histological types as squamous cell carcinoma (high weight molecular cytokeratins/HWMC, adenosquamous carcinoma (CK7, TTF1, HWMA, neuroendocrine carcinoma (Chrg, Syn, CD56, TTF1, Ki67, adenocarcinoma (CK7, CK20, TTF1 and bring the polymorphic and pleomorphic carcinomas under a single banner of pleomorphic carcinoma (Ck7, TTF1, HWMC, VMT, Desmin, Actin which shelters large cell carcinomas and sarcomatoid carcinomas.Lung cancer chemotherapy will still be based on platinum and gemcitabine for the near future and the IBPCC is a simple and efficient tool for streamlining the registration of lung cancer histological characteristics in biopsies and other reduced samples to support clinical evidence and trials. Resumo: Os conhecimentos actuais da patologia molecular do cancro do pulmão requerem outra caracterização histológica, para além de carcinoma de células pequenas e carcinoma não pequenas células para suporte da terapia personalizada e entendimento do valor real dos fármacos actualmente disponíveis.Como o diagnóstico e seguimento clínico da maioria dos casos de cancro do pulmão se baseia em produtos de biópsia e citologia, a classificação imunoistoquímica do carcinoma

  15. Cytodiagnosis of myxoid adrenocortical carcinoma and role of immunocytochemistry to differentiate it from renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Mondal

    2014-01-01

    Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy and cytodiagnosis of this tumor is not routinely encountered by a cytopathologist. Here, we report a case of ACC initially diagnosed by computed tomography (CT-guided fine needle aspiration cytology (FNAC with the help of immunocytochemistry. A 48-year-old lady presented with flank pain and abdominal mass for the last 6 months. A CT scan of her abdomen revealed a large mass arising from the upper part of the left kidney. CT-guided FNAC was performed. Cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells had a high nucleocytoplasmic ratio, anisonucleosis and conspicuous nucleoli. Based on cytomorphology, differential diagnoses of ACC and renal cell carcinoma (RCC were made. On immunocytochemistry, the tumor cells were synaptophysin, inhibin, vimentin and Melan-A positive but cytokeratin and epithelial membrane antigen negative. Thus, a cytodiagnosis of myxoid ACC was made and histopathologic examination was suggested. Subsequent histologic examination and immunohistochemistry proved the case to be myxoid ACC.

  16. Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

    Directory of Open Access Journals (Sweden)

    Akira Suzuki

    2012-01-01

    Full Text Available Alpha-fetoprotein-producing carcinoma (AFPC/hepatoid adenocarcinoma (HAC and neuroendocrine carcinoma (NEC are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component.

  17. Current concepts in neuroendocrine disruption.

    Science.gov (United States)

    León-Olea, Martha; Martyniuk, Christopher J; Orlando, Edward F; Ottinger, Mary Ann; Rosenfeld, Cheryl; Wolstenholme, Jennifer; Trudeau, Vance L

    2014-07-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  18. Current Concepts in Neuroendocrine Disruption

    Science.gov (United States)

    2014-01-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  19. EGF Prevents the Neuroendocrine Differentiation of LNCaP Cells Induced By Serum Deprivation: The Modulator Role of P13K/Akt

    Directory of Open Access Journals (Sweden)

    Rosa M. Martín-Orozco

    2007-08-01

    Full Text Available The primary focus of this investigation was to study the relationship between neuroendocrine (NE differentiation, epidermal growth factor (EGF because both have been implicated in the progression of prostate cancer. For this purpose, we used gefitinib, trastuzumab, which are inhibitors of EGF receptor (EGFR, ErbB2, respectively. EGF prevents NE differentiation induced by androgen depletion. This effect is prevented by gefitinib, which blocks the activation of EGFR, ErbB2, stimulation of mitogen-activated protein kinase (MAPK, cell proliferation induced by EGF. Conversely, trastuzumab does not inhibit the effect of EGF on EGFR phosphorylation, MAPK activity, cell proliferation, NE differentiation, although it reduces ErbB2 levels specifically, suggesting that ErbB2 is not necessary to inhibit NE differentiation. Prevention of NE differentiation by EGF is mediated by a MAPK-dependent mechanism, requires constitutive Akt activation. The abrogation of the PI3K/Akt pathway changes the role of EGF from inhibitor to inductor of NE differentiation. We show that EGFR tyrosine kinase, MAPK, PI3K inhibitors inhibit the cell proliferation stimulated by EGF but induce the acquisition of NE phenotype. Altogether, the present data should be borne in mind when designing new clinical schedules for the treatment of prostate cancer, including the use of ErbB receptors, associated signaling pathway inhibitors.

  20. Merkel cell carcinoma of the head and neck.

    NARCIS (Netherlands)

    Pellitteri, P.K.; Takes, R.P.; Lewis JS, J.r.; Devaney, K.O.; Harlor, E.J.; Strojan, P.; Rodrigo, J.P.; Suarez, C.; Rinaldo, A.; Medina, J.E.; Woolgar, J.A.; Ferlito, A.

    2012-01-01

    Merkel cell carcinomas are uncommon, but aggressive, cutaneous malignancies of neuroendocrine differentiation. To the pathologist, these lesions appear as sheets of undifferentiated tumor cells with little cytoplasm and dense nuclear chromatin. They are members of the group of "small round blue cell

  1. Sebaceous carcinoma with apocrine differentiation: A rare entity with aggressive behavior

    Directory of Open Access Journals (Sweden)

    Nishat Afroz

    2013-01-01

    Full Text Available Sebaceous carcinomas are rare neoplasms but have aggressive behavior. Although they can be found anywhere in the body ocular region is the most common site which comprises 75% of all cases of sebaceous carcinomas. Due to their rarity, varied histopathological features, and diverse clinical presentation, their diagnosis is often delayed, sometimes by a year. They are divided on the basis of histological differentiation into well and poorly differentiated. Apocrine differentiation is a still rarer finding and only two cases have been reported in the literature so far. We report a case of sebaceous carcinoma with apocrine differentiation in a 60-year-old male who presented with a painless swelling in right upper eyelid for 2 months which was gradually progressive. Computed tomography (CT scan was performed and a provisional diagnosis of hemangioma was made. The mass was excised and histopathological examination revealed it to be sebaceous carcinoma. However, there were areas with decapitation secretions and granular eosinophilic cytoplasm. These were positive for cytokeratin (CK 7 and CK 19 which confirmed their apocrine nature. Therefore, a final diagnosis of sebaceous carcinoma with apocrine differentiation was made. Thus, it can be concluded that ocular sebaceous carcinomas with apocrine differentiation are extremely rare and have significant clinical importance since they can mimic a benign lesion and the nature of surgical intervention and follow up is more aggressive than that of simple sebaceous carcinoma alone.

  2. Anaplastic thyroid carcinoma with rhabdomyoblastic differentiation : A case report with a good clinical outcome

    NARCIS (Netherlands)

    Olthof, Marijke; Persoon, Adrienne C. M.; Plukker, John T. M.; van der Wal, Jacqueline E.; Links, Thera P.

    2008-01-01

    Anaplastic thyroid carcinoma is a rare and highly malignant disease. Usually, this type of tumor is irresectable, and almost all patients die within 1 year after diagnosis. We present a case of anaplastic thyroid carcinoma with rhabdomyoblastic differentiation and good therapeutic outcome. A

  3. Cytomegalovirus Replicates in Differentiated but not in Undifferentiated Human Embryonal Carcinoma Cells

    Science.gov (United States)

    Gonczol, Eva; Andrews, Peter W.; Plotkin, Stanley A.

    1984-04-01

    To study the mode of action of human cytomegalovirus, an important teratogenic agent in human populations, the susceptibility of a pluripotent human embryonal carcinoma cell line to the virus was investigated. Viral antigens were not expressed nor was infectious virus produced by human embryonal carcinoma cells after infection, although the virus was able to penetrate these cells. In contrast, retinoic acid-induced differentiated derivatives of embryonal carcinoma cells were permissive for antigen expression and infectious virus production. Replication of human cytomegalovirus in human teratocarcinoma cells may therefore depend on cellular functions associated with differentiation.

  4. Endocrine Mucin-Producing Sweat Gland Carcinoma, a Histological Challenge.

    Science.gov (United States)

    Brett, Mary Anne; Salama, Samih; Gohla, Gabriella; Alowami, Salem

    2017-01-01

    Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare adnexal tumor of the skin with low-grade cytological features and neuroendocrine differentiation. It has a predilection for the skin of the eyelid, but has also been reported in the face and rarely extra-facial locations. The tumor is seen more frequently in women and on average affects the elderly. It is histologically and immunohistochemically analogous to solid papillary carcinoma of the breast/endocrine ductal carcinoma in situ with a nodular, solid, papillary, and/or cribriforming architecture, neuroendocrine differentiation, and mucin production. Since it was first described by Flieder et al. in 1997, less than 60 cases have been reported in literature. We describe the morphological and immunohistochemical features of another case with a review of the common histological differential diagnoses and emphasize the salient features that help distinguish this rare neoplasm.

  5. Endocrine Mucin-Producing Sweat Gland Carcinoma, a Histological Challenge

    Directory of Open Access Journals (Sweden)

    Mary Anne Brett

    2017-01-01

    Full Text Available Endocrine mucin-producing sweat gland carcinoma (EMPSGC is a rare adnexal tumor of the skin with low-grade cytological features and neuroendocrine differentiation. It has a predilection for the skin of the eyelid, but has also been reported in the face and rarely extra-facial locations. The tumor is seen more frequently in women and on average affects the elderly. It is histologically and immunohistochemically analogous to solid papillary carcinoma of the breast/endocrine ductal carcinoma in situ with a nodular, solid, papillary, and/or cribriforming architecture, neuroendocrine differentiation, and mucin production. Since it was first described by Flieder et al. in 1997, less than 60 cases have been reported in literature. We describe the morphological and immunohistochemical features of another case with a review of the common histological differential diagnoses and emphasize the salient features that help distinguish this rare neoplasm.

  6. Solution NMR structure of zinc finger 4 and 5 from human INSM1, an essential regulator of neuroendocrine differentiation.

    Science.gov (United States)

    Zhu, Jiang; Wang, Huapu; Ramelot, Theresa A; Kennedy, Michael A; Hu, Rui; Yue, Xiali; Liu, Maili; Yang, Yunhuang

    2017-05-01

    Human INSM1 containing five C-terminal C2H2-type zinc fingers (ZFs), is a key regulator of neuroendocrine development. Previous research reported that full-length INSM1 containing all five ZFs recognized a consensus DNA sequence. Structure elucidation of human INSM1 ZFs is currently insufficient to understand the DNA binding mechanism. Herein, we present the solution NMR structure of ZF4-5, in which the two ZFs adopt a head-to-tail arrangement and each ZF features a canonical ββα fold. NMR titrations and isothermal titration calorimetry experiments showed that ZF4-5 binds weakly to the consensus DNA sequence. Proteins 2017; 85:957-962. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

    Directory of Open Access Journals (Sweden)

    Sonia Gon

    2013-01-01

    Full Text Available Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bladder represent a challenge both to the pathologist and urologists for its diagnosis and treatment, respectively.

  8. Calcitonin-negative primary neuroendocrine tumor of the thyroid ...

    African Journals Online (AJOL)

    nonmedullary" in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of ...

  9. Differential diagnosis of non-functional islet cell tumor and pancreatic carcinoma with sonography

    Energy Technology Data Exchange (ETDEWEB)

    Yang Wei [Department of Ultrasound, School of Oncology, Peking University, Beijing 100036 (China); Chen Minhua [Department of Ultrasound, School of Oncology, Peking University, Beijing 100036 (China)]. E-mail: minhuachen@vip.sina.com; Yan Kun [Department of Ultrasound, School of Oncology, Peking University, Beijing 100036 (China); Wu Wei [Department of Ultrasound, School of Oncology, Peking University, Beijing 100036 (China); Dai Ying [Department of Ultrasound, School of Oncology, Peking University, Beijing 100036 (China); Zhang Hui [Department of Ultrasound, School of Oncology, Peking University, Beijing 100036 (China)

    2007-06-15

    Objective: To investigate the differential diagnosis of non-functional islet cell tumor (NFICT) and pancreatic ductal adenocarcinoma (pancreatic carcinoma) with clinical presentation and sonographic features. Materials and methods: Twenty cases of NFICT were investigated in the study, and 41 cases of pancreatic carcinoma were included as the control group. Among them, 5 NFICT and 32 pancreatic carcinomas underwent CEUS with SonoVue. Clinical presentation and sonographic characteristics were evaluated with Logistic regression analysis. Furthermore, the preliminary result of contrast enhanced ultrasound (CEUS) was analyzed. Results: Statistic analysis showed four significant factors in differential diagnosis for NFICT and pancreatic carcinoma, including age (P < 0.001), tumor size (P = 0.006), tumor margin (P < 0.001) and vascularity of tumor (P = 0.004). Combined these four factors, the sensitivity, specificity and accuracy are 95.0%, 95.1% and 95.1%, respectively. When the patient is younger than 60 years, and tumor is smaller than 5 cm with well-defined margin and hypervascular, it would be most likely a NFICT other than pancreatic carcinoma. NFICT often shows early enhancement and more homogeneous infusion than pancreatic carcinoma on CEUS (P = 0.005 and 0.008). Conclusions: Sonography is able to provide useful differential information for NFICT, which is often misdiagnosed as pancreatic carcinoma.

  10. Reproductive and menstrual factors and risk of differentiated thyroid carcinoma : The EPIC study

    NARCIS (Netherlands)

    Zamora-Ros, Raul; Rinaldi, Sabina; Biessy, Carine; Tjonneland, Anne; Halkjaer, Jytte; Fournier, Agnes; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Tikk, Kaja; Fortner, Renee T.; Boeing, Heiner; Foerster, Jana; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Papatesta, Eleni-Maria; Masala, Giovanna; Tagliabue, Giovanna; Panico, Salvatore; Tumino, Rosario; Polidoro, Silvia; Peeters, Petra H. M.; Bueno-de-Mesquita, H. B(as); Weiderpass, Elisabete; Lund, Eiliv; Argueelles, Marcial; Agudo, Antonio; Molina-Montes, Esther; Navarro, Carmen; Barricarte, Aurelio; Larranaga, Nerea; Manjer, Jonas; Almquist, Martin; Sandstrom, Maria; Hennings, Joakim; Tsilidis, Konstantinos K.; Schmidt, Julie A.; Khaw, Kay-Thee; Wareham, Nicholas J.; Romieu, Isabelle; Byrnes, Graham; Gunter, Marc J.; Riboli, Elio; Franceschi, Silvia

    2015-01-01

    Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among

  11. Carcinoma Showing Thymus-Like Differentiation (CASTLE of Thyroid: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Leong-Perng Chan

    2008-11-01

    Full Text Available Carcinoma showing thymus-like differentiation (CASTLE is a rare malignant neoplasm that occurs in the thyroid gland, or head and neck. This tumor arises from either ectopic thymus tissue or remnants of branchial pouches, which retain the potential to differentiate along the thymus line. Clinical presentation and imaging can be consistent with a malignant lesion such as thyroid cancer or thymic carcinoma. Immunohistochemical staining with CD5 can differentiate CASTLE from other malignant thyroid neoplasms. A 54-year-old male had initially presented with a painless, left neck mass for 3 months. He underwent left thyroid lobectomy via a median sternotomy approach. Carcinoma showing thymus-like differentiation was the final histopathologic diagnosis. After 36 months of follow-up, no evidence of recurrence was observed. A median sternotomy is an excellent approach for CASTLE with anterior mediastinum involvement. Complete resection is important to improve the long-term survival rate and the locoregional recurrence rate.

  12. [Comparative rate of regional metastasis of high differentiated carcinoma of the thyroid gland].

    Science.gov (United States)

    Konstantinova, N N; Evmenova, T D; Drozdova, D É

    2014-01-01

    The rate of metastasis of high differentiated carcinoma of the thyroid glands to the neck lymph nodes was studied in people of Kemerovo Region. The metastatic lesions of pretracheal lymph nodes (VI group) were detected in 49.5% patients with papillary carcinoma and 21.0% of patients with follicular cancer. Metastases in jungular lymph nodes were revealed in 37.3% patients with papillary carcinoma. It was noted that an extension of metastatic lesions of regional lymph nodes was observed in the case of primary tumour foci spread beyond borders of the capsula glandularis in patients with papillary carcinoma. There wasn't such a relation in a case of follicular cancer. Metastases in regional lymph nodes were detected more often (67.6%) in the case of papillary carcinoma in uncontaminated zone of the thyroid gland compared with other thyroid pathology (31.7%).

  13. Immunohistochemical identification of neuron-specific enolase, synaptophysin, chromogranin and endocrine granule constituent in neuroendocrine tumours

    DEFF Research Database (Denmark)

    Vyberg, M; Horn, T; Francis, D

    1990-01-01

    Immunohistochemical identification of neuroendocrine tumour markers in paraffin embedded material from 22 tumours (5 small cell carcinomas of the lung (SCCL), 12 carcinoids, 2 medullary thyroid carcinomas, 2 pheochromocytomas and one paraganglioma) with electron microscopically verified dense...

  14. Pancreatic neuroendocrine tumour (PNET): Staging accuracy of MDCT and its diagnostic performance for the differentiation of PNET with uncommon CT findings from pancreatic adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Hoon; Lee, Jeong Min; Han, Joon Koo; Choi, Byung-Ihn [Seoul National University Hospital, Department of Radiology, 101 Daehangno, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul (Korea, Republic of); Eun, Hyo Won [Yonsei University College of Medicine, Department of Radiology, Severance Hospital, Seodaemun-ku, Seoul (Korea, Republic of); Kim, Young Jae [Soonchunhyang University Hospital, Department of Radiology, 657 Hannam-Dong, Youngsan-Ku, Seoul (Korea, Republic of)

    2016-05-15

    To investigate staging accuracy of multidetector CT (MDCT) for pancreatic neuroendocrine tumour (PNET) and diagnostic performance for differentiation of PNET from pancreatic adenocarcinoma. We included 109 patients with surgically proven PNET (NETG1 = 66, NETG2 = 31, NEC = 12) who underwent MDCT. Two reviewers assessed stage and presence of predefined CT findings. We analysed the relationship between CT findings and tumour grade. Using PNETs with uncommon findings, we also estimated the possibility of PNET or adenocarcinoma. Accuracy for T stage was 85-88 % and N-metastasis was 83-89 %. Common findings included well circumscribed, homogeneously enhanced, hypervascular mass, common in lower grade tumours (p < 0.05). Uncommon findings included ill-defined, heterogeneously enhanced, hypovascular mass and duct dilation, common in higher grade tumours (p < 0.05). Using 31 PNETs with uncommon findings, diagnostic performance for differentiation from adenocarcinoma was 0.760-0.806. Duct dilatation was an independent predictor for adenocarcinoma (Exp(B) = 4.569). PNETs with uncommon findings were associated with significantly worse survival versus PNET with common findings (62.7 vs. 95.7 months, p < 0.001). MDCT is useful for preoperative evaluation of PNET; it not only accurately depicts the tumour stage but also prediction of tumour grade, because uncommon findings were more common in higher grade tumours. (orig.)

  15. Differential diagnosis of groove pancreatic carcinomas vs. groove pancreatitis: Usefulness of the portal venous phase

    International Nuclear Information System (INIS)

    Ishigami, Kousei; Tajima, Tsuyoshi; Nishie, Akihiro; Kakihara, Daisuke; Fujita, Nobuhiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Irie, Hiroyuki; Nakamura, Masafumi; Takahata, Shunichi; Ito, Tetsuhide; Honda, Hiroshi

    2010-01-01

    Purpose: To clarify if the portal venous phase is helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis. Materials and methods: MDCT and MRI of groove pancreatic carcinomas (n = 7) and groove pancreatitis (n = 15) were retrospectively reviewed by two radiologists independently. The signal intensity on T2-weighted images was subjectively assessed. The presence or absence of common bile duct (CBD) and main pancreatic duct (MPD) strictures, calcifications, and cystic lesions was evaluated. Additionally, the appearance of groove pancreatic carcinoma and that of groove pancreatitis in the portal venous phase on dynamic MDCT and MRI were compared. Results: There were no significant differences in the signal intensity on T2-weighted images and in the presence or absence of CBD and MPD strictures, calcifications, and cystic lesions between groove pancreatic carcinomas and groove pancreatitis. However, patchy focal enhancement in the portal venous phase was more commonly observed in groove pancreatitis than groove pancreatic carcinoma (Reviewers 1 and 2: 14/15 [93.3%] vs. 1/7 [14.3%], P < 0.0001). In addition, peripheral enhancement was only seen in groove pancreatic carcinomas (Reviewer 1: 4/7 [57.1%] vs. 0/15 [0%], P < 0.005, and Reviewer 2: 3/7 [42.9%] vs. 0/15 [0%], P < 0.05). Conclusion: The portal venous phase may be helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis.

  16. Poorly differentiated carcinoma arising in the setting of erythema ab igne.

    Science.gov (United States)

    Sigmon, Justin R; Cantrell, Jacob; Teague, Daniel; Sangueza, Omar; Sheehan, Daniel J

    2013-08-01

    Erythema ab igne (EAI) is a reticulated, erythematous, or hyperpigmented dermatosis that is caused by chronic exposure to infrared radiation. Chronic lesions of EAI have significant potential for malignant transformation. We report a case of poorly differentiated carcinoma arising within a patch of long-standing EAI on the lower extremity of a 92-year-old female. This case highlights the importance of recognizing EAI early and counseling patients to avoid further exposure to the offending infrared source to reduce the risk of malignant transformation. EAI has been associated with several different types of cutaneous neoplasms including the Merkel cell carcinoma, squamous cell carcinoma, and cutaneous marginal zone lymphoma.

  17. Maternal and obstetrical outcome in 35 cases of well-differentiated thyroid carcinoma during pregnancy

    DEFF Research Database (Denmark)

    Boucek, Jan; de Haan, Jorine; Halaska, Michael J

    2018-01-01

    study. Data on histopathological characteristics, diagnostic and therapeutic interventions, outcome (obstetrical, neonatal, and maternal) and maternal follow-up were analyzed. RESULTS: Thirty-five patients with well-differentiated thyroid carcinoma were eligible. All 35 patients underwent surgery, 29...... of primary well-differentiated thyroid carcinoma during pregnancy and fetal and maternal outcomes. STUDY DESIGN: This is an international cohort study. METHODS: Primary thyroid cancer patients were identified from the database of the International Network on Cancer, Infertility, and Pregnancy registration...... outcomes were uncomplicated, regardless of gestational age during surgery. CONCLUSIONS: Well-differentiated thyroid carcinoma diagnosed during pregnancy has a favorable outcome for both mother and child. Surgical management during pregnancy has no negative impact on the pregnancy regardless...

  18. Prognostic significance of Gleason score 7 (3+4 and Gleason score 7 (4+3 in prostatic adenocarcinoma in relation to clinical stage, androgen tissue status and degree of neuroendocrine differentiation

    Directory of Open Access Journals (Sweden)

    Mijović M.

    2014-01-01

    Full Text Available Prognosis and choice of treatment of adenocarcinoma of the prostate (ADCP directly depend on the numerous of predictive factors, among which the most important are summary histological tumor grade (Gleason score, which is the sum of the first and second dominant histological grade and clinical stage. According to recent research these factors include androgen tissue status and degree of neuroendocrine differentiation. The importance of the first and second dominant histological grade becomes particularly important in ADCP Gleason score 7. Tumors with worse prognosis considered to be ADCP of higher Gleason score, the advanced clinical stage, androgen independent tumors and tumors that show a higher degree of neuroendocrine differentiation. The aim of the study was to determine the predictive significance of ADCP Gleason score 7 (3+4 and ADCP Gleason score 7 (4+3 in relation to clinical stage, androgen tissue status and degree of focal neuroendocrine differentiation. The study included 33 ADCP of Gleason score 7,26 (78.79% ADCP 7 (3+4 and 7 (21.21% ADCP 7 (4+3. All tumors are most often diagnosed with stage D2, when there are already distant metastases. ADCP of Gleason score 7 (4+3 were diagnosed more often at this stage, among them there are more androgen independent tumors and they show a greater degree of focal neuroendocrine differentiation. All the results are in accordance with data from the literature suggesting that ADCP of Gleason score 7 (4+3 have a worse prognosis than ADCP of Gleason score 7 (3 +4.

  19. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  20. Head and neck region consolidation radiotherapy and prophylactic cranial irradiation with hippocampal avoidance delivered with helical tomotherapy after induction chemotherapy for non-sinonasal neuroendocrine carcinoma of the upper airways

    International Nuclear Information System (INIS)

    Franco, Pierfrancesco; La Porta, Maria Rosa; Girelli, Giuseppe; Borca, Valeria Casanova; Pasquino, Massimo; Tofani, Santi; Ozzello, Franca; Ricardi, Umberto; Numico, Gianmauro; Migliaccio, Fernanda; Catuzzo, Paola; Cante, Domenico; Ceroni, Paola; Sciacero, Piera; Carassai, Pierpaolo; Canzi, Paolo

    2012-01-01

    Non-sinonasal neuroendocrine carcinomas (NSNECs) of the head and neck are considered an unfrequent clinico-pathological entity. Combined modality treatment represents an established therapeutic option for undifferentiated forms where distant metastasis is a common pattern of failure. We report on a case of NSNEC treated with sequential chemo-radiation consisting of 6 cycles of cisplatin and etoposide followed by loco-regional radiation to the head and neck and simultaneous prophylactic cranial irradiation to prevent from intracranial spread, delivered with helical tomotherapy with the 'hippocampal avoidance' technique in order to reduce neuro-cognitive late effects. One year after the end of the whole combined modality approach, the patient achieved complete remission, with no treatment-related sub-acute and late effects. The present report highlights the importance of multidisciplinary management for NSNECs of the head and neck, as the possibility to achieve substantial cure rates with mild side effects with modern radiotherapy techniques

  1. Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Min Jeong Kim

    2018-01-01

    Full Text Available Mitotic counts in the World Health Organization (WHO grading system have narrow cutoff values. True mitotic figures, however, are not always distinguishable from apoptotic bodies and darkly stained nuclei, complicating the ability of the WHO grading system to diagnose well-differentiated neuroendocrine tumors (NETs. The mitosis-specific marker phosphohistone H3 (PHH3 can identify true mitoses and grade tumors reliably. The aim of this study was to investigate the correspondence of tumor grades, as determined by PHH3 mitotic index (MI and mitotic counts according to WHO criteria, and to determine the clinically relevant cutoffs of PHH3 MI in rectal and nonrectal gastrointestinal NETs. Mitotic counts correlated with both the Ki-67 labeling index and PHH3 MI, but the correlation with PHH3 MI was slightly higher. The PHH3 MI cutoff ≥4 correlated most closely with original WHO grades for both rectal NETs. A PHH3 MI cutoff ≥4, which could distinguish between G1 and G2 tumors, was associated with disease-free survival in patients with rectal NETs, whereas that cutoff value showed marginal significance for overall survival in patient with rectal NETs. In conclusion, the use of PHH3 ≥4 correlated most closely with original WHO grades.

  2. O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine Tumors.

    Science.gov (United States)

    Raj, Nitya; Klimstra, David S; Horvat, Natally; Zhang, Liying; Chou, Joanne F; Capanu, Marinela; Basturk, Olca; Do, Richard Kinh Gian; Allen, Peter J; Reidy-Lagunes, Diane

    2017-07-01

    Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.

  3. Lanreotide autogel every 6 weeks compared with Lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: a Phase III Study.

    Science.gov (United States)

    Bajetta, Emilio; Procopio, Giuseppe; Catena, Laura; Martinetti, Antonia; De Dosso, Sara; Ricci, Sergio; Lecchi, Alberto S; Boscani, Paolo F; Iacobelli, Stefano; Carteni, Giacomo; De Braud, Filippo; Loli, Paola; Tartaglia, Andreas; Bajetta, Roberto; Ferrari, Leonardo

    2006-11-15

    The noninferiority of a 6-week dosing schedule of lanreotide Autogel (Lan ATG) at a dose of 120 mg compared with a 3-week dosing schedule of lanreotide microparticles (Lan MP) at a dose of 60 mg was investigated in patients with neuroendocrine tumors (NET). Patients who had sporadic, well differentiated NET with a low grade of malignancy were recruited for this open-label, Phase III, multicenter trial. Patients were randomized to receive either 3 deep subcutaneous injections of Lan ATG (120 mg, every 6 weeks) or 6 intramuscular injections of Lan MP (60 mg, every 3 weeks). Tumor markers, tumor size, and symptoms were assessed between baseline and Week 18. Success was classified as a response that ranged from disappearance to an increase <25% in tumor marker, tumor size, or symptom frequency. Sixty patients were randomized, and 46 patients completed the study. Both for tumor markers and for tumor size, Lan ATG was not inferior to Lan MP (55% and 59% of patients responded on tumor markers, respectively; 68% and 66% of patients responded on tumor size, respectively). There were too few symptomatic patients to compare carcinoid symptoms. Both treatments were tolerated well, and no safety concerns were identified. Lan ATG at a dose of 120 mg every 6 weeks was as effective for controlling NET as Lan MP at a dose of 60 mg every 3 weeks.

  4. The role of thyrotropin suppression in patients with differentiated thyroid carcinoma.

    LENUS (Irish Health Repository)

    Deasy, J

    2010-07-01

    Thyroid carcinoma is the commonest endocrine malignancy. The majority of these are differentiated thyroid carcinomas, which have a good overall prognosis. Treatment includes surgical excision, radio-iodine ablation and long-term thyrotropin suppression. The degree and length of suppression required, as well as the potential side-effect remain controversial. Therefore, the aim of this study was to establish the degree of thyrotropin suppression achieved in a cohort of patients with differentiated thyroid carcinoma. A retrospective review was performed of a prospectively maintained database. All patients with a diagnosis of differentiated thyroid carcinoma between January 1998 and January 2008 were identified. Demographic data, pathological stage and the treatment that the patient received was documented. TSH and free T4 levels were identified at specific time points post-operatively. Eighty-eight patients with differentiated thyroid carcinoma were identified. Seventy patients (79.5%) were female. The mean age was 55, with a range of 18 to 79 years. The majority of patients underwent a total thyroidectomy (n=79; 89.7%) and of those 29 (32.9%) had an associated modified neck dissection. Accurate follow-up was available on forty-nine patients. TSH and free T4 were measured at 3 and 6 months, as well as at 1 and 2 years post-operatively. Adequate TSH suppression was taken at a level < 0.1 mU\\/L. The majority of patients (69.5%) had achieved adequate TSH suppression at 2 years. However, 65% of these same patients had a high free T4 at 2 years indicating a degree of hyperthyroidism. This study has demonstrated that TSH suppression is being adequately achieved in the majority of patients with differentiated thyroid carcinoma. However, this must be carefully weighed against the potential detrimental side-effects of long-term sub-clinical hyperthyroidism.

  5. Ultrasonic differential diagnosis of stones and carcinomas in the extrahepatic biliary tree

    International Nuclear Information System (INIS)

    Cho, Dai Hyun; Kim, Kie Tae; Shinn, Kyung Sub; Bang, Chan Young; Yoon, Sei Chul; Bahk, Yong Whee

    1983-01-01

    Ultrasonography is a simple, noninvasive and relatively accurate method to differentiate carcinomas from stones in the extrahepatic biliary tree. We analysed ultrasonic findings in 18 sto en cases and 10 carcinoma cases of the extrahepatic biliary tree, which were confirmed by microscopic examination or percutaneous transhepatic cholangiography during the period of May 1980 through May 1982 in Kangnam St. Mary's Hospital. The results were as follows: 1. The number of incidences of multiple echogenecities was 11 out of the 18 stone cases (61.1%) but there were no incidences of multiple echogenecities among the carcinoma cases. Eight cases, four of stones and carcinomas each, were not detected by sonography. 2. The average diameter of the stones was below 20 mm in 13 of the 18 cases (72.2%) and the number of the stones over 20 mm in diameter was only one of the 18 (5.6%), while the number of carcinomas over 20 mm was three of the 10 cases (30%). 3. In the 18 patients with stones, the degree of echogenecity was uniformly high in seven (38.9%) and mixed- moderate in seven (38.9%). All the carcinomas, however, presented mixed slight echogenecity. The marginal sharpness was well defined in nine of the 18 stone cases (50%), but only one among the carcinomas. 4. The obstructive site in the biliary tree in the stone cases showed a typical meniscus in 10 (55.6%), abrupt cutting in four (22.2%) and were indiscernible in four (22.2%). But of the 10 carcinoma cases four (40%) were of abrupt cutting, two (20%) funnel-shaped and were indiscernible in four (40%). 5. The frequency of posterior acoustic shadows was 11 (61.1%) in the stones and only one in the carcinomas. 6. The diameter of the extrahepatic biliary tree proximal to the obstructive site did not seem to be defines factor in differentiating carcinomas from stones since both stone and carcinoma cases showed dilatation of the extrahepatic bile duct. 7. The extrahepatic biliary stones in general were characteristic of

  6. A Case of Basal Cell Carcinoma with Outer Hair Follicle Sheath Differentiation

    Directory of Open Access Journals (Sweden)

    Masazumi Onishi

    2015-12-01

    Full Text Available A 70-year-old Japanese man presented at our hospital with an asymptomatic, blackish, irregularly shaped plaque with a gray nodule in the periphery on his left lower leg. The lesion had been present for 10 years and had recently enlarged, associated with bleeding. Histopathologically, the tumor consisted of three distinct parts: The first part showed massive aggregation of basophilic basaloid cells with peripheral palisading and abundant melanin granules, and was diagnosed as solid-type basal cell carcinoma. The second part showed aggregation of clear cells with squamous eddies, and was diagnosed as proliferating trichilemmal tumor. The third part showed reticular aggregation of basaloid cells with infundibular cysts in the papillary dermis, and was diagnosed as infundibulocystic basal cell carcinoma. We diagnosed this tumor as basal cell carcinoma with various forms of hair follicle differentiation, including differentiation into the outer root sheath.

  7. Interleukin-6: a bone marrow stromal cell paracrine signal that induces neuroendocrine differentiation and modulates autophagy in bone metastatic PCa cells.

    Science.gov (United States)

    Delk, Nikki A; Farach-Carson, Mary C

    2012-04-01

    Autophagy reallocates nutrients and clears normal cells of damaged proteins and organelles. In the context of metastatic disease, invading cancer cells hijack autophagic processes to survive and adapt in the host microenvironment. We sought to understand how autophagy is regulated in the metastatic niche for prostate cancer (PCa) cells where bone marrow stromal cell (BMSC) paracrine signaling induces PCa neuroendocrine differentiation (NED). In PCa, this transdifferentiation of metastatic PCa cells to neuronal-like cells correlates with advanced disease. Because autophagy provides a survival advantage for cancer cells and promotes cell differentiation, we hypothesized that autophagy mediates PCa NED in the bone. Thus, we determined the ability of paracrine factors in conditioned media (CM) from two separate BMSC subtypes, HS5 and HS27a, to induce autophagy in C4-2 and C4-2B bone metastatic PCa cells by characterizing the autophagy marker, LC3. Unlike HS27a CM, HS5 CM induced LC3 accumulation in PCa cells, suggesting autophagy was induced and indicating that HS5 and HS27a secrete a different milieu of paracrine factors that influence PCa autophagy. We identified interleukin-6 (IL-6), a cytokine more highly expressed in HS5 cells than in HS27a cells, as a paracrine factor that regulates PCa autophagy. Pharmacological inhibition of STAT3 activity did not attenuate LC3 accumulation, implying that IL-6 regulates NED and autophagy through different pathways. Finally, chloroquine inhibition of autophagic flux blocked PCa NED; hence autophagic flux maintains NED. Our studies imply that autophagy is cytoprotective for PCa cells in the bone, thus targeting autophagy is a potential therapeutic strategy.

  8. Biologic markers in axillary node-negative breast cancer: differential expression in invasive ductal carcinoma versus invasive lobular carcinoma.

    Science.gov (United States)

    Gonzalez-Angulo, Ana Maria; Sahin, Aysegul; Krishnamurthy, Savitry; Yang, Ying; Kau, Shu-Wan; Hortobagyi, Gabriel N; Cristofanilli, Massimo

    2006-12-01

    The objective of this study was to compare the differential expression of established histopathologic and biologic markers of proliferation, apoptosis, and angiogenesis in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in a group of axillary node-negative breast cancers. Two hundred twenty patients with axillary node-negative ILC and IDC who underwent surgery at the University of Texas M. D. Anderson Cancer Center between 1978 and 1995 had tissue available for analysis. Of these, 206 (94%) had IDC and 14 (6%) had ILC. Estrogen receptors, progesterone receptors, tumor and stromal expression of vascular endothelial growth factor receptor 2, CD44, laminin-5, E-cadherin, and topoisomerase-2 were evaluated by immunohistochemical analysis. HER2/neu and alpha6beta4 integrin were evaluated by in situ hybridization. The Fisher exact test was used to calculate significant differences between ILC and IDC. Median age was 59 years. Invasive lobular carcinoma was more likely to occur in patients aged > 50 years. Invasive lobular carcinoma tended to be > 2 cm (50% vs. 39%), have a nuclear grade of 1/2 (100% vs. 72%), be estrogen receptor positive (93% vs. 70%), HER2/neu negative (92% vs. 68%), have high CD44 expression (31% vs. 16%), low stromal vascular endothelial growth factor receptor 2 expression (36% vs. 47%), no E-cadherin expression (0 vs. 90%), and low laminin-5 expression (15% vs. 25%), compared with IDC. Invasive lobular carcinoma and IDC might be distinct histologic types of breast cancer with different expression of biologic markers. These differences, not all being statistically significant in this small study, might generate hypotheses to develop tailored options for future systemic therapy.

  9. Application of AGES prognostic rate for treatment of a well differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Sosa Martin, Gimel; Morales Portuondo, Kelvis; Martinez Valenzuela, Noslen

    2009-01-01

    At the present times, the selection a suitable surgical treatment for patients presenting with an early differentiated thyroid carcinoma is a controversial question. The aim of present research was to describe and to assessment the diagnosis results and the treatment of this condition during 5 years

  10. Is outcome of differentiated thyroid carcinoma influenced by tumor stage at diagnosis?

    NARCIS (Netherlands)

    Clement, S.C.; Kremer, L.C.M.; Links, T.P.; Mulder, R.L.; Ronckers, C.M.; van Eck-Smit, B.L.; van Rijn, R.R.; Pal van der, H.J.H.; Tissing, W.J.E.; Janssens, G.O.; van den Heuvel-Eibrink, M.M.; Neggers, S.J.; Nieveen van Dijkum, E.J.; Peeters, R.P.; van Santen, H.M.

    Background: There is no international consensus on surveillance strategies for differentiated thyroid carcinoma (DTC) after radiotherapy for childhood cancer. Ultrasonography could allow for early detection of DTC, however, its value is yet unclear since the prognosis of DTC is excellent. We

  11. Immunohistochemical staining for the differentiation of subungual keratoacanthoma from subungual squamous cell carcinoma.

    LENUS (Irish Health Repository)

    Connolly, M

    2008-08-01

    Subungual keratotic tumours are rare. The clinical and histological distinctions between subungual keratoacanthomas (SUKAs) and subungual squamous cell carcinomas (SCCs) are important, but often difficult. Adequate methods of differentiation between the two are required, both for the purpose of management and for assessment of prognosis.

  12. Transitional cell carcinoma of the bladder in childhood: radiological findings and differential diagnosis

    International Nuclear Information System (INIS)

    Casado, L.; Mansilla, F.; Mansilla, M.D.; Marin, A.

    1998-01-01

    We present a case of transitional cell carcinoma of the bladder in an 11-year-old boy. The rarity of these tumors during childhood is pointed out. The radiological and ultrasonographic findings are described and the differential diagnosis is discussed with respect to other bladder tumors occurring in childhood. (Author) 11 refs

  13. Progression of Intravesical Condyloma Acuminata to Locally Advanced Poorly Differentiated Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    A. Khambati

    2016-07-01

    Full Text Available Condyloma acuminata (CA is a common sexually transmitted disease caused by Human Papilloma Virus (HPV infection. CA of the bladder, however, is an exceedingly rare lesion. We present a rare case of poorly differentiated locally invasive squamous cell carcinoma (SCC arising from recurrent CA of the bladder in an immunocompetent patient and discuss pathophysiology and management of this unusual condition.

  14. [Comparison of differentiated thyroid carcinoma staging systems in a Spanish population].

    Science.gov (United States)

    Andía Melero, Víctor Manuel; Martín de Santa-Olalla Llanes, María; Sambo Salas, Marcel; Percovich Hualpa, Juan Carlos; Motilla de la Cámara, Marta; Collado Yurrita, Luis

    2015-04-01

    Differentiated thyroid carcinoma staging is increasingly important due to the current trends to a less intensive therapy in low-risk patients. The TNM system is most widely used, but other systems based on follow-up of several patient cohorts have been developed. When these systems have been applied to other populations, results have been discordant. Our study evaluates the suitability of several differentiated thyroid carcinoma staging systems in a Spanish population. 729 patients with differentiated thyroid carcinoma and staging data available were enrolled. Mean follow-up time was 10.8 years. The TNM, EORTC, AMES, Clinical class, MACIS, Ohio, NTCTCS, and Spanish systems were applied to all histological types. The Kaplan-Meier survival curves for each system were analyzed, and compared using the proportion of explained variation (PEV). The demographic and clinical characteristics of our population were similar to those of other Spanish and international cohorts reported. The best systems were NTCTCS, with 74.7% PEV, and TNM (68.3%), followed by the Ohio, MACIS, EORTC, and AMES systems with minimal differences between them, while the least adequate were the Spanish (55.2%) and Clinical class (47.1%) systems. The NTCTCS staging system was found to be better than TNM in our population but, because of its simplicity and greater dissemination, the TNM appears to be recommended for staging of patients with differentiated thyroid carcinoma. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  15. Imaging of hepatocellular carcinoma: practical guide to differential diagnosis.

    Science.gov (United States)

    Anis, Munazza; Irshad, Abid

    2011-05-01

    Hepatocellular carcinoma (HCC) is most commonly seen in patients with cirrhosis. Criteria for diagnosis include arterial-phase enhancement, venous-phase washout, and a capsule on delayed sequences. Tiny HCC are best detected with magnetic resonance imaging using the new hepatocyte-specific gadolinium agents; otherwise, short-term follow up versus biopsy is considered. Diffuse HCC can be difficult to diagnose because of the inherent heterogeneous hepatic parenchyma in cirrhosis, however, portal vein expansion due to thrombosis is a helpful sign. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Insights into Novel Prognostic and Possible Predictive Biomarkers of Lung Neuroendocrine Tumors.

    Science.gov (United States)

    Moris, Dimitrios; Ntanasis-Stathopoulos, Ioannis; Tsilimigras, Diamantis I; Adam, Mohamad A; Yang, Chi-Fu Jeffrey; Harpole, David; Theocharis, Stamatios

    2018-01-01

    Primary lung neuroendocrine tumors (NETs) consist of typical and atypical carcinoids, large-cell neuroendocrine carcinomas and small-cell lung carcinomas. NETs are highly heterogeneous in histological characteristics, clinical presentation and natural history. While there are morphological and immunohistochemical criteria to establish diagnosis, there is a lack of universal consensus for prognostic factors or therapeutic targets for personalized treatment of the disease. Thus, identifying potential markers of neuroendocrine differentiation and prognostic factors remains of high importance. This review provides an insight into promising molecules and genes that are implicated in NET carcinogenesis, cell-cycle regulation, chromatin remodeling, apoptosis, intracellular cascades and cell-cell interactions. Additionally it supports a basis for classifying these tumors into categories that distinct molecular characteristics and disease natural history, which may have a direct impact on treatment options. In light of the recent approval of everolimus, mammalian target of rapamycin pathway inhibition and related biomarkers may play a central role in the treatment of pulmonary NETs. Future clinical trials that integrate molecular profiling are deemed necessary in order to treat patients with NET on a personalized basis. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. Full Length Article Role of glypican-3 immunocytochemistry in differentiating hepatocellular carcinoma from metastatic carcinoma of the liver utilizing fine needle aspiration cytology

    International Nuclear Information System (INIS)

    Zaakook, M.; Abu Sinna, E.; Ayoub, M.; El-Sheikh, S.

    2013-01-01

    Purpose: Evaluation of the sensitivity and specificity of glypican3 (GPC3) in differentiating hepatocellular carcinoma (HCC) from metastatic carcinomas of the liver in cell block material. Patients and methods: Sixty cell blocks were prepared from liver FNAs performed in the radiodiagnosis department, National Cancer Institute, in the period between August 2011 and May 2012. Cases diagnosed as hepatocellular carcinoma, or metastatic carcinoma were included in the study. Cell block sections were stained with anti GPC-3. Sensitivity, specificity, and positive and negative predictive values, of GPC3 were calculated. The final diagnosis was based on the triple approach of clinical data, radiological findings, as well as cytomorphologic features aided by GPC-3 results. Results: 70% of cases were diagnosed as HCC, and 30% as metastatic carcinomas. 95.2% of HCC cases expressed GPC3. Poorly differentiated cases showed the highest GPC3 sensitivity (100%), followed by moderately differentiated cases (96.5%), while well differentiated cases expressed GPC3 in 90% of cases. 83.3% of metastatic carcinomas were negative for GPC3. In this study, sensitivity of GPC-3 in HCC was 95.2%, specificity was 83.3%, positive and negative predictive values were 93% and 88.2% respectively, and total accuracy was 91.7%. Conclusion: Immunocytochemical staining for GPC3 in cell block material is a highly sensitive and specific method capable of distinguishing HCC from the vast majority of metastatic carcinomas of the liver

  18. Bcl-2 and CD10 expression in the differential diagnosis of trichoblastoma, basal cell carcinoma, and basal cell carcinoma with follicular differentiation.

    Science.gov (United States)

    Córdoba, Alicia; Guerrero, David; Larrinaga, Begoña; Iglesias, Maria Eugenia; Arrechea, Maria Asunción; Yanguas, Juan Ignacio

    2009-07-01

    Both trichoblastoma and basal cell carcinoma (BCC) of the skin are characterized morphologically by the proliferation of basaloid cells; however, BCCs are clinically associated with a more aggressive behavior. An accurate diagnosis of these lesions is essential for effective, timely treatment and appropriate therapeutic decisions. This study includes 40 lesions. Bcl-2 and CD10 immunohistochemistry were performed in all cases and the patterns of expression were analyzed. Bcl-2 is useful for the detection of BCC with diffuse expression in nests of basaloid cells, but cannot distinguish between BCC with follicular differentiation and trichoblastoma, as both lesions show the same pattern with positive and negative areas. Conversely, CD10 expression can distinguish between trichoblastomas with peritumoral stromal staining and BCCs with epithelial staining. If both stromal and epithelial areas are stained, these cases are classified as BCC with follicular differentiation. CD10 is useful for distinguishing between BCC with widespread follicular differentiation and trichoblastomas.

  19. Evaluation of MR diffusion-weighted imaging in differentiating endometriosis infiltrating the bowel from colorectal carcinoma

    International Nuclear Information System (INIS)

    Busard, M.P.H.; Pieters-van den Bos, I.C.; Mijatovic, V.; Van Kuijk, C.; Bleeker, M.C.G.; Waesberghe, J.H.T.M. van

    2012-01-01

    Objective: Endometriosis infiltrating the bowel may be difficult to differentiate from colorectal carcinoma in cases that present with non-specific clinical and imaging features. The aim of this study is to assess the value of MR diffusion-weighted imaging (DWI) in differentiating endometriosis infiltrating the bowel from colorectal carcinoma. Methods: In 66 patients, MR DWI was added to the standard imaging protocol in patients visiting our outdoor MR clinic for the analysis of suspected or known deep infiltrating endometriosis (DIE). In patients diagnosed with DIE infiltrating the bowel on MR imaging, high b-value diffusion-weighted images were qualitatively assessed by two readers in consensus and compared to high b-value diffusion weighted images in 15 patients evaluated for colorectal carcinoma. In addition, ADC values of lesions were calculated, using b-values of 50, 400 and 800 s/mm 2 . Results: A total of 15 patients were diagnosed with DIE infiltrating the bowel on MR imaging. Endometriosis infiltrating the bowel showed low signal intensity on high b-value diffusion-weighted images in all patients, whereas colorectal carcinoma showed high signal intensity on high b-value diffusion-weighted images in all patients. Mean ADC value in endometriosis infiltrating the bowel (0.80 ± 0.06 × 10 −3 mm 2 /s) was significantly lower compared to mean ADC value in colorectal carcinoma (0.86 ± 0.06 × 10 −3 mm 2 /s), but with considerable overlap between ADC values. Conclusion: Only qualitative assessment of MR DWI may be valuable to facilitate differentiation between endometriosis infiltrating the bowel and colorectal carcinoma.

  20. Survival after resection of cutaneous adnexal carcinomas with eccrine differentiation: risk factors and trends in outcomes.

    Science.gov (United States)

    Avraham, Jacob B; Villines, Dana; Maker, Vijay K; August, Carey; Maker, Ajay V

    2013-07-01

    Current staging systems do not specifically address cutaneous adnexal carcinomas with eccrine differentiation. Due to their rarity, prognosis and management strategies are not well established. A population-based study was performed to determine prognostic factors and survival. Patients diagnosed with cutaneous adnexal carcinomas with eccrine differentiation were identified using the surveillance, epidemiology, and end results population-based cancer registry. Associations between risk factors, treatment modalities, and survival were calculated using logistical regression, Kaplan-Meier estimates and log-rank analysis. The incidence of distinct eccrine subtypes was determined within 1,045 patients with cutaneous adnexal tumors containing eccrine differentiation. All-cause 5-year survival (OS) was 82%, while age-adjusted survival was 94%. Patients with microcystic adnexal carcinoma had improved OS (90%) compared to patients with hidradenocarcinoma (74%), spiradenocarcinoma (77%), porocarcinoma (79%), and eccrine adenocarcinoma (81%). The majority of patients were treated with surgical excision and a small subset with surgery plus radiation, with similar OS. Patients with well-to-moderately differentiated tumors demonstrated improved OS compared to those with poorly differentiated/anaplastic disease. Histological subtype and grade were associated with survival, and should be specified in biopsies and excised specimens. Surgical excision is appropriate, and the addition of adjuvant radiation may not be associated with survival. These results highlight survival data and high-risk prognostic factors that warrant prospective validation, and may augment current staging systems. Copyright © 2013 Wiley Periodicals, Inc.

  1. Cyclin D1 Expression and Its Correlation with Histopathological Differentiation in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Swati Saawarn

    2012-01-01

    Full Text Available Background. Cyclin D1 regulates the G1 to S transition of cell cycle. Its deregulation or overexpression may lead to disturbance in the normal cell cycle control and tumour formation. Overexpression of cyclin D1 has been reported in various tumors of diverse histogenesis. This case control retrospective study was carried out to study the immunohistochemical reactivity and expression of cyclin D1 and its association with site, clinical staging, and histopathological differentiation of oral squamous cell carcinoma (OSCC. Methods. Forty formalin-fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclin D1. Results. Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate with site and clinical staging. Highest expression was seen in well-differentiated, followed by moderately differentiated, and poorly differentiated squamous cell carcinomas, with a statistically significant correlation. Conclusion. Cyclin D1 expression significantly increases with increase in differentiation.

  2. Early prenatal androgen exposure reduces testes size and sperm concentration in sheep without altering neuroendocrine differentiation and masculine sexual behavior.

    Science.gov (United States)

    Scully, C M; Estill, C T; Amodei, R; McKune, A; Gribbin, K P; Meaker, M; Stormshak, F; Roselli, C E

    2018-01-01

    Prenatal androgens are largely responsible for growth and differentiation of the genital tract and testis and for organization of the control mechanisms regulating male reproductive physiology and behavior. The aim of the present study was to evaluate the impact of inappropriate exposure to excess testosterone (T) during the first trimester of fetal development on the reproductive function, sexual behavior, and fertility potential of rams. We found that biweekly maternal T propionate (100 mg) treatment administered from Day 30-58 of gestation significantly decreased (P sexually attracted to estrous females. In summary, these results suggest that exposure to exogenous T during the first trimester of gestation can negatively impact spermatogenesis and compromise the reproductive fitness of rams. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Interferon treatment of neuroendocrine tumour xenografts as monitored by MRI

    International Nuclear Information System (INIS)

    Elvin, A.; Oeberg, K.; Lindgren, P.G.; Lundkvist, M.; Wilander, E.; Ericsson, A.; Hemmingsson, A.

    1994-01-01

    The neuroendocrine-differentiated colonic carcinoma cell line (LCC-18) was transplanted to 29 nude mice (Balb/c). The purpose of the present study was to establish an animal model that would allow monitoring with magnetic resonance imaging (MRI) of changes induced by interferon (IFN) therapy and to evaluate whether the therapeutic response, as expressed by changes in MR signal characteristics and tumour proliferative activity, could be modulated by different IFN dosages. IFN did not seem to have any obvious antiproliferative effect on the LCC-18 tumour cell line transplanted to nude mice and no convincing treatment-related changes in rho values or T1 and T2 relaxation values were observed. The animal model was probably unsuitable for demonstration of IFN effects. (orig.)

  4. Adipokines and inflammation markers and risk of differentiated thyroid carcinoma

    DEFF Research Database (Denmark)

    Dossus, Laure; Franceschi, Silvia; Biessy, Carine

    2018-01-01

    Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight...

  5. Tumor neuroendócrino primário de mama: relato de três casos e revisão de literatura Primary neuroendocrine carcinoma of the breast: case report and literature review

    Directory of Open Access Journals (Sweden)

    Mariana Novaes Pinheiro

    2012-04-01

    Full Text Available Os tumores neuroendócrinos primários de mama (TNPMs são incomuns e não há consenso quanto a tratamento e prognóstico. No presente trabalho, foram revisados os diagnósticos de 1.184 pacientes com câncer de mama atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP/USP, identificando três casos que preenchiam os critérios de TNPM, segundo classificação estabelecida pela Organização Mundial da Saúde (OMS em 2003. Foram avaliados os achados clinicopatológicos e imuno-histoquímicos e as terapias realizadas, buscando caracterizar os padrões histopatológicos e de comportamento distintos dos carcinomas convencionais de mama.Primary neuroendocrine breast carcinomas (NECs are uncommon. Moreover, there is no consensus as to its treatment and prognosis. In this study, the diagnoses of 1,184 cases of breast cancer treated at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto/Universidade de São Paulo (HCFMRP/USP were reviewed. Three among them fulfilled the criteria for primary NEC according to the classification established by the World Health Organization (WHO in 2003. Clinicopathological, immunohistochemical features and treatments were assessed in order to characterize histopathological and distinct patterns of conventional breast carcinomas.

  6. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P

    2015-01-01

    BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were...... carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...

  7. CT manifestation of the carcinoma of ovary: diagnosis and differential diagnosis

    International Nuclear Information System (INIS)

    Liu Mingjuan; Guo Yan; Zhang Ling; Huang Zhaomin

    2007-01-01

    Objective: To study the CT manifestations of carcinoma of ovary and the CT findings that mimic the carcinoma of ovary. Methods: CT findings were retrospectively studied in 47 cases of pelvic masses including 42 cases of carcinoma of ovary and 5 misdiagnosed as carcinoma of ovary. Misdiagnosis was made in 8 of the 42 cases of carcinoma of ovary. Non-contrast and enhanced CT scan were performed in all cases. Results: Pelvic or abdominal-pelvic masses were demonstrated in 92.4% cases. The lesions were parenchymatous, cystic, or cystic-parenchymatous masses, in which the parenchyma and septum were remarkably enhanced after the contrast agent was given intravenously. No mass was found in 7.6% cases, in which the ascites and thickening of the omentum were noted on CT images. Ascites was shown in 57.2% cases. Calicification was manifested in 19.0% cases. Abscess or tuberculosis located in pelvis could have the similar CT findings with cystic carcinoma of ovary, while these infectious lesions presented with regular or smooth wall and septum, instead of mural nodule. Another characteristic sign of abscess or tuberculosis was air density identified within the cavity of the cysts. Chocolate cysts with recent hemorrhage or subserous leiomyoma uteri with cystic degeneration were cystic-parenchymatous mass during the non-contrast enhanced scan. No enhancement could be revealed in parenchyma of the former and slight enhancement could be identified in the parenchymatous component of the latter. Conclusion: Contrast enhanced CT scan can demonstrate the structure of the mass and the adjacent organs, and reveal the enhancement of the lesions, which plays a valuable role in diagnosis or differential diagnosis of carcinoma of ovary with atypical CT findings. (authors)

  8. Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future

    Directory of Open Access Journals (Sweden)

    Akihiro Ohmoto

    2017-01-01

    Full Text Available Pancreatic neuroendocrine neoplasms (pNENs are rare tumors accounting for only 1%–2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC, will be needed to improve the prognosis.

  9. The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms.

    Science.gov (United States)

    Matos, Leandro Luongo; Suarez, Eloah Rabello; Theodoro, Thérèse Rachell; Trufelli, Damila Cristina; Melo, Carina Mucciolo; Garcia, Larissa Ferraz; Oliveira, Olivia Capela Grimaldi; Matos, Maria Graciela Luongo; Kanda, Jossi Ledo; Nader, Helena Bonciani; Martins, João Roberto Maciel; Pinhal, Maria Aparecida Silva

    2015-01-01

    The search for a specific marker that could help to distinguish between differentiated thyroid carcinoma and benign lesions remains elusive in clinical practice. Heparanase (HPSE) is an endo-beta-glucoronidase implicated in the process of tumor invasion, and the heparanase-2 (HPSE2) modulates HPSE activity. The aim of this study was to evaluate the role of heparanases in the development and differential diagnosis of follicular pattern thyroid lesions. HPSE and HPSE2 expression by qRT-PCR, immunohistochemistry evaluation, western blot analysis and HPSE enzymatic activity were evaluated. The expression of heparanases by qRT-PCR showed an increase of HPSE2 in thyroid carcinoma (P = 0.001). HPSE activity was found to be higher in the malignant neoplasms than in the benign tumors (P<0.0001). On Western blot analysis, HPSE2 isoforms were detected only in malignant tumors. The immunohistochemical assay allowed us to establish a distinct pattern for malignant and benign tumors. Carcinomas showed a typical combination of positive labeling for neoplastic cells and negative immunostaining in colloid, when compared to benign tumors (P<0.0001). The proposed diagnostic test presents sensitivity and negative predictive value of around 100%, showing itself to be an accurate test for distinguishing between malignant and benign lesions. This study shows, for the first time, a distinct profile of HPSE expression in thyroid carcinoma suggesting its role in carcinogenesis.

  10. Periampullary carcinomas.

    Science.gov (United States)

    Filiz, Gulaydan; Yerci, Omer; Adim, Saduman Balaban; Gurel, Selim; Dolar, Enver; Memik, Faruk

    2007-06-01

    The purpose of this study was to determine predictors of survival after resection for periampullary neoplasms. In this study, we reevaluated our 17 cases of this type tumor which we had reported as periampullar site tumors, in advanced stages with undetermined localization, in our pathology department of the Uludag University faculty of medicine. Six of our cases were female, and 11 were male with a mean age of 60.6 years (range 31-77). Their main complaints were loss of weight, anorexia, jaundice and fatigue. Physical and endoscopic examination of these patients revealed periampullary mass and Whipple operations were performed on all of them. Histopathologic examinations of these tumors revealed adenocarcinoma in 15, small cell (neuroendocrin) carcinoma in two. All were in the advanced stages. Eight of them were alive and free of disease after 1.5- to 20-month follow-ups, while ten died because of disease. Periampullary carcinoma is a problem with increasing clinical significance. Tumor size, tumor type and differentiation, lymph node status appears to be prognostic markers.

  11. Mucin-producing sweat gland carcinoma of the eyelid: diagnostic and prognostic considerations.

    Science.gov (United States)

    Hoguet, Ambika; Warrow, David; Milite, James; McCormick, Steven A; Maher, Elizabeth; Della Rocca, Robert; Della Rocca, David; Goldbaum, Andrew; Milman, Tatyana

    2013-03-01

    To describe the clinical and pathologic characteristics of mucin-producing sweat gland carcinoma of the eyelid and to determine whether neuroendocrine differentiation is of prognostic significance. Retrospective interventional case series. Search of the New York Eye and Ear Infirmary pathology database between 1990 and 2011 identified 16 patients with mucin-producing sweat gland carcinoma. Clinical, histopathologic, and immunohistochemical analyses were performed on all identified cases. The patients presented with vascularized, focally cystic, nonulcerated eyelid margin lesions. Histopathologic evaluation showed that 4 lesions (25%) had a cystic, papillary, and solid growth pattern with an in situ component, 7 (44%) were pure invasive mucinous carcinomas, and 5 (31%) demonstrated both growth patterns. Immunohistochemical analysis of 15 tumors showed that pure cystic/papillary lesions had a significantly greater percentage of synaptophysin-immunoreactive cells (P = .036). There was no significant difference in the number of neuroendocrine markers expressed or in the intensity of immunostaining among the 3 different growth patterns. Re-excision for margin clearance was performed in 8 of 13 cases (61.5%). Two of 13 lesions recurred (15%); 1 of these was an in situ tumor with cystic morphology and neuroendocrine differentiation and the other was pure invasive mucinous carcinoma. None of the lesions metastasized. Mucin-producing sweat gland carcinoma pathologically represents a continuum, from an in situ lesion to a classic, invasive mucinous carcinoma. Immunohistochemical evidence of neuroendocrine differentiation can be observed in all lesions and does not appear to have a prognostic significance, arguing against the utility of immunohistochemical subtyping of mucinous sweat gland carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Characterization of prostate neuroendocrine cancers and therapeutic management: a literature review.

    Science.gov (United States)

    Sargos, P; Ferretti, L; Gross-Goupil, M; Orre, M; Cornelis, F; Henriques de Figueiredo, B; Houédé, N; Merino, C; Roubaud, G; Dallaudiére, B; Richaud, P; Fléchon, A

    2014-09-01

    Neuroendocrine prostate cancers (NEPCs) are rare. The current lack of consensus for clinical, biological and pathological characterization as well as therapeutic approach makes the management of those tumors a clinical challenge. This literature review aims to summarize available data on the characterization and management of patients with prostate cancer with a neuroendocrine element. We try to identify major controversies and uncertainties in order to understand all aspects of this particular entity. We searched for all articles published and registered in the MEDLINE database before 31 November 2013 with the following search terms: (('prostatic neoplasms' (MeSH Terms)) AND ('carcinoma, neuroendocrine' (MeSH Terms)) OR ('carcinoma, small cell' (MeSH Terms))) AND (English (Language)). Case reports, letters or comments were excluded. We then selected relevant articles from titles and abstracts. Overall, 278 articles published between 1976 and November 2013 were identified. No definition of NEPC seems to be clearly established. Natural history of the disease reveals poor prognosis with median survival of up to 10 to 13 months. Histological characterization appears difficult. Serum markers could be helpful with some controversies in terms of prognostic significance. Concerning management, the majority of patients received local treatment combined with chemotherapy in case of early and localized disease. Few clinical trials described strategy for metastatic disease. The exploration of the different pathways implicated in the neuroendocrine differentiation of prostate cancers is essential for the comprehension of castration-resistance mechanisms. It will enable the identification of optimal therapeutic strategies for which no recommendation is currently established. Inclusion in prospective clinical trials appears necessary to identify the adequate strategy.

  13. Proteomic analysis of differentially expressed proteins in hepatitis B virus-related hepatocellular carcinoma tissues

    OpenAIRE

    Li, Ning; Long, Yunzhu; Fan, Xuegong; Liu, Hongbo; Li, Cui; Chen, Lizhang; Wang, Zhiming

    2009-01-01

    Abstract Background Hepatocellular carcinoma (HCC), a major cause of cancer death in China, is preceded by chronic hepatitis and liver cirrhosis (LC). Although hepatitis B virus (HBV) has been regarded as a clear etiology of human hepatocarcinogenesis, the mechanism is still needs to be further clarified. In this study, we used a proteomic approach to identify the differential expression protein profiles between HCC and the adjacent non-tumorous liver tissues. Methods Eighteen cases of HBV-re...

  14. Differentiated thyroid carcinoma in a scintigraphically hot nodule: diagnosis and interdisciplinary therapeutical approach

    International Nuclear Information System (INIS)

    Stahl, A.; Hess, U.; Langhammer, H.; Harms, J.; Zwicknagl, M.

    2002-01-01

    A hyperfunctioning differentiated thyroid carcinoma is a rare occurrence. Nevertheless, this diagnosis must be considered in a scintigraphically hot nodule if there is a clinical or sonographic suggestion of malignancy. The case of a 57-year old patient with hyperthyreosis and a scintigraphically hot thyroid nodule is presented. Further evaluation led to the diagnosis of a differentiated thyroid carcinoma with extensive lymph node and pulmonary metastases (pT2b, pN1b, pM1). The scintigraphically hot nodule corresponded to the primary tumor, whereas scintigraphic detection of the lymph node metastases was only possible postoperatively. Extensive resection of the lymph node metastases was achieved by the intraoperative application of a gamma probe (2nd operation). This allowed sufficient uptake of radioiodine in the pulmonary metastases for their detection and subsequent devitalization by radioiodine therapy. Complete elimination of all tumor tissue was documented at a control follow-up after six months. Gamma probe-guided surgery may allow for additional removement of non-palpable lymph node metastases. In selected cases this may optimize the surgical results and thereby facilitate the subsequent radioiodine elimination of advanced differentiated thyroid carcinomas. (author)

  15. Identification of differentially expressed genes in oral squamous cell carcinoma TCA8113 cells.

    Science.gov (United States)

    Wang, Jun; Li, Lifeng; Gao, Lina; Guan, Chao; Su, Kexin; Li, Linlin; Luo, Wenping; Chen, Hongying; Ji, Ping

    2017-12-01

    Previous studies have demonstrated that cancer cells with increased levels of aldehyde dehydrogenase 'bright' activity (ALDH br ) exhibit stem cell properties compared with cells exhibiting decreased ALDH activity (ALDH low ). To screen possible biomarkers of cancer stem cells in tongue squamous cell carcinoma, ALDH br and ALDH low cells were isolated from the tongue squamous cell carcinoma TCA8113 cell line, and suppression subtractive hybridization was performed to identify differentially expressed genes in the two subpopulations. A total of 240 positive clones were randomly selected for sequencing and were functionally characterized using bioinformatical tools. The results of the present study identified the differential expression of 104 clones, 62 of which corresponded to known genes and 42 of which corresponded to unknown genes. Cluster analysis revealed that the known genes were involved in the regulation of the cell cycle and cell differentiation. In addition, analysis of 10 signaling pathways revealed that genes were markedly altered in the ALDH br cell subpopulation. Additional study is required to identify the function that these genes serve in the biomolecular regulatory mechanisms of cancer stem cells and to assist in explaining the biological behavior of oral squamous cell carcinoma.

  16. Use of social media to conduct a cross-sectional epidemiologic and quality of life survey of patients with neuroendocrine carcinoma of the cervix: a feasibility study.

    Science.gov (United States)

    Zaid, Tarrik; Burzawa, Jennifer; Basen-Engquist, Karen; Bodurka, Diane C; Ramondetta, Lois M; Brown, Jubilee; Frumovitz, Michael

    2014-01-01

    To determine the feasibility of using social media to perform cross-sectional epidemiologic and quality-of-life research on patients with rare gynecologic tumors, we performed a survey of patients with neuroendocrine tumors of the cervix using Facebook. After approval from our Institutional Review Board, a support group of patients with neuroendocrine tumors of the cervix was identified on Facebook. Group members were asked to complete a survey comprising 84 questions evaluating clinical presentation; treatment; recurrence; quality of life; and sexual function. The survey was posted for 30 days, during which 57 women responded from 8 countries across 4 continents treated at 51 centers. All respondents provided a detailed clinical and tumor history. The mean age was 38.5 years. The stage distribution was stage I, 36 patients (63%); II, 13 (23%); III, 2 (4%); and IV, 6 (11%). Forty-nine patients (86%) had small cell and 8 (14%) had large cell tumors. Forty-five of the respondents (79%) had completed primary therapy and were without evidence of disease. Five (9%) had recurrence, 3 (5%) had persistent disease after therapy, and 4 (7%) were still under treatment. Forty-one patients (72%) reported symptoms at time of presentation. Thirty-seven patients (65%) received multimodality primary therapy. Quality of life instruments demonstrated high scores for anxiety and a negative impact of anxiety and cancer on functional and emotional well-being. Sexual function scores did not differ significantly between respondents and the PROMIS reference population. Use of a social media network to perform epidemiologic and quality of life research on patients with rare gynecologic tumors is feasible and permits such research to be conducted efficiently and rapidly. © 2013.

  17. Progressive dysphagia in a dog caused by a scirrhous, poorly differentiated perioesophageal carcinoma.

    Science.gov (United States)

    Wray, J D; Blunden, A S

    2006-01-01

    Investigation of canine dysphagia is performed by a combination of diagnostic imaging, direct visualisation of the upper gastrointestinal tract, and ancillary diagnostic testing to differentiate between structural and functional causes. Video fluoroscopy may be especially helpful. The case of a seven-year-old Border collie that presented with a history of progressive pharyngeal dysphagia is described. Fluoroscopic investigation was initially suggestive of functional pharyngeal disease, but magnetic resonance imaging and surgical exploration demonstrated the presence of a diffuse, scirrhous, poorly differentiated carcinoma with extensive oesophageal involvement. This case highlights that, in some circumstances, fluoroscopy may occasionally be of limited use in the investigation of dysphagia in the dog.

  18. Novel Treatment of Small-Cell Neuroendocrine of the Vagina

    Directory of Open Access Journals (Sweden)

    Kathryn Kostamo

    2018-01-01

    Full Text Available Background. Primary vaginal small-cell neuroendocrine carcinoma is an extremely rare and highly aggressive malignancy. Eighty-five percent of patients die within one year of diagnosis from metastatic disease despite multimodal therapy. Gene expression profiling of tumor tissue may be useful for treatment options for various malignancies. Case. A 34-year-old nulliparous woman was diagnosed with primary vaginal small-cell neuroendocrine carcinoma. Twenty weeks after the initial visit, she was diagnosed with recurrence and started on chemoradiation based on the results of gene expression profile of tumor tissue. She died 34 months after the initial visit and had a 14-month progression-free survival (PFS. Conclusion. Gene expression profile of tumor tissue in the management of primary vaginal small-cell neuroendocrine carcinoma may be helpful in extending progression-free survival.

  19. Differential diagnosis of gallbladder wall thickening by two phase spiral CT : gallbladder carcinoma versus cholicystitis

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    Park, Sun; Cho, Soon Gu; Kim, Mi Young; Woo, Je Hong; Shin, Seok Hwan; Lee, Kykung Hee; Suh, Chang Hae [Inha Univ. College of Medicine, Inchon (Korea, Republic of)

    2001-04-01

    To determine whether an analysis of two-phase CT features provides a sound basis for differential diagnosis between gallbladder carcinoma and cholecystitis. We reviewed a total of 89 cases of gallbladder carcinoma (n=35) or cholecystitis (n=54) in patients who had undergone two-phase spiral CT. For this, a GE Highspeed Advantage scanner (GE Medical Systems, Milwaukee, U . S . A .) was used. A total of 120ml of contrast material was injected at a rate of 2-3 ml/sec. Arterial and venous phase scans were obtained 35 and 65 seconds, respectively, after the initiation of contrast infusion. All cases of gallbladder carcinoma and 468 of cholecystitis (of a total of 482) were confirmed by histopathology. We reviewed the two phase spiral CT features, analyzing and assessing thickness of the lesion, the enhancement pattern seen during the arterial and the venous phase, invasion of liver, pericholecystic fat infiltration, dilatation of intrahepatic ducts, and other associated findings. Mean wall thickness was 12.6 mm in the gallbladder carcinoma group, and 7.2 mm in the cholecystitis group. The common enhancement patterns seen in gallbladder carcinoma were 1) a highly enhanced thick inner wall layer during the arterial phase which became iso attenuated with adjacent liver parenchyma during the venous phase (16/35; 45.7%) and 2) highly enhanced thick inner wall layer during both the arterial and venous phase (8/35; 22.9%). The most common enhancement pattern in cholecystitis cases was an iso attenuated thin inner wall layer during both the arterial and the venous phase (44/54; 81.5%). Findings of intrahepatic mass formation by direct invasion (9/35), lymph node enlargement (12/35), and metastasis to other organs (7/35) occurred only in cases of gallbladder carcinoma (18/35, 51.4%) than of cholecystitis (10/54, 18.5%). The incidence of pericholecystic fat infiltration and fluid collection was not significantly different between the gallbladder cancer and cholecystitis groups

  20. 131I treatment for brain metastases from differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Yu Yongli; Lu Hankui; Zhu Reisen; Ma Jixiao

    2004-01-01

    To assess the clinical value of treatment with 131 I for brain metastases from differentiated thyroid cancer (DTC), the authors have observed 8 cases of brain metastases from DTC who received follow-up after 131 I therapy (2 male, 6 female, aged 12-65 years). The results of 131 I therapy were evaluated with clinical presentation, imaging scan and survival analysis. The main results are as follows. (1) All cases had been survival for 2-35 years in follow-up. (2) A space-occupying lesion in right cerebellum was reduced after taking 20.65 GBq and disappeared after 23.61 GBq, demonstrated by computed tomography. (3) The sequences and doses of 131 I therapy were clearly decreased for the cases with total thyroidectomy in comparison with those with semithyroidectomy (p 131 I for brain metastases from DTC after undergoing thyroidectomy may improve clinical symptoms and lift quality, reduce lesions, and prolong survival. (authors)

  1. [Effects of differentially expressed proteins in hepatocellular carcinoma cell treated by different telomerase inhibitors].

    Science.gov (United States)

    Wei, Xiao; Zhang, Zhiyong; He, Min; Wang, Xia; Zheng, Weiwei

    2010-03-01

    To detect differentially expressed proteins in hepatocellular carcinoma cell line SMMC-7721 treated separately by eight telomerase inhibitors including antisense oligodeoxynuclectide of human telomerase RNA (hTR-ASODN), sense oligodeoxynuclectide of hTR (hTR-SODN), ASODN of human telomerase reverse transcriptase (hTERT-ASODN), SODN of hTERT (hTERT-SODN), epigallocatechin gallate (EGCG), 3'-azido-3'-deoxythymidine (AZT), all trans-retinoic acid (ATRA) and adriamycin (ADM) using surface enhanced laser desorption/ionization time of flight-mass spectrom (SELDI-TOF-MS) technology. SELDI-TOF-MS technology and weak cation exchanger (WCX-2) protein chip were used to detect differentially expressed secretory and cytoplasmic proteins of SMMC-7721 cell treated separately by eight telomerase inhibitors. The control group was hepatocellular carcinoma SMMC-7721 cell without any disposal. The results of WCX-2 protein chip showed that the secretory and cytoplasmic proteins were differentially expressed in SMMC-7721 cell treated separately by eight telomerase inhibitors. But some proteins were down-regulated or up-regulated together in all experimental groups. The molecular weight of these differential proteins were all less than 10,000 Da. Differentially expressed and common changes of proteins in SMMC-7721 cell treated separately by eight telomerase inhibitors would associate with telomerase activity.

  2. 99mTc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment.

    Science.gov (United States)

    Czepczyński, Rafał; Gryczyńska, Maria; Ruchała, Marek

    2016-01-01

    In majority of cases of differentiated thyroid carcinoma (DTC), the ablative radioiodine treatment shows high efficacy. In a small number of patients, mechanism of selective iodine uptake by the DTC cells is insufficient and alternative methods of diagnosis and treatment are needed. As demonstrated in vitro, DTC cells show expression of somatostatin recep-tors. Radiolabeled somatostatin analogs are widely used in the diagnosis of neuroendocrine tumors. The aim of the study was to evaluate the utility of peptide receptor scintigraphy with the use of 99mTc-EDDA/HYNIC-TOC in the diagnosis of DTC in patients with elevated thyroglobulin concentrations (Tg), negative WBS and no effect of the consecutive radioiodine therapies. Whole body scintigraphy as well as SPECT of neck and chest were performed 3 and 24 h after i.v. administration of 740 MBq 99mTc-EDDA/HYNIC-TOC. The obtained images were compared with other radionuclide and ra-diological imaging methods. Forty-three patients with DTC after surgery and ablative radioiodine treatment with negative WBS and elevated Tg were qualified. Patients' age: 18-83 years (mean 58.0). SRS showed foci of tracer accumulation in 29 cases (67.4%). Sensitivity was 69.0% specificity 78.6%. SRS correctly identified local recurrence in 8 pts., metastatic lymph nodes in 19 pts., lung metastases in 12 pts. and bone metastases in 5 pts. SRS showed high sensitivity in the detection of metastatic lymph nodes (100%) and bone metastases (83.3%) and lung metastases (63.2%). Positive SRS was found in pts. with higher Tg concentrations (130 ± 144 vs. 30 ± 54 ng/ml). Scintigraphy with the use of the studied technetium-99m-labeled somatostatin analog is useful in the evaluation of patients with advanced DTC. It shows relatively good sensitivity and specificity but not high enough to be recommended as a routine imaging method. The role of somatostatin receptor scintigraphy in DTC is complementary to other imaging modalities.

  3. Differentiation between endobronchial tuberculosis and bronchogenic carcinoma associated with atelectasis or obstructive pneumonitis: CT evaluation

    International Nuclear Information System (INIS)

    Chung, Hwan Hoon; Oh, Yu Whan; Kim, Kyeong Ah; Kim, Jung Hyuk

    1995-01-01

    Endobronchial tuberculosis and bronchogenic cancer are common causes of atelectasis or obstructive pneumonitis in Korea. Differentiation between endobronchial tuberculosis and bronchogenic carcinoma is important for the treatment and prognosis but it is sometimes difficult to differentiate these two lesions with radiologic examinations. The purpose of this study was to find the differential points between endobronchial tuberculosis and bronchogenic carcinoma associated with atelectasis or obstructive pneumonitis. Forty patients in whom atelectasis or obstructive pneumonitis was detected on chest radiographs comprised the study. A definite mass opacity was not observed on chest radiographs in all patients. In these patients, the causes of obstruction were endobronchial tuberculosis (n = 20) and bronchogenic cancer (n = 20) which were microbiologically or pathologically confirmed. Double obstructive lesions were more frequently found in endobronchial tuberculosis (8/20) than in bronchogenic cancer (1/20). Multiple calcification along the bronchial wall and severe distortion of bronchi were observed only in endobronchial tuberculosis (4/20) and associated low density mass at obstruction site was only observed in bronchogenic cancer (6/20). Bronchial dilatation (11/20) and parenchymal calcifications (14/20) distal to obstruction site, air containing bronchogram at post obstructive bronchus (14/20) were more frequently found in endobronchial tuberculosis. Contour bulging at obstruction site (14/20), and only mucus bronchogram at post obstructive bronchus (14/20) were more frequently found in bronchogenic carcinoma. In patients with atelectasis or obstructive pneumonitis, endobronchial tuberculosis is characterized by double obstructive lesion, multiple calcifications at the bronchial wall, and severe distortion of the bronchi. Endobronchial carcinoma is characterized by a low density mass at the obstructive site

  4. Differential retention of tumor- and differentiation-suppressor functions in cells derived from a human squamous cell carcinoma.

    Science.gov (United States)

    Jaffe, D R; Montero-Puerner, Y; Beckett, M A; Cowan, J M; Weichselbaum, R R; Diamond, A M

    1992-01-01

    Three morphologically distinct cell lines--F.2a, V, and B.2--were isolated from a single human squamous cell carcinoma. Although all three cell lines can grow indefinitely in culture, they differ in a number of important transformation-related phenotypes. Only B.2 is strongly tumorigenic when injected into the flanks of nude mice, and only V can efficiently grow in semisolid media. The dominance of these traits was investigated by generating somatic cell hybrids among the three cell lines. F.2a was able to suppress the tumorigenicity of B.2 cells, whereas B.2 inhibited the capacity for anchorage-independent growth of V, the latter trait being a function of the ability of these epithelial cells to differentiate when deprived of support. The influence of exogenously added growth factors was also evaluated. This study indicates that the particular tumor we examined consisted of a heterogeneous population of cells with distinct growth and differentiation capacities.

  5. Head and neck region consolidation radiotherapy and prophylactic cranial irradiation with hippocampal avoidance delivered with helical tomotherapy after induction chemotherapy for non-sinonasal neuroendocrine carcinoma of the upper airways

    Directory of Open Access Journals (Sweden)

    Franco Pierfrancesco

    2012-02-01

    Full Text Available Abstract Background Non-sinonasal neuroendocrine carcinomas (NSNECs of the head and neck are considered an unfrequent clinico-pathological entity. Combined modality treatment represents an established therapeutic option for undifferentiated forms where distant metastasis is a common pattern of failure. Methods We report on a case of NSNEC treated with sequential chemo-radiation consisting of 6 cycles of cisplatin and etoposide followed by loco-regional radiation to the head and neck and simultaneous prophylactic cranial irradiation to prevent from intracranial spread, delivered with helical tomotherapy with the 'hippocampal avoidance' technique in order to reduce neuro-cognitive late effects. Results One year after the end of the whole combined modality approach, the patient achieved complete remission, with no treatment-related sub-acute and late effects. Conclusions The present report highlights the importance of multidisciplinary management for NSNECs of the head and neck, as the possibility to achieve substantial cure rates with mild side effects with modern radiotherapy techniques.

  6. Mediastinal Teratoma with Neuroendocrine Features in 34-Year-Old Male with Syncope

    Directory of Open Access Journals (Sweden)

    Peter A. Andrawes

    2015-01-01

    Full Text Available Neuroendocrine tumors that arise in an extragonadal teratoma are extremely rare. Somatic-type malignancy, defined as any sarcoma, carcinoma, leukemia, or lymphoma developing in a germ cell tumor, occurs in approximately 2% of all germ cell tumors. Our case represents a mediastinal mass that was incidentally found in a patient with syncope. Surgical resection confirmed mature teratoma with neuroendocrine features.

  7. Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection.

    Science.gov (United States)

    Blochin, Elen B; Park, Kay J; Tickoo, Satish K; Reuter, Victor E; Al-Ahmadie, Hikmat

    2012-11-01

    Squamous cell carcinomas of the urinary bladder are rare in the Western world; the majority of cases are reported in countries endemic to Schistosoma parasitic infections. Unlike squamous tumors of the uterine cervix or oropharynx, the human papillomavirus (HPV) is not commonly associated with bladder squamous cell carcinomas. We report on two cases of HPV-positive urothelial carcinomas of the urinary bladder with extensive squamous differentiation showing the typical basaloid, poorly differentiated morphology of HPV-associated tumors. These occurred in patients with neurogenic bladders who had long-standing histories of self-catheterization with tumors that tested positive for HPV by in situ hybridization. A retrospective review of our institutional database revealed four additional patients with bladder tumors showing squamous differentiation arising in the setting of neurogenic bladder. Review of these cases showed the more common well-differentiated keratinizing appearance of squamous cell carcinomas of the bladder. These tumors showed only patchy positivity for p16 immunohistochemical stain (not the diffuse strong staining seen in HPV-positive tumors), and the one tested case was negative for HPV by in situ hybridization. HPV infection and neurogenic bladder have been independently associated with increased risk of developing carcinoma in the urinary bladder; however, this is the first report of squamous tumors arising in the setting of concurrent neurogenic bladder and HPV infection. The morphology of these tumors is similar to that of other high-risk HPV-associated squamous carcinomas with a basaloid, poorly differentiated appearance and little to no keratin formation.

  8. Horrifying Basal Cell Carcinoma: Cytological, Immunohistochemical, and Ultrastructural Findings

    Directory of Open Access Journals (Sweden)

    Yuichi Kinoshita

    2014-07-01

    Full Text Available Basal cell carcinoma (BCC is a slow-growing and frequently occurring tumor of the eyelids. Among BCC cases, there is a subtype of aggressive cases called horrifying BCC (HBCC. There are also rare BCC cases that show neuroendocrine differentiation. Here, we describe a case of HBCC with neuroendocrine differentiation. The patient, a 41-year-old woman, presented with abnormal left eye tearing and left cheek pain. On computed tomography imaging, a tumor that extended to the left orbit was detected in the left cheek. On cytological examination of fine-needle aspiration (FNA samples, the tumor cells were observed as sheet-like clusters and single bare nuclei with a clear background; peripheral palisading was not clearly seen. On examination of the biopsy specimen taken after FNA, the tumor was found to be composed of cancer cell nests with scattered peripheral palisading in the dermis. Immunohistochemically, the tumor cells were positive for cytokeratin (CK 7 and CD56 and were negative for CK20, synaptophysin, and chromogranin A. Membrane-bound dense-core granules were detected on ultrastructural study. A HBCC case with neuroendocrine differentiation has not been previously reported. The correlation between the presence of neuroendocrine differentiation in HBCC and patient prognosis should be further studied.

  9. Endocrine mucin-producing sweat gland carcinoma: report of two cases of an under-recognized malignant neoplasm and review of the literature.

    Science.gov (United States)

    Dhaliwal, Catharine A; Torgersen, Antonia; Ross, Jonathan J; Ironside, James W; Biswas, Asok

    2013-02-01

    Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade sweat gland carcinoma with a strong predilection to the eyelid region. It is histologically analogous to endocrine ductal carcinoma/solid papillary carcinoma of the breast and is characterized by a multinodular solid cystic mucinous tumor with immunoreactivity to neuroendocrine markers. Only 20 cases of this unusual tumor have been reported. We present the clinical and histopathologic findings of 2 new cases of EMPSGC and review the relevant literature. The histological differential diagnosis is discussed and attention drawn to the role of immunohistochemistry in clarifying the nosological position of EMPSGC within the spectrum of cutaneous mucinous neoplasms.

  10. The ROCK isoforms differentially regulate the morphological characteristics of carcinoma cells.

    Science.gov (United States)

    Jerrell, Rachel J; Leih, Mitchell J; Parekh, Aron

    2017-06-26

    Rho-associated kinase (ROCK) activity drives cell migration via actomyosin contractility. During invasion, individual cancer cells can transition between 2 modes of migration, mesenchymal and amoeboid. Changes in ROCK activity can cause a switch between these migration phenotypes which are defined by distinct morphologies. However, recent studies have shown that the ROCK isoforms are not functionally redundant as previously thought. Therefore, it is unclear whether the ROCK isoforms play different roles in regulating migration phenotypes. Here, we found that ROCK1 and ROCK2 differentially regulate carcinoma cell morphology resulting in intermediate phenotypes that share some mesenchymal and amoeboid characteristics. These findings suggest that the ROCK isoforms play unique roles in the phenotypic plasticity of mesenchymal carcinoma cells which may have therapeutic implications.

  11. Regulation and patterns of endogenous and exogenous gene expression during differentiation of embryonal carcinoma cells

    International Nuclear Information System (INIS)

    Astigiano, S.; Sherman, M.I.; Abarzua, P.

    1989-01-01

    Embryonal carcinoma (EC) cells offer an interesting model system for evaluating differentiation because the cells are pluripotent, thus resembling germ cells and embryonic stem cells, and because a number of agents have been defined that are capable of promoting the differentiation of these cells. This chapter examines how EC cells might be triggered to differentiate, with emphasis on retinoic acid because this compound is a potent, naturally occurring inducer that has been studied extensively in this system. The nature of alterations in gene expression during EC cell differentiation is reviewed from the perspective of evaluating whether these changes are likely to be responsible for, or a result of, the differentiation event. Finally, the authors consider in molecular terms why EC cells, but not their differentiated derivatives, are refractory to the expression of many viral genomes following infection. Based upon these studies, they propose that fundamental changes in gene expression that are observed when differentiation is triggered in EC cells are likely to be due to the disappearance or neutralization of strong repressor elements

  12. Neuroendocrine tumor presenting like lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Vincenzi Bruno

    2011-10-01

    Full Text Available Abstract Introduction Neuroendocrine tumors are a rare but diverse group of malignancies that arise in a wide range of organ systems, including the mediastinum. Differential diagnosis includes other masses arising in the middle mediastinum such as lymphoma, pericardial, bronchogenic and enteric cysts, metastatic tumors, xanthogranuloma, systemic granuloma, diaphragmatic hernia, meningocele and paravertebral abscess. Case presentation We present a case of 42-year-old Caucasian man with a neuroendocrine tumor of the middle-posterior mediastinum and liver metastases, which resembled a lymphoma on magnetic resonance imaging. Conclusion The differential diagnosis in patients with mediastinal masses and liver lesions should include neuroendocrine tumor.

  13. Is CA-125 an additional help to radiologic findings for differentiation borderline ovarian tumor from stage I carcinoma?

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Joo; Kim, See Hyung; Kim, Young Hwan; Lee, Hee Jung (Dept. of Radiology, Keimyung Univ. Dongsan Hospital, College of Medicine, Daegu (Korea, Republic of)), email: kseehdr@dsmc.or.kr

    2011-05-15

    Background Borderline ovarian tumors (BOTs) are difficult to differentiate from stage I carcinoma using radiological findings. Little is known about the correlation between CA-125 levels and radiological findings for predicting BOTs or carcinoma. Purpose To assess the role of CA-125, in addition to that of radiological findings, in differentiating BOTs from stage I carcinoma. Material and Methods The study received institutional review board approval, with waiver of informed consent. We evaluated 100 patients (two groups: BOT, 58 patients; stage I carcinoma, 42 patients) using radiological findings, including location and size of each tumor, number and size of septations, papillary projections and vegetations, peritoneal implants, ascites, and preoperative CA-125 levels. The differences in CA-125 levels according to bilateral location, solid components, and thickness of septations between the two groups were evaluated using the McNemar test. Correlations of CA-125 level to size and number of septations were evaluated by the independent sample t test. Results No statistical correlation was found between CA-125 level and location, size, and number of septations between the two groups. Solid components within the tumors were similar in the two groups, but the CA-125 level was significantly higher in stage I carcinoma than in BOTs. The number of septations per tumor was similar in the two groups; thick septations were more frequent in stage I carcinoma than in BOTs, and a significantly higher titer of CA-125 was found in stage I carcinoma. Discriminant analysis of solid components and thickness of septations resulted in accurate diagnosis of 70.6% of the tumors (80.6% of BOTs and 69.7% of stage I carcinomas). Conclusion CA-125 levels for solid components and thickness of septations are lower in BOTs. These may be helpful in predicting the risk of carcinoma, even if BOTs cannot be conclusively differentiated from stage I carcinoma

  14. Is CA-125 an additional help to radiologic findings for differentiation borderline ovarian tumor from stage I carcinoma?

    International Nuclear Information System (INIS)

    Lee, Eun Joo; Kim, See Hyung; Kim, Young Hwan; Lee, Hee Jung

    2011-01-01

    Background Borderline ovarian tumors (BOTs) are difficult to differentiate from stage I carcinoma using radiological findings. Little is known about the correlation between CA-125 levels and radiological findings for predicting BOTs or carcinoma. Purpose To assess the role of CA-125, in addition to that of radiological findings, in differentiating BOTs from stage I carcinoma. Material and Methods The study received institutional review board approval, with waiver of informed consent. We evaluated 100 patients (two groups: BOT, 58 patients; stage I carcinoma, 42 patients) using radiological findings, including location and size of each tumor, number and size of septations, papillary projections and vegetations, peritoneal implants, ascites, and preoperative CA-125 levels. The differences in CA-125 levels according to bilateral location, solid components, and thickness of septations between the two groups were evaluated using the McNemar test. Correlations of CA-125 level to size and number of septations were evaluated by the independent sample t test. Results No statistical correlation was found between CA-125 level and location, size, and number of septations between the two groups. Solid components within the tumors were similar in the two groups, but the CA-125 level was significantly higher in stage I carcinoma than in BOTs. The number of septations per tumor was similar in the two groups; thick septations were more frequent in stage I carcinoma than in BOTs, and a significantly higher titer of CA-125 was found in stage I carcinoma. Discriminant analysis of solid components and thickness of septations resulted in accurate diagnosis of 70.6% of the tumors (80.6% of BOTs and 69.7% of stage I carcinomas). Conclusion CA-125 levels for solid components and thickness of septations are lower in BOTs. These may be helpful in predicting the risk of carcinoma, even if BOTs cannot be conclusively differentiated from stage I carcinoma

  15. Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting

    International Nuclear Information System (INIS)

    Snow, Grace E; Kasper, Allison C; Busch, Alexander M; Schwarz, Elisabeth; Ewings, Katherine E; Bee, Thomas; Spinella, Michael J; Dmitrovsky, Ethan; Freemantle, Sarah J

    2009-01-01

    Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency. Human embryonal carcinoma cells were stably infected with a lentiviral construct carrying a canonical Wnt responsive reporter to assess Wnt signalling activity following induced differentiation. Cells were differentiated with all-trans retinoic acid (RA) or by targeted repression of pluripotency factor, POU5F1. A Wnt pathway real-time-PCR array was used to evaluate changes in gene expression as cells differentiated. Highlighted Wnt pathway genes were then specifically repressed using siRNA or stable shRNA and transfected EC cells were assessed for proliferation, differentiation status and levels of core pluripotency genes. Canonical Wnt signalling activity was low basally in undifferentiated EC cells, but substantially increased with induced differentiation. Wnt pathway gene expression levels were compared during induced differentiation and many components were altered including ligands (WNT2B), receptors (FZD5, FZD6, FZD10), secreted inhibitors (SFRP4, SFRP1), and other effectors of Wnt signalling (FRAT2, DAAM1, PITX2, Porcupine). Independent repression of FZD5, FZD7 and WNT5A using transient as well as stable methods of RNA interference (RNAi) inhibited cell growth of pluripotent NT2/D1 human EC cells, but did not appreciably induce differentiation or repress key pluripotency genes. Silencing of FZD7 gave the greatest growth suppression in all human EC cell lines tested including NT2/D1, NT2/D1-R1, Tera-1 and 833

  16. Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting

    Directory of Open Access Journals (Sweden)

    Bee Thomas

    2009-10-01

    Full Text Available Abstract Background Testicular germ cell tumors (TGCTs are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency. Methods Human embryonal carcinoma cells were stably infected with a lentiviral construct carrying a canonical Wnt responsive reporter to assess Wnt signalling activity following induced differentiation. Cells were differentiated with all-trans retinoic acid (RA or by targeted repression of pluripotency factor, POU5F1. A Wnt pathway real-time-PCR array was used to evaluate changes in gene expression as cells differentiated. Highlighted Wnt pathway genes were then specifically repressed using siRNA or stable shRNA and transfected EC cells were assessed for proliferation, differentiation status and levels of core pluripotency genes. Results Canonical Wnt signalling activity was low basally in undifferentiated EC cells, but substantially increased with induced differentiation. Wnt pathway gene expression levels were compared during induced differentiation and many components were altered including ligands (WNT2B, receptors (FZD5, FZD6, FZD10, secreted inhibitors (SFRP4, SFRP1, and other effectors of Wnt signalling (FRAT2, DAAM1, PITX2, Porcupine. Independent repression of FZD5, FZD7 and WNT5A using transient as well as stable methods of RNA interference (RNAi inhibited cell growth of pluripotent NT2/D1 human EC cells, but did not appreciably induce differentiation or repress key pluripotency genes. Silencing of FZD7 gave the greatest growth suppression in all human EC cell lines

  17. [Molecular mechanism of cardiac differentiation in P19 embryonal carcinoma cells regulated by Foxa2].

    Science.gov (United States)

    Zhu, Hong; Zhang, Zhen; Liu, Yi; Chen, Yan; Tan, Yongjun

    2013-04-01

    To investigate the involvement of transcription factor Foxa2 in cardiac differentiation in P19 embryonal carcinoma cells and its molecular mechanism. P19 cells were induced to differentiate into cardiomyocytes by adding dimethyl sulfoxide (DMSO) into the culture medium of their embryoid bodies (EBs). The mRNA levels of pluripotency markers of embryonic pluripotent stem cells, cardiac differentiation related genes, and Foxa2 in the cell samples at different time points of cardiac differentiation were detected by reverse transcription PCR (RT-PCR). Differentiated and mature cardiomyocytes were identified by immunofluorescence. Eukaryotic expression plasmid pCMV-rFoxa2 (rat Foxa2) was transfected into P19 cells, and clonal populations of P19 cells that stably expressed green fluorescence protein (GFP)-rFoxa2 were isolated to enhance the expression levels of Foxa2 in P19 cells. The mRNA and protein levels of pluripotency markers and cardiac differentiation related genes in the above cell samples were detected by RT-PCR and Western blot. The mRNA levels of cardiac differentiation related genes in EBs differentiation system were also examined. P19 cells differentiated into cardiomyocytes in the presence of DMSO, accompanied by stimulated expression of Foxa2. Transfection of pCMV-rFoxa2 plasmids into P19 cells upregulated rFoxa2 expression transiently and activated the transcription of its downstream cardiac inducer Cerberus1 (Cer1). The expression of pluripotency marker Nanog was suppressed and the expression of cardiac inducer Sonic Hedgehog (Shh) was elevated in GFP-rFoxa2 P19 cells. The expression of Cer1 and cardiac muscle marker actin, alpha cardiac muscle 1 (Actc1) was upregulated in EBs of GFP-rFoxa2 P19 cells. Foxa2 participates in cardiac differentiation in P19 embryonal carcinoma cells. Foxa2 may inhibit Nanog expression and stimulate the expression of Cer1 and Shh directly during cardiac differentiation in P19 cells in the presence of DMSO.

  18. Neuroendocrine cells during human prostate development: does neuroendocrine cell density remain constant during fetal as well as postnatal life?

    NARCIS (Netherlands)

    Xue, Y.; van der Laak, J.; Smedts, F.; Schoots, C.; Verhofstad, A.; de la Rosette, J.; Schalken, J.

    2000-01-01

    Knowledge concerning differentiation of neuroendocrine (NE) cells during development of the human prostate is rather fragmentary. Using immunohistochemistry combined with a morphometric method, we investigated the distribution and density of NE cells in the developing human prostate, with special

  19. Expression and Clinicopathologic Significance of Human Achaete-scute Homolog 1 in Pulmonary Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Donghan ZHENG

    2010-04-01

    Full Text Available Background and objective Human achaete-scute homolog 1 (hASH1 gene plays a critical role in development of the central nervous system, automatic nervous system, adrenal medullary chromaffin cells, thyroid C cells and pulmonary neuroendocrine cells. The aim of this study is to determine hASH1 gene expression in the normal lung tissue and various types of lung tumors, to analyze whether its expression correlated with pulmonary neuroendocrine markers, and to explore the possibility of hASH1 as clinical pathological markers in the neuroendocrine tumors compared with previous neuroendocrine tumor markers. Methods hASH1, Chromogranin A, Synaptophysin and CD56 expression were examined in lung tumor specimens (lung inflammatory pseudotumor, squamous cell carcinoma, adenocarcinomas, large cell carcinoma, typical carcinoids, atypical carcinoids, large cell neuroendocrine carcinomas and small cell lung carcinoma and corresponding normal lung specimens using immunohistochemistry (S-P method. Western blot and reverse transcription polymerase chain reaction (RT-PCR assay were applied to detect the expressions of hASH1 protein and mRNA in lung cancer tissues. Results hASH1 expression was positive in 2/16 (12.5% typical carcinoids, 15/20 (75% atypical carcinoids, 6/10 (60% large cell neuroendocrine carcinomas and 31/40 (77.5% small cell lung carcinoma, respectively, but not in any normal lung tissue (0/10, lung inflammatory pseudotumor (0/49, squamous cell carcinoma (0/30, adenocarcinomas (0/30 or large cell carcinoma (0/20. There was a significant difference in hASH1 expression between typical carcinoids and atypical carcinoids (P 0.05. hASH1 expression highly closely correlated with Chromogranin A, Synaptophysin and CD56 expression (P < 0.05. Conclusion hASH1 is a new kind of highly specific markers of pulmonary neuroendocrine tumours, and may be applied to clinical pathology diagnosis of the pulmonary neuroendocrine tumors.

  20. Proteomic analysis reveals novel proteins associated with progression and differentiation of colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Yi Gan

    2014-01-01

    Full Text Available Aim: The objective of this study is to characterize differential proteomic expression among well-differentiation and poor-differentiation colorectal carcinoma tissues and normal mucous epithelium. Materials and Methods: The study is based on quantitative 2-dimensional gel electrophoresis and analyzed by PDquest. Results: Excluding redundancies due to proteolysis and posttranslational modified isoforms of over 600 protein spots, 11 proteins were revealed as regulated with statistical variance being within the 95 th confidence level and were identified by peptide mass fingerprinting in matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Progression-associated proteins belong to the functional complexes of tumorigenesis, proliferation, differentiation, metabolism, and the regulation of major histocompatibility complex processing and other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in CRC. Among various differentiation stage of CRC tissues, we identified calreticulin precursor, MHC class I antigen (human leukocyte antigen A , glutathione S-transferase pi1, keratin 8, heat shock protein 27, tubulin beta chain, triosephosphate, fatty acid-binding protein, hemoglobin (deoxy mutant with val b 1 replaced by met (HBB, and zinc finger protein 312 (FEZF2. Conclusions: Their functional networks were analyzed by Ingenuity systems Ingenuity Pathways Analysis and revealed the potential roles as novel biomarkers for progression in various differentiation stages of CRC.

  1. Fractal Dimension as a Diagnostic Tool of Complex Endometrial Hyperplasia and Well-differentiated Endometrioid Carcinoma.

    Science.gov (United States)

    Bikou, Olga; Delides, Alexander; Drougou, Aggeliki; Nonni, Afroditi; Patsouris, Efstratios; Pavlakis, Kitty

    Fractal dimension (FD) is widely used in medicine and biology as a tool for defining features of structure. This study aimed to compare pathological endometrium (simple-complex hyperplasia and endometrial carcinoma), as well as the endometrial changes, during the phases of the menstrual cycle. The main goal was the objective measurement of fractal dimension and to refrain from subjective evaluation. Two thousand cases of endometrial tissue from patients who underwent dilatation and curettage (D&C) were reviewed. Out of these, 137 cases were eligible for the study. In each case, immunohistochemistry with cytokeratin Ae1/AE3 was performed in order to simplify the evaluation of the FD. Endometria with carcinoma, simple or complex hyperplasia showed significant differences only in the immunohistochemically stained fractal dimensions. As expected, significant differences were also found between atrophic and secretory endometrium and carcinoma. FD is an objective, rapid and simple procedure for the differential diagnosis between complex hyperplasia and endometrial adenocarcinoma. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Metabolic PET tracers for neuroendocrine tumors

    NARCIS (Netherlands)

    Koopmans, Klaas Pieter

    2008-01-01

    Neuroendocrine tumors originate from the diffuse neuroendocrine system. Embryologically the diffuse neuroendocrine system is derived from the neuoectoderm and the endoderm (gut). The function of diffuse neuroendocrine system cells is to regulate neighbouring cells (paracrine regulation) by the

  3. ROLE OF CT IN DIFFERENTIATION OF MUCINOUS AND NON-MUCINOUS CARCINOMAS OF THE RECTUM

    Directory of Open Access Journals (Sweden)

    Piyush Joshi

    2017-01-01

    Full Text Available BACKGROUND Colorectal carcinomas can broadly be classified as either non-mucinous or mucinous. Usually, mucinous adenocarcinomas present at a more advanced stage, have more aggressive local spread and have an increased incidence of lymph node involvement. Those cancers occurring in the rectum are considered more aggressive and require careful planning for treatment. Screening Computed Tomography (CT is widely used for the initial evaluation of these tumours. The aim of the study is to retrospectively analyse the CT images of rectal adenocarcinomas and suggest parameters to aid differentiation of mucinous and non-mucinous tumours. MATERIALS AND METHODS The CT images of 24 cases of mucinous and 26 cases of non-mucinous adenocarcinoma were retrospectively reviewed and evaluated for parameters like morphology, wall thickness, size, pattern and degree of enhancement and the presence or absence of calcification. Also, evaluated was involvement of adjacent structures, lymph nodes and distant metastases. RESULTS All the parameters were analysed for significance using the chi-square test. Mucinous adenocarcinomas of the rectum showed a greater propensity for eccentric bowel thickening, heterogenous enhancement and calcification with a p value less than 0.05. Heterogenous enhancement showed the greatest sensitivity (75% and calcification the greatest specificity (83.3%. The other parameters did not show any difference between the two groups. CONCLUSION CT features most likely to suggest rectal mucinous carcinoma are heterogenous contrast enhancement, eccentric wall thickening and intratumoural calcification. As mucinous carcinomas follow an aggressive course, if a diagnosis of mucinous carcinoma of the rectum can be suggested on the staging CT, it may influence patient management.

  4. Metastatic Renal Cell Carcinoma: The Importance of Immunohistochemistry in Differential Diagnosis

    Directory of Open Access Journals (Sweden)

    Sandra Custódio

    2012-01-01

    Full Text Available Introduction: Clear cell carcinoma accounts for 75% of all types of renal neoplasms. Approximately one third presents with metastatic disease at diagnosis. Immunohistochemical studies play a significant diagnostic role. Case Report: We report the case of a 48-year-old heavy smoker who presented with productive cough and progressive dyspnea. The study revealed a renal mass and lung alterations compatible with primary tumor of the lung. The patient underwent a right complete nephrectomy. The anatomopathological exam showed clear cell renal carcinoma (pT1bN0Mx. After transthoracic needle aspiration biopsy, the clinical diagnosis was stage IV adenocarcinoma of the lung. Initially, the patient received one cycle of chemotherapy (cisplatin/pemetrexed. Two weeks later, the immunohistochemistry tests revealed a secondary lesion with probable renal origin. Chemotherapy was stopped and the patient was started on sunitinib treatment. After two cycles the disease progressed. A second-line treatment with everolimus was proposed; however, the patient died 2 weeks later due to terminal respiratory insufficiency. Discussion: Clear cell renal cell carcinoma remains one of the great mimickers in pathology. Immunohistochemistry is a valuable tool in the differential diagnosis of lung carcinomas. With the help of thyroid transcription factor 1, it is possible to distinguish a primary lung tumor from a metastasis with a reasonable degree of certainty. The present case report illustrates the challenge of making a definitive and adequate diagnosis. The immunohistochemistry added information that changed the whole treatment strategy. For the best treatment approach, it is fundamental that clinicians await all possible test results, before establishing a treatment plan.

  5. Radioiodine concentration by the thymus in differentiated thyroid carcinoma: report of five cases

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Maria Eduarda; Flamini, Rodrigo C.; Corbo, Rossana; Mamede, Marcelo [Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear], e-mail: mamede@inca.gov.br

    2009-10-15

    The radioactive iodine has been used with great value as a diagnostic and therapeutic method in patients with differentiated thyroid carcinoma previously submitted to total thyroidectomy. False-positive whole-body scans may occur due to misinterpretation of the physiologic distribution of the radioisotope or lack of knowledge on the existence of other pathologies that could eventually present radioiodine uptake. Thymic uptake is an uncommon cause of false-positive whole-body scan, and the mechanism through which it occurs is not completely understood. The present paper reports five cases of patients with differentiated thyroid cancer who presented a mediastinum uptake of radioiodine in a whole-body scan during follow-up. The patients had either histological or radiological confirmation of the presence of residual thymus gland. It is very important to know about the possibility of iodine uptake by the thymus in order to avoid unnecessary treatment, such as surgery or radioiodine therapy. (author)

  6. Mucoepidermoid carcinoma misdiagnosed as palatal odontogenic infection: an overview on the differential diagnosis of palatal lesions.

    Science.gov (United States)

    Brajdić, Davor; Virag, Mihajlo; Manojlović, Spomenka; Luksić, Ivica; Franćeski, Dalibor; Biocić, Josip; Bosan-Kilibarda, Ingrid; Zajc, Ivan; Macan, Darko

    2010-12-01

    Mucoepidermoid carcinoma (MEC) accounts for approximately 30% of malignant salivary gland tumors and approximately 30% occur in minor salivary glands. The palate is the most frequent localization for those arising in minor glands. A 33-year-old male patient with MEC of the hard palate was treated as an acute odontogenic infection, which was not cured after tooth endodontic treatments, repeated incisions and antibiotics. On the hard palate ovoid, a hard painless mass, which had not extended over the middle palatal line, was observed. Partial maxillectomy was performed. A review of the literature was performed in order to provide a coherent overview on the differential diagnosis of palatal lesions. To the best of authors' knowledge, this is the first report in English literature describing palatal MEC misdiagnosed and treated as odontogenic infection. Considering the extensive list of MEC's differential diagnoses on the hard palate, acute odontogenic infection can now be added to that list.

  7. Carcinomas neuroendocrinos de colon y recto: Experiencia de una unidad en seis años Neuroendocrine carcinomas of the colon and rectum: A unit's experience over six years

    Directory of Open Access Journals (Sweden)

    R. Vilallonga

    2008-01-01

    Full Text Available Introducción: los tumores neuroendocrinos de colon y recto son poco frecuentes. Suelen ser tumores poco diferenciados, diagnosticados por el patólogo y de especial agresividad en su comportamiento clínico. El pronóstico suele ser malo, con tendencia a la rápida metastatización. Material y métodos: se ha revisado la experiencia de una Unidad de Coloproctología durante un periodo de seis años. Se han revisado de manera retrospectiva los pacientes con un tumor de estirpe neuroendocrina. Se han excluido los tumores carcinoides. Resultados: durante este periodo, se han intervenido 2.155 pacientes por cáncer de colon y recto y se han hallado cinco pacientes con tumores neuroendocrinos. La edad media fue de 66 años, tres varones y dos hembras. Se localizaron uno en ciego, dos en recto y dos en sigma. Dos pacientes presentaban diseminación del tumor a distancia. Se realizó cirugía en todos los pacientes con quimioterapia posterior en dos de ellos. Un paciente falleció por insuficiencia hepática postoperatoria, otro a los dos meses y otro al año. Dos pacientes siguen vivos con un seguimiento medio de ocho meses. Conclusiones: los tumores neuroendocrinos son unos tumores de aparición rara en el colon y recto. La clínica de presentación no difiere de la que podrían tener los adenocarcinomas. En el momento del diagnóstico estos tumores suelen presentar enfermedad a distancia, como en dos de los cinco casos presentados, relacionándose con un mal pronóstico para el enfermo. El tratamiento quirúrgico y quimioterápico combinado es el que puede alargar más la supervivencia de los pacientes.Introduction: neuroendocrine tumours of the colon and rectum are infrequent. They are usually undifferentiated, easy to diagnose for the pathologist and are especially aggressive in their clinical behaviour. Prognosis is usually poor and they have a high tendency to metastase early. Material and methods: we have reviewed our experience in a

  8. WHO Grade 2 Neuroendocrine Tumor in a 15-Year-Old Male: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Eric Johannesen

    2014-01-01

    Full Text Available Neuroendocrine tumors, distinguished from adenocarcinomas by their neuroendocrine differentiation, are the most common pediatric epithelial malignancy that most often occurs in the appendix. In 2010, the WHO classified neuroendocrine neoplasms into three grades based on morphology, mitotic count, and Ki67 proliferation index. A 15-year-old male with a history of anemia and failure to thrive was diagnosed with a well-differentiated neuroendocrine tumor in the jejunum that invaded into the subserosal soft tissue and metastasized to four lymph nodes. Pediatric neuroendocrine tumors frequently arise within hereditary tumor syndromes with pancreatic neuroendocrine tumors being the most common. Several studies also indicate an elevated risk of small intestinal neuroendocrine tumors in which children born to a parent with a history of neuroendocrine tumors in the small intestine have a significant increased risk of developing one.

  9. [Small cell bladder carcinoma in age extremes: Report of two cases.

    Science.gov (United States)

    Vallejo-Benítez, Ana; Rodríguez-Zarco, Enrique; Pabón-Carrasco, Sara; Espinal, Paula Sofía

    2018-03-01

    We report 2 cases of small cell neuroendocrine carcinomas (CCP) of the urinary bladder in patients aged 37 and 80 years. CCP is a malignancy with poor prognosis. We review the literature, under the current WHO classification (2016). Paraffin blocks were cut for HE staining and immunohistochemistry to analyze the expression of neuroendocrine differentiation. The main diagnosis was based on histopathologic features, which revealed a diffuse growth pattern of small cells with scant cytoplasm and hyperchromatic nuclei. The result of the additional technical immunoreaction was positive for synaptophysin and CD56. Our cases have been reviewed with the literature to discuss the evolution and differential diagnosis of small cell carcinoma of the urinary bladder. This is a rare tumor with very aggressive behavior and its diagnosis lies in its morphology, and immunohistochemical profile.

  10. Focal Bronchiectasis Causing Abnormal Pulmonary Radioiodine Uptake in a Patient with Well-Differentiated Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Ash Gargya

    2012-01-01

    Full Text Available Background. False-positive pulmonary radioactive iodine uptake in the followup of differentiated thyroid carcinoma has been reported in patients with certain respiratory conditions. Patient Findings. We describe a case of well-differentiated papillary thyroid carcinoma treated by total thyroidectomy and radioiodine ablation therapy. Postablation radioiodine whole body scan and subsequent diagnostic radioiodine whole body scans have shown persistent uptake in the left hemithorax despite an undetectable stimulated serum thyroglobulin in the absence of interfering thyroglobulin antibodies. Contrast-enhanced chest computed tomography has confirmed that the abnormal pulmonary radioiodine uptake correlates with focal bronchiectasis. Summary. Bronchiectasis can cause abnormal chest radioactive iodine uptake in the followup of differentiated thyroid carcinoma. Conclusions. Recognition of potential false-positive chest radioactive iodine uptake, simulating pulmonary metastases, is needed to avoid unnecessary exposure to further radiation from repeated therapeutic doses of radioactive iodine.

  11. Assessment of female fertility and carconogenesis after iodine-131 therapy for differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dottorini, M.E.; Lomuscio, G.; Mazzucchelli, L. [U.O. Medicina Nucleare, Buto Arsizio (Italy)] [and others

    1995-01-01

    The aim of this study was to evaluate female fertility, carcinogenic, and genetic effects after treatment with {sup 131}I of differentiated thyroid carcinoma. A total of 814 females of child-bearing age were studied. The fertility of 627 females who received {sup 131}I therapy was compared to 187 untreated females. Birth histories of the children born from these women were registered. The carcinogenic effect was evaluated by comparing the incidence of tumors in 730 patients treated with {sup 131}I with an internal control group, as well as with local population incidence. There was no significant difference in the fertility rate, birth weight and prematurity between the two groups. Only one case of a ventricular septal defect was observed in a child born to a woman treated with {sup 131}I. The overall standardized incidence ratio (SIR) of second tumors was 1.19 (95% CI: 0.76-1.77) in patients treated with {sup 131}I. An elevated SIR was registered for salivary gland tumors and melanoma. No case of leukemia was registered. The risk of long-term effects of {sup 131}I treatment of differentiated thyroid carcinoma is quite low. Iodine-131 may be safely used in treating cases with a high risk of recurrence. 35 refs., 7 tabs.

  12. Guidelines on radioiodine therapy for differentiated thyroid carcinoma. Impact on clinical practice

    International Nuclear Information System (INIS)

    Biermann, M.; Pixberg, M.K.; Schober, O.; Doerr, U.; Dietlein, M.; Schlemmer, H.; Grimm, J.; Zajic, T.; Nestle, U.; Ladner, S.; Sepehr-Rezai, S.; Rosenbaum, S.; Puskas, C.; Fostitsch, P.; Heinecke, A.; Schuck, A.; Willich, N.; Schmid, K.W.; Dralle, H.

    2005-01-01

    Aim: For the examination of the impact on clinical practice of the guidelines for differentiated thyroid carcinoma (DTC), treatment data from the ongoing multicenter study differentiated thyroid carcinoma (MSDS) were analyzed. Patients, methods: patients were randomized to adjuvant external beam radiotherapy (RTx) or no RTx in addition to standard therapy in TNM stages pT4 pNO/1/x MO/x (UICC, 5 th ed. 1997). All patients were to receive the same treatment regimen consisting of thyroidectomy, ablative radioiodine therapy (RIT), and a diagnostic 131 I whole-body scintigraphy (WBS) 3-4 months after RIT. Results: Of 339 eligible patients enrolled between January 2000 and March 2004, 273 could be analyzed. Guideline recommendations by the German Society for Nuclear Medicine from 1999 and 1992 were complied with within 28% and 82% with regard to the interval between surgery and RIT (4 vs. 4-6 weeks), in 33% and 84% with regard to 131 I activity for RIT (1-3 vs. 1-4 GBq; ±10%), and in 16% and 60% with regard to 131 I activity for WBS (100-300 vs. 100-400 MBq; ±10%). Conclusions: the 1999 guideline revision appears to have had little impact on clinical practice. Further follow-up will reveal if guideline compliance had an effect on outcomes. (orig.)

  13. Identifying the optimal gene and gene set in hepatocellular carcinoma based on differential expression and differential co-expression algorithm.

    Science.gov (United States)

    Dong, Li-Yang; Zhou, Wei-Zhong; Ni, Jun-Wei; Xiang, Wei; Hu, Wen-Hao; Yu, Chang; Li, Hai-Yan

    2017-02-01

    The objective of this study was to identify the optimal gene and gene set for hepatocellular carcinoma (HCC) utilizing differential expression and differential co-expression (DEDC) algorithm. The DEDC algorithm consisted of four parts: calculating differential expression (DE) by absolute t-value in t-statistics; computing differential co-expression (DC) based on Z-test; determining optimal thresholds on the basis of Chi-squared (χ2) maximization and the corresponding gene was the optimal gene; and evaluating functional relevance of genes categorized into different partitions to determine the optimal gene set with highest mean minimum functional information (FI) gain (Δ*G). The optimal thresholds divided genes into four partitions, high DE and high DC (HDE-HDC), high DE and low DC (HDE-LDC), low DE and high DC (LDE‑HDC), and low DE and low DC (LDE-LDC). In addition, the optimal gene was validated by conducting reverse transcription-polymerase chain reaction (RT-PCR) assay. The optimal threshold for DC and DE were 1.032 and 1.911, respectively. Using the optimal gene, the genes were divided into four partitions including: HDE-HDC (2,053 genes), HED-LDC (2,822 genes), LDE-HDC (2,622 genes), and LDE-LDC (6,169 genes). The optimal gene was microtubule‑associated protein RP/EB family member 1 (MAPRE1), and RT-PCR assay validated the significant difference between the HCC and normal state. The optimal gene set was nucleoside metabolic process (GO\\GO:0009116) with Δ*G = 18.681 and 24 HDE-HDC partitions in total. In conclusion, we successfully investigated the optimal gene, MAPRE1, and gene set, nucleoside metabolic process, which may be potential biomarkers for targeted therapy and provide significant insight for revealing the pathological mechanism underlying HCC.

  14. DMBT1 is frequently downregulated in well-differentiated gastric carcinoma but more frequently upregulated across various gastric cancer types

    DEFF Research Database (Denmark)

    Conde, Ana R; Martins, Ana P; Brito, Miguel

    2007-01-01

    Well-differentiated gastric carcinomas are considered to represent a distinct entity emerging via specific molecular changes different from those found in other gastric carcinoma types. The gene deleted in malignant brain tumours 1 (DMBT1) at 10q25.3-q26.1 codes for a protein presumably involved ...... preferentially take place in well-differentiated gastric carcinoma. However, an upregulation of DMBT1 expression is more frequently found across all gastric cancer types.......Well-differentiated gastric carcinomas are considered to represent a distinct entity emerging via specific molecular changes different from those found in other gastric carcinoma types. The gene deleted in malignant brain tumours 1 (DMBT1) at 10q25.3-q26.1 codes for a protein presumably involved...... in cell differentiation and protection and has been proposed as a candidate tumour suppressor for brain and epithelial cancer. One study reported a loss of DMBT1 expression in 12.5% (5/40) of gastric cancer samples. Here, we examined in more detail DMBT1 protein and mRNA expression in 78 primary gastric...

  15. Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum

    International Nuclear Information System (INIS)

    Gao, Hua-Jun; Chen, Ya-Jing; Zuo, Duo; Xiao, Ming-Ming; Li, Ying; Guo, Hua; Zhang, Ning; Chen, Rui-Bing

    2015-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Lectin affinity chromatography (LAC) was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography (LC) separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain (FGG), FOS-like antigen 2 (FOSL2), and α-1,6-mannosylglycoprotein 6-β-N-acetylglucosaminyltransferase B (MGAT5B) were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC

  16. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones

    NARCIS (Netherlands)

    F.R.E. Nobels (Frank); D.J. Kwekkeboom (Dirk Jan); W. Coopmans; C.H.H. Schoenmakers (Christian); J. Lindemans (Jan); E.P. Krenning (Eric); R. Bouillon (Roger); S.W.J. Lamberts (Steven); W.W. de Herder (Wouter)

    1997-01-01

    textabstractChromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other

  17. Prognostic indicators in well-differentiated thyroid carcinoma when controlling for stage and treatment.

    Science.gov (United States)

    Krook, Kaelyn A; Fedewa, Stacey A; Chen, Amy Y

    2015-04-01

    The incidence of thyroid carcinoma is rising. Few studies have examined patient characteristics that influence survival when adjusting for treatment and tumor stage/extent. Retrospective analysis was performed using the Surveillance Epidemiology and End Results registry data among patients diagnosed with well-differentiated thyroid (WDT) carcinoma during 1988-2009. Kaplan-Meir survival curves were used to estimate 5- and 10-year cause-specific and overall survival differences by sociodemographics, clinical characteristics, and treatment. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 83,985 patients were identified with WDT carcinoma. Blacks had higher hazard of death at 5 years (HR, 1.67; 95% CI, 1.42-1.96) and 10 years (HR, 1.57; 95% CI, 1.37-1.80) when compared to Caucasians, but there were no significant differences in cause-specific deaths. Hispanics had higher overall and cause-specific 5-year and 10-year hazard of death (5-year cause-specific: HR, 1.56; 95% CI, 1.23-1.99). Age was the most significant predictor of cause-specific and overall survival, with risk increasing in a nonlinear fashion. After age 45 years, the HR for 5- and 10-year cause-specific survival rose drastically, reaching an HR of 153 for individuals aged 85 years and older (HR, 153.45; 95% CI, 97.84-240.67). Age was the strongest factor associated with WDT cancer in our study. African Americans had worse overall survival, although only Hispanics had a significantly worse cause-specific survival. These factors should be taken into account in counseling patients and treatment planning. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Differentiated exophytic vulvar intraepithelial lesions are genetically distinct from keratinizing squamous cell carcinomas and contain mutations in PIK3CA.

    Science.gov (United States)

    Watkins, Jaclyn C; Howitt, Brooke E; Horowitz, Neil S; Ritterhouse, Lauren L; Dong, Fei; MacConaill, Laura E; Garcia, Elizabeth; Lindeman, Neal I; Lee, Larissa J; Berkowitz, Ross S; Nucci, Marisa R; Crum, Christopher P

    2017-03-01

    Human papillomavirus-negative keratinizing vulvar cancers typically harbor TP53 mutations as do their precursors, differentiated vulvar intraepithelial neoplasia. However, atypical verruciform proliferations are also associated with these malignancies and their pathogenesis is poorly understood. This study compared 11 atypical verruciform lesions, including atypical verruciform hyperplasia, vulvar acanthosis with altered differentiation, and verruciform lichen simplex chronicus, with 14 human papillomavirus-negative keratinizing squamous cell carcinomas. Extracted tissue DNA was subjected to targeted massively parallel sequencing of the exonic regions of 300 genes. Eight (73%) and six (55%) of eleven atypical verruciform lesions contained mutations in PIK3CA and ARID2, respectively. No TP53 mutations were identified. Eleven (79%) and five (36%) of fourteen keratinizing squamous cell carcinomas tested contained TP53 and CDKN2A mutations, respectively. Keratinizing squamous cell carcinomas displayed the majority of copy number variations with some variations (7p gain and 8p loss) shared by some cases in both groups. One patient developed atypical verruciform lesions with PIK3CA mutations followed by a keratinizing carcinoma with mutations in both PIK3CA and TP53. This study, for the first time segregates atypical verruciform lesions by virtue of a unique genotype (PIK3CA mutant/TP53 wild type) illustrating an example of progression to a TP53-mutated keratinizing carcinoma. The findings indicate that although PIK3CA mutations are found in signature, we propose the term 'differentiated exophytic vulvar intraepithelial lesion' for this group. Whether they function as direct precursors to a less common form of squamous cell carcinoma will require further study, but carcinomas associated with these lesions might warrant testing for PIK3CA mutations to address this question.

  19. Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents.

    Science.gov (United States)

    Iliadou, Paschalia K; Effraimidis, Grigoris; Konstantinos, Michalakis; Grigorios, Panagiotou; Mitsakis, Periklis; Patakiouta, Frideriki; Pazaitou-Panayiotou, Kalliopi

    2015-12-01

    The association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer is an interesting topic. The aim of the present study was to evaluate if demographic and histological characteristics as well as the long-term outcome of thyroid cancer was different in children and adolescents with and without CLT. The medical records of children and adolescents (≤21 years old) were reviewed. The following data were recorded: gender, year and age at diagnosis, family history of thyroid cancer, history of external radiation therapy, histological type (papillary and variants, follicular and variants), tumour size, multifocality, infiltration of thyroid parenchyma or surrounding soft tissues, vascular invasion, presence of lymph node and distant metastases. Information about the presence of TgAb and TPOAb was also collected. One hundred eight children and adolescents (median age 19.0, interquartile range 4.0 years) were diagnosed with differentiated thyroid carcinoma (DTC); 31 patients (28.7%) presented histological characteristics compatible with CLT. Infiltration of thyroid parenchyma was more frequent in patients with CLT compared to patients without (74.2% vs 48.1% respectively, P=0.024). Familial papillary thyroid carcinoma (PTC) was more frequent in patients with CLT compared to those without CLT (20.7% vs 2.8% respectively, P=0.009). There was no better outcome with respect to the presence of CLT or not. Children and adolescents with CLT present more frequently familial PTC as well as thyroid cancer with invasive characteristics. © 2015 European Society of Endocrinology.

  20. [Postoperative radioiodine ablation in patients with low risk differentiated thyroid carcinoma].

    Science.gov (United States)

    Díez, Juan J; Grande, Enrique; Iglesias, Pedro

    2015-01-06

    Most patients with newly diagnosed differentiated thyroid carcinoma have tumors with low risk of mortality and recurrence. Standard therapy has been total or near total thyroidectomy followed by postoperative radioiodine remnant ablation (RRA). Although RRA provides benefits, current clinical guidelines do not recommend it universally, since an increase in disease-free survival or a decrease in mortality in low risk patients has not been demonstrated so far. Advancements in our understanding of the biological behavior of thyroid cancer have been translated into the clinic in a personalized approach to the patients based on their individual risk of recurrence and mortality. Current evidence suggests that RRA is not indicated in most low-risk patients, especially those with papillary carcinomas smaller than 1cm, without extrathyroidal extension, unfavorable histology, lymph node involvement or distant metastases. Follow-up of these patients with serial measurements of serum thyroglobulin and neck ultrasound is adequate. Careful evaluation of all risk factors of clinical relevance will allow a more realistic assessment of each individual patient. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  1. Paracrine control of differentiation in the alveolar carcinoma, A549, by human foetal lung fibroblasts.

    Science.gov (United States)

    Speirs, V; Ray, K P; Freshney, R I

    1991-10-01

    Synthesis of pulmonary surfactant (PS) is necessary for normal functioning of the lungs and its production is indicative of normal differentiated lung. The human alveolar carcinoma, A549, has been found to synthesis and secrete PS in vitro. The purpose of this study was to optimise the culture conditions for PS synthesis by A549 as well as to determine the potential role of foetal lung fibroblasts in the induction of PS by glucocorticoids. A549 cells growing in filter wells produced higher levels of PS in response to steroid, a 5-fold increase on the filter well compared to only a 1.5-fold increase when the cells were cultured on a conventional plastic substrate. A549 cells grown in filter wells responded to coculture with fibroblasts whether in direct contact or separated co-culture. A 20-fold increase in PS over control values was observed in separated steroid-treated co-cultures, suggesting the presence of a diffusible factor. A partially purified factor was isolated from fibroblast conditioned medium which was capable of inducing differentiation and other phenotypic changes in A549, namely induction of PS, reduction of plasminogen activator activity and reduction in the in vivo growth of A549 xenografts in nude mice. These results suggest that, under the correct conditions, A549 cells, although transformed, still retain the capacity to respond to differentiation-inducing signals from normal fibroblasts.

  2. Control of treatment of differentiated thyroid carcinoma by measurement of thyroglobulin in serum

    International Nuclear Information System (INIS)

    Hagemann, J.; Schneider, C.

    1978-01-01

    The presence of thyroglobulin in serum of patients with differentiated thyroid carcinoma was studied by a specific radioimmunoassay. Seventy-three patients with thyroid carcinomata were examined, 16 of whom had pulmonary or skeletal metastase, 11 local metastases, and the others no metastases. Patients with generalized metastases had very high serum thyroglobulin concentrations while those with local metastases had slightly elevated or normal concentrations. Those with remaining thyroid tissue had mainly normal thyroglobulin levels and patients with neither metastases nor remaining thyroid tissue had undetectable serum thyroglobulin. In seven patients with metastases it was possible to observe the development of serum thyroglobulin after 131 I treatment. In all cases the serum thyroglobulin concentration paralleled the development of the clinical status. Elevated serum thyroglobulin was also found in benign thyroid diseases such as hyperthyroidism and endemic goitre. Measurement of thyroglobulin in serum is therefore of little value in differentiating between benign and malignant thyroid diseases, but it is a good method for the follow-up control of patients with differentiated thyroid carcinomata. Because normal thyroglobulin levels do not exclude local metastases, additional examinations are necessary if normal thyroglobulin levels are found. When thyroglobulin is undetectable, metastases can be excluded and the measurement of thyroglobulin in serum can replace all other methods in the follow-up control. (author)

  3. DMBT1 is frequently downregulated in well-differentiated gastric carcinoma but more frequently upregulated across various gastric cancer types

    DEFF Research Database (Denmark)

    Conde, Ana R; Martins, Ana P; Brito, Miguel

    2007-01-01

    in cell differentiation and protection and has been proposed as a candidate tumour suppressor for brain and epithelial cancer. One study reported a loss of DMBT1 expression in 12.5% (5/40) of gastric cancer samples. Here, we examined in more detail DMBT1 protein and mRNA expression in 78 primary gastric...... preferentially take place in well-differentiated gastric carcinoma. However, an upregulation of DMBT1 expression is more frequently found across all gastric cancer types....

  4. Testicular impact of the treatment with I-131 in patients with differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Chebel, G.; Gutierrez, S.; Fadel, A.; Suarez, S.; Levalle, O.

    2007-01-01

    Young patients carriers differentiated thyroid carcinoma (DTC) are treated with high doses of I-131 for much of his life with very good prognosis and projects with paternity. However, there is scarce information on the effect of radioiodine on the male gonad and their future fertility. This therapy may compromise on a temporary and / or definitively the role of the germinal cells. The testicular irradiation depends on the blood flow, the dose of I-131 administered and of the presence or absence of metastasis pelvic near to the gonads. A single dose of 100 mCi of I-131 throws an absorbed dose at gonadal level of 50-150 cGy. It has been reported that absorbed doses of 50 cGy can produce transitory decrease spermatogenesis and higher doses can also affect the function of the Leydig cells [es

  5. Thyroglobulin and other tumor markers in the follow-up of differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Reiners, C.; Becker, W.; Berger, P.; Eilles, C.; Gerhards, W.; Rendl, J.; Schaede, B.; Scheler, S.; Schneider, P.; Spiegel, W.

    1986-04-01

    The diagnostic value of thyroglobulin (hTg) serum measurements for the follow-up of papillary, follicular and oncocytic thyroid carcinoma has been re-evaluated after more than 6 years of clinical experience with this tumor marker in 370 cancer patients. The sensitivity of hTg RIA for the detection of metastases or recurrence amounts to 94%, provided that residual thyroid tissue has been totally ablated and that serum samples are drawn after withdrawal of thyroid hormone replacement. The I-131 scan may be replaced under certain conditions by hTg RIA which has proven a valid, reasonable and convenient diagnostic method for long time follow-up of differentiated thyroid cancer. The somewhat reduced sensitivity of hTg determinations under continued thyroid hormone medication can be tolerated, provided that a standardised follow-up protocol is used including clinical, sonographic and radiological investigations. (orig./TRV).

  6. Thyroglobulin and other tumor markers in the follow-up of differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Reiners, C.; Becker, W.; Berger, P.; Eilles, C.; Gerhards, W.; Rendl, J.; Schaede, B.; Scheler, S.; Schneider, P.; Spiegel, W.; Boerner, W.

    1986-01-01

    The diagnostic value of thyroglobulin (hTg) serum measurements for the follow-up of papillary, follicular and oncocytic thyroid carcinoma has been re-evaluated after more than 6 years of clinical experience with this tumor marker in 370 cancer patients. The sensitivity of hTg RIA for the detection of metastases or recurrence amounts to 94%, provided that residual thyroid tissue has been totally ablated and that serum samples are drawn after withdrawal of thyroid hormone replacement. The I-131 scan may be replaced under certain conditions by hTg RIA which has proven a valid, reasonable and convenient diagnostic method for long time follow-up of differentiated thyroid cancer. The somewhat reduced sensitivity of hTg determinations under continued thyroid hormone medication can be tolerated, provided that a standardised follow-up protocol is used including clinical, sonographic and radiological investigations. (orig./TRV) [de

  7. Axillary node metastasis from differentiated thyroid carcinoma with hürthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings

    International Nuclear Information System (INIS)

    Chiofalo, Maria Grazia; Losito, Nunzia Simona; Fulciniti, Franco; Setola, Sergio Venanzio; Tommaselli, Antonio; Marone, Ugo; Di Cecilia, Maria Luisa; Pezzullo, Luciano

    2012-01-01

    Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis. Here we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with 'signet ring cells' and Hürthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml. Currently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. 'Signet ring cell' is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare 'signet ring cells' carcinomas so far described

  8. Proteomic analysis reveals differential protein expression in variants of papillary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Yasemin Ucal

    2017-12-01

    Full Text Available Introduction: Fine Needle Aspiration Biopsy (FNAB allows the cytological differentiation of benign and malignant thyroid nodules. However, the method itself is not adequate in determining some cases. For example, the diagnosis of Follicular Variant Papillary Thyroid Carcinoma (FV-PTC can be challenging. In the current study we investigate the protein profiles of FV-PTC and classical variant PTC (CV-PTC with no lymph node metastasis and compare it with benign thyroid tissue. Method: We used CV-PTC (n = 6, FV-PTC (n = 6 and benign thyroid tissues (n = 6 to prepare tissue lysates. Proteins from each group were trypsin and lys-C digested. The samples were analyzed on a Q Exactive Orbitrap mass spectrometer. Results: We identified 2560 proteins across all 18 specimens. Protein profiles revealed that there was no clear distinction between benign and FV-PTC samples. However, further examination of our data showed that proteins in energy metabolism have altered in FV-PTC. Proteomic pathway analysis showed marked alteration of the actin cytoskeleton proteins, especially several members of Arp2/3 complex were significantly increased in CV-PTC. We made the novel observation that IQGAP1 protein was significantly increased in CV-PTC, whereas IQGAP2 protein was highly expressed in FV-PTC lesions, suggesting differential roles of IQGAP proteins in thyroid pathology. Conclusion: In the present study, mass spectrometry based label free quantification approach was applied to investigate the protein profiles of FV-PTC, CV-PTC and benign thyroid tissues. This study pointed out that actin cytoskeleton proteins, IQGAP proteins and changes in energy metabolism play predominant roles in thyroid pathology. Keywords: Papillary thyroid carcinoma, IQGAP, Proteomics, Mass spectrometry

  9. Multicenter study differentiated thyroid carcinoma (MSDS). Diminished acceptance of adjuvant external beam radiotherapy

    International Nuclear Information System (INIS)

    Biermann, M.; Pixberg, M.K.; Schober, O.; Schuck, A.; Willich, N.; Heinecke, A.; Koepke, W.; Schmid, K.W.; Dralle, H.

    2003-01-01

    Aim: The Multicenter Study Differentiated Thyroid Carcinoma (MSDS) is an ongoing study in Germany, Austria, and Switzerland on the clinical benefit of adjuvant external beam radiotherapy (RTx) for locally invasive differentiated thyroid carcinoma (DTC) in TNM stages pT4 pNO/1/xMO/x (5th ed. 1997). Methods: MSDS was designed as a prospective randomized trial. Patients receive thyroidectomy, radioiodine therapy (RIT) to ablate the thyroid remnant, and TSH-suppressive L-thyroxine therapy with or without RTx after documented elimination of cervical iodine-131 uptake (http://msds-studie.uni-muenster.de). Results: 311 patients were enrolled between January 2000 and March 2003. 279 patients met the trial's inclusion criteria. 45 consented to randomization, of whom 17 were randomized into treatment arm A (RTx) and 18 into arm B (no RTx). Advised by the trial's independent Data Monitoring and Safety Committee, the MSDS steering committee decided to terminate randomization in April 2003 and continue MSDS as a prospective cohort study. 23 of the 234 patients in the observation arm of the trial were prescribed RTx by their physicians. Thus, 14% of the trial cohort were randomized or assigned to receive RTx (intention-to-treat analysis). In contrast, at least 44% of all patients with pT4 papillary DTC in Germany in the nationwide PCES study underwent RTx in 1996 (p 2 -test). Conclusions: Acceptance of external beam RTx as a treatment modality for DTC has receded to a degree that accrual of a sufficient number of patients for a randomized trial has been impossible. Observation of the trial cohort is continued in order to assess clinical event rates with and without RTx and chronic RTx toxicity. (orig.) [de

  10. Differential Expression of Sonic Hedgehog Protein in Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

    Science.gov (United States)

    Al-Bahrani, Redha; Nagamori, Seishi; Leng, Roger; Petryk, Anna; Sergi, Consolato

    2015-09-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA) are the two most common primary liver malignancies in adult patients. The molecular mechanisms underlying the pathogenesis of HCC and CCA are still poorly understood. Sonic hedgehog (SHH) signaling plays an essential role during mammalian development, i.e., promoting organ growth, tissue differentiation, and cell polarity. The upregulation of SHH has been observed during carcinogenesis, including colorectal carcinoma. Our aim was to investigate the expression pattern of SHH in HCC and CCA. We investigated 40 malignant tumors of the liver, including 21 HCC and 19 of intrahepatic CCA cases by immunohistochemistry (IHC) using a polyclonal antibody against SHH and Avidin-Biotin Complex method. We also investigated the co-localization of SHH and Bone morphogenetic protein 4 (BMP4) in CCA using indirect double IHC. Moreover, we examined whether SHH is expressed in two HCC cell lines HepG2 and HuH-7 and three CCA cell lines OZ, HuCCT1 and HuH28. We found that SHH was expressed in 15 out of 21 cases (71.4 %) of HCC and 100 % of CCA cases by immunohistochemistry. SHH expression showed a positive trend in liver tumors (HCC, CCA) with high grade (G2-G3). SHH localized to the epithelial cells, while BMP4 was expressed in the stromal cells in CCA by double IHC. However, both HCC and CCA cell lines showed SHH expression by Western blot analysis. In conclusion, SHH seems to be an interesting marker of de-differentiation in liver tumors and the simultaneous epithelial-mesenchymal expression may be an intriguing prompt to investigate cross-talks between SHH and BMP4.

  11. GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ...

    African Journals Online (AJOL)

    Pavel M.E., Baum U., Hahn E.G., Hensen J. Doxorubucin and streptozocin after failed biotherapy of Neuroendocrine tumors. Int J. Gastrointest Cancer 2005; 35 179-185. 33. Yao J.C., Phan A., Hoff P.M., et al. Targeting vas- cular endothelial growth factor in advanced carci- noid tumors: a random assignment phase II study.

  12. Neuroendocrine-immune interaction

    NARCIS (Netherlands)

    Kemenade, van Lidy; Cohen, Nicholas; Chadzinska, Magdalena

    2017-01-01

    It has now become accepted that the immune system and neuroendocrine system form an integrated part of our physiology. Immunological defense mechanisms act in concert with physiological processes like growth and reproduction, energy intake and metabolism, as well as neuronal development. Not only

  13. Different gene-expression profiles for the poorly differentiated carcinoma and the highly differentiated papillary adenocarcinoma in mammary glands support distinct metabolic pathways

    Directory of Open Access Journals (Sweden)

    Barash Itamar

    2008-09-01

    Full Text Available Abstract Background Deregulation of Stat5 in the mammary gland of transgenic mice causes tumorigenesis. Poorly differentiated carcinoma and highly differentiated papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate the cellular processes and metabolic pathways utilized to preserve these phenotypes, gene-expression profiles were analyzed. Methods Mammary tumors were excised from transgenic mice carrying a constitutively active variant of Stat5, or a Stat5 variant lacking s transactivation domain. These tumors displayed either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared from each tumor were hybridized to an Affymetrix GeneChip® Mouse Genome 430A 2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway analysis were performed to distinct the two types of tumors. Histopathology and immunofluorescence staining complemented the comparison between the tumor phenotypes. Results The nucleus-cytoskeleton-plasma membrane axis is a major target for differential gene expression between phenotypes. In the carcinoma, stronger expression of genes coding for specific integrins, cytoskeletal proteins and calcium-binding proteins highlight cell-adhesion and motility features of the tumor cells. This is supported by the higher expression of genes involved in O-glycan synthesis, TGF-β, activin, their receptors and Smad3, as well as the Notch ligands and members of the γ-secretase complex that enable Notch nuclear localization. The Wnt pathway was also a target for differential gene expression. Higher expression of genes encoding the degradation complex of the canonical pathway and limited TCF expression in the papillary adenocarcinoma result in membranal accumulation of β-catenin, in contrast to its nuclear translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and response to DNA damage were more highly expressed in the papillary adenocarcinomas, as opposed to

  14. Different gene-expression profiles for the poorly differentiated carcinoma and the highly differentiated papillary adenocarcinoma in mammary glands support distinct metabolic pathways

    International Nuclear Information System (INIS)

    Eilon, Tali; Barash, Itamar

    2008-01-01

    Deregulation of Stat5 in the mammary gland of transgenic mice causes tumorigenesis. Poorly differentiated carcinoma and highly differentiated papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate the cellular processes and metabolic pathways utilized to preserve these phenotypes, gene-expression profiles were analyzed. Mammary tumors were excised from transgenic mice carrying a constitutively active variant of Stat5, or a Stat5 variant lacking s transactivation domain. These tumors displayed either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared from each tumor were hybridized to an Affymetrix GeneChip ® Mouse Genome 430A 2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway analysis were performed to distinct the two types of tumors. Histopathology and immunofluorescence staining complemented the comparison between the tumor phenotypes. The nucleus-cytoskeleton-plasma membrane axis is a major target for differential gene expression between phenotypes. In the carcinoma, stronger expression of genes coding for specific integrins, cytoskeletal proteins and calcium-binding proteins highlight cell-adhesion and motility features of the tumor cells. This is supported by the higher expression of genes involved in O-glycan synthesis, TGF-β, activin, their receptors and Smad3, as well as the Notch ligands and members of the γ-secretase complex that enable Notch nuclear localization. The Wnt pathway was also a target for differential gene expression. Higher expression of genes encoding the degradation complex of the canonical pathway and limited TCF expression in the papillary adenocarcinoma result in membranal accumulation of β-catenin, in contrast to its nuclear translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and response to DNA damage were more highly expressed in the papillary adenocarcinomas, as opposed to favored G2/M regulation in the carcinoma tumors. At least

  15. Quantification of epithelial cell differentiation in mammary glands and carcinomas from DMBA- and MNU-exposed rats.

    Directory of Open Access Journals (Sweden)

    Deepak Sharma

    Full Text Available Rat mammary carcinogenesis models have been used extensively to study breast cancer initiation, progression, prevention, and intervention. Nevertheless, quantitative molecular data on epithelial cell differentiation in mammary glands of untreated and carcinogen-exposed rats is limited. Here, we describe the characterization of rat mammary epithelial cells (RMECs by multicolor flow cytometry using antibodies against cell surface proteins CD24, CD29, CD31, CD45, CD49f, CD61, Peanut Lectin, and Thy-1, intracellular proteins CK14, CK19, and FAK, along with phalloidin and Hoechst staining. We identified the luminal and basal/myoepithelial populations and actively dividing RMECs. In inbred rats susceptible to mammary carcinoma development, we quantified the changes in differentiation of the RMEC populations at 1, 2, and 4 weeks after exposure to mammary carcinogens DMBA and MNU. DMBA exposure did not alter the percentage of basal or luminal cells, but upregulated CD49f (Integrin α6 expression and increased cell cycle activity. MNU exposure resulted in a temporary disruption of the luminal/basal ratio and no CD49f upregulation. When comparing DMBA- or MNU-induced mammary carcinomas, the RMEC differentiation profiles are indistinguishable. The carcinomas compared with mammary glands from untreated rats, showed upregulation of CD29 (Integrin β1 and CD49f expression, increased FAK (focal adhesion kinase activation especially in the CD29hi population, and decreased CD61 (Integrin β3 expression. This study provides quantitative insight into the protein expression phenotypes underlying RMEC differentiation. The results highlight distinct RMEC differentiation etiologies of DMBA and MNU exposure, while the resulting carcinomas have similar RMEC differentiation profiles. The methodology and data will enhance rat mammary carcinogenesis models in the study of the role of epithelial cell differentiation in breast cancer.

  16. Staging of gastroenteropancreatic neuroendocrine tumors: how we do it based on an evidence-based approach.

    LENUS (Irish Health Repository)

    McDermott, Shaunagh

    2013-01-01

    In contrast to other common types of malignant tumors, the vast majority of gastroenteropancreatic neuroendocrine tumors are well differentiated and slowly growing with only a minority showing aggressive behavior. It is important to accurately stage patients radiologically so the correct treatment can be implemented and to improve prognosis. In this article, we critically appraise the current literature in an effort to establish the current role of radiologic imaging in the staging of neuroendocrine tumors. We also discuss our protocol for staging neuroendocrine tumors.

  17. A massive hepatic tumor demonstrating hepatocellular, cholangiocarcinoma and neuroendocrine lineages: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Rachel E. Beard

    2017-01-01

    Conclusion: This is one of the only reports of a hepatic tumor arising from hepatocellular carcinoma, cholangiocarcinoma and neuroendocrine lineages. Increased awareness of this tumor type may optimize improve future management.

  18. Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells

    Science.gov (United States)

    Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

    2015-01-01

    Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased γ-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity.Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively

  19. The Contrasting Role of p16Ink4A Patterns of Expression in Neuroendocrine and Non-Neuroendocrine Lung Tumors: A Comprehensive Analysis with Clinicopathologic and Molecular Correlations.

    Directory of Open Access Journals (Sweden)

    Nicola Fusco

    Full Text Available Lung cancer encompasses a constellation of malignancies with no validated prognostic markers. p16Ink4A expression has been reported in different subtypes of lung cancers; however, its prognostic value is controversial. Here, we sought to investigate the clinical significance of p16Ink4A immunoexpression according to specific staining patterns and its operational implications. A total of 502 tumors, including 277 adenocarcinomas, 84 squamous cell carcinomas, 22 large cell carcinomas, 47 typical carcinoids, 12 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 32 small cell carcinomas were reviewed and subjected to immunohistochemical analysis for p16Ink4A and Ki67. The spectrum of p16Ink4A expression was annotated for each case as negative, sporadic, focal, or diffuse. Expression at immunohistochemical level showed intra-tumor homogeneity, regardless tumor histotype. Enrichments in cells expressing p16Ink4A were observed from lower- to higher-grade neuroendocrine malignancies, whereas a decrease was seen in poorly and undifferentiated non-neuroendocrine carcinomas. Tumor proliferation indices were higher in neuroendocrine tumors expressing p16Ink4A while non-neuroendocrine malignancies immunoreactive for p16Ink4A showed a decrease in Ki67-positive cells. Quantitative statistical analyses including each histotype and the p16Ink4A status confirmed the independent prognostic role of p16Ink4A expression, being a high-risk indicator in neuroendocrine tumors and a marker of good prognosis in non-neuroendocrine lung malignancies. In this study, we provide circumstantial evidence to suggest that the routinary assessment of p16Ink4A expression using a three-tiered scoring algorithm, even in a small biopsy, may constitute a reliable, reproducible, and cost-effective substrate for a more accurate risk stratification of each individual patient.

  20. Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ionta, M. [Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas MG (Brazil); Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Rosa, M.C.; Almeida, R.B.; Freitas, V.M.; Rezende-Teixeira, P.; Machado-Santelli, G.M. [Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil)

    2012-05-25

    Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3β) and liver differentiation [E-cadherin, connexin 26 (Cx26), and connexin 32 (Cx32)]. RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3β (inactive form) expression while the expression of Cx43, Tyr216-GSK-3β (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.

  1. SPIO-Enhanced MRI Findings of Well-Differentiated Hepatocellular Carcinomas: Correlation with MDCT Findings

    International Nuclear Information System (INIS)

    Kim, Seong Hyun; Lee, Won Jae; Lim, Hyo K.; Park, Cheol Keun

    2009-01-01

    This study was designed to assess superparamagnetic iron oxide (SPIO)-enhanced MRI findings of well-differentiated hepatocellular carcinomas (HCCs) correlated with their multidetector-row CT (MDCT) findings. Seventy-two patients with 84 pathologically proven well-differentiated HCCs underwent triple-phase MDCT and SPIO-enhanced MRI at a magnetic field strength of 1.5 Tesla (n = 49) and 3.0 Tesla (n = 23). Two radiologists in consensus retrospectively reviewed the CT and MR images for attenuation value and the signal intensity of each tumor. The proportion of hyperintense HCCs as depicted on SPIO-enhanced T2- or T2*-weighted images were compared in terms of tumor size ( 1 cm), five CT attenuation patterns based on arterial and equilibrium phases and magnetic field strength, by the use of univariate and multivariate analyses. Seventy-eight (93%) and 71 (85%) HCCs were identified by CT and on SPIO-enhanced T2- and T2*-weighted images, respectively. For the CT attenuation pattern, one (14%) of seven isodense-isodense, four (67%) of six hypodense- hypodense, four (80%) of five isodense-hypodense, 14 (88%) of 16 hyperdense- isodense and 48 (96%) of 50 hyperdense-hypodense HCCs were hyperintense (Cochran-Armitage test for trend, p 0.05). Most well-differentiated HCCs show hyperintensity on SPIOenhanced MRI, although the lesions show various CT attenuation patterns. The CT attenuation pattern is the main factor that affects the proportion of hyperintense well-differentiated HCCs as depicted on SPIO-enhanced MRI

  2. Development of the Neuroendocrine Hypothalamus.

    Science.gov (United States)

    Burbridge, Sarah; Stewart, Iain; Placzek, Marysia

    2016-03-15

    The neuroendocrine hypothalamus is composed of the tuberal and anterodorsal hypothalamus, together with the median eminence/neurohypophysis. It centrally governs wide-ranging physiological processes, including homeostasis of energy balance, circadian rhythms and stress responses, as well as growth and reproductive behaviours. Homeostasis is maintained by integrating sensory inputs and effecting responses via autonomic, endocrine and behavioural outputs, over diverse time-scales and throughout the lifecourse of an individual. Here, we summarize studies that begin to reveal how different territories and cell types within the neuroendocrine hypothalamus are assembled in an integrated manner to enable function, thus supporting the organism's ability to survive and thrive. We discuss how signaling pathways and transcription factors dictate the appearance and regionalization of the hypothalamic primordium, the maintenance of progenitor cells, and their specification and differentiation into neurons. We comment on recent studies that harness such programmes for the directed differentiation of human ES/iPS cells. We summarize how developmental plasticity is maintained even into adulthood and how integration between the hypothalamus and peripheral body is established in the median eminence and neurohypophysis. Analysis of model organisms, including mouse, chick and zebrafish, provides a picture of how complex, yet elegantly coordinated, developmental programmes build glial and neuronal cells around the third ventricle of the brain. Such conserved processes enable the hypothalamus to mediate its function as a central integrating and response-control mediator for the homeostatic processes that are critical to life. Early indications suggest that deregulation of these events may underlie multifaceted pathological conditions and dysfunctional physiology in humans, such as obesity. Copyright © 2016 John Wiley & Sons, Inc.

  3. [Contemporary nuclear medicine diagnostics of neuroendocrine tumors].

    Science.gov (United States)

    2015-01-01

    The new positron emission tomography (PET/CT) methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1) somatostatin analogues labeled with indium-111 (111In-pentetreotide) or technetium-99m (99mTc-EDDA/HYNIC-TOC); 2) noradrenaline analogue labeled with iodine-131 or -123 (131/123I-MIBG); or 3) 99mTc(V)-DMSA. Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor imaging, after intravenous injection of pharmaceuticals labeled with positron emitters [fluorine-18 (18F), galium-68 (68Ga), or carbon-11 (11C)]: 1) glucose analogue (18FDG); 2) somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga-DOTANOC); 3) aminoacid precursors of bioamines: [a) dopamine precursor 18F-DOPA (6-18F-dihydroxyphenylalanine), b) serotonin precursor 11C-5HTP (11C-5-hydroxytryptophan)]; or 4) dopamine analogue 18F-DA (6-18F-fluorodopamine). Conventional and contemporary (PET/ CT) somatostatin receptor detection showed identical high spe- cificity (92%), but conventional had very low sensitivity (52%) compared to PET/CT (97%). It means that almost every second neuroendocrine tumor detected by contemporary method cannot be discovered using conventional (classic) method. In metastatic pheochromocytoma detection contemporary (PET/ CT) methods (18F-DOPA and 18F-DA) have higher sensitivity than conventional (131I/123I-MIBG). In medullary thyroid carcinoma diagnostics contemporary method ([18F-DOPA) is more sensitive than conventional 99mTc(V)-DMSA method, and is similar to 18FDG, computed tomography and magnetic resonance. In carcinoid detection contemporary method (18F-DOPA) shows similar results with contemporary somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine tumors it is worse. To conclude, contemporary (PET

  4. Assessment of Semiquantitative Parameters of Dynamic Contrast-Enhanced Perfusion MR Imaging in Differentiation of Subtypes of Renal Cell Carcinoma

    International Nuclear Information System (INIS)

    Abdel Razek, Ahmed Abdel Khalek; Mousa, Amani; Farouk, Ahmed; Nabil, Nancy

    2016-01-01

    To assess semiquantitative parameters of dynamic contrast-enhanced perfusion MR imaging (DCE) in differentiation of subtypes of renal cell carcinoma (RCC). Prospective study conducted upon 34 patients (27 M, 7 F, aged 25–72 ys: mean 45 ys) with RCC. Abdominal dynamic contrast-enhanced gradient-recalled echo MR sequence after administration of gadopentetate dimeglumine was obtained. The time signal intensity curve (TIC) of the lesion was created with calculation of enhancement ratio (ER), and washout ratio (WR). The subtypes of RCC were as follows: clear cell carcinomas (n=23), papillary carcinomas (n=6), and chromophobe carcinomas (n=5). The mean ER of clear cell, papillary and chromophobe RCC were 188±49.7, 35±8.9, and 120±41.6 respectively. The mean WR of clear cell, papillary and chromophobe RCCs were 28.6±6.8, 47.6±5.7 and 42.7±10, respectively. There was a significant difference in ER (P=0.001) and WR (P=0.001) between clear cell RCC and other subtypes of RCC. The threshold values of ER and WR used for differentiating clear cell RCC from other subtypes of RCC were 142 and 38 with areas under the curve of 0.937 and 0.895, respectively. We concluded that ER and WR are semiquantitative perfusion parameters useful in differentiation of clear cell RCC from chromophobe and papillary RCCs

  5. Differentiation between autoimmune pancreatitis and pancreatic carcinoma based on endoscopic retrograde cholangiopancreatography findings

    International Nuclear Information System (INIS)

    Nishino, Takayoshi; Oyama, Hiroyasu; Shiratori, Keiko; Toki, Fumitake

    2010-01-01

    We have reviewed the endoscopic retrograde cholangiopancreatography (ERCP) images of patients with autoimmune pancreatitis (AIP) and pancreatic carcinoma (Pca) in an attempt to identify findings that would facilitate making a differential diagnosis between AIP and Pca. The study cohort consisted of 39 patients diagnosed with AIP and 62 patients diagnosed with Pca. The ERCP findings in the pancreatic duct and biliary tract were compared between the two groups. The ERCP images revealed that AIP patients had a higher prevalence of narrowing of the main pancreatic duct (MPD) for ≥3 cm of its length and a higher prevalence for the presence of side branches in the narrowed portion of the MPD than Pca patients (p 5 cm of its length and the presence of side branches. Among our patient cohort, the ERCP findings in terms of the length of the narrowed portion of the MPD, the presence of side branches, and maximal diameter of the upstream MPD enabled differential diagnosis between AIP and Pca in most of the cases. However, it must be borne in mind that some Pca patients have ERCP findings similar to those of AIP patients. (author)

  6. [Expression features of glypican-3 and its diagnostic and differential values in hepatocellular carcinoma].

    Science.gov (United States)

    Bian, Yin-zhu; Yao, Deng-fu; Zhang, Chong-guo; Li, Shan-shan; Wu, Wei; Dong, Zhi-zhen; Qiu, Li-wei; Yu, Dan-dan

    2011-04-01

    To investigate the expression features of glypican-3 (GPC-3) and its diagnostic and differential values in hepatocellular carcinoma (HCC). Rat hepatoma models were made and the dynamic expression features of GPC-3 protein and its gene were investigated by Western blotting and RT-PCR respectively. Liver specimens from 36 HCC patients were collected by self-control method and the expression and clinicopathological features of GPC-3 were analyzed by immunohistochemistry. Serum GPC-3 levels were quantitatively detected by ELISA and its efficiency for HCC diagnosis was evaluated in patients with liver diseases. The incidence of GPC-3 was 0% in control, 83.3% in degeneration, 100% in precancerosis and 100% in canceration during dynamic formation of rat hepatoma, respectively. The positive GPC-3 was brown granule- like staining localized in membrane and cytoplasm in human HCC. The GPC-3 positive rates were 80.6% in HCC, 41.7% in surrounding tissues and none in distal tissues (P differentiation grade or the number of tumor except of tumor size (Z = 2.941, P expression closely associated with HCC and might be useful for early diagnosis of HCC.

  7. Evaluation of hepatocellular carcinoma using SonoVue, a second generation ultrasound contrast agent: correlation with cellular differentiation.

    Science.gov (United States)

    Nicolau, Carlos; Catalá, Violeta; Vilana, Ramón; Gilabert, Rosa; Bianchi, Luis; Solé, Manel; Pagés, Mario; Brú, Concepció

    2004-06-01

    The appearance of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS) in the vascular phase is described and evaluated as to whether the enhancement pattern correlates with the degree of cellular differentiation. One hundred four HCCs were prospectively evaluated with CEUS using coherent-contrast imaging (CCI) and SonoVue with a low mechanical index (SonoVue revealed enhancement in the arterial phase in >95% of HCCs, with a few well-differentiated cases not being diagnosed due to the absence of enhancement. Echogenicity in the portal and late phases correlated with cellular differentiation.

  8. An immunohistochemical study of a carcinoma of the parotid gland exhibiting both ductal and acinic cell differentiation.

    Science.gov (United States)

    Smith, J A; Warhol, M J; Brodsky, G L

    1983-03-01

    A 76-year-old man underwent a subtotal parotidectomy for removal of a 3 cm. multicystic mass. The tumor was a salivary gland carcinoma, with both infiltrating and intraductal/intra-acinar components, exhibiting three histologic patterns: cribriform, papillary, and comedo-like. Immunohistochemical stain for keratin by the immunoperoxidase technique was strongly reactive in the vast majority of the tumor cells, indicating ductal differentiation of the tumor. Ultrastructural studies indicated primarily ductal differentiation of the tumor cells, with additional areas of acinous and myoepithelial differentiation.

  9. Basal Cell Carcinoma With Matrical Differentiation: Clinicopathologic, Immunohistochemical, and Molecular Biological Study of 22 Cases.

    Science.gov (United States)

    Kyrpychova, Liubov; Carr, Richard A; Martinek, Petr; Vanecek, Tomas; Perret, Raul; Chottová-Dvořáková, Magdalena; Zamecnik, Michal; Hadravsky, Ladislav; Michal, Michal; Kazakov, Dmitry V

    2017-06-01

    Basal cell carcinoma (BCC) with matrical differentiation is a fairly rare neoplasm, with about 30 cases documented mainly as isolated case reports. We studied a series of this neoplasm, including cases with an atypical matrical component, a hitherto unreported feature. Lesions coded as BCC with matrical differentiation were reviewed; 22 cases were included. Immunohistochemical studies were performed using antibodies against BerEp4, β-catenin, and epithelial membrane antigen (EMA). Molecular genetic studies using Ion AmpliSeq Cancer Hotspot Panel v2 by massively parallel sequencing on Ion Torrent PGM were performed in 2 cases with an atypical matrical component (1 was previously subjected to microdissection to sample the matrical and BCC areas separately). There were 13 male and 9 female patients, ranging in age from 41 to 89 years. Microscopically, all lesions manifested at least 2 components, a BCC area (follicular germinative differentiation) and areas with matrical differentiation. A BCC component dominated in 14 cases, whereas a matrical component dominated in 4 cases. Matrical differentiation was recognized as matrical/supramatrical cells (n=21), shadow cells (n=21), bright red trichohyaline granules (n=18), and blue-gray corneocytes (n=18). In 2 cases, matrical areas manifested cytologic atypia, and a third case exhibited an infiltrative growth pattern, with the tumor metastasizing to a lymph node. BerEP4 labeled the follicular germinative cells, whereas it was markedly reduced or negative in matrical areas. The reverse pattern was seen with β-catenin. EMA was negative in BCC areas but stained a proportion of matrical/supramatrical cells. Genetic studies revealed mutations of the following genes: CTNNB1, KIT, CDKN2A, TP53, SMAD4, ERBB4, and PTCH1, with some differences between the matrical and BCC components. It is concluded that matrical differentiation in BCC in most cases occurs as multiple foci. Rare neoplasms manifest atypia in the matrical areas

  10. Merkel cell carcinoma with an unusual immunohistochemical profile

    Directory of Open Access Journals (Sweden)

    L. Pilloni

    2009-12-01

    Full Text Available The clinical and morphological picture of Merkel cell carcinoma (MCC may be rather challenging; therefore, the immunohistochemical profile plays a relevant role in confirming the microscopic diagnosis. A panel of antibodies including cytokeratins 20, 7 and epithelial membrane antigen, and neuronspecific enolase is used in confirming the morphological diagnosis of MCC. The majority of MCCs express CK20 and are CK7-negative. Herein, we present a case of primary cutaneous neuroendocrine carcinoma with an atypical immunohistochemical pattern. A 83-years old woman presented with a painless plaque, red to violaceous in colour, located in the leg. The skin tumor was excided, formalin-fixed and paraffinembedded. Tissue sections were immunostained with a panel of antibodies routinely utilized in complex primary skin tumors for evidencing epithelial and neuroendocrine differentiation of tumor cells. The neuroendocrine differentiation of tumor cells was evidenced by their immunoreactivity for synaptophysin, chromograninA and neuron-specific enolase. Tumor cells also showed diffuse cytoplasmic staining for CK7. No immunoreactivity was detected for CK20 and thyroid transcription factor-1. Our data, together with previous rare reports of CK20-/CK7+ MCCs, lay stress on the importance of routinely utilizing a panel of antibodies in the differential diagnosis of complex primary carcinomas of the skin and may have important implications in expanding the differential diagnosis of skin tumors. In particular, caution should be taken in excluding the diagnosis of MCC only on the basis of the absence of reactivity of tumor cells for CK20, favouring the wrong diagnosis of less aggressive skin tumors.

  11. SPECTRUM OF NEUROENDOCRINE TUMOURS- A TERTIARY CARE CENTRE EXPERIENCE

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    Pasupuleti Prathima

    2016-11-01

    Full Text Available BACKGROUND Neuroendocrine tumours occur at various sites in the human body. They are considered as one of the close differentials for many tumours. Various benign and malignant tumours undergo neuroendocrine differentiation. Its incidence is slightly increasing due to advanced imaging modalities. Although rare, they can be seen in breast, gallbladder and skin. The aim of the study is to study the spectrum of neuroendocrine tumours from various sites, their clinical presentation, histomorphological features with immunohistochemistry and review of literature. MATERIALS AND METHODS This is a retrospective study for a period of 3 years (June 2013-June 2016. Surgical resection specimens were included in the study. Out of the total specimens received, 24 cases were of neuroendocrine tumours. Differential diagnosis of small round cell tumours also was considered and a panel of immunohistochemical markers were included to rule out them. Biopsy specimens were excluded from the study. RESULTS Out of the 24 cases, 18 cases were benign lesions. 6 cases were malignant lesions. Female preponderance was noted. Peak incidence was seen in 20-30 years of age group. CONCLUSION Neuroendocrine tumours can occur anywhere in the body and it should be considered in one of the differential diagnosis. Diagnosis must be accurately made.

  12. Dynamic expression patterns of differential proteins during early invasion of hepatocellular carcinoma.

    Science.gov (United States)

    Chen, Rong-Xin; Song, Hai-Yan; Dong, Yin-Ying; Hu, Chao; Zheng, Qiong-Dan; Xue, Tong-Chun; Liu, Xiao-Hui; Zhang, Yang; Chen, Jie; Ren, Zheng-Gang; Liu, Yin-Kun; Cui, Jie-Feng

    2014-01-01

    Tumor cell invasion into the surrounding matrix has been well documented as an early event of metastasis occurrence. However, the dynamic expression patterns of proteins during early invasion of hepatocellular carcinoma (HCC) are largely unknown. Using a three-dimensional HCC invasion culture model established previously, we investigated the dynamic expression patterns of identified proteins during early invasion of HCC. Highly metastatic MHCC97H cells and a liver tissue fragment were long-term co-cultured in a rotating wall vessel (RWV) bioreactor to simulate different pathological states of HCC invasion. The established spherical co-cultures were collected on days 0, 5, 10, and 15 for dynamic expression pattern analysis. Significantly different proteins among spheroids at different time points were screened and identified using quantitative proteomics of iTRAQ labeling coupled with LC-MS/MS. Dynamic expression patterns of differential proteins were further categorized by K-means clustering. The expression modes of several differentially expressed proteins were confirmed by Western blot and qRT-PCR. Time course analysis of invasion/metastasis gene expressions (MMP2, MMP7, MMP9, CD44, SPP1, CXCR4, CXCL12, and CDH1) showed remarkable, dynamic alterations during the invasion process of HCC. A total of 1,028 proteins were identified in spherical co-cultures collected at different time points by quantitative proteomics. Among these proteins, 529 common differential proteins related to HCC invasion were clustered into 25 types of expression patterns. Some proteins displayed significant dynamic alterations during the early invasion process of HCC, such as upregulation at the early invasion stage and downregulation at the late invasion stage (e.g., MAPRE1, PHB2, cathepsin D, etc.) or continuous upregulation during the entire invasion process (e.g., vitronectin, Met, clusterin, ICAM1, GSN, etc.). Dynamic expression patterns of candidate proteins during the early invasion

  13. Proteomic analysis of differentially expressed proteins in hepatitis B virus-related hepatocellular carcinoma tissues

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    Li Cui

    2009-08-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC, a major cause of cancer death in China, is preceded by chronic hepatitis and liver cirrhosis (LC. Although hepatitis B virus (HBV has been regarded as a clear etiology of human hepatocarcinogenesis, the mechanism is still needs to be further clarified. In this study, we used a proteomic approach to identify the differential expression protein profiles between HCC and the adjacent non-tumorous liver tissues. Methods Eighteen cases of HBV-related HCC including 12 cases of LC-developed HCC and 6 cases of chronic hepatitis B (CHB-developed HCC were analyzed by two-dimensional electrophoresis (2-DE combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS, and the results were compared to those of paired adjacent non-tumorous liver tissues. Results A total of 17 differentially expressed proteins with diverse biological functions were identified. Among these, 10 proteins were up-regulated, whereas the other 7 proteins were down-regulated in cancerous tissues. Two proteins, c-Jun N-terminal kinase 2 and ADP/ATP carrier protein were found to be up-regulated only in CHB-developed HCC tissues. Insulin-like growth factor binding protein 2 and Rho-GTPase-activating protein 4 were down-regulated in LC-developed and CHB-developed HCC tissues, respectively. Although 11 out of these 17 proteins have been already described by previous studies, or are already known to be involved in hepatocarcinogenesis, this study revealed 6 new proteins differentially expressed in HBV-related HCC. Conclusion These findings elucidate that there are common features between CHB-developed HCC and LC-developed HCC. The identified proteins are valuable for studying the hepatocarcinogenesis, and may be potential diagnostic markers or therapeutic targets for HBV-related HCC.

  14. Proteomic analysis of differentially expressed proteins in hepatitis B virus-related hepatocellular carcinoma tissues.

    Science.gov (United States)

    Li, Ning; Long, Yunzhu; Fan, Xuegong; Liu, Hongbo; Li, Cui; Chen, Lizhang; Wang, Zhiming

    2009-08-28

    Hepatocellular carcinoma (HCC), a major cause of cancer death in China, is preceded by chronic hepatitis and liver cirrhosis (LC). Although hepatitis B virus (HBV) has been regarded as a clear etiology of human hepatocarcinogenesis, the mechanism is still needs to be further clarified. In this study, we used a proteomic approach to identify the differential expression protein profiles between HCC and the adjacent non-tumorous liver tissues. Eighteen cases of HBV-related HCC including 12 cases of LC-developed HCC and 6 cases of chronic hepatitis B (CHB)-developed HCC were analyzed by two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), and the results were compared to those of paired adjacent non-tumorous liver tissues. A total of 17 differentially expressed proteins with diverse biological functions were identified. Among these, 10 proteins were up-regulated, whereas the other 7 proteins were down-regulated in cancerous tissues. Two proteins, c-Jun N-terminal kinase 2 and ADP/ATP carrier protein were found to be up-regulated only in CHB-developed HCC tissues. Insulin-like growth factor binding protein 2 and Rho-GTPase-activating protein 4 were down-regulated in LC-developed and CHB-developed HCC tissues, respectively. Although 11 out of these 17 proteins have been already described by previous studies, or are already known to be involved in hepatocarcinogenesis, this study revealed 6 new proteins differentially expressed in HBV-related HCC. These findings elucidate that there are common features between CHB-developed HCC and LC-developed HCC. The identified proteins are valuable for studying the hepatocarcinogenesis, and may be potential diagnostic markers or therapeutic targets for HBV-related HCC.

  15. Radiology of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Hako, R.; Hakova, H.; Gulova, I.

    2011-01-01

    Neuroendocrine tumors arise in the bronchopulmonary or gastrointestinal tract, but they can arise in almost any organ. The tumors have varied malignant potential depending on the site of their origin. Metastases may be present at the time of diagnosis, which often occurs at a late stage of the disease. Most NETs have nonspecific imaging characteristics. Imaging plays a pivotal role in the localization and staging of neuroendocrine tumors and in monitoring the treatment response. Imaging should involve multi-phase computed tomography, contrast material-enhanced magnetic resonance imaging, contrast-enhanced ultrasonography and other one. Hepatic metastatic disease in particular lends itself to a wide range of interventional treatment options. Transcatheter arterial embolization may be used alone or in combination with chemo embolization. Ablative techniques, hepatic cryotherapy and percutaneous ethanol injection may then be undertaken. A multidisciplinary approach to treatment and follow-up is important. (author)

  16. Thymic carcinoma

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    Vitória Homem Machado

    2016-10-01

    Full Text Available Thymic carcinomas are a heterogeneous group of aggressive, invasive epithelial malignancies. Their incidence is rare, occurring predominantly in middle-aged men. Here we present the typical imaging findings of a thymic carcinoma. The combination of imaging characteristics with tumor location and patient age provides a roadmap for approaching the differential diagnosis. Keywords: Thymus Gland; carcinoma; mediastinal neoplasms

  17. Loss of CDX2 Expression and Microsatellite Instability Are Prominent Features of Large Cell Minimally Differentiated Carcinomas of the Colon

    Science.gov (United States)

    Hinoi, Takao; Tani, Masachika; Lucas, Peter C.; Caca, Karel; Dunn, Rodney L.; Macri¶, Ettore; Loda¶, Massimo; Appelman, Henry D.; Cho, Kathleen R.; Fearon, Eric R.

    2001-01-01

    Most large bowel cancers are moderately to well-differentiated adenocarcinomas comprised chiefly or entirely of glands lined by tall columnar cells. We have identified a subset of poorly differentiated colon carcinomas with a distinctive histopathological appearance that we term large cell minimally differentiated carcinomas (LCMDCs). These tumors likely include a group of poorly differentiated carcinomas previously described by others as medullary adenocarcinomas. To better understand the pathogenesis of these uncommon neoplasms, we compared molecular features of 15 LCMDCs to those present in 25 differentiated adenocarcinomas (DACs) of the colon. Tumors were examined for alterations commonly seen in typical colorectal carcinomas, including increased p53 and β-catenin immunoreactivity, K-ras gene mutations, microsatellite instability, and loss of heterozygosity of markers on chromosomes 5q, 17p, and 18q. In addition, tumors were evaluated by immunohistochemistry for CDX2, a homeobox protein whose expression in normal adult tissues is restricted to intestinal and colonic epithelium. Markedly reduced or absent CDX2 expression was noted in 13 of 15 (87%) LCMDCs, whereas only 1 of the 25 (4%) DACs showed reduced CDX2 expression (P < 0.001). Nine of 15 (60%) LCMDCs had the high-frequency microsatellite instability phenotype, but only 2 of 25 (8%) DACs had the high-frequency microsatellite instability phenotype (P = 0.002). Our findings provide support for the hypothesis that the molecular pathogenesis of LCMDCs is distinct from that of most DACs. CDX2 alterations and DNA mismatch repair defects have particularly prominent roles in the development of LCMDCs. PMID:11733373

  18. Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe 1-Tyr 3-octreotide and chromogranin A assay in patients with neuroendocrine tumours.

    Science.gov (United States)

    Rodrigues, Margarida; Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Griesmacher, Andrea; Virgolini, Irene

    2008-10-01

    Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide ((111)In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p<0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p<0.05) in patients with PDNECs and tumours of hindgut origin. Overall, (111)In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.

  19. Neuroendocrine tumors and smoking

    Directory of Open Access Journals (Sweden)

    Tanja Miličević

    2016-12-01

    Full Text Available Neuroendocrine cells are dispersed around the body and can be found within the gastrointestinal system, lungs, larynx, thymus, thyroid, adrenal, gonads, skin and other tissues. These cells form the so-called ''diffuse neuroendocrine system'' and tumors arising from them are defined as neuroendocrine tumors (NETs. The traditional classification of NETs based on their embryonic origin includes foregut tumors (lung, thymus, stomach, pancreas and duodenum, midgut tumors (beyond the ligament of Treitz of the duodenum to the proximal transverse colon and hindgut tumors (distal colon and rectum. NETs at each site are biologically and clinically distinct from their counterparts at other sites. Symptoms in patients with early disease are often insidious in onset, leading to a delay in diagnosis. The majority of these tumors are thus diagnosed at a stage at which the only curative treatment, radical surgical intervention, is no longer an option. Due to the increasing incidence and mortality, many studies have been conducted in order to identify risk factors for the development of NETs. Still, little is known especially when it comes to preventable risk factors such as smoking. This review will focus on smoking and its contribution to the development of different subtypes of NETs.

  20. Neuroendocrine Role for VGF

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    Jo Edward Lewis

    2015-02-01

    Full Text Available The vgf gene (non-acronymic is highly conserved and was identified on the basis of its rapid induction in vitro by nerve growth factor, although can also be induced by brain derived neurotrophic factor, and glial derived growth factor. The VGF gene gives rise to a 68kDa precursor polypeptide which is induced robustly, relatively selectively and is synthesized exclusively in neuronal and neuroendocrine cells. Post-translational processing by neuroendocrine specific pro-hormone convertases in these cells results in the production of a number of smaller peptides. The VGF gene and peptides are widely expressed throughout the brain, particularly the hypothalamus and hippocampus, and in peripheral tissues including the pituitary gland, the adrenal glands and the pancreas, and in the gastrointestinal tract in both the myenteric plexus and in endocrine cells. VGF peptides have been associated with a number of neuroendocrine roles and in this mini-review we aim to describe these roles to highlight the importance of VGF as therapeutic target for a number of disorders, particularly those associated with energy metabolism, pain, reproduction and cognition.

  1. Neuroendocrine aspects of prostate oncogenesis

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    P.V. Glybochko

    2010-03-01

    Full Text Available The prostate cancer is a widespread disease in Russia with high growth rate and high death rate. Active work in discovery of methods of early diagnostics of prostate cancer is carrying out. it will allow to increase considerably the efficiency of treatment. the data on topography, structural and functional organization, physiology and regulatory effect of neuroendocrine cells and neuroendocrine hormones and peptides of prostate produced by neuroendocrine cells are presented in the review. Neuroendocrine mechanisms of development, prospects of early diagnostics and prognosis of prostate cancer are analyzed

  2. A predictive diagnostic model using multiparametric MRI for differentiating uterine carcinosarcoma from carcinoma of the uterine corpus.

    Science.gov (United States)

    Kamishima, Yuki; Takeuchi, Mitsuru; Kawai, Tatsuya; Kawaguchi, Takatsune; Yamaguchi, Ken; Takahashi, Naoki; Ito, Masato; Arakawa, Toshinao; Yamamoto, Akiko; Suzuki, Kazushi; Ogawa, Masaki; Takeuchi, Moe; Shibamoto, Yuta

    2017-08-01

    To construct a diagnostic model for differentiating carcinosarcoma from carcinoma of the uterus. Twenty-six patients with carcinosarcomas and 26 with uterine corpus carcinomas constituted a derivation cohort. The following nine MRI features of the tumors were evaluated: inhomogeneity, predominant signal intensity, presence of hyper- and hypointense areas, conspicuity of tumor margin, cervical canal extension on T2WI, presence of hyperintense areas on T1WI, contrast defect area volume percentage, and degree of enhancement. Two predictive models-with and without contrast-were constructed using multivariate logistic regression analysis. Fifteen other patients with carcinosarcomas and 30 patients with carcinomas constituted a validation cohort. The sensitivity and specificity of each model for the validation cohort were calculated. Inhomogeneity, predominant signal intensity on T2WI, and presence of hyperintense areas on T1WI were significant predictors in the unenhanced-MRI-based model. Presence of hyperintensity on T1WI, contrast defect area volume percentage, and degree of enhancement were significant predictors in the enhanced-MRI-based model. The sensitivity/specificity of unenhanced MRI were 87/73 and 87/70% according to reviewer 1 and 2, respectively. The sensitivity/specificity of the enhanced-MRI-based model were 87/70% according to both reviewers. Our diagnostic models can differentiate carcinosarcoma from carcinoma of the uterus with high sensitivity and moderate specificity.

  3. Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma

    NARCIS (Netherlands)

    van de Nieuwenhof, Hedwig P.; Bulten, Johan; Hollema, Harrie; Dommerholt, Rianne G.; Massuger, Leon F. A. G.; van der Zee, Ate G. J.; de Hullu, Joanne A.; van Kempen, Leon C. L. T.

    Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a

  4. Focus on Merkel cell carcinoma: diagnosis and staging

    Energy Technology Data Exchange (ETDEWEB)

    Grandhaye, Marion; Teixeira, Pedro Gondim; Blum, Alain [Imagerie Guilloz CHU de Nancy Hopital Central, Nancy (France); Henrot, Philippe [Service de Radiologie Institut de Cancerologie de Lorraine, Vandoeuvre les Nancy (France); Morel, Olivier [Medecine Nucleaire CHU Nancy Hopital Brabois, Vancoeuvre les Nancy (France); Sirveaux, Francois [Service de Chirurgie Centre chirurgical Emile Galle, Nancy (France); Verhaeghe, Jean-Luc [Service de Chirurgie Institut de Cancerologie de Lorraine, Vandoeuvre les Nancy (France)

    2015-06-01

    Merkel cell carcinoma is a rare lymphophilic skin tumor of neuroendocrine origin with the potential for rapid progression. Small, localized lesions are diagnosed and treated clinically, but advanced tumors often undergo imaging evaluation. Due to its rarity, radiologists are unaware of evocative imaging features and usually do not consider Merkel cell carcinoma in the differential diagnosis of soft tissue tumors. Appropriate staging is important to determine appropriate treatment and has an impact on patient prognosis. Multimodality imaging is usually needed, and there is no consensus on the optimal imaging strategy. The purpose of this article is to review various aspects of Merkel cell carcinoma imaging and look in detail at how optimal multimodality staging should be carried out. (orig.)

  5. [Endocrine mucin-producing sweat gland carcinoma. three case reports with a brief review of the literature].

    Science.gov (United States)

    Rütten, A; Mentzel, T; Requena, L

    2014-09-01

    Endocrine mucin-producing sweat gland carcinoma (EMPS) is a rare low-grade sweat gland carcinoma with an infiltrating growth pattern. It occurs mostly in women and shows a predilection for the periorbital region. Histopathologically, the tumor shows analogous features to endocrine ductal carcinoma/solid papillary carcinoma of the breast and shares some clinical and morphological similarities with primary mucinous carcinoma of the skin. The tumor is characterized by large monomorphous epithelial cells with little nuclear pleomorphism and only a few mitotic figures. The solid cystic tumor shows mucin-filled small cystic spaces, cribriform areas and expresses the neuroendocrine markers synaptophysin, chromogranin and neuron-specific enolase with varying staining intensities. The tumor cells are also positive for estrogen and progesterone receptors. We present three cases of this rare tumor with typical clinical, histopathological and immunohistochemical findings, give a short summary of the literature and discuss the most relevant differential diagnoses.

  6. Neuroendocrine tumors of the lung: major radiologic findings in a series of 22 histopathologically confirmed cases

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Marcel Koenigkam, E-mail: marcelk46@yahoo.com.br [Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (HCFMRP-USP), SP (Brazil); Department of Diagnostic and Interventional Radiology, Heidelberg University (Germany); Barreto, Andre Rodrigues Facanha [Clinica Radius, Clinica Sao Carlos Imagem and Santa Casa de Misericordia de Fortaleza, Fortaleza, CE (Brazil); Chagas Neto, Francisco Abaete [Program of Health Sciences Applied to the Locomotor System - Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRP-USP), Ribeirao Preto, SP (Brazil); Muglia, Valdair Francisco; Elias Junior, Jorge [Division of Radiology, Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRPUSP), Ribeirao Preto, SP (Brazil)

    2012-07-15

    Objective: To describe key imaging findings in a series of cases of primary neuroendocrine tumors of the lung (NTLs), with emphasis on computed tomography changes. Materials And Methods: Imaging studies of 22 patients (12 men, mean age 60 years) with histopathologically confirmed diagnosis, evaluated in the author's institution during the last five years were retrospectively reviewed by two radiologists, with findings being consensually described focusing on changes observed at computed tomography. Results: The authors have described five typical carcinoids, three atypical carcinoids, three large-cell neuroendocrine carcinomas (LCNCs), and 11 small-cell lung cancers (SCLCs). Only one typical carcinoid presented the characteristic appearance of central endobronchial nodule with distal pulmonary atelectasis, while the others were pulmonary nodules or masses. The atypical carcinoids corresponded to peripheral heterogeneous masses. One out of the three LCNCs was a peripheral homogeneous mass, while the others were ill-defined and heterogeneous. The 11 SCLCs corresponded to central, infiltrating and heterogeneous masses with secondary pleuropulmonary changes. Calcifications were absent both in LGNCs and SCLCs. Metastases were found initially and also at follow-up of all the cases of LCNCs and SCLCs. Conclusion: Although some imaging features may be similar, radiologic findings considered together with clinical information may play a relevant role in the differentiation of histological types of NTLs. (author)

  7. Recombinant TSH in follow-up and therapy of differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Luster, M.; Reiners, C.

    2000-01-01

    I-131-scintigraphy and serum thyroglobulin testing - if possible under stimulation of thyrotropin - are besides physical examination and ultrasonography crucial for the optimal follow-up of patients with well-differentiated thyroid carcinoma. This required physicians to withdraw patients from thyroid hormone suppression therapy (THST) for several weeks in order to raise endogenous TSH-levels. Clinical hypothyroidism often results in substantial patient discomfort, with sometimes major psychic alterations; the subsequent disability to work is occasionally an unpleasant consequence from an economical point of view. The temporary use of bovine, and for a short period of time human TSH is obsolete today because of a high risk of allergic reactions or the potential transmission of the Creutzfeldt-Jakob disease, respectively. Lately recombinant human TSH (rhTSH, Thyrogen trademark ), a hormone that was developed with the help of genetic engineering techniques, is available; its pharmacological safety has been demonstrated in previous phase-I/II-studies. The results of a phase-III-study showed in the majority of patients a marked rise in thyroglobulin levels after rhTSH. In all cases an adequate TSH level (>100 mU/l) was achieved after i.m. injection of recombinant TSH. Wholebody-scans showed a high level of accordance (>90%) in addition to a substantially lower background-activity. A tumour-background-ratio corresponding to conventional imaging could be demonstrated. (orig.) [de

  8. Side effects of rational dose iodine-131 therapy for metastatic well-differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Van Nostrand, D.; Neutze, J.; Atkins, F.

    1986-01-01

    Benua, Leeper, and others (BEL) have advocated the estimation of radiation exposure to the blood to select a more rational maximum safe dose of radioiodine (dosimetry) to treat metastatic functioning well-differentiated thyroid carcinoma. After adopting the BEL dosimetry approach, we reviewed the immediate (during hospitalization) and intermediate (from discharge up to 3 mo) side effects after our initial 15 therapies in ten patients. The doses ranged from 51 mCi (1887 MBq) to 450 mCi (16.65 GBq). Immediate side effects were observed in 12/15 (80%), are described in detail, and were as follows: gastrointestinal 10/15, salivary 9/15, nonsalivary neck pain, swelling, etc. 2/15, pulmonary 0/15. Intermediate side effects were observed in 10/15 (67%), are described in detail, and were as follows: gastrointestinal 0/15, salivary 3/15, nonsalivary neck pain, swelling, etc. 3/15, nasal complaints 2/15, transient bone marrow suppression 9/10, pulmonary 0/15. No patient required blood transfusions or had complications secondary to reduced blood counts. All patient complaints resolved; however, several patients may have reduced baseline blood counts one year after therapy. No other long-term side effect has been noted but the mean follow-up has been only 15 mo. In our opinion, we have not observed any side effect to date which would contraindicate the continued use and evaluation of the BEL dosimetry approach

  9. Side effects of rational dose iodine-131 therapy for metastatic well-differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Van Nostrand, D.; Neutze, J.; Atkins, F.

    1986-10-01

    Benua, Leeper, and others (BEL) have advocated the estimation of radiation exposure to the blood to select a more rational maximum safe dose of radioiodine (dosimetry) to treat metastatic functioning well-differentiated thyroid carcinoma. After adopting the BEL dosimetry approach, we reviewed the immediate (during hospitalization) and intermediate (from discharge up to 3 mo) side effects after our initial 15 therapies in ten patients. The doses ranged from 51 mCi (1887 MBq) to 450 mCi (16.65 GBq). Immediate side effects were observed in 12/15 (80%), are described in detail, and were as follows: gastrointestinal 10/15, salivary 9/15, nonsalivary neck pain, swelling, etc. 2/15, pulmonary 0/15. Intermediate side effects were observed in 10/15 (67%), are described in detail, and were as follows: gastrointestinal 0/15, salivary 3/15, nonsalivary neck pain, swelling, etc. 3/15, nasal complaints 2/15, transient bone marrow suppression 9/10, pulmonary 0/15. No patient required blood transfusions or had complications secondary to reduced blood counts. All patient complaints resolved; however, several patients may have reduced baseline blood counts one year after therapy. No other long-term side effect has been noted but the mean follow-up has been only 15 mo. In our opinion, we have not observed any side effect to date which would contraindicate the continued use and evaluation of the BEL dosimetry approach.

  10. Use of MRI in Differentiation of Papillary Renal Cell Carcinoma Subtypes: Qualitative and Quantitative Analysis.

    Science.gov (United States)

    Doshi, Ankur M; Ream, Justin M; Kierans, Andrea S; Bilbily, Matthew; Rusinek, Henry; Huang, William C; Chandarana, Hersh

    2016-03-01

    The purpose of this study was to determine whether qualitative and quantitative MRI feature analysis is useful for differentiating type 1 from type 2 papillary renal cell carcinoma (PRCC). This retrospective study included 21 type 1 and 17 type 2 PRCCs evaluated with preoperative MRI. Two radiologists independently evaluated various qualitative features, including signal intensity, heterogeneity, and margin. For the quantitative analysis, a radiology fellow and a medical student independently drew 3D volumes of interest over the entire tumor on T2-weighted HASTE images, apparent diffusion coefficient parametric maps, and nephrographic phase contrast-enhanced MR images to derive first-order texture metrics. Qualitative and quantitative features were compared between the groups. For both readers, qualitative features with greater frequency in type 2 PRCC included heterogeneous enhancement, indistinct margin, and T2 heterogeneity (all, p Quantitative analysis revealed that apparent diffusion coefficient, HASTE, and contrast-enhanced entropy were greater in type 2 PRCC (p quantitative and qualitative model had an AUC of 0.859. Qualitative features within the model had interreader concordance of 84-95%, and the quantitative data had intraclass coefficients of 0.873-0.961. Qualitative and quantitative features can help discriminate between type 1 and type 2 PRCC. Quantitative analysis may capture useful information that complements the qualitative appearance while benefiting from high interobserver agreement.

  11. CT, MRI, and FDG PET/CT findings of sinonasal sarcoma: Differentiation from squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kim, Jin Ho; Yoon, Dae Young; Baek, Sora; Park, Min Woo; Kwon, Kee Hwan; Rho, Young Soo

    2016-01-01

    To evaluate computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) findings for the differentiation of sinonasal sarcoma from squamous cell carcinoma (SCC). We retrospectively reviewed CT, MRI, and FDG PET/CT results in 20 patients with pathologically proven sinonasal sarcoma (n = 7) and SCC (n = 13). Imaging characteristics of tumors, such as the shape, size, margin, MRI signal intensity, pattern of enhancement, local tumor invasion, and maximum standardized uptake value (SUVmax) were analyzed and compared between sarcoma and SCC. The SUVmax of sarcomas (7.4 ± 2.1) was significantly lower than the SUVmax of the SCCs (14.3 ± 4.5) (p = 0.0013). However, no significant difference in the shape, size, margin, MRI signal intensity, pattern of enhancement, and local tumor invasion was observed between sarcoma and SCC. Although CT and MR imaging features are nonspecific, FDG PET/CT is useful in distinguishing between sinonasal sarcoma and SCC based on the SUVmax value

  12. Poorly differentiated endocrine carcinoma of the pancreas responded to gemcitabine: Case report

    Science.gov (United States)

    Nakazuru, Shoichi; Yoshio, Toshiyuki; Suemura, Shigeki; Itoh, Mari; Araki, Manabu; Yoshioka, Chiaki; Ohta, Makiyo; Sueyoshi, Yuka; Ohta, Takashi; Hasegawa, Hiroko; Morita, Kaori; Toyama, Takashi; Kuzushita, Noriyoshi; Kodama, Yoshinori; Mano, Masayuki; Mita, Eiji

    2010-01-01

    Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as third-line chemotherapy. After two cycles of gemcitabine (1000 mg/m2 on days 1, 8 and 15 every 4 wk), a partial tumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments. PMID:20698050

  13. Correlation between serum thyroglobulin levels and whole body scans in patients with differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Hristova, N.; Piperkova, E.; Sergieva, S.; Tsingilev, D.; Fanariotov, D.; Kirilova, B.; Dimitrova, M.

    1999-01-01

    Postoperative follow-up study of patients with differentiated thyroid carcinoma (DTC) is currently based on periodic whole body scan (WBS) and serum thyroglobulin (Tg) assessment. The correlation between Tg levels measured and WB scans of 84 DTC patients is investigated. WBS are performed on a rotation gamma camera DIACAM (Siemens) at 48 and 72 hours after per os administration of 185-222 MBq 131 I. The levels of Tg are determined by IRMA method and kits of BYK, Germany. Normal Tg values are obtained at a control group of 27 patients free of thyroid disease. Increased Tg levels are found at 2 cases (4%) of the group of 50 patients with total thyroidectomy given 131 I without any evidence of recurrences or metastases. At the third group consisting of 18 patients with total thyroidectomy, following 131 I therapy and recurrences and/or metastases, increased Tg values were obtained in 8 cases or 44.4%. Also increased Tg levels were obtained at 4 from 16 patients (25%) subjected to total thyroidectomy but with a residual thyroid tissue proved by scintigraphy. In conclusion, a combination of both methods should be applied for improving the diagnostic and therapeutic results at the postoperative control of DTC patients

  14. Thyroid Carcinoma Showing Thymic-Like Differentiation Causing Fracture of the Trachea

    Directory of Open Access Journals (Sweden)

    Aikaterini Marini

    2016-01-01

    Full Text Available Thyroid carcinoma showing thymic-like differentiation (CASTLE comprises a rare neoplasm of the thyroid gland which arises from ectopic thymic tissue or remnants of brachial pouches. CASTLE is regarded as an indolent neoplasm with a favorable prognosis, irrespective of its metastatic potential. Diagnosis is difficult as clinicopathological features have not been yet well-defined. Radiological findings are not specific and only immunohistochemical positivity for CD5 and CD117 staining is highly suggestive of CASTLE. Despite lack of universally accepted treatment recommendations, the mainstay treatment includes thyroidectomy and systematic lymph node dissection. We report a case of CASTLE tumour with very uncommon characteristics developed in a 76-year-old man, who presented with rapidly deteriorating dyspnea and severe cough, resulting in respiratory failure. At surgery, a suspicious looking tumour arising from the upper pole of the right lobe of the thyroid gland, surrounding the trachea and displacing the right common carotid artery, was identified. The patient underwent en bloc resection of the tumour with the thyroid gland and regional lymph node dissection. This is the first reported case of CASTLE causing tracheal ring fracture.

  15. TPO genetic variants and risk of differentiated thyroid carcinoma in two European populations.

    Science.gov (United States)

    Cipollini, Monica; Pastor, Susana; Gemignani, Federica; Castell, Juan; Garritano, Sonia; Bonotti, Alessandra; Biarnés, Josefina; Figlioli, Gisella; Romei, Cristina; Marcos, Ricard; Cristaudo, Alfonso; Elisei, Rossella; Landi, Stefano; Velázquez, Antonia

    2013-12-15

    Thyroid cancer risk involves the interaction of genetic and environmental factors. The thyroperoxidase (TPO) has a key role in the iodine metabolism, being essential for the thyroid function. Mutations in the TPO gene are common in congenital hypothyroidism, and there are also signs of the implication of TPO in thyroid cancer. We performed a case-control association study of genetic variants in TPO and differentiated thyroid carcinoma (DTC) in 1,586 DTC patients and 1,769 controls including two European populations (Italy: 1,190 DTC and 1,290 controls; Spain: 396 DTC and 479 controls). Multivariate logistic regression analyses were performed separately for each population and each single-nucleotide polymorphism (SNP). From the three studied polymorphisms, significant associations were detected between DTC and rs2048722 and rs732609 in both populations (p TPO polymorphism in the Italian and the Spanish populations. Our results, for the first time, point to TPO as a gene involved in the risk of DTC, and suggest the importance of interactions between TPO variants and other unidentified population-specific factors in determining thyroid cancer risk. Copyright © 2013 UICC.

  16. Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

    Science.gov (United States)

    Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

    2015-08-01

    To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

  17. Unraveling tumor grading and genomic landscape in lung neuroendocrine tumors.

    Science.gov (United States)

    Pelosi, Giuseppe; Papotti, Mauro; Rindi, Guido; Scarpa, Aldo

    2014-06-01

    Currently, grading in lung neuroendocrine tumors (NETs) is inherently defined by the histological classification based on cell features, mitosis count, and necrosis, for which typical carcinoids (TC) are low-grade malignant tumors with long life expectation, atypical carcinoids (AC) intermediate-grade malignant tumors with more aggressive clinical behavior, and large cell NE carcinomas (LCNEC) and small cell lung carcinomas (SCLC) high-grade malignant tumors with dismal prognosis. While Ki-67 antigen labeling index, highlighting the proportion of proliferating tumor cells, has largely been used in digestive NETs for assessing prognosis and assisting therapy decisions, the same marker does not play an established role in the diagnosis, grading, and prognosis of lung NETs. Next generation sequencing techniques (NGS), thanks to their astonishing ability to process in a shorter timeframe up to billions of DNA strands, are radically revolutionizing our approach to diagnosis and therapy of tumors, including lung cancer. When applied to single genes, panels of genes, exome, or the whole genome by using either frozen or paraffin tissues, NGS techniques increase our understanding of cancer, thus realizing the bases of precision medicine. Data are emerging that TC and AC are mainly altered in chromatin remodeling genes, whereas LCNEC and SCLC are also mutated in cell cycle checkpoint and cell differentiation regulators. A common denominator to all lung NETs is a deregulation of cell proliferation, which represents a biological rationale for morphologic (mitoses and necrosis) and molecular (Ki-67 antigen) parameters to successfully serve as predictors of tumor behavior (i.e., identification of pathological entities with clinical correlation). It is envisaged that a novel grading system in lung NETs based on the combined assessment of mitoses, necrosis, and Ki-67 LI may offer a better stratification of prognostic classes, realizing a bridge between molecular alterations

  18. An immunohistochemical panel to differentiate metastatic breast carcinoma to skin from primary sweat gland carcinomas with a review of the literature.

    Science.gov (United States)

    Rollins-Raval, Marian; Chivukula, Mamatha; Tseng, George C; Jukic, Drazen; Dabbs, David J

    2011-08-01

    Approximately 25% of patients with breast cancer develop cutaneous metastases. Sweat gland carcinomas (SGCs) account for about 0.05% of all cutaneous neoplasms. Cutaneous metastases of breast carcinoma (CMBCs) (especially the ductal type) can be difficult to distinguish from SGCs. Treatment and prognoses for these 2 types of tumors differ radically, making accurate histologic diagnosis crucial. Although a few studies attempt to differentiate these entities employing immunohistochemical (IHC) studies (some of which we review here), to date, no panel of IHC stains exists, to our knowledge, to distinguish these entities. To devise a panel of IHC stains to distinguish CMBC from SGC. Twelve cases of ductal CMBCs (11 not otherwise specified type, and 1 basal phenotype), 11 cases of SGCs (5 eccrine carcinomas, 3 porocarcinomas, and 3 microcystic adnexal carcinomas), 2 benign sweat gland neoplasm cases, and 2 primary breast cancer cases were retrieved and analyzed with the following IHC panel: mammaglobin, gross cystic disease fluid protein (GCDFP) 15, p63, basal cytokeratins (CK5, CK14, and CK17), androgen receptor, and PAX5. The p63 was only weakly expressed in 1 of 12 CMBC cases (8.3%), whereas it was strongly expressed in 10 of 11 SGC cases (90.9%) (P < .001). Basal cytokeratins demonstrated a similar immunoprofile in the SGC group, with 10 of 11 cases (90.9%) expressing all 3 markers, and a variable immunoprofile in the CMBC group with 0% (CK14) (P < .001) to 16.7% (2 of 12 cases; CK5 and CK17) (P < .001) expression. Mammaglobin was expressed in 8 of 12 cases (66.7%) of CMBC. Together, these 5 IHC stains were combined to make a panel that was 100% sensitive and 91% specific in distinguishing between CMBC and SGC.

  19. Characterization of Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Helen H Yu

    2016-08-01

    Full Text Available Aim To identify and characterize cancer stem cells (CSC in moderately differentiated buccal mucosa squamous cell carcinoma (MDBMSCC. Methods 4μm-thick formalin-fixed paraffin-embedded MDBMSCC samples from six patients underwent 3,3-diaminobenzidine (DAB immunohistochemical (IHC staining for the embryonic stem cell (ESC markers NANOG, OCT4, SALL4, SOX2 and pSTAT3; cancer stem cell marker CD44; squamous cell carcinoma (SCC marker EMA; and endothelial marker CD34. The transcriptional activities of the genes encoding NANOG, OCT4, SOX2, SALL4, STAT3 and CD44 were studied using NanoString gene expression analysis and colorimetric in situ hybridization (CISH for NANOG, OCT4, SOX2, SALL4 and STAT3. Results DAB and immunofluorescent (IF IHC staining demonstrated the presence of (1 an EMA+/CD44+/SOX2+/SALL4+/OCT4+/pSTAT3+/NANOG+ CSC subpopulation within the tumor nests; (2 an EMA-/CD44-/CD34-/SOX2+/OCT4+/pSTAT3+/NANOG+ subpopulation within the stroma between the tumor nests; and (3 an EMA-/CD44-/CD34+/SOX2+/ SALL4+/OCT4+/pSTAT3+/NANOG+ subpopulation on the endothelium of the microvessels within the stroma. The expression of CD44, SOX2, SALL4, OCT4, pSTAT3 and NANOG was confirmed by the presence of mRNA transcripts, using NanoString analysis and NANOG, OCT4, SOX2, SALL4 and STAT3 by CISH staining. Conclusion This study demonstrated a novel finding of three separate CSC subpopulations within MDBMSCC: (1 within the tumor nests expressing EMA, CD44, SOX2, SALL4, OCT4, pSTAT3 and NANOG; (2 within the stroma expressing SOX2, SALL4, OCT4, pSTAT3 and NANOG; and (3 on the endothelium of the microvessels within the stroma expressing CD34, SOX2, SALL4, OCT4, pSTAT3 and NANOG.

  20. Biopsy-Proven Metastatic Merkel Cell Carcinoma to the Orbit: Case Report and Review of Literature.

    Science.gov (United States)

    Cugley, Dean R; Roberts-Thomson, Samuel J; McNab, Alan A; Pick, Zelda

    2018-03-02

    Merkel cell carcinoma is a rare neuroendocrine tumor of subspecialized dermal mechanoreceptors, associated with immunosuppression. The usual ophthalmic presentation is an eyelid lesion. The authors present a case of biopsy-proven orbital metastatic Merkel cell carcinoma in the absence of any eyelid lesion, in an immunosuppressed patient with a history of multiple cancers. There are to the authors' knowledge only 2 other case reports of presumed metastatic Merkel cell carcinoma to the orbit, though neither were biopsied. Despite its rarity, metastatic Merkel cell carcinoma should be included in the differential of a metastatic orbital lesion, in the patient with a known or suspected cutaneous primary. The patient has had an excellent response to combined radiotherapy and programmed death-1 inhibitor pembrolizumab, and this case highlights the potential benefit of an exciting new biologic therapy.

  1. Dynamic expression patterns of differential proteins during early invasion of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Rong-Xin Chen

    Full Text Available Tumor cell invasion into the surrounding matrix has been well documented as an early event of metastasis occurrence. However, the dynamic expression patterns of proteins during early invasion of hepatocellular carcinoma (HCC are largely unknown. Using a three-dimensional HCC invasion culture model established previously, we investigated the dynamic expression patterns of identified proteins during early invasion of HCC.Highly metastatic MHCC97H cells and a liver tissue fragment were long-term co-cultured in a rotating wall vessel (RWV bioreactor to simulate different pathological states of HCC invasion. The established spherical co-cultures were collected on days 0, 5, 10, and 15 for dynamic expression pattern analysis. Significantly different proteins among spheroids at different time points were screened and identified using quantitative proteomics of iTRAQ labeling coupled with LC-MS/MS. Dynamic expression patterns of differential proteins were further categorized by K-means clustering. The expression modes of several differentially expressed proteins were confirmed by Western blot and qRT-PCR.Time course analysis of invasion/metastasis gene expressions (MMP2, MMP7, MMP9, CD44, SPP1, CXCR4, CXCL12, and CDH1 showed remarkable, dynamic alterations during the invasion process of HCC. A total of 1,028 proteins were identified in spherical co-cultures collected at different time points by quantitative proteomics. Among these proteins, 529 common differential proteins related to HCC invasion were clustered into 25 types of expression patterns. Some proteins displayed significant dynamic alterations during the early invasion process of HCC, such as upregulation at the early invasion stage and downregulation at the late invasion stage (e.g., MAPRE1, PHB2, cathepsin D, etc. or continuous upregulation during the entire invasion process (e.g., vitronectin, Met, clusterin, ICAM1, GSN, etc..Dynamic expression patterns of candidate proteins during the

  2. Predictors of long-term outcome in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-octreotate.

    Science.gov (United States)

    Ezziddin, Samer; Attassi, Mared; Yong-Hing, Charlotte J; Ahmadzadehfar, Hojjat; Willinek, Winfried; Grünwald, Frank; Guhlke, Stefan; Biersack, Hans-Jürgen; Sabet, Amir

    2014-02-01

    Outcome analyses for patients with gastroenteropancreatic neuroendocrine tumors (GEP NET) after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. Using a single-center analysis, we aimed to establish predictors of survival. We retrospectively analyzed a consecutive cohort of 74 patients who had metastatic GEP NET and underwent PRRT with (177)Lu-octreotate (mean activity of 7.9 GBq per cycle, aimed at 4 treatment cycles at standard intervals of 3 mo). Patients (33 with pancreatic NET and 41 with nonpancreatic GEP NET) had unresectable metastatic disease graded as G1 or G2 (G1/G2) and documented morphologic or clinical progression within less than 12 mo or uncontrolled disease under somatostatin analog treatment. Responses were evaluated according to modified Southwest Oncology Group criteria. Potential predictors of survival were analyzed with the Kaplan-Meier curve method (log-rank test) and multivariate analysis (P < 0.05). The response rates were 36.5% partial response, 17.6% minor response, 35.1% stable disease, and 10.8% progressive disease for the entire cohort; 54.5% partial response, 18.2% minor response, 18.2% stable disease, and 9.1% progressive disease for pancreatic NET; and 22.0% partial response, 17.1% minor response, 48.8% stable disease, and 12.2% progressive disease for nonpancreatic GEP NET. The median progression-free survival and overall survival were 26 mo (95% confidence interval, 18.3-33.7) and 55 mo (95% confidence interval, 48.8-61.2), respectively. Besides the Ki-67 index, a Karnofsky performance score of less than or equal to 70%, a hepatic tumor burden of greater than or equal to 25%, and a baseline plasma level of neuron-specific enolase of greater than 15 ng/mL independently predicted shorter overall survival (hazard ratio, 2.1-3.1). Patients with a Ki-67 index of greater than 10% still had median progression-free survival and overall survival of 19 and 34 mo

  3. Maximal safe dose therapy of I-131 after failure of standard fixed dose therapy in patients with differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Lee, Jong Jin; Seok, Ju Won; Uh, Jae Sun

    2005-01-01

    In patients with recurrent or metastatic differentiated thyroid carcinoma, residual disease despite repetitive fixed dose I-131 therapy presents an awkward situation in terms of treatment decision making. Maximal safe dose (MSD) administration base on bone marrow radiation allows the delivery of a large amount I-131 to thyroid cancer tissue within the safety margin. We investigated the efficacy of MSD in differentiated thyroid cancers, which had persisted after conventional fixed dose therapy. Forty-six patients with differentiated thyroid carcinoma who had non-responsible residual disease despite repetitive fixed dose I-131 therapy were enrolled in this study. The postoperative pathology consisted of 43 papillary carcinomas and 3 follicular carcinomas. MSD was calculated according the Memorial Sloan Kettering Cancer Center protocol using blood samples. MSDs were administered at intervals of at least 6 months. Treatment responses were evaluated using I-131 whole body scan (WBS) and serum thyroglobulin measurements. Mean calculated MSD was 12.5±2.1 GBq. Of the 46 patients, 6 (13.0%) showed complete remission, 15 (32.6%) partial response, 19 (41.3%) stable disease, and 6 (13.0%) disease progression. Thus, about a half of the patients showed complete or partial remission, and of these patients, 14 (67%) showed response after a single MSD administration and 6 (29%) showed response after the second dose of MSD administrations. Twenty-nine patients (63%) experienced transient cytopenia after therapy, and recovered spontaneously with the exception of one. MSD administration is an effective method even in the patients who failed to be treated by conventional fixed dose therapy. MSD therapy of I-131 can be considered in the patients who failed by fixed dose therapy

  4. Iodine excretion during stimulation with rhTSH in differentiated thyroid carcinoma

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    Loeffler, M.; Weckesser, M.; Franzius, C.; Kies, P.; Schober, O. [Muenster Univ. (Germany). Dept. of Nuclear Medicine

    2003-12-01

    Aim: Elevated iodine intake is a serious problem in the diagnostic and therapeutic application of {sup 131}iodine in patients with differentiated thyroid cancer. Therefore, iodine avoidance is necessary 3 months in advance. Additionally, endogenous stimulation requires withdrawal of thyroid hormone substitution for 4 weeks. Exogenous stimulation using recombinant human TSH (rhTSH) enables the continuous substitution of levothyroxine, which contains 65.4% of its molecular weight in iodine. Thus, a substantial source of iodine intake is maintained during exogenous stimulation. Although this amount of stable iodine is comparable to the iodine intake in regions of normal iodine supply, it may reduce the accumulation of radioiodine in thyroid carcinoma tissue. The aim of this study was to assess the iodine excretion depending on different ways of stimulation. Methods: Iodine excretion was measured in 146 patients in the long term follow up after differentiated thyroid carcinoma. Patients were separated into 2 groups, those on hormone withdrawal (G I) and rhTSH-stimulated patients on hormone substitution (G II). Results: Iodine excretion was significantly lower in hypothyroid patients (G I, median 50 {mu}g/l, range: 25-600 {mu}g/l) than in those under levothyroxine medication (G II, median 75 {mu}g/l, 25-600 {mu}g/l, p<0.027). TSH in G I (median 57.0 {mu}U/ml, range: 14.4-183 {mu}U/ml) was significantly lower (p<0.001) than in G II (117 {mu}U/ml, 32.2-281 {mu}U/ml). Conclusion: Iodine excretion was higher in patients under rhTSH-stimulation than after hormone withdrawal. This may indicate an increased iodine pool in rhTSH-stimulated patients (deiodination of levothyroxine), thus limiting the sensitivity of radioiodine scanning to the level of endogenous stimulation despite significantly higher TSH levels during rhTSH-stimulation. (orig.) [German] Ziel: Eine erhoehte Iodzufuhr ist ein erhebliches Problem in der diagnostischen und therapeutischen Anwendung von {sup 131}Iod

  5. Biological dosimetry study in differentiated thyroid carcinoma patients treated with 131Iodine

    International Nuclear Information System (INIS)

    Vallerga, Maria Belen

    2008-11-01

    Biological Dosimetry allows individual dose assessments based on the effect produced by ionizing radiation on a given biological parameter. The current biological endpoint being scored is chromosomal aberrations, relying on a lymphocytes culture from the patient's blood. The measured yield of chromosome aberrations is referred to a calibration curve obtaining the whole body dose. Different scenarios of overexposure can be taken into account by modifying the calculations leading to the dose estimate. Differentiated Thyroid Carcinoma patients undergo thyroidectomy followed by internal radiotherapy with 131 I. The treatment's success entails the delivery of a lethal dose to the tumour within the maximum tolerable dose to a critical organ (blood doses over 2 Gy could lead to bone marrow depression). Currently, there is no established agreement for the selection of radioiodine dosage. Historically, the empiric approach, based on clinical and biochemical data, has been recommended. Nevertheless, this method may not be associated with optimal outcomes. On the other hand, the dosimetric approach attempts to determine the maximum allowable activity to be administered, establishing its biokinetics by a diagnostic 131 I study. The methodology may be modified to further individualized treatment, however it requires validation. Biological dosimetry provides an independent measure of radiotherapy effect, as such it might aid in the validation process. Nonetheless, biological dosimetry has traditionally been applied in cases of external and accidental overexposure to ionizing radiation. Accordingly, it is mandatory to assess its value in medical internal incorporations (main objective of the present study). The applied treatment strategy comprises whole body dose assessment by biological and internal dosimetry in order to administer a personalized therapeutic activity. Overall, 20 patients with differentiated thyroid carcinoma were included in the study. For biological dosimetry

  6. Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Pitoia, Fabian; El Tamer, Elias; Schere, Daniel B.; Passerieu, Mariano; Bruno, Oscar D.; Niepominiszcze, Hugo

    2006-01-01

    The published studies confirming the safety and efficacy of rh TSH for diagnostic purposes have led to an increased interest in its use for preparation for radioiodine (RI) dose administration in patients with recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RI therapy after rh TSH, we have reviewed 39 rh TSH-aided radioiodine treatments in a series of 28 DTC patients. Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin (Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease. Median follow-up after the first rh TSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months). Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease. In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, in four in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels were undetectable after rh TSH. In the follow-up, two patients with lateral neck uptake were rendered disease free, four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. In conclusion, rh TSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients (GI). rh TSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rh TSH is a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing the quality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patients only with stimulated Tg levels. (author) [es

  7. Lean body mass-based levothyroxine replacement in young athyrotic patients with differentiated carcinoma of thyroid

    Directory of Open Access Journals (Sweden)

    Fatima Begum

    2013-01-01

    Full Text Available Objective: The objective of this study was to optimize dose of levothyroxine (LT4 based on lean body mass (LBM in young athyrotic patients with differentiated carcinoma of thyroid (DCT which has not been properly addressed in Bangladesh before. Materials and Methods: Sixty patients with DCT (age, range: 20-39 years having total thyroidectomy followed by radioiodine ablative therapy (RIT and 23 euthyroid volunteers were recruited. Clinical, biochemical parameters were obtained from all patients after 2 months of RIT and on LT4 replacement at a dose of 200 μg/day as first follow up visit and also from control subjects. Then 60 patients were divided into two groups consisting of 30 patients each. Patients of Group-I received LT4 replacement based on LBM measured by dual energy X-ray absorptiometry (DXA and Group-II continued LT4 replacement in conventional dose. Patients of both groups were assessed again for same parameters at 6 to 12 months at the second visit. Results: Optimized dose of LT4 based on LBM by DXA (131 ±23 μg/day significantly reduced thyroid hormones and kept thyroid stimulating hormone (TSH in expected levels in patients of Group-I at the second visit compared to patients of Group-II who continued conventional LT4 dose (200 μg/day. Hyperthyroid symptom scale (HSS was significantly reduced to 2 ± 1 in patients of Group-I but not in patients of Group-II, HSS, 8 ±1 ( P < 0.001. Conclusion: Optimization of LT4 dose based on LBM can avoid chronic exposure of mild excess of thyroid hormone in young patients with low risk DCT.

  8. Xanthogranulomatous cholecystitis: contrast-enhanced ultrasound features and differential diagnosis from wall-thickening gallbladder carcinoma.

    Science.gov (United States)

    Yuan, Hai-Xia; Wang, Wen-Ping; Wen, Jie-Xian; Ji, Zheng-Biao; Ding, Hong; Huang, Bei-Jian; Li, Chao-Lun

    2016-02-01

    The purpose of this study is to evaluate the value of contrast-enhanced ultrasound (CEUS) in differential diagnosis of Xanthogranulomatous cholecystitis (XGC). Patients of 17 XGCs and 43 wall-thickening gallbladder carcinomas (GBCs) were enrolled in this study. Firstly, we compared the ability of conventional ultrasound (CUS) and CEUS in detecting gallbladder (GB) features. Secondly, XGCs and GBCs features were compared on CEUS. Finally, all valuable indicators were ranked by Odds ratio. Significant differences were found in detecting GB wall thickness, GB stones, and hypoechoic nodules frequencies by CEUS and CUS. The mean GB wall thickness was 8.53 mm on CEUS, whereas the thickness measured 9.47 mm on CUS (p=0.011). GB stones and hypoechoic nodules were detected in 43 cases (71.7%) and 21 cases (30.0%) on CEUS, respectively, compared to 29 cases (48.3%) and 8 cases (13.3%) on CUS (p=0.009, p=0.027), respectively. Secondly, hypoenhancement time was longer in XGC (mean 78.9 s) than in GBC (mean 56.0 s) (p=0.002). Diffuse GB wall thickening, continuous inner wall, and hypoechoic nodules in the GB wall were observed in 12 patients (70.6%), 12 patients (70.6%) and 10 patients (58.8%) with XGC, respectively, compared to detection in 10 patients (23.3%), 4 patients (9.3%) and 11 patients (25.6%) by GBC (p=0.001, p=0.000 and p=0.015), respectively. Thirdly, the continuous inner wall was the most valuable indicator, with ORs of 23.4. The second valuable indicator was hypoenhancement time >80.5 s, with ORs of 11.9. CEUS demonstrated superior detection of GB wall thickness, GB stone and hypoechoic nodules compared to CUS. A continuous inner wall, hypoenhancement times greater than 80.5 s, diffuse thickening, and hypoechoic nodules were valuable indicators in XGCs.

  9. Differentiated thyroid carcinoma presentation may be more aggressive in children and adolescents than in young adults.

    Science.gov (United States)

    Zirilli, Giuseppina; Cannavò, Laura; Vermiglio, Francesco; Violi, Maria Antonia; Luca, Filippo De; Wasniewska, Malgorzata

    2018-01-17

    The available studies concerning the influence of age on the phenotypical expression of differentiated thyroid carcinoma (DTC) have hitherto compared DTC presentation either between pre-pubertal and pubertal children or between pediatric patients and aged adults; aim of this study was to ascertain for the first time whether presentation of DTC may significantly vary according to age, even within a peculiar study population covering only young patients aged less than 30 years. The main clinical, biochemical and pathologic data at DTC diagnosis were retrospectively recorded in 2 selected cohorts including, respectively, 18 children and adolescents aged less than 18 years (Group A) or 45 young adults aged between 20 and 29.8 years (Group B). The statistical distribution of DTC cases in the different age ranges was found to progressively increase with increasing age; furthermore, the patients of Group A exhibited at diagnosis a more severe clinical involvement and a higher rate of extra-regional metastases; finally, also the association with both autoimmune thyroid diseases (AITDs) and a biochemical hypothyroid pattern was more common in Group A patients. In a study population younger than 30 years: a) the risk of developing DTC increases with age, achieving its zenith during the 3rd decade of life; b) clinical presentation is more severe in children and adolescents younger than 18 years than in the patients aged between 20 and 30; c) in the cohort of children and adolescents DTC is more often associated with AITDs, which might play some role in conditioning the more aggressive phenotypical presentation of DTC in this patient group.

  10. The impact of 131I therapy on the recurrence of differentiated thyroid carcinoma after thyroidectomy

    International Nuclear Information System (INIS)

    Yu Yongli; Luo Quanyong; Chen Libo; Lu Haikui; Zhu Ruisen; Ma Jixiao

    2004-01-01

    Objective: To investigate the effects of some factors on recurrence after thyroidectomy of differentiated thyroid carcinoma (DTC). Methods: Three groups of DTC cases were studied during follow-up. All cases (n=298) of group 1 with diagnosed recurrence were analyzed statistically on age, gender, thyroid-operating mode and pathologic nature at first diagnosis. One hundred and eight cases of group 2 had received thyroid hormone-replaced therapy and 124 cases of group 3 had received thyroid hormone-replaced plus 131 I ablating therapy after thyroidectomy, and were analyzed and compared statistically by their therapeutic outcomes. Results: 1) From group 1, the ratios of male/female (1:1.5) and follicular/papillary (1:4) were higher than primary cases reported in literatures (1:2-3 and 1:8). The recurrence rates in the cases had primary lesion excised, unilateral thyroid or bilateral thyroid excised were decreased 47.3%, 34.2% and 18.5%, respectively. Recurrence mainly occurred at first 5 years after thyroidectomy (65.1%). 2) From group 2, recurrence rates were 4.63%, 8.33% and 12.04%, respectively at 1, 5 and 10 years, and 53.84% and 30.77%, respectively as local recurrence and distant metastases. From group 3, recurrence rates were 0.81%, 4.03% and 7.26%, respectively in 1, 5 and 10 years, and 5/9 and 2/9 as local recurrence and distant metastases, respectively. The statistic difference was significant (P 131 I ablating therapy after thyroidectomy may improve the prognosis of DTC (prolonging recurrence-free time, reducing recurrence rate and decreasing distant metastases). (authors)

  11. Lean body mass-based levothyroxine replacement in young athyrotic patients with differentiated carcinoma of thyroid

    Science.gov (United States)

    Begum, Fatima; Ahmed, Chaudhury M.; Afroz, Shahana; Kabir, Enamul; Alam, Faridul; Banerjee, Sajal; Zaman, Nazma

    2013-01-01

    Objective: The objective of this study was to optimize dose of levothyroxine (LT4) based on lean body mass (LBM) in young athyrotic patients with differentiated carcinoma of thyroid (DCT) which has not been properly addressed in Bangladesh before. Materials and Methods: Sixty patients with DCT (age, range: 20-39 years) having total thyroidectomy followed by radioiodine ablative therapy (RIT) and 23 euthyroid volunteers were recruited. Clinical, biochemical parameters were obtained from all patients after 2 months of RIT and on LT4 replacement at a dose of 200 μg/day as first follow up visit and also from control subjects. Then 60 patients were divided into two groups consisting of 30 patients each. Patients of Group-I received LT4 replacement based on LBM measured by dual energy X-ray absorptiometry (DXA) and Group-II continued LT4 replacement in conventional dose. Patients of both groups were assessed again for same parameters at 6 to 12 months at the second visit. Results: Optimized dose of LT4 based on LBM by DXA (131 ±23 μg/day) significantly reduced thyroid hormones and kept thyroid stimulating hormone (TSH) in expected levels in patients of Group-I at the second visit compared to patients of Group-II who continued conventional LT4 dose (200 μg/day). Hyperthyroid symptom scale (HSS) was significantly reduced to 2 ± 1 in patients of Group-I but not in patients of Group-II, HSS, 8 ±1 (P > 0.001). Conclusion: Optimization of LT4 dose based on LBM can avoid chronic exposure of mild excess of thyroid hormone in young patients with low risk DCT. PMID:23776898

  12. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  13. Differentiation of dysplastic nodule from hepatocellular carcinoma on contrast-enhanced power and pulsed Doppler US

    International Nuclear Information System (INIS)

    Shin, Jung Hee; Baek, Seung Yon; Kang, Byung Chul; Chung, Hye Kyung

    2001-01-01

    The purpose of this study was to differentiate dysplastic (DN) from hepatocellular carcinoma (HCC) in patients with liver cirrhosis on contrast-enhanced power and pulsed Doppler US. Twenty-one patients with liver cirrhosis and a focal lesion were included. They consisted of biopsy proven 12 DNs (mean diameter; 1.8 cm, M : F = 5 :7, mean age 60) and 9 HCCs (mean diameter: 2.3 cm, M : F = 6 : 3,mean age 63). All the patients were prospectively examined with Acusion Computed Sonography 128XP/10 and 4 MHz vector transducer. Gray-scale US was done to assess the echogenicity of the focal lesion. Vascular flow signals within the focal lesion were examined with power Doppler US. After the injection of 7 ml (300 mg/ml) suspension of US contrast agent (Levovist, Schering, Berlin, Germary), vascular flow signals were graded to 4 grades on power Doppler US. Arterial and/or venous flow pattern on pulsed Doppler US were evaluated. Statistical analysis was done using chi-square method. On gray-scale US, 10 (83%) DNs showed hypoechogenicity and the other two (17%) showed hyperechogenicity 7 (78%) HCCs were hypoechoic and two (22%) were hyperechoic. On non-enhanced power Doppler US, all 12 cases (100%) of DNs had no vascular flow signal and four cases of nine HCCs (grade II: three, grade III: one) revealed vascular flow signals (p=0.429). On contrast-enhanced power Doppler US, 11 cases(92%) of DNs and all cases (100%) of HCCs showed increased vascular flow signals. Three (24%) of DNs and 7 (78%) of HCCs showed grade III and IV. There was a statistical difference in the grade of vascular flow signals between two groups (p=0.03). On pulsed Doppler US, the arterial flow was present in 2 (17%) DNs and 8 (89%) HCCs (p=0.002) and venous flow was present in 11 (92%) DNs and 5 (56%) HCCs. Combined flow appeared in 2 cases (16%) of DNs and 4 cases (44%) of HCCs. In differentiating DN from HCC, the higher probability of HCC can be considered if a focal lesion in cirrhotic patients has grade

  14. Differential expression of Rab27A/B correlates with clinical outcome in hepatocellular carcinoma.

    Science.gov (United States)

    Dong, Wei-Wei; Mou, Quan; Chen, Jian; Cui, Jian-Tao; Li, Wen-Mei; Xiao, Wen-Hua

    2012-04-21

    To investigate the association of Rab27A and Rab27B expression with clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC). We used reverse transcription polymerase chain reaction (RT-PCR), real-time PCR, and Western blotting to detect Rab27A and Rab27B mRNA and protein expression in 5 human HCC lines and the immortalized hepatic HL-7702 cell line. We further examined 148 primary HCC samples matched with adjacent normal tissue and 80 non-HCC specimens by immunohistochemistry to evaluate the correlation of Rab27A and Rab27B expression with clinicopathological features and prognosis. Our data showed that Rab27A and Rab27B were differentially expressed in cell lines and primary HCC tumors. Rab27A mRNA and protein were detected in 67% (4/6) of human cell lines and 80% (4/5) of HCC cell lines, while Rab27B was found in 50% (3/6) of human lines and 40% (2/5) of HCC lines. Rab27A expression was higher in primary HCC (46.2%, 66/143) than in matched adjacent tissue (24.3%, 33/136, P expression and tumor tumor-node-metastasis (TNM) classification (P = 0.046 and P = 0.027, respectively), and between strong Rab27A expression and tumor differentiation grade (P = 0.008). Survival analyses revealed that patients with Rab27A(+) or Rab27B(+) tumors had significantly reduced overall survival compared with that of patients with Rab27A(-) or Rab27B(-) tumors (P = 0.015 and P = 0.005, respectively). Risk analyses revealed that Rab27B(+) and TNM III-IV were independent poor prognosis factors associated with a 3.36- and 3.37-fold higher relative risk of death, respectively. Rab27A and Rab27B expression were closely correlated with tumor progression and can be valuable prognostic indicators for HCC patients.

  15. Use of BI-RADS-MRI descriptors for differentiation between mucinous carcinoma and fibroadenoma.

    Science.gov (United States)

    Igarashi, Takao; Ashida, Hirokazu; Morikawa, Kazuhiko; Motohashi, Kenji; Fukuda, Kunihiko

    2016-06-01

    We evaluated the latest breast imaging reporting and data system (BI-RADS) magnetic resonance imaging (MRI) (5th edition) descriptors and non BI-RADS MRI factors that contribute to differentiation between mucinous carcinomas (MCs) and fibroadenomas (FAs). This retrospective study included 27 patients with P-MCs or M-MCs similar to P-MCs and 22 patients with FAs who underwent breast MRI between October 2008 and July 2014 at our institution. Definitive histopathological diagnoses were made for all of the MCs and FAs. The latest BI-RADS MRI descriptors for abnormal enhancement, including maximum diameter, shape (irregular or round/oval), margin (irregular or circumscribed), rim enhancement (present or absent), dark internal septation (absent or present), delayed internal enhancement (heterogeneous or homogeneous), and the time-intensity curve pattern (not persistent or persistent) were evaluated. As additional non BI-RADS MRI factors related to differentiation between MC and FA, age, signal intensity in the T2-weighted image (high or not high), extent of lobulation (strong or weak), enhancing internal septation (present or absent), and the apparent diffusion coefficient value were also evaluated. One radiologist retrospectively evaluated interpreted MR findings and analyzed the findings. Statistically significant findings were identified through univariate and multivariate analyses. Then, three blinded radiologists reviewed the MR images where MR findings had shown a significant association with outcomes during univariate analyses. Independently, the three blinded readers reviewed the MR images for the evaluation of inter-observer variability, and then arrived at a consensus for the evaluation of observer performance. Observer performance and inter-observer variability were determined via a receiver-operating-characteristic curve analysis and weighted k statistics. The sensitivity, specificity, and accuracy of each of the MR findings were calculated. Univariate

  16. Endocannabinoid Regulation of Neuroendocrine Systems.

    Science.gov (United States)

    Tasker, Jeffrey G; Chen, Chun; Fisher, Marc O; Fu, Xin; Rainville, Jennifer R; Weiss, Grant L

    2015-01-01

    The hypothalamus is a part of the brain that is critical for sustaining life through its homeostatic control and integrative regulation of the autonomic nervous system and neuroendocrine systems. Neuroendocrine function in mammals is mediated mainly through the control of pituitary hormone secretion by diverse neuroendocrine cell groups in the hypothalamus. Cannabinoid receptors are expressed throughout the hypothalamus, and endocannabinoids have been found to exert pronounced regulatory effects on neuroendocrine function via modulation of the outputs of several neuroendocrine systems. Here, we review the physiological regulation of neuroendocrine function by endocannabinoids, focusing on the role of endocannabinoids in the neuroendocrine regulation of the stress response, food intake, fluid homeostasis, and reproductive function. Cannabis sativa (marijuana) has a long history of recreational and/or medicinal use dating back to ancient times. It was used as an analgesic, anesthetic, and antianxiety herb as early as 2600 B.C. The hedonic, anxiolytic, and mood-elevating properties of cannabis have also been cited in ancient records from different cultures. However, it was not until 1964 that the psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol, was isolated and its chemical structure determined (Gaoni & Mechoulam, 1964). © 2015 Elsevier Inc. All rights reserved.

  17. Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study

    NARCIS (Netherlands)

    Sen, Abhijit; Tsilidis, Konstantinos K.; Allen, Naomi E.; Rinaldi, Sabina; Appleby, Paul N.; Almquist, Martin; Schmidt, Julie A.; Dahm, Christina C.; Overvad, Kim; Tjønneland, Anne; Rostgaard-Hansen, Agnetha L.; Clavel-Chapelon, Françoise; Baglietto, Laura; Boutron-Ruault, Marie Christine; Kühn, Tilman; Katze, Verena A.; Boeing, Heiner; Trichopoulou, Antonia; Tsironis, Christos; Lagiou, Pagona; Palli, Domenico; Pala, Valeria; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Bueno-de-Mesquita, H. B.; Peeters, Petra H.; Hjartåker, Anette; Lund, Eiliv; Weiderpass, Elisabete; Quirós, J. Ramón; Agudo, Antonio; Sánchez, María José; Arriola, Larraitz; Gavrila, Diana; Gurrea, Aurelio Barricarte; Tosovic, Ada; Hennings, Joakim; Sandström, Maria; Romieu, Isabelle; Ferrari, Pietro; Zamora-Ros, Raul; Khaw, Kay Tee; Wareham, Nicholas J.; Riboli, Elio; Gunter, Marc; Franceschi, Silvia

    2015-01-01

    Background: Results from several cohort and case-control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered. Methods: The association between

  18. Comparison of the prognostic values of {sup 68}Ga-DOTANOC PET/CT and {sup 18}F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Punit; Naswa, Niraj; Kc, Sudhir Suman; Yadav, Yashwant; Kumar, Rakesh; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Alvarado, Luis Andres; Dwivedi, Alok Kumar [Texas Tech University Health Sciences Center, Division of Biostatistics and Epidemiology, El Paso, TX (United States); Ammini, Ariachery C. [All India Institute of Medical Sciences, Department of Endocrinology and Metabolism, New Delhi (India)

    2014-12-15

    To determine the prognostic value of {sup 68}Ga-DOTANOC PET/CT in patients with well-differentiated neuroendocrine tumor (NET), and to compare the prognostic value with that of {sup 18}F-FDG PET/CT and other conventional clinicopathological prognostic factors. Data from 37 consecutive patients (age 46.6 ± 13.5 years, 51 % men) with well-differentiated NET who underwent {sup 68}Ga-DOTANOC PET/CT and {sup 18}F-FDG PET/CT were analyzed. All patients underwent a baseline visit with laboratory and radiological examinations. Clinical and imaging follow-up was performed in all patients. Progression-free survival (PFS) was measured from the date of the first PET/CT scan to the first documentation of progression of disease. {sup 68}Ga-DOTANOC PET/CT was positive in 37 of the 37 patients and {sup 18}F-FDG PET/CT was positive in 21. During follow-up 10 patients (27 %) showed progression of disease and 27 (73 %) showed no progression (24 stable disease, 3 partial response). The median follow-up was 25 months (range 2 - 52 months). Among the variables evaluated none was significantly different between the progressive disease and nonprogressive disease groups, with only SUVmax on {sup 68}Ga-DOTANOC PET/CT being borderline significant (P = 0.073). In the univariate analysis for PFS outcome, SUVmax on {sup 68}Ga-DOTANOC PET/CT (HR 0.122, 95 % CI 0.019 - 0.779; P = 0.026) and histopathological tumor grade (HR 4.238, 95 % CI 1.058 - 16.976; P = 0.041) were found to be associated with PFS. Other factors including age, sex, primary site, Ki-67 index, TNM stage, {sup 18}F-FDG PET/CT status (positive/negative), SUVmax on {sup 18}F-FDG PET/CT and type of treatment were not significant. In multivariable analysis, only SUVmax on {sup 68}Ga-DOTANOC PET/CT was found to be an independent positive predictor of PFS (HR 0.122, 95 % CI 0.019 - 0.779; P = 0.026). SUVmax measured on {sup 68}Ga-DOTANOC PET/CT is an independent, positive prognostic factor in patients with well-differentiated NET and

  19. MRI findings of small cell neuroendocrime carcinoma of the uterine cervix: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Won, You Sun; Yi, Boem Ha; Lee, Hae Kyung; Lee, Min Hee; Choi, Seo Youn; Kwak, Jeong Ja [Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon (Korea, Republic of)

    2015-10-15

    Small cell neuroendocrine carcinoma of the uterine cervix is a rare primary neoplasm, accounting for less than 5% of all uterine cervical cancers. The tumor is known to have an aggressive behavior and poor prognosis. In this article, we present the MRI findings of 5 cases of pathologically-proven small cell neuroendocrine carcinoma of the uterine cervix, including diffusion-weighted images.

  20. Differential expression of argininosuccinate synthetase in serous and non‐serous ovarian carcinomas

    Science.gov (United States)

    Cheon, Dong‐Joo; Walts, Ann E; Beach, Jessica A; Lester, Jenny; Bomalaski, John S; Walsh, Christine S; Ruprecht Wiedemeyer, W; Karlan, Beth Y

    2014-01-01

    Abstract The current standard of care for epithelial ovarian cancer does not discriminate between different histologic subtypes (serous, clear cell, endometrioid and mucinous) despite the knowledge that ovarian carcinoma subtypes do not respond uniformly to conventional platinum/taxane‐based chemotherapy. Exploiting addictions and vulnerabilities in cancers with distinguishable molecular features presents an opportunity to develop individualized therapies that may be more effective than the current ‘one size fits all' approach. One such opportunity is arginine depletion therapy with pegylated arginine deiminase, which has shown promise in several cancer types that exhibit low levels of argininosuccinate synthetase including hepatocellular and prostate carcinoma and melanoma. Based on the high levels of argininosuccinate synthetase previously observed in ovarian cancers, these tumours have been considered unlikely candidates for arginine depletion therapy. However, argininosuccinate synthetase levels have not been evaluated in the individual histologic subtypes of ovarian carcinoma. The current study is the first to examine the expression of argininosuccinate synthetase at the mRNA and protein levels in large cohorts of primary and recurrent ovarian carcinomas and ovarian cancer cell lines. We show that the normal fallopian tube fimbria and the majority of primary high‐grade and low‐grade serous ovarian carcinomas express high levels of argininosuccinate synthetase, which tend to further increase in recurrent tumours. In contrast to the serous subtype, non‐serous ovarian carcinoma subtypes (clear cell, endometrioid and mucinous) frequently lack detectable argininosuccinate synthetase expression. The in vitro sensitivity of ovarian cancer cell lines to arginine depletion with pegylated arginine deiminase was inversely correlated with argininosuccinate synthetase expression. Our data suggest that the majority of serous ovarian carcinomas are not susceptible

  1. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  2. Following-up the efficiency of 131-Iodine therapy in differentiated thyroid carcinoma (excluding medullary) - Moroccan situation

    International Nuclear Information System (INIS)

    Ben Rais Aouad, N.

    2004-01-01

    Full text: Since 1985, the department of nuclear medicine of IBN SINA Hospital in the Rabat University hospital centre is the only centre in Morocco, where all patients of differentiated thyroid carcinoma after surgery are treated with 3.7 GBq of Iodine-131. The number of patients on follow-up is more than two thousands. The endemic zone represents the main origin of thyroid carcinoma. The sex ratio (F/M) is 3.5/1; the mean age is 42.5 years. The papillary carcinoma constitutes about 65.5% of the 26% of well-differentiated carcinoma and 12.5 of moderately differentiated carcinoma (MDC). The tumour size at diagnosis was more than 2 cm in 70% of cases. Prognosis factors are the age, the histology and tumour size. After the surgery, the patients receive 131-Iodine therapy (3.7 GBq) and a regular follow-up by clinical examination, neck ultrasonography and thyroglobulin (Tg) blood level. The aim is to obtain a negative whole body scan (WBS) and undetectable Tg. All the patients also receive a suppressive hormone therapy (thyroxin: 2.4 μg/kg/day). In the same patient, the Tg level is also compared with and without suppression therapy, but taking TSH levels into account. The efficiency of 131-Iodine treatment and the following up, depends on the type of patients: (a) Patients without metastasis: the success of Iodine-131 therapy depended on surgery and it was more than 92% (b) Patients with local metastasis to lymph nodes: the success of 131-Iodine therapy depended of nodal status and complete dissection is possible in 70% cases only. (c) Patients with distant metastasis: The efficiency of 131-Iodine therapy depended on the uptake, the homogeneity and the size of metastasis. In lung metastasis, the efficiency of 131-Iodine is about 40-42% (70%: miliary and micro nodules) and only 6.6% in bone metastasis. After treatment, the patients were regularly followed-up clinically till the next WBS and Tg estimation. In some cases, it was interesting to compare WBS and MIBI

  3. Clinical features and prognostic factors for survival in patients with poorly differentiated thyroid carcinoma and comparison to the patients with the aggressive variants of papillary thyroid carcinoma

    International Nuclear Information System (INIS)

    Jung, Tae-Sik; Kim, Tae-Yong; Kim, Kyung-Won

    2007-01-01

    We performed this study to compare the clinicopathologic features and outcomes between the patients with poorly differentiated thyroid carcinoma (PDTC) and the patients with the aggressive variants of papillary thyroid carcinoma (PTC). To evaluate the prognostic factors for survival of the patients with PDTC, we selected 49 patients with PDTC and 23 patients with the aggressive variants of PTC from three hospitals during the recent 15 years. The five-year survival rate and clinicopathologic features of the patients with PDTC were not different from those of the patients with the aggressive variants of PTC. Univariate analysis revealed the significant poor prognostic factors for survival of the patients with PDTC and the aggressive variants of PTC as follows: an age more than 45 years, a tumor size larger than 4 cm, the presence of tumor invasion to extrathyroidal tissue or the trachea, the presence of cervical lymph node invasion, the presence of distant metastasis, the absence of high-dose radioactive iodine (RAI) therapy, and tumor, nodes and metastasis (TNM) stage II, III and IV. Distant metastasis and high-dose RAI therapy were independent significant predictors for survival of the patients with PDTC and the aggressive variants of PTC on multivariate analysis. However, distant metastasis was the only independent significant predictors for survival of the patients with PDTC excluding patients with the aggressive variants of PTC. (author)

  4. Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2013-08-01

    Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Differentiation of Renal Oncocytoma and Renal Clear Cell Carcinoma Using Relative CT Enhancement Ratio

    Directory of Open Access Journals (Sweden)

    An Ren

    2015-01-01

    Full Text Available Background: The difference between renal oncocytomas (RO and renal clear cell carcinomas (RCCs presents the greatest diagnostic challenge. The aim of this study was to retrospectively determine if RO and RCCs could be differentiated on computed tomography (CT images on the basis of their enhancement patterns with a new enhancement correcting method. Methods: Forty-six patients with a solitary renal mass who underwent total or partial nephrectomy were included in this study. Fourteen of those were RO and 32 were RCCs. All patients were examined with contrast-enhanced CT. The pattern and degree of enhancement were evaluated. We selected the area that demonstrated the greatest degree of enhancement of the renal lesion in the corticomedullary nephrographic and excretory phase images. Regions of interest (ROI were also placed in adjacent normal renal cortex for normalization. We used the values of the normal renal cortex that were measured at the same time as divisors. The ratios of lesion-to-renal cortex enhancement were calculated for all three phases. The Student′s t-test and Pearson′s Chi-square test were used for statistical analyses. Results: All RCCs masses showed contrast that appeared to be better enhanced than RO on all contrast-enhanced phases of CT imaging, but there was no significant difference in absolute attenuation values between these two diseases (P > 0.05. The ratio of lesion-to-cortex attenuation in the corticomedullary phase showed significantly different values between RO and RCCs. The degree of contrast enhancement in RCCs was equal to or greater than that of the normal renal cortex, but it was less than that of the normal cortex in RO in the corticomedullary phase. The ratio of lesion-to-cortex attenuation in the corticomedullary phase was higher than the cut off value of 1.0 in most RCCs (84%, 27/32 and lower than 1.0 in most RO (93%, 13/14 (P < 0.05. In the nephrographic phase, the ratio of lesion-to-cortex attenuation

  6. Syndrome differentiation in traditional Chinese medicine and E-cadherin/ICAM-1 gene protein expression in gastric carcinoma.

    Science.gov (United States)

    Sun, Da-Zhi; Xu, Ling; Wei, Pin-Kang; Liu, Long; He, Jin

    2007-08-28

    To explore the syndrome differentiation in traditional Chinese medicine (TCM) and gene protein expression in gastric carcinoma. Preoperative data of gastric cancer cases were collected from the General Surgery Department and classified according to the criteria for syndrome differentiation in TCM. E-cadherin (E-cad) and ICAM-1 gene protein expressions were detected in postoperative specimens from these cases by the immunohistochemical EnVision two-step method. The E-cad positive expression rate was 90% in 100 cases of gastric carcinoma. The difference in E-cad expression was significant between the different syndrome differentiation types in TCM (P cad expression between the stagnation of phlegm-damp type and the deficiency in both qi and blood and the deficiency-cold of stomach and spleen types, where E-cad expression was high. There was no significant difference between the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type, where E-cad expression was relatively low. The ICAM-1 positive expression rate was 58%, and there was no statistically significant difference between the two groups (c2 = 8.999, P > 0.05). E-cad expression is relatively low in the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type, where tumor development and metastasis may be associated with low E-cad expression, or with low homogeneous adhesiveness between tumor cells.

  7. Clinical reevaluation of radioimmunological thyroglobulin (hTg) determination in follow-up of differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Boettger, I.; Kanitz, W.; Pabst, W.H.

    1985-01-01

    A reevaluation of the clinical value of radioimmunological thyroglobulin (hTg) determination during follow-up of differentiated thyroid carcinoma, in general, confirms our previous results already published in 1980 and 1981. A total of 163 patients with differentiated thyroid carcinoma, 53 with papillary and 110 with follicular carcinoma, was studied up to January 1984. 586 sera are included in this study. The differentiation of suspicious from nonsuspicious findings was found to be based upon a cut-off concentration of 10 μg/l. Pathological findings were associated with hTg concentrations above 20 μg/l. Diagnostic accuracy was calculated to be between 95 and 97%, sensitivity of the method in comparison to be radioiodine whole-body scan was 98 versus 83%, respectively, and specificity 94%. At first 5 false negative and 6 false positive hTg findings have been obtained. 7.6% of the patients demonstrated endogeneous hTg antibodies by Boyden test. 7.7% of Boyden test negative sera showed an unacceptable hTg recovery of worse than +- 50%, which was possibly due to endogeneous antibodies. Again, endogenous TSH was able to stimulate hTg secretion in the form of elevated levels, yet did not affect the clinical diagnosis. Examples of the behaviour of hTg levels during follow-up are demonstrated. Specifically, the cases with false hTg findings are discussed. Basically, the conclusions are the same as in 1980 and 1981: hTg determination is able to replace the routinely performed radioiodine whole-body scan during follow-up, if once residual thyroid tissue and metastases have been excluded by means of radioiodine and an optimal follow-up program is used. (orig.) [de

  8. Neuroendocrine targets of endocrine disruptors.

    Science.gov (United States)

    Gore, Andrea C

    2010-01-01

    The central neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, as well as stress responsiveness. These processes are initiated by signals in the central nervous system, specifically the hypothalamus, and are conveyed first by neural and then by endocrine effectors. The neuroendocrine systems, as the links between the brain and peripheral endocrine organs, play critical roles in the ability of an organism to respond to its environment under normal circumstances. When neuroendocrine homeostasis is disrupted by environmental endocrine-disrupting chemicals, a variety of perturbations can ensue, particularly when endocrine disruption occurs during critical developmental time periods. This article will discuss the evidence for environmental endocrine disruption of neuroendocrine systems and the effects on endocrine and reproductive functions.

  9. Inhibition of miR-29c promotes proliferation, and inhibits apoptosis and differentiation in P19 embryonic carcinoma cells

    OpenAIRE

    CHEN, BIN; SONG, GUIXIAN; LIU, MING; QIAN, LINGMEI; WANG, LIHUA; GU, HAITAO; SHEN, YAHUI

    2016-01-01

    In our previous study, the upregulation of microRNA (miR)-29c was identified in the mother of a fetus with a congenital heart defect. However, the functional and regulatory mechanisms of miR-29c in the development of the heart remain to be elucidated. In the present study, the role and mechanism of miR-29c inhibition in heart development were investigated in an embryonic carcinoma cell model. Inhibition of miR-29c promoted proliferation, and suppressed the apoptosis and differentiation of P19...

  10. Distinguishing synchronous from metachronous manifestation of distant metastases: a prognostic feature in differentiated thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir [University Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany); Saarland University Hospital, Department of Nuclear Medicine, Homburg (Germany); Binse, Ina; Koch, Andrea; Rosenbaum-Krumme, Sandra J. [University Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany); Dogan, Semih; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Biermann, Kim [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Confessional Hospital ' ' Barmherzige Brueder' ' , Department of Radiology and Nuclear Medicine, Trier (Germany); Ezziddin, Samer [Saarland University Hospital, Department of Nuclear Medicine, Homburg (Germany); University Hospital, Department of Nuclear Medicine, Bonn (Germany)

    2017-02-15

    Distant metastasis has a negative impact on survival in differentiated thyroid carcinoma (DTC). The timing of this manifestation, however, is of unknown prognostic relevance. The aim of this retrospective study was to investigate the potential significance of discriminating synchronous versus metachronous distant metastases (SDM vs. MDM) for the outcome of patients with DTC. We retrospectively analyzed a consecutive cohort of n = 89 patients with distant metastases of DTC (43 with follicular, 46 with papillary DTC histology; mean age 52.6 ± 17.7 years) undergoing radioiodine treatment at our institution. All patients were treated with the same protocol consisting of ablative radioiodine therapy (RIT, 3.7 GBq) and one post-ablation treatment after 3 months (3.7-11.1 GBq). Further cycles of RIT were administered for recurrent, progressive or newly developed metastatic disease. We distinguished 2 types of distant metastases according to the time of manifestation: SDM (within ≤12 months after DTC diagnosis) and MDM (occurring >12 months after diagnosis). Tumor-related survival was analyzed using the Kaplan-Meier method. Uni- and multivariate analyses including the Cox proportional hazards model were performed with a significance level of p < 0.05. The mean follow-up period was 13.8 ± 1.2 years. SDM were present in 49 (55.1 %), MDM in 40 (44.9 %) patients. MDM were associated with shorter tumor-related survival (p = 0.002). 5-year and 10-year survival rates were 68.5 % and 34.8 % for MDM, and 84.3 % and 66.9 % for SDM, respectively. Within both age subgroups of <45 and ≥45 years, SDM were also linked with longer survival. No effect on tumor-related survival was found for the co-variables sex, lymph node metastases and histologic type. Distinguishing synchronous from metachronous manifestation of distant metastases may add an important prognostic feature to risk stratification in DTC, as proven metachronous appearance is associated with impaired survival. (orig.)

  11. Optimization of the therapeutic dose of 131I for thyroid differentiated carcinoma

    International Nuclear Information System (INIS)

    Lima, Fabiana Farias de

    2002-09-01

    organs, such as the narrow and gonads, of up to 78.4%.Possible benefits to the institution also include the use of less radioactive material and a reduction in radiation exposures to the staff during the manipulation and administration of the 131 I. To facilitate the calculations of the optimum therapeutic activity of 131 I for individual patients, a simple and fast dose planning program was created (PlanDose). The program has been set up to evaluate thryroid remant ablation, but it can also be used for the calculation of the activity to be administered for treatment of hyperthyroidism. This protocol of calculated optimal patient-specific 131 I. activities allows a better determination of the necessary ablative dose for patients with differentiated carcinoma of the thyroid, and is an example of optimizing the practice of radiation protection. (author)

  12. Combined use of heat-shock protein 70 and glutamine synthetase is useful in the distinction of typical hepatocellular adenoma from atypical hepatocellular neoplasms and well-differentiated hepatocellular carcinoma

    Science.gov (United States)

    Nguyen, Thuy B; Roncalli, Massimo; Tommaso, Luca Di; Kakar, Sanjay

    2017-01-01

    Well-differentiated hepatocellular carcinoma can mimic high-grade dysplastic nodule in cirrhotic liver and hepatocellular adenoma in non-cirrhotic liver. This study evaluates the efficacy of combined use of heat-shock protein 70 (HSP70), glutamine synthetase (GS) and glypican-3 in this setting. Immunohistochemistry for these three markers was done in 17 typical hepatocellular adenoma, 15 high-grade dysplastic nodules, 20 atypical hepatocellular neoplasms (14 clinically atypical and 6 pathologically atypical), 14 very well-differentiated hepatocellular carcinoma, and 43 well-differentiated hepatocellular carcinoma. All three markers were negative in typical adenomas. HSP70 was positive in 10, 71, and 67% of atypical neoplasms, very well-differentiated and well-differentiated HCC, respectively, while GS was positive in 60, 50, and 60% of atypical neoplasms, very well-differentiated and well-differentiated hepatocellular carcinoma, respectively. Glypican-3 was negative in all atypical neoplasms and very well-differentiated hepatocellular carcinoma, and was positive in 27% of well-differentiated hepatocellular carcinoma. Positive staining with at least one marker (HSP70 and/or GS) was seen in 85% of very well-differentiated hepatocellular carcinoma, which was similar to well-differentiated hepatocellular carcinoma (78%, P = 0.4), and pathologically atypical cases (100%, P = 0.5), but significantly higher compared with clinically atypical cases (43%. P = 0.03) and none of typical adenomas (P hepatocellular carcinoma compared with atypical neoplasms (45 vs 10%, P = 0.004). Both these markers were also more often expressed in very well-differentiated hepatocellular carcinoma compared with atypical cases (38 vs 10%, P = 0.06). In conclusion, the combined use of GS and HSP70 can be useful in the diagnosis of very well-differentiated hepatocellular carcinoma. These stains can also help in the distinction of typical adenoma from atypical hepatocellular neoplasms. Glypican-3

  13. Combined use of heat-shock protein 70 and glutamine synthetase is useful in the distinction of typical hepatocellular adenoma from atypical hepatocellular neoplasms and well-differentiated hepatocellular carcinoma.

    Science.gov (United States)

    Nguyen, Thuy B; Roncalli, Massimo; Di Tommaso, Luca; Kakar, Sanjay

    2016-03-01

    Well-differentiated hepatocellular carcinoma can mimic high-grade dysplastic nodule in cirrhotic liver and hepatocellular adenoma in non-cirrhotic liver. This study evaluates the efficacy of combined use of heat-shock protein 70 (HSP70), glutamine synthetase (GS) and glypican-3 in this setting. Immunohistochemistry for these three markers was done in 17 typical hepatocellular adenoma, 15 high-grade dysplastic nodules, 20 atypical hepatocellular neoplasms (14 clinically atypical and 6 pathologically atypical), 14 very well-differentiated hepatocellular carcinoma, and 43 well-differentiated hepatocellular carcinoma. All three markers were negative in typical adenomas. HSP70 was positive in 10, 71, and 67% of atypical neoplasms, very well-differentiated and well-differentiated HCC, respectively, while GS was positive in 60, 50, and 60% of atypical neoplasms, very well-differentiated and well-differentiated hepatocellular carcinoma, respectively. Glypican-3 was negative in all atypical neoplasms and very well-differentiated hepatocellular carcinoma, and was positive in 27% of well-differentiated hepatocellular carcinoma. Positive staining with at least one marker (HSP70 and/or GS) was seen in 85% of very well-differentiated hepatocellular carcinoma, which was similar to well-differentiated hepatocellular carcinoma (78%, P=0.4), and pathologically atypical cases (100%, P=0.5), but significantly higher compared with clinically atypical cases (43%. P=0.03) and none of typical adenomas (Phepatocellular carcinoma compared with atypical neoplasms (45 vs 10%, P=0.004). Both these markers were also more often expressed in very well-differentiated hepatocellular carcinoma compared with atypical cases (38 vs 10%, P=0.06). In conclusion, the combined use of GS and HSP70 can be useful in the diagnosis of very well-differentiated hepatocellular carcinoma. These stains can also help in the distinction of typical adenoma from atypical hepatocellular neoplasms. Glypican-3 has low

  14. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

    OpenAIRE

    de Faria, J

    1985-01-01

    The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

  15. Neuroendocrine immunoregulation in multiple sclerosis.

    Science.gov (United States)

    Deckx, Nathalie; Lee, Wai-Ping; Berneman, Zwi N; Cools, Nathalie

    2013-01-01

    Currently, it is generally accepted that multiple sclerosis (MS) is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

  16. Neuroendocrine Immunoregulation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2013-01-01

    Full Text Available Currently, it is generally accepted that multiple sclerosis (MS is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

  17. PBK/TOPK in the differential diagnosis of cholangiocarcinoma from hepatocellular carcinoma and its involvement in prognosis of human cholangiocarcinoma.

    Science.gov (United States)

    He, Furong; Yan, Qingguo; Fan, Linni; Liu, Yixiong; Cui, Jihong; Wang, Juanhong; Wang, Lu; Wang, Yingmei; Wang, Zhe; Guo, Ying; Huang, Gaosheng

    2010-03-01

    The increased expression of PDZ binding kinase/lymphokine-activated killer T-cell-originated protein kinase (PBK/TOPK) is associated with some human malignant tumors. In this study, we analyzed PBK/TOPK expression in hepatic primary tumor and explored its role in cholangiocarcinoma biology. Seventy-four cholangiocarcinomas, 33 hepatocellular carcinomas, and 10 normal liver tissues were prepared from paraffin-embedded specimens. PBK/TOPK protein was assessed by immunohistochemical staining, and the survival time was analyzed with the Kaplan-Meier method. The protein, mRNA of PBK/TOPK, and cell cycle of cholangiocarcinoma cell line after PBK/TOPK suppression with small interfere RNA were studied by Western blot, semiquantitative reverse transcriptase-polymerase chain reaction, and flow cytometry, respectively. PBK/TOPK was usually expressed in normal bile duct epithelial cells and much more frequently expressed in cholangiocarcinoma (68/74) but never expressed in hepatocytes and hepatocellular carcinomas (0/33). PBK/TOPK down-regulation was related to the poor prognosis of patients with cholangiocarcinoma (P = .013). Epidermal growth factor can enhance PBK/TOPK expression in cholangiocarcinoma QBC 939 cells, but suppression of PBK/TOPK in the cells did not affect their proliferation. PBK/TOPK protein could serve as a useful indicator for histopathologic differentiation between cholangiocarcinoma and hepatocellular carcinomas and the low expression of PBK/TOPK is predicative of poor survival in cholangiocarcinoma patients. Copyright 2010 Elsevier Inc. All rights reserved.

  18. p75 Neurotrophin receptor differentiates between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma: insights into the histogenesis of adnexal tumours based on embryology and hair follicle biology.

    Science.gov (United States)

    Krahl, D; Sellheyer, K

    2010-07-01

    Tumour development is frequently described in the basic pathology literature as a recapitulation of embryogenesis. However, a link between the embryology of the skin and the histogenesis of adnexal tumours has been largely overlooked. The low-affinity p75 neurotrophin receptor (p75NTR) has a profound role in hair follicle biology. We therefore speculated that it is involved in the histogenesis of follicular adnexal tumours. One of the most challenging diagnoses in dermatopathology is differentiating morphoeic basal cell carcinoma from desmoplastic trichoepithelioma. To describe the expression pattern of p75NTR during cutaneous embryogenesis, in the adult hair follicle and in morphoeic basal cell carcinoma and desmoplastic trichoepithelioma. Evaluation of the staining pattern for p75NTR was performed using standard immunohistochemical techniques. For comparison, we examined staining for cytokeratin 20 which highlights Merkel cells. All 17 desmoplastic trichoepitheliomas were immunoreactive with > 80% of the cells stained, whereas 12 of the 14 (86%) morphoeic basal cell carcinomas were p75NTR negative. In the two positive cases of morphoeic basal cell carcinoma basal cell carcinoma favours a concept of this tumour as a more primitive follicular lesion with the characteristics of a carcinoma and not a hamartoma. We suggest including p75NTR as a tool in the differential diagnosis between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma.

  19. Intensity-Based Assessment of Microbubble-Enhanced Ultrasonography: Phase-Related Diagnostic Ability for Cellular Differentiation of Hepatocellular Carcinoma.

    Science.gov (United States)

    Kondo, Takayuki; Maruyama, Hitoshi; Kiyono, Soichiro; Sekimoto, Tadashi; Shimada, Taro; Takahashi, Masanori; Ogasawara, Sadahisa; Suzuki, Eiichiro; Ooka, Yoshihiko; Tawada, Akinobu; Chiba, Tetsuhiro; Kanai, Fumihiko; Yokosuka, Osamu

    2015-12-01

    This prospective study aimed to elucidate the effect of phase-related quantitative parameters of contrast-enhanced ultrasound (CEUS) with perflubutane microbubble agent to assess the cellular differentiation of hepatocellular carcinoma (HCC). Intensity was analyzed in 94 lesions (19.4 ± 4.9 mm, 86 patients), 47 well-differentiated HCCs (wHCCs) and 47 moderately-differentiated HCCs (mHCCs): I(e) (early phase) = I(te) (tumor) - I(le) (liver), I(p) (post-vascular phase) = I(tp) (tumor) - I(lp) (liver), I(ep) = I(e) - I(p). The area under the receiver operating characteristic curve with the best cutoff value (I(e), 13.2, I(p), -4.5, I(ep), 21.3) for discriminating between wHCC and mHCC was 0.6922 for Ie, 0.7680 for Ip and 0.7925 for Iep, which indicated a significantly greater ability to differentiate between wHCC and mHCC compared with visual/qualitative assessment (early phase, 0.6170, p = 0.04; post-vascular phase, 0.6702, p = 0.01; both phases, 0.7021, p = 0.04). In conclusion, I(ep) was found to have the highest diagnostic ability, suggesting it is a promising parameter for the cellular differentiation of HCCs with CEUS. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  20. Differentiation-associated genes regulated by c-Jun and decreased in the progression of esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Aiping Luo

    Full Text Available Transcription factor c-Jun plays a key role in controlling epithelium cell proliferation, apoptosis and differentiation. However, molecular mechanism and biological functions of c-Jun in squamous differentiation and the progression of esophageal squamous cell carcinoma (ESCC remain elusive. In this study, we found that c-Jun bound directly to the promoter region, and activated the transcription of differentiation-associated genes including cystatin A, involucrin and SPRR3 in vivo. Ectopic expression of c-Jun enhanced SPRR3 transactivation in KYSE450 cells. Conversely, TAM67, a dominant negative mutant of c-Jun, inhibited SPRR3 transactivation. c-Jun increased expression of SPPR3 mainly via a PKC/JNK pathway in response to TPA in KYSE450 cells. Furthermore, c-Jun was remarkably reduced in esophageal cancer. Interestingly, cystatin A, involucrin and SPRR3 were significantly downregulated as well, and associated with differentiation grade. Expression of c-Jun was correlated with the expression of these genes in normal epithelium and ESCC. Importantly, the expression of these genes was remarkably decreased during the malignant transformation from normal epithelium to low-grade intraepithelial neoplasia (LGIN or high-grade intraepithelial neoplasia (HGIN. The expression of cystatin A and involucrin was significantly reduced from LGIN to HGIN. These results suggest c-Jun was involved in the regulation of differentiation-associated genes in ESCC. These genes might serve as the potential markers in distinguishing normal epithelium from esophageal squamous intraepithelial neoplasia.

  1. Rewiring of an Epithelial Differentiation Factor, miR-203, to Inhibit Human Squamous Cell Carcinoma Metastasis

    Directory of Open Access Journals (Sweden)

    Nathan Benaich

    2014-10-01

    Full Text Available Metastatic colonization of distant organs underpins the majority of human-cancer-related deaths, including deaths from head and neck squamous cell carcinoma (HNSCC. We report that miR-203, a miRNA that triggers differentiation in multilayered epithelia, inhibits multiple postextravasation events during HNSCC lung metastasis. Inducible reactivation of miR-203 in already established lung metastases reduces the overall metastatic burden. Using an integrated approach, we reveal that miR-203 inhibits metastasis independently of its effects on differentiation. In vivo genetic reconstitution experiments show that miR-203 inhibits lung metastasis by suppressing the prometastatic activities of three factors involved in cytoskeletal dynamics (LASP1, extracellular matrix remodeling (SPARC, and cell metabolism (NUAK1. Expression of miR-203 and its downstream effectors correlates with HNSCC overall survival outcomes, indicating the therapeutic potential of targeting this signaling axis.

  2. Investigation of extracellular microRNAs in oral squamous cell carcinoma, rheumatoid arthritis and mesenchymal stem cell differentiation

    DEFF Research Database (Denmark)

    Yan, Yan

    Extracellular microRNAs (miRNAs) refer to cell-free miRNAs that are protected by extracellular vesicles (EVs) and protein complexes from degradation. Extracellular miRNAs are also known as circulating miRNAs that can circulate in bodily fluids. Studies have reported that extracellular miRNAs can...... serve as biomarkers for human diseases and can also act as mediators in cell-cell communication. In cancer, the abnormal expression of miRNAs in plasma has been observed. However, there is no report on the association of plasma miRNA expression with oral squamous cell carcinoma (OSCC) recurrence after...... MSCs contained differentially regulated miRNAs. However, the change in EV miRNA derived from BMSCs and ASCs during osteogenesis has not been characterized by NGS. In the third project, it was found that osteogenic differentiation regulated miRNA expression in BMSCs and ASCs, as well as their EV mi...

  3. Invasive lobular carcinoma with extracellular mucin production-a novel pattern of lobular carcinomas of the breast. Clinico-pathological description of eight cases.

    Science.gov (United States)

    Cserni, Gábor; Floris, Giuseppe; Koufopoulos, Nektarios; Kovács, Anikó; Nonni, Afroditi; Regitnig, Peter; Stahls, Anders; Varga, Zsuzsanna

    2017-07-01

    Invasive lobular carcinoma of the breast is known to produce intracellular mucin and has been recognized in single-case reports to show extracellular mucin production, as well. This latter morphology is not only rare but must also be under- or misdiagnosed. The aim was to better characterize this entity. Cases of lobular cancers demonstrating extracellular mucin formation were identified in a multi-institutional effort and their clinical and morphologic features were assessed. Immunohistochemistry was used to characterize the E-cadherin-membrane complex, neuroendocrine differentiation, and to some extent, mucin formation. All but one of the eight cases occurred in postmenopausal patients. Extracellular mucin production was present in 5 to 50% of the tumour samples and rarely also appeared in nodal and distant metastases. The tumours were completely E-cadherin negative and showed cytoplasmic p120 positivity. The majority (n = 6/8) was also completely negative for β-catenin, but two tumours displayed focal β-catenin positivity in the mucinous area. MUC1 and MUC2 expression was observed in all and 7/8 tumours, respectively; neuroendocrine differentiation was present in only one. Invasive lobular carcinoma with extracellular mucin formation is a rare morphologic variant of lobular carcinoma prone to be misdiagnosed and warranting further studies.

  4. Oral-specific ablation of Klf4 disrupts epithelial terminal differentiation and increases premalignant lesions and carcinomas upon chemical carcinogenesis.

    Science.gov (United States)

    Paparella, María L; Abrigo, Marianela; Bal de Kier Joffe, Elisa; Raimondi, Ana R

    2015-11-01

    Squamous cell carcinoma (SSC) of the head and neck is the sixth most common cancer and is rarely diagnosed in early stages. The transcription factor Krϋppel-like factor 4 (Klf4) suppresses cell proliferation and promotes differentiation. Inducible mice carrying an oral-specific ablation of Klf4 (K14-CreER(tam) /Klf4(flox/flox) ) develop mild dysplastic lesions and abnormal differentiation in the tongue. Aiming to analyze whether Klf4 cooperate in oral chemical carcinogenesis,we applied 4-nitroquinoline 1-oxide (4NQO), a tobacco surrogate, to this conditional Klf4 knockout mice. K14-CreER(tam) /Klf4(flox/flox) and control mice were treated with 4NQO for 16 weeks and monitored until week 30. Histopathological samples were used for diagnostic purposes and immunofluorescence detection of epithelial differentiation markers. 4NQO-treated K14-CreER(tam) /Klf4(flox/flox) mice (Klf4KO 4NQO) showed a significant weight loss and developed more severe dysplastic lesions than control mice with 4NQO (P oral SCC and a marked keratinization pattern in dysplasias, in situ carcinomas and SCC. Also, tongues derived from Klf4KO 4NQO mice exhibited reduced terminal differentiation as judged by cytokeratin 1 staining when compared with 4NQO-treated controls. Klf4 ablation results in more severe dysplastic lesions in oral mucosa, with a tendency to higher incidence of SCC, after chemical carcinogenesis. We show here, in a context similar to the human carcinogenesis, that absence of Klf4 accelerates carcinogenesis and correlates with the absence of cytokeratin 1 expression. These results suggest a potential role for KLF4 as a tumor suppressor gene for the tongue epithelium. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Maximal safe dose of I-131 after failure of standard fixed dose therapy in patients with differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Lee, Jong-Jin; Chung, June-Key; Kim, Sung-Eun; Kang, Won-Jun; Park, Do-Joon; Lee, Dong-Soo; Cho, Bo-Youn; Lee, Myung-Chul

    2008-01-01

    The maximal safe dose (MSD) on the basis of bone marrow irradiation levels allows the delivery of a large amount of I-131 to thyroid cancer tissue. The efficacy of MSD therapy in differentiated metastatic thyroid cancers that persisted after conventional fixed dose therapy is investigated. Forty-seven differentiated thyroid carcinoma patients with non-responsive residual disease despite repetitive fixed dose I-131 therapy were enrolled in this study. Their postoperative pathologies were 43 papillary carcinomas and 4 follicular carcinomas. The MSD was calculated with the Memorial Sloan-Kettering Cancer Center protocol using serial blood samples. The MSDs were administered at intervals of 6 months. Treatment responses were evaluated using I-131 whole-body scans and serum thyroglobulin measurements. The mean calculated MSD was 12.5±2.1 GBq (339.6±57.5 mCi). Of the 46 patients, 7 (14.9%) showed complete remission, 15 (31.9%) partial remission, 19 (40.4%) stable disease, and 6 (12.8%) disease progression. Of the patients who showed complete or partial remission, 15 (65%) showed response after the first MSD session and 6 (26%) showed response after the second session. Twenty-nine patients (62%) experienced transient cytopenia after therapy, but three did not recover to the baseline level. The maximal safe dose provides an effective means of treatment in patients who failed to respond adequately to conventional fixed dose therapy. I-131 MSD therapy can be considered in patients who fail fixed dose therapy. (author)

  6. Polymorphous Sweat Gland Carcinoma: An Immunohistochemical and Molecular Study.

    Science.gov (United States)

    Ronen, Shira; Aguilera-Barrantes, Irene; Giorgadze, Tamara; Šteiner, Petr; Grossmann, Petr; Suster, Saul

    2018-03-06

    Polymorphous sweat gland carcinoma is an uncommon low-grade malignant adnexal tumor with a marked predilection for the distal extremities. Histologically, the lesions are characterized by a cellular proliferation showing a combination of growth patterns, including trabecular, solid, tubular, cribriform, or adenoid cystic and pseudopapillary. The immunohistochemical and molecular profile of these tumors has not yet been properly addressed. We have studied 3 cases of polymorphous sweat gland carcinoma using a broad panel of immunohistochemical markers including cytokeratin AE1/AE3, CK5/6, MOC31, p40, p63, p16, chromogranin, synaptophysin, CD56, MIB-1, estrogen receptor, progesterone receptor, androgen receptor, BER-EP4, smooth muscle actin, epithelial membrane antigen, carcinoembryonic antigen, CD117, S100 protein, HBME-1, DOG1, vimentin, and mammaglobin. We also examined for the MYB-NFIB fusion by fluorescent in situ hybridization (ISH) and for human papilloma virus by ISH. Our studies show that cytokeratin AE1/AE3, CK5/6, p40, p63, p16, chromogranin, and CD56 stains were positive in all 3 cases. All 3 cases were negative for MYB-NFIB fusion by fluorescent ISH which rules out adenoid cystic carcinoma. DNA ISH studies for high-risk human papilloma virus were negative in all cases. MIB-1 proliferation index was very high (30%-70% nuclear positivity), supporting a malignant phenotype. The positivity for chromogranin and CD56 suggests partial neuroendocrine differentiation. The differential diagnosis includes metastases from internal malignancies, basal cell carcinoma, and other benign and malignant adnexal neoplasms such as adenoid cystic carcinoma, ductal eccrine carcinoma, and microcystic carcinoma. Positivity for p16 in combination with chromogranin and CD56 may be potentially good markers for differentiating this tumor from other adnexal tumors.

  7. Carcinoma epidermoide (variante pequenas células vs. carcinoma de pequenas células do pulmão: diagnóstico diferencial em material de biópsia Small cell variant of squamous cell carcinoma vs. small cell carcinoma of the lung: differential diagnosis in biopsies

    Directory of Open Access Journals (Sweden)

    Rachel Martins Marinho

    2010-04-01

    Full Text Available O diagnóstico diferencial entre a variante pequenas células do carcinoma epidermoide e do carcinoma de pequenas células nem sempre é fácil. Apesar de os descritores alertarem que o primeiro deva manter suas características morfológicas e, muitas vezes, diferenciação escamosa focal, a escassez de material aliada a artefatos de fixação frequentes nessas biópsias podem dificultar a vida do patologista. Entretanto, a definição entre um e outro pode alterar significativamente a escolha da modalidade terapêutica do paciente e, em alguns casos, influenciar seu prognóstico. Procuramos nesta publicação alertar para o problema e facilitar essa diferenciação, sugerindo um painel imuno-histoquímico.The differential diagnosis between small cell variant of squamous carcinoma and small cell carcinoma is not always simple. Despite the fact that studies show the former keeps its morphologic characteristics and focal squamous differentiation, the scarcity of the material as well as frequent fixation artifacts in these biopsies may hinder analysis. However, this differentiation between them may change significantly the choice of therapeutic approach and, in some cases, influence prognosis. In this paper, we draw attention to this problem and suggest a immunohistochemical panel to facilitate this differential diagnosis.

  8. Basaloid Carcinoma of the Breast Mimicking Cutaneous Basaloid Neoplasms.

    Science.gov (United States)

    Solus, Jason F; Goyal, Amrita; Duncan, Lyn M; Nazarian, Rosalynn M

    2015-09-01

    Basaloid carcinoma of the breast (BCB) is a rare, triple-negative aggressive primary breast tumor that can closely mimic cutaneous basal cell carcinoma (BCC), neuroendocrine tumors, adnexal neoplasms, and other primary breast tumors. Accurate diagnosis of this tumor is critical for appropriate clinical management. We add to the literature 2 female patients with BCB presenting with a nipple mass. Histopathologic findings from both patients showed dermal nests and cords of atypical basaloid cells with epidermal involvement, closely resembling cutaneous BCC. A panel of immunohistochemical stains, including the novel use of CK17, is essential for differentiating BCB from mimickers. BCB is a rare primary breast tumor that follows an aggressive clinical course and closely mimics many basaloid neoplasms, including cutaneous BCC clinicopathologically. Increased awareness of BCB among dermatologists and dermatopathologists is critical for accurate diagnosis and patient care.

  9. Br-DIF-1 accelerates dimethyl sulphoxide-induced differentiation of P19CL6 embryonic carcinoma cells into cardiomyocytes.

    Science.gov (United States)

    Seya, K; Kanemaru, K; Matsuki, M; Hongo, K; Kitahara, H; Kikuchi, H; Oshima, Y; Kubohara, Y; Okumura, K; Motomura, S; Furukawa, K-I

    2012-02-01

    Stem cell transplantation therapy is a promising option for treatment of severe ischaemic heart disease. Dimethyl sulphoxide (DMSO) differentiates P19CL6 embryonic carcinoma cells into cardiomyocyte-like cells, but with low differentiation capacity. To improve the degree of this differentiation, we have assessed several derivatives of the differentiation-inducing factor-1 (DIF-1), originally found in the cellular slime mould Dictyostelium discoideum, on P19CL6 cells. P19CL6 cells were cultured with each derivative and 1% DMSO for up to 16 days. Differentiation was assessed by measuring the number of beating and non-beating aggregates, and the expression of genes relevant to cardiac tissue. The mechanism of action was investigated using a T-type Ca(2+) channel blocker. Of all the DIF-1 derivatives tested only Br-DIF-1 showed any effects on cardiomyocyte differentiation. In the presence of 1% DMSO, Br-DIF-1 (0.3-3 µM) significantly and dose-dependently increased the number of spontaneously beating aggregates compared with 1% DMSO alone, by day 16. Expression of mRNA for T-type calcium channels was significantly increased by Br-DIF-1 + 1% DMSO compared with 1% DMSO alone. Mibefradil (a T-type Ca(2+) channel blocker; 100 nM) and a small interfering RNA for the T-type Ca(2+) channel both significantly decreased the beating rate of aggregates induced by Br-DIF-1 + 1% DMSO. Br-DIF-1 accelerated the differentiation, induced by 1% DMSO, of P19CL6 cells into spontaneously beating cardiomyocyte-like cells, partly by enhancing the expression of the T-type Ca(2+) channel gene. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  10. Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells.

    Directory of Open Access Journals (Sweden)

    Roman J Krawetz

    Full Text Available The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK play pivotal roles in cell migration, apoptosis (membrane blebbing, cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the

  11. Technetium-99m DISIDA hepatobiliary agent in diagnosis of hepatocellular carcinoma: relationship between detectability and tumor differentiation

    International Nuclear Information System (INIS)

    Calvet, X.; Pons, F.; Bruix, J.; Bru, C.; Lomena, F.; Herranz, R.; Brugera, M.; Faus, R.; Rodes, J.

    1988-01-01

    The present investigation was aimed to assess the usefulness of biliary agents scintigraphy in the diagnosis of hepatocellular carcinoma (HCC) and to ascertain the relationship between the uptake of these agents and the degree of HCC differentiation. Forty-four patients with this hepatic cancer were included in the study. Liver scans were performed 20 min and 3 hr after the administration of 99mTc diisopropyliminodiacetic acid (DISIDA). DISIDA scintigraphy could not be assessed in six cases. In 16 (42%) out of the remaining 38 patients, the tumor exhibited equal or greater radioactivity uptake than the surrounding liver. In six out of these 16 patients, tumor uptake was apparent in the early and delayed hepatic scans, while in the other ten subjects radioactivity uptake by the HCC could only be detected in the 3-hr delayed scans. In the remaining 22 patients, HCC appeared as a cold area. Tumor location by this technique did not differ from that observed by 99mTc-sulfur colloid scan or ultrasound. DISIDA uptake was significantly related to tumor differentiation: 70% of those well differentiated tumors exhibited DISIDA uptake, whereas it was found in only 30% of those moderately differentiated and in none of those poorly differentiated (p less than 0.05). These results show that DISIDA scintigraphy can be useful in the diagnosis of HCC. Since its sensitivity is related to the degree of tumor differentiation, it may be indicated when aspiration cytology is unable to distinguish between well differentiated HCC and reactive changes due to hepatic cirrhosis

  12. {sup 68}Ga-DOTA{sup 0}-Tyr{sup 3}-octreotide positron emission tomography in nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Schartinger, Volker H.; Dudas, Jozsef; Url, Christoph; Riechelmann, Herbert [Medical University Innsbruck, Department of Otorhinolaryngology, Innsbruck (Austria); Reinold, Susanne [Medical University Innsbruck, Institute of Pathology, Innsbruck (Austria); Virgolini, Irene J.; Kroiss, Alexander; Uprimny, Christian [Medical University Innsbruck, Department for Nuclear Medicine, Innsbruck (Austria)

    2015-01-15

    PET/CT with {sup 68}Ga-labelled [DOTA{sup 0},Tyr{sup 3}]-octreotide ({sup 68}Ga-DOTA-TOC PET/CT) is a routinely used imaging modality for neuroendocrine tumours expressing somatostatin receptors (SSTR). Recent studies have shown SSTR expression in head and neck squamous cell carcinoma, albeit lower than in highly differentiated neuroendocrine tumours. We sought to determine whether nasopharyngeal carcinoma (NPC) positive for Epstein-Barr virus (EBV), a rare subtype of head and neck cancer, shows increased {sup 68}Ga-DOTA-TOC uptake indicating expression of SSTR. Five patients with untreated, histologically proven EBV-positive NPC were referred for {sup 68}Ga-DOTA-TOC PET/CT. Tracer uptake in tumour lesions was assessed visually and semiquantitatively measuring maximum standardized uptake values (SUVmax) and tumour to background ratios. Increased tumour-specific uptake was detected in all five patients with a median SUVmax of 10.6 (range 3.6 - 17.1) in the primary tumour and 13.2 (range 6.1 - 14.5) in cervical lymph node metastases. {sup 68}Ga-DOTA-TOC PET/CT demonstrated tracer uptake in EBV-positive NPC comparable to that in highly differentiated neuroendocrine tumours. This observation is consistent with increased SSTR expression in EBV-positive NPC and may open new diagnostic and therapeutic windows in NPC. (orig.)

  13. Differentiation between healthy thyroid remnants and tumor tissue after radioiodine therapy in patients with differentiated thyroid carcinoma using in-vitro phosphorus-31 magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Moka, D.; Dietlein, M.; Schicha, H.; Raffelt, K.; Hahn, J.

    2002-01-01

    Full text: In many tumors, tumor growth and spread is triggered by changes in cell membrane metabolism, which can lead to systemic alterations in levels of phospholipids. The aim of this study was to differentiate between healthy remnants of thyroid tissue and residual/recurrent tumor tissue or metastases in patients with thyroid carcinoma by measurement of plasma levels of various phospholipids. Phospholipid concentrations was measured by in-vitro phosphorus-31-magnetic resonance spectroscopy ( 31 P-MRS) in blood samples from 30 patients with thyroid cancer, who had been rendered hypothyroid in preparation for diagnostic/therapeutic administration of iodine-131. All patients were already thyroidectomized. 131 I-whole-body scintigraphy and measurements of thyroglobulin values in a 2-year-follow-up were used to distinguish between patients in remission, patients with only healthy thyroid remnants and patients with cancerous thyroid tissue and/or metastases. Significantly lower blood plasma levels of systemic sphingomyelin (0.33±0.06 vs. 0.46±0.03 (controls) mmol/l; p 31 P-MRS can be used to differentiate between the presence of tumor tissue, healthy remnants of thyroid tissue not requiring further treatment and remission in patients with thyroid cancer. In future, therefore, plasma 31 P-MRS could be developed as an additional diagnostic tool for the follow-up of differentiated thyroid cancer. (author)

  14. Treatment of a mixed acinar-endocrine carcinoma with uptake on 68Gallium-DOTATOC positron emission tomography-computed tomography: A case report.

    Science.gov (United States)

    De Both, Anneleen; De Man, Marc; Troisi, Roberto; Van Vlierberghe, Hans; Hoorens, Anne; Geboes, Karen

    2017-07-01

    The case of a 35-year old female patient with a diagnosis of metastatic mixed acinar-endocrine carcinoma (MAEC) is investigated in the present study. The patient was believed to have a well-differentiated neuroendocrine tumor (NET) with a high Ki-67 index and uptake on 68 Gallium-DOTATOC positron emission tomography-computed tomography for 9 years, and was treated accordingly. The patient had long lasting disease control by treatment with sunitinib, and a response was observed in numerous lesions with peptide receptor radionuclide therapy (PRRT). Following treatment for metastatic disease for >4 years, liver transplantation was performed, as an exception to normal recommendations, at the time of progression of a centrally located liver lesion inducing obstructive jaundice. Following transplantation, the diagnosis of a Grade 3 NET, as defined by the WHO 2010 classification, was challenged and changed to MAEC. MAEC is a rare type of tumor of the pancreas, exhibiting endocrine and acinar differentiation. It is difficult to diagnose, often being misidentified as acinar cell carcinoma or predominantly as neuroendocrine neoplasms. Immunohistochemical labelling provides the only evidence for the dual differentiation of neuroendocrine (synaptophysin and chromogranin) and acinar (lipase, trypsin and chymotrypsin) cell markers. Studies investigating MAECs with a clear histopathological diagnosis are scarce, in addition to evidence of disease behaviour and treatment options. It is generally agreed that surgery is the primary treatment in patients with resectable tumors. The responses to sunitinib and PRRT suggested that treatments considered or developed for NETs may be beneficial in MAEC cases.

  15. Differentiation-inducing factor-1 induces cyclin D1 degradation through the phosphorylation of Thr286 in squamous cell carcinoma

    International Nuclear Information System (INIS)

    Mori, Jun; Takahashi-Yanaga, Fumi; Miwa, Yoshikazu; Watanabe, Yutaka; Hirata, Masato; Morimoto, Sachio; Shirasuna, Kanemitsu; Sasaguri, Toshiyuki

    2005-01-01

    Differentiation-inducing factors (DIFs) are morphogens which induce cell differentiation in Dictyostelium. We reported that DIF-1 and DIF-3 inhibit proliferation and induce differentiation in mammalian cells. In this study, we investigated the effect of DIF-1 on oral squamous cell carcinoma cell lines NA and SAS, well differentiated and poorly differentiated cell lines, respectively. Although DIF-1 did not induce the expression of cell differentiation makers in these cell lines, it inhibited the proliferation of NA and SAS in a dose-dependent manner by restricting the cell cycle in the G 0 /G 1 phase. DIF-1 induced cyclin D1 degradation, but this effect was prevented by treatment with lithium chloride and SB216763, the inhibitors of glycogen synthase kinase-3β (GSK-3β). Depletion of endogenous GSK-3β by RNA interference also attenuated the effect of DIF-1 on cyclin D1 degradation. Therefore, we investigated the effect of DIF-1 on GSK-3β and found that DIF-1 dephosphorylated GSK-3β on Ser 9 and induced the nuclear translocation of GSK-3β, suggesting that DIF-1 activated GSK-3β. Then, we examined the effect of DIF-1 on cyclin D1 mutants (Thr286Ala, Thr288Ala, and Thr286/288Ala). We revealed that Thr286Ala and Thr286/288Ala mutants were highly resistant to DIF-1-induced degradation compared with wild-type cyclin D1, indicating that the phosphorylation of Thr 286 was critical for cyclin D1 degradation induced by DIF-1. These results suggest that DIF-1 induces degradation of cyclin D1 through the GSK-3β-mediated phosphorylation of Thr 286

  16. Poorly Differentiated Thyroid Carcinoma Arising in Struma Ovarii: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Pisutt Srichaikul

    2016-03-01

    Full Text Available An 81-year-old woman presented with a pelvic mass. The computed tomography scan showed a non- calcifiedsolidcysticmass,10.4x11.5x6.7centimeters.Sheunderwent totalabdominalhysterectomy withbilateral salpingo-oophorectomy,omentectomyandascitic fluidforcytology. Histopathologyreportedpoorlydifferentiated thyroid carcinoma arising in struma ovarii. Currently she has been free of disease for 5 months from the date of diagnosis.

  17. Characterization of novel monoclonal antibodies that target proteins differentially expressed in hepatocellular carcinoma : a proteomics approach

    OpenAIRE

    Öztaş, Emin

    2011-01-01

    Ankara : The Department of Molecular Biology and Genetics and the Institute of Engineering and Science of Bilkent University, 2011. Thesis (Ph. D.) -- Bilkent University, 2011. Includes bibliographical references leaves 85-91. Hepatocellular carcinoma (HCC) is the sixth common cancer in the world. Because of the late diagnosis of the disease, survival rates are still poor in the HCC patients. Surveillance strategies have to be developed in populations with high risk groups hav...

  18. Contribution of mono-exponential, bi-exponential and stretched exponential model-based diffusion-weighted MR imaging in the diagnosis and differentiation of uterine cervical carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Meng; Yu, Xiaoduo; Chen, Yan; Ouyang, Han; Zhou, Chunwu [Chinese Academy of Medical Sciences, Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Beijing (China); Wu, Bing; Zheng, Dandan [GE MR Research China, Beijing (China)

    2017-06-15

    To investigate the potential of various metrics derived from mono-exponential model (MEM), bi-exponential model (BEM) and stretched exponential model (SEM)-based diffusion-weighted imaging (DWI) in diagnosing and differentiating the pathological subtypes and grades of uterine cervical carcinoma. 71 newly diagnosed patients with cervical carcinoma (50 cases of squamous cell carcinoma [SCC] and 21 cases of adenocarcinoma [AC]) and 32 healthy volunteers received DWI with multiple b values. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), water molecular diffusion heterogeneity index (alpha), and distributed diffusion coefficient (DDC) were calculated and compared between tumour and normal cervix, among different pathological subtypes and grades. All of the parameters were significantly lower in cervical carcinoma than normal cervical stroma except alpha. SCC showed lower ADC, D, f and DDC values and higher D* value than AC; D and DDC values of SCC and ADC and D values of AC were lower in the poorly differentiated group than those in the well-moderately differentiated group. Compared with MEM, diffusion parameters from BEM and SEM may offer additional information in cervical carcinoma diagnosis, predicting pathological tumour subtypes and grades, while f and D showed promising significance. (orig.)

  19. MashI Expression Is Induced in Neuroendocrine Prostate Cancer Upon the Loss of Foxa2

    OpenAIRE

    Gupta, Aparna; Yu, Xiuping; Case, Tom; Paul, Manik; Shen, Michael M.; Kaestner, Klaus H.; Matusik, Robert J.

    2012-01-01

    Neuroendocrine (NE) prostate tumors and neuroendocrine differentiation (NED) in prostatic adenocarcinomas have been associated with poor prognosis. In this study, we used the TRAMP mouse model that develops NE prostate tumors to identify key factors that can lead to NED. We have previously reported that NE tumors express the forkhead transcription factor, Foxa2, Mash1 (mouse achaete scute homolog-1), as well as Synaptophysin. In TRAMP, the prostatic intraepithelial neoplasia (PIN) first expre...

  20. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    Science.gov (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Ovarian transitional cell carcinoma represents a poorly differentiated form of high-grade serous or endometrioid adenocarcinoma.

    Science.gov (United States)

    Takeuchi, Tadahisa; Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kobayashi, Hiroaki; Kato, Kiyoko; Oda, Yoshinao

    2013-07-01

    Ovarian transitional cell tumors include Brenner tumors (BTs) and transitional cell carcinoma (TCC; non-BTs) according to the most recent World Health Organization classification. However, it remains a matter of debate whether TCC represents a distinct entity or a morphologic variant of high-grade serous adenocarcinoma (HG-SC). The purpose of this study was to resolve the above question by clarifying the morphologic, immunohistochemical, and molecular features of TCC. We reviewed 488 cases of epithelial ovarian carcinomas and reclassified them on the basis of the most recent World Health Organization classification with the modifications proposed by Köbel and colleagues, and 35 cases of TCC were identified; 25 and 6 TCCs were admixed with HG-SC and endometrioid adenocarcinoma (EC), respectively, and the remaining 4 cases were pure TCC. TCC components were not observed in any clear cell carcinomas or mucinous adenocarcinomas. Only 2 cases of malignant BT were identified. In addition to TCCs, malignant BTs, and related adenocarcinomas, benign and borderline BTs were included in the following immunohistochemical and molecular analyses. Immunohistochemically, pure TCCs, TCCs admixed with HG-SC, and pure HG-SCs were characterized by frequent aberrant p53 expression (diffuse or null pattern) and WT1+/ER+/PR+/IMP2+ immunophenotype, whereas BTs, including benign, borderline, and malignant BTs, were characterized by lack of aberrant p53 expression and WT1-/ER-/PR-/IMP2- immunophenotype. In contrast to the BTs, pure ECs and TCCs admixed with EC showed an ER+/PR+ immunophenotype. Nearly all the tumors with a TP53 gene mutation by molecular analysis showed aberrant p53 staining patterns. In conclusion, TCC is not a distinct entity but a poorly differentiated form of serous or EC, as (1) most TCCs coexist with HG-SC (mostly) or EC (occasionally), and (2) the immunophenotype and molecular features are similar to those of HG-SC or EC but different from those of BTs.

  2. Two cases of breast carcinoma with osteoclastic giant cells: Are the osteoclastic giant cells pro-tumoural differentiation of macrophages?

    Directory of Open Access Journals (Sweden)

    Shishido-Hara Yukiko

    2010-08-01

    Full Text Available Abstract Breast carcinoma with osteoclastic giant cells (OGCs is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1 had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2 with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K and a histiocyte marker (CD68, but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.

  3. Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells

    KAUST Repository

    Moritz, Tom

    2016-02-05

    The tumour protein D52 isoform 1 (PC-1), a member of the tumour protein D52 (TPD52) protein family, is androgen-regulated and prostate-specific expressed. Previous studies confirmed that PC-1 contributes to malignant progression in prostate cancer with an important role in castration-resistant stage. In the present work, we identified its impact in mechanisms leading to neuroendocrine (NE) transdifferentiation. We established for long-term PC-1 overexpression an inducible expression system derived from the prostate carcinoma cell line LNCaP. We observed that PC-1 overexpression itself initiates characteristics of neuroendocrine cells, but the effect was much more pronounced in the presence of the cytokine interleukin-6 (IL-6). Moreover, to our knowledge, this is the first report that treatment with IL-6 leads to a significant upregulation of PC-1 in LNCaP cells. Other TPD52 isoforms were not affected. Proceeding from this result, we conclude that PC-1 overexpression enhances the IL-6-mediated differentiation of LNCaP cells into a NE-like phenotype, noticeable by morphological changes and increased expression of typical NE markers, like chromogranin A, synaptophysin or beta-3 tubulin. Immunofluorescent staining of IL-6-treated PC-1-overexpressing LNCaP cells indicates a considerable PC-1 accumulation at the end of the long-branched neuron-like cell processes, which are typically formed by NE cells. Additionally, the experimentally initiated NE transdifferentiation correlates with the androgen receptor status, which was upregulated additively. In summary, our data provide evidence for an involvement of PC-1 in NE transdifferentiation, frequently associated with castration resistance, which is a major therapeutic challenge in the treatment of advanced prostate cancer.

  4. Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Pavel, Marianne E; Singh, Simron; Strosberg, Jonathan R; Bubuteishvili-Pacaud, Lida; Degtyarev, Evgeny; Neary, Maureen P; Carnaghi, Carlo; Tomasek, Jiri; Wolin, Edward; Raderer, Markus; Lahner, Harald; Valle, Juan W; Pommier, Rodney; Van Cutsem, Eric; Tesselaar, Margot E T; Fave, Gianfranco Delle; Buzzoni, Roberto; Hunger, Matthias; Eriksson, Jennifer; Cella, David; Ricci, Jean-François; Fazio, Nicola; Kulke, Matthew H; Yao, James C

    2017-10-01

    In the phase 3 RADIANT-4 trial, everolimus increased progression-free survival compared with placebo in patients with advanced, progressive, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (NETs). We now report the health-related quality of life (HRQOL) secondary endpoint. RADIANT-4 is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 97 centres in 25 countries worldwide. Adults (aged ≥18 years) were eligible for the study if they had pathologically confirmed, advanced (unresectable or metastatic), non-functional, well-differentiated (grade 1 or 2) NETs of lung or gastrointestinal origin. Patients were randomly allocated (2:1) using block randomisation (block size of three) by an interactive voice response system to receive oral everolimus (10 mg per day) or placebo, both with best supportive care, with stratification by tumour origin, WHO performance status, and previous somatostatin analogue treatment. HRQOL was assessed with the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline (visit 2, day 1), every 8 weeks (± 1 week) during the study for the first 12 months after randomisation, and every 12 weeks thereafter until study drug discontinuation. The primary endpoint, reported previously, was progression-free survival assessed by central review; HRQOL was a prespecified secondary endpoint. The prespecified secondary outcome measure was time to definitive deterioration (≥7 points) in FACT-G total score. Analyses were done on the full analysis set, consisting of all randomised patients, by intention to treat. Only data obtained while receiving the randomly allocated treatment were included in this analysis. Enrolment for RADIANT-4 was completed on Aug 23, 2013, but the trial is ongoing pending final analysis of the key secondary endpoint of overall survival. This trial is registered with ClinicalTrials.gov, number NCT01524783. Between April 3, 2012, and Aug 23

  5. Complexes of γ-tubulin with nonreceptor protein tyrosine kinases Src and Fyn in differentiating P19 embryonal carcinoma cells

    International Nuclear Information System (INIS)

    Kukharskyy, Vitaliy; Sulimenko, Vadym; Macurek, Libor; Sulimenko, Tetyana; Draberova, Eduarda; Draber, Pavel

    2004-01-01

    Nonreceptor protein tyrosine kinases of the Src family have been shown to play an important role in signal transduction as well as in regulation of microtubule protein interactions. Here we show that γ-tubulin (γ-Tb) in P19 embryonal carcinoma cells undergoing neuronal differentiation is phosphorylated and forms complexes with protein tyrosine kinases of the Src family, Src and Fyn. Elevated expression of both kinases during differentiation corresponded with increased level of proteins phosphorylated on tyrosine. Immunoprecipitation experiments with antibodies against Src, Fyn, γ-tubulin, and with anti-phosphotyrosine antibody revealed that γ-tubulin appeared in complexes with these kinases. In vitro kinase assays showed tyrosine phosphorylation of proteins in γ-tubulin complexes isolated from differentiated cells. Pretreatment of cells with Src family selective tyrosine kinase inhibitor PP2 reduced the amount of phosphorylated γ-tubulin in the complexes. Binding experiments with recombinant SH2 and SH3 domains of Src and Fyn kinases revealed that protein complexes containing γ-tubulin bound to SH2 domains and that these interactions were of SH2-phosphotyrosine type. The combined data suggest that Src family kinases might have an important role in the regulation of γ-tubulin interaction with tubulin dimers or other proteins during neurogenesis

  6. Clinical features of bone metastasis for differentiated thyroid carcinoma: A study of 21 patients from a Tunisian center

    Directory of Open Access Journals (Sweden)

    Faouzi Kallel

    2014-01-01

    Full Text Available Introduction: The differentiated thyroid cancers have a good prognosis unless the presence of metastasis. These distant metastases, especially in bone, are a major cause of impaired quality of life and death requiring intensive management. The aim of our work was to study the patients′ data, the disease characteristics and to analyze the therapeutic management of these patients. Results: This study concerned a cohort of 21 patients treated for differentiated thyroid cancer during the period from 1995 to 2011. Eighteen of our patients were aged over 45 years. A majority of them had follicular carcinoma. Bone metastases were often multiple and located at the axial skeleton. They were associated with other types of metastases, especially lung metastasis. A majority of patients received 131I treatment, following surgery or external beam radiotherapy for a palliative purpose. Overall survival was 65% at 5 years and 49% at 10 years. A long-term survival was achieved in 10% of the patients benefiting from a multidisciplinary care adapted to each case. Conclusion: Bone metastases often have a pejorative turning in the natural history of differentiated thyroid cancers. The right selection of individuals with better prognosis, for whom more aggressive curative treatment was indicated, requires a better understanding of the features of bone involvement.

  7. Different expression of EZH2, BMI1 and Ki67 in low and high grade neuroendocrine tumors of the lung

    DEFF Research Database (Denmark)

    Bondgaard, Anna-Louise Reinert Ørsum; Poulsen, Thomas Tuxen; Poulsen, Hans Skovgaard

    2012-01-01

    Enhancer of Zeste Homolog 2 (EZH2) and B lymphoma Mo-MLV Insertion region 1 polycomb ring finger (BMI1) are involved in malignant transformation of many human carcinomas. Still, in neuroendocrine tumors of the lung (NELT) their expression pattern is largely unknown. This study evaluated their exp......Enhancer of Zeste Homolog 2 (EZH2) and B lymphoma Mo-MLV Insertion region 1 polycomb ring finger (BMI1) are involved in malignant transformation of many human carcinomas. Still, in neuroendocrine tumors of the lung (NELT) their expression pattern is largely unknown. This study evaluated...

  8. Prospective differentiation of clinically difficult to distinguish nodular basal cell carcinomas and intradermal nevi by non-invasive Reflectance Confocal Microscopy: a case series study

    NARCIS (Netherlands)

    Hoogedoorn, L.; Peppelman, M.; Blokx, W.A.M.; Erp, P.E.J. van; Gerritsen, M.J.P.

    2015-01-01

    BACKGROUND: Clinical differentiation between a nodular basal cell carcinoma (nBCC) and a benign intradermal nevus can be difficult. Even with additional dermoscopic evaluation, a correct diagnosis may be difficult. Currently, histopathological examination of a biopsy is the gold standard to

  9. In vivo assessment of optical properties of basal cell carcinoma and differentiation of BCC subtypes by high-definition optical coherence tomography

    DEFF Research Database (Denmark)

    Boone, Marc; Suppa, Mariano; Miyamoto, Makiko

    2016-01-01

    High-definition optical coherence tomography (HD-OCT) features of basal cell carcinoma (BCC) have recently been defined. We assessed in vivo optical properties (IV-OP) of BCC, by HD-OCT. Moreover their critical values for BCC subtype differentiation were determined. The technique of semi-log plot...

  10. Pigmented Nodular Basal Cell Carcinomas in Differential Diagnosis with Nodular Melanomas: Confocal Microscopy as a Reliable Tool for In Vivo Histologic Diagnosis

    International Nuclear Information System (INIS)

    Casari, A.; Pellacani, G.; Seidenari, S.; Pepe, P.; Longo, C.; Cesinaro, A. M.; Beretti, F.

    2011-01-01

    Nodular basal cell carcinoma, especially when pigmented, can be in differential diagnosis with nodular melanomas, clinically and dermoscopically. Reflectance confocal microscopy is a relatively new imaging technique that permits to evaluate in vivo skin tumors with a nearly histological resolution. Here, we present four cases of challenging nodular lesions where confocal microscopy was able to clarify the diagnosis.

  11. Proteomic analysis of differential proteins in pancreatic carcinomas: Effects of MBD1 knock-down by stable RNA interference

    Directory of Open Access Journals (Sweden)

    Ni Quanxing

    2008-04-01

    Full Text Available Abstract Background Methyl-CpG binding domain protein 1 (MBD1, a suppressor of gene transcription, may be involved in inactivation of tumor suppressor genes during tumorigenesis. Over-expression of MBD1 has been reported in human pancreatic carcinomas. Methods In this study, we established a MBD1-knock-down pancreatic cancer cell line (BxPC-3 using stable RNA interference, to compare the proteomic changes between control and MBD1-knock-down cells using two-dimensional gel electrophoresis and mass spectrometry. Results We identified five proteins that were up-regulated and nine proteins that were down-regulated. Most of the identified proteins are involved in tumorigenesis, some are prognostic biomarkers for human malignant tumors. Conclusion Our data suggest that these differential proteins may be associated with the function of MBD1, and provide some insight into the functional mechanism of MBD1 in the development of pancreatic cancer.

  12. Elevated level of serum growth differentiation factor 15 is associated with oral leukoplakia and oral squamous cell carcinoma.

    Science.gov (United States)

    Yang, Cheng-Zhe; Ma, Jie; Luo, Qing-Qiong; Neskey, David M; Zhu, Dong-Wang; Liu, Ying; Myers, Jeffrey N; Zhang, Chen-Ping; Zhang, Zhi-Yuan; Zhong, Lai-Ping

    2014-01-01

    Although molecular mechanism of growth differentiation factor 15 (GDF15) in tumorigenesis of oral squamous cell carcinoma (OSCC) is not clear, the diagnostic and prognostic value of serum GDF15 detection has been noticed. However, serum GDF15 levels in patients with oral leukoplakia and GDF15 as a potential predictive biomarker for response to induction chemotherapy in patients with OSCC have not been reported. Pretreatment serum GDF15 concentration was detected using an enzyme-linked immunosorbent assay in 30 healthy persons, 24 patients with oral leukoplakia, and 60 patients with OSCC. Serum GDF15 concentration was significantly higher in patients with oral leukoplakia and OSCC, compared with healthy controls (F = 13.701, df = 2, P oral leukoplakia, but also a prognostic/predictive biomarker associated with decreased survival and diminished response to induction chemotherapy for patients with OSCC. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Differential expression of anterior gradient protein 3 in intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

    Science.gov (United States)

    Brychtova, Veronika; Zampachova, Vita; Hrstka, Roman; Fabian, Pavel; Novak, Jiri; Hermanova, Marketa; Vojtesek, Borivoj

    2014-06-01

    Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer next to hepatocellular carcinoma (HCC). Despite the significant difference of the therapeutic strategy for both diseases, their histological appearance may be very similar. Thus the correct diagnosis is crucial for treatment choice but is often difficult to achieve. The aim of our study was to evaluate anterior gradient 3 (AGR3) as a new diagnostic marker helping to distinguish between ICC and HCC. AGR3 is a putative transmembrane protein implicated in breast, prostate and ovary tumorigenesis and belongs to the family of protein disulfide isomerases. Since there is little information on how AGR3 is expressed in normal and diseased tissues and what its exact function is, we analyzed its expression pattern in normal liver and tumor tissue of ICC and HCC. The immunohistochemical analysis in normal tissue revealed specific AGR3 expression in intrahepatic bile duct cholangiocytes which was not present in liver hepatocytes. Consequently we analyzed AGR3 expression in 74 representative samples of puncture biopsies, tissue excisions and resection specimens from which 48 samples were diagnosed as HCC and 26 as ICC. Our results showed AGR3 expression negative and weakly positive respectively in hepatocellular carcinomas compared to stronger AGR3 positivity in cholangiocellular carcinomas. AGR3 expression statistically significantly correlated to acid mucopolysaccharide expression and negatively correlated to glypican-3 expression. We conclude that according to receiver operating characteristics (ROC) analysis AGR3 expression is relatively specific for ICC and is potentially linked to mucosecretion, which may indicate potential implication in treatment resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Cognitive functions and mood during chronic thyrotropin-suppressive therapy with L-thyroxine in patients with differentiated thyroid carcinoma.

    Science.gov (United States)

    Jaracz, J; Kucharska, A; Rajewska-Rager, A; Lacka, K

    2012-09-01

    Subclinical thyroid dysfunctions may cause cognitive deficits and mood disorders. Chronic TSH-suppressive therapy with L-T(4) causing subclinical hyperthyroidism has been widely used in treatment of patients with thyroid differentiated carcinoma. The impact of this therapy on cognitive functions and mood have not been systematically studied. The aim of this study was to asses executive functions, working memory, attention, and depression in patients with subclinical hyperthyroidism in the course of TSH-suppressive therapy. Thirty-one patients with subclinical hyperthyroidism in the course of suppressive treatment with L-T(4) following the total thyroidectomy and radioiodine ablative therapy were included in the study. Cognitive functioning in patients and control group were investigated using the battery of neuropsychological tests [Wisconsin Card Sorting Test (WCST), The Oral Word Association Test (OWAT), Trail Making Test, The Stroop Color-Word Interference test and Digit span]. Psychometric evaluation was performed using 17-items the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The performance on tests assessed executive functions, psychomotor speed, and attention was significantly lower in patients group. There was no differences in results of Stroop test and Digit Span forward and backwards between both groups. The intensity of depressive symptoms negatively correlated with a number of completed categories on WCST and results of OWAT. Cognitive deficits were still observed when patients with concomitant general medical conditions and depression were excluded from the analysis. Our findings provide evidence of neuropsychological impairment in patients with differentiated thyroid carcinoma treated with chronic TSH-suppressive therapy.

  15. Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma

    International Nuclear Information System (INIS)

    Kim, Yun-Sook; Hwan Do, Jin; Bae, Sumi; Bae, Dong-Han; Shick Ahn, Woong

    2010-01-01

    Most patients with ovarian cancer are diagnosed with advanced stage disease (i.e., stage III-IV), which is associated with a poor prognosis. Differentially expressed genes (DEGs) in stage III serous ovarian carcinoma compared to normal tissue were screened by a new differential display method, the annealing control primer (ACP) system. The potential targets for markers that could be used for diagnosis and prognosis, for stage III serous ovarian cancer, were found by cluster and survival analysis. The ACP-based reverse transcriptase polymerase chain reaction (RT PCR) technique was used to identify DEGs in patients with stage III serous ovarian carcinoma. The DEGs identified by the ACP system were confirmed by quantitative real-time PCR. Cluster analysis was performed on the basis of the expression profile produced by quantitative real-time PCR and survival analysis was carried out by the Kaplan-Meier method and Cox proportional hazards multivariate model; the results of gene expression were compared between chemo-resistant and chemo-sensitive groups. A total of 114 DEGs were identified by the ACP-based RT PCR technique among patients with stage III serous ovarian carcinoma. The DEGs associated with an apoptosis inhibitory process tended to be up-regulated clones while the DEGs associated with immune response tended to be down-regulated clones. Cluster analysis of the gene expression profile obtained by quantitative real-time PCR revealed two contrasting groups of DEGs. That is, a group of genes including: SSBP1, IFI6 DDT, IFI27, C11orf92, NFKBIA, TNXB, NEAT1 and TFG were up-regulated while another group of genes consisting of: LAMB2, XRCC6, MEF2C, RBM5, FOXP1, NUDCP2, LGALS3, TMEM185A, and C1S were down-regulated in most patients. Survival analysis revealed that the up-regulated genes such as DDAH2, RNase K and TCEAL2 might be associated with a poor prognosis. Furthermore, the prognosis of patients with chemo-resistance was predicted to be very poor when genes such

  16. Identification of Differentially Expressed Genes in Metastatic and Non-Metastatic Nasopharyngeal Carcinoma Cells by Suppression Subtractive Hybridization

    Directory of Open Access Journals (Sweden)

    Xu-Yu Yang

    2005-01-01

    Full Text Available Background & Objective: Nasopharyngeal carcinoma (NPC is an epithelial neoplasm with high occurrence rates in southern China. The disease often metastasizes to regional lymphnodes at a very early stage. Local recurrences and metastasis occur frequently in patients with NPC and are a leading cause of death, despite improvements on treatment modalities. The molecular mechanism underlying the metastasis of nasopharyngeal carcinoma remains poorly understood, however, and requires additional elucidation. The aim of this study was to explore possible NPC gene candidates that may play key roles in NPC metastasis. Methods: Subtractive suppression hybridization (SSH was performed to isolate differentially expressed clones between the metastatic 5-8F and non-metastatic 6-10B nasopharyngeal carcinoma cell lines. Differentially expressed clones were screened and confirmed by reverse Northern blotting. The sequences of cDNA fragments were subsequently analyzed and compared to known sequences in Genbank. Results & Discussion: The SSH library contained thousands of positive clones. Random analysis of 300 clones by PCR demonstrated that 269 clones contained inserted fragments. Reverse Northern blot confirmed that 20 out of 192 clones examined were significantly up-regulated in the 5-8F cell line. Among these 20 clones, 16 were previously identified genes (flotilin-2, ezrin, pim-3, fli-1, mel, neugrin, znf216, ASB1, raly, UBE2A, keratin6A, TMED7, EIF3S9, FTL, two ribosomal proteins RPL21 and RPL16, two were predicted genes (c9orf74 and MDS006, and two sequences shared no homology with known genes listed in GenBank and may represent novel genes. The proposed functions of the genes identified in this study include cell signal transduction, cell survival, transcription regulation, cell mobility, protein synthesis, and DNA damage repair. Flotillin-2, fli-1, pim-3 and ezrin have previously been reported to be associated with tumor metastasis and progression. The

  17. Gastrointestinal Surgery of Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Hansen, Carsten Palnæs; Olsen, Ingrid Marie Holst; Knigge, Ulrich

    2015-01-01

    Surgery is the only treatment that may cure the patient with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) and should always be considered as the first-line treatment if radical resection can be achieved. Even in cases where radical surgery is not possible, palliative resection may...

  18. Differential diagnosis of lung carcinoma with three-dimensional quantitative molecular vibrational imaging

    Science.gov (United States)

    Gao, Liang; Hammoudi, Ahmad A.; Li, Fuhai; Thrall, Michael J.; Cagle, Philip T.; Chen, Yuanxin; Yang, Jian; Xia, Xiaofeng; Fan, Yubo; Massoud, Yehia; Wang, Zhiyong; Wong, Stephen T. C.

    2012-06-01

    The advent of molecularly targeted therapies requires effective identification of the various cell types of non-small cell lung carcinomas (NSCLC). Currently, cell type diagnosis is performed using small biopsies or cytology specimens that are often insufficient for molecular testing after morphologic analysis. Thus, the ability to rapidly recognize different cancer cell types, with minimal tissue consumption, would accelerate diagnosis and preserve tissue samples for subsequent molecular testing in targeted therapy. We report a label-free molecular vibrational imaging framework enabling three-dimensional (3-D) image acquisition and quantitative analysis of cellular structures for identification of NSCLC cell types. This diagnostic imaging system employs superpixel-based 3-D nuclear segmentation for extracting such disease-related features as nuclear shape, volume, and cell-cell distance. These features are used to characterize cancer cell types using machine learning. Using fresh unstained tissue samples derived from cell lines grown in a mouse model, the platform showed greater than 97% accuracy for diagnosis of NSCLC cell types within a few minutes. As an adjunct to subsequent histology tests, our novel system would allow fast delineation of cancer cell types with minimum tissue consumption, potentially facilitating on-the-spot diagnosis, while preserving specimens for additional tests. Furthermore, 3-D measurements of cellular structure permit evaluation closer to the native state of cells, creating an alternative to traditional 2-D histology specimen evaluation, potentially increasing accuracy in diagnosing cell type of lung carcinomas.

  19. [Clinical guideline for management of patients with low risk differentiated thyroid carcinoma].

    Science.gov (United States)

    Díez, Juan José; Oleaga, Amelia; Álvarez-Escolá, Cristina; Martín, Tomás; Galofré, Juan Carlos

    2015-01-01

    Incidence of thyroid cancer is increasing in Spain and worldwide. Overall thyroid cancer survival is very high, and stratification systems to reliably identify patients with worse prognosis have been developed. However, marked differences exist between the different specialists in clinical management of low-risk patients with thyroid carcinoma. Almost half of all papillary thyroid carcinomas are microcarcinomas, and 90% are tumors < 2 cm that have a particularly good prognosis. However, they are usually treated more aggressively than needed, despite the lack of adequate scientific support. Surgery remains the gold standard treatment for these tumors. However, lobectomy may be adequate in most patients, without the need for total thyroidectomy. Similarly, prophylactic lymph node dissection of the central compartment is not required in most cases. This more conservative approach prevents postoperative complications such as hypoparathyroidism or recurrent laryngeal nerve injury. Postoperative radioiodine remnant ablation and strict suppression of serum thyrotropin, although effective for the more aggressive forms of thyroid cancer, have not been shown to be beneficial for the treatment of low risk patients, and may impair their quality of life. This guideline provides recommendations from the task force on thyroid cancer of the Spanish Society of Endocrinology and Nutrition for adequate management of patients with low-risk thyroid cancer. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  20. Neuroendocrine dysfunction in Sjogren's syndrome.

    Science.gov (United States)

    Tzioufas, Athanasios G; Tsonis, John; Moutsopoulos, Haralampos M

    2008-01-01

    Interactions among the immune, nervous and endocrine systems, which are mediated by hormones, neuropeptides, neurotransmitters, cytokines and their receptors, appear to play an important role in modulating host susceptibility and resistance to inflammatory disease. The neuroendocrine system has two main components: the central and the peripheral. The central compartment is located in the locus ceruleus, the brainstem centers of the autonomic system and the paraventricular nucleus; the peripheral mainly consists of the sympathetic/adrenomedullary system, the hypothalamic-pituitary-adrenal axis (HPA), the hypothalamic-pituitary-gonadal (HPG) axis, and the neuroendocrine tissue located in several organs throughout the body. Hormones and neuropeptides may influence the activities of lymphoid organs and cells via endocrine and local autocrine/paracrine pathways or alter the function of different cell types in target organs. Recent studies highlighted alterations of the neuroendocrine system in systemic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and Sjogren's syndrome (SS). SS, a prototype autoimmune disorder, has a wide clinical spectrum, extending from organ involvement (autoimmune exocrinopathy) to systemic disease and B cell lymphoma. In SS, several functions of the neuroendocrine system are impaired. First, the HPA axis appears to be disturbed, since significantly lower basal ACTH and cortisol levels were found in patients with SS and were associated with a blunted pituitary and adrenal response to ovine corticotropin-releasing factor compared to normal controls. Second, HPG axis is also involved, since lack of estrogens is associated with human disease and the development of autoimmune exocrinopathy in several experimental models. Finally, exocrine glands are enriched with neuroendocrine-related molecules, adjacent to local autoimmune lesions. Certain clinical manifestations of the disease, including the sicca manifestations

  1. Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder

    Directory of Open Access Journals (Sweden)

    Igor Sterle

    2014-01-01

    Full Text Available Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5 and transient receptor potential vanilloid channels (TRPV1, and TRPV4. Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

  2. Differential expression of OPN, VEGF-A, and HIF-1α and its clinical significance in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHENG Yan

    2013-01-01

    Full Text Available ObjectiveTo investigate the expression patterns of osteopontin (OPN, vascular endothelial growth factor-A (VEGF-A, and hypoxia-inducible factor-1α(HIF-1α in primary hepatocellular carcinoma (HCC and determine the clinical significance of this differential expression profile. MethodsImmunohistochemical staining of OPN, VEGF-A, and HIF-1α was carried out on primary HCC tissues from 90 patients, HCC-adjacent cirrhosis tissues from 20 of those patients, and normal liver tissues from 15 healthy controls. Correlations between expression levels and HCC clinicopathological characteristics were assessed by Spearman's correlation coefficient. ResultsThe majority of HCC tissues showed positive immunostaining for OPN (69/90, 76.67%, VEGF-A (64/90, 71.11%, and HIF-1α (66/90, 73.33%. OPN- and VEGF-A-positivity were significantly higher than the results from the cirrhosis tissues and normal tissues. HIF-1α-positivity was similar between the HCC and cirrhosis tissues, but both were significantly different from the normal tissues. The differential expressions of OPN, VEGF-A, and HIF-1α were significantly correlated with tumor thrombus, capsular integrity, tumor differentiation and stage, and metastasis (P<0.05. ConclusionHCC tissues overexpress OPN, VEGF-A, and HIF-1α and this differential profile may be related to HCC progression. Future investigations of this triad of factors may provide novel insights into the biological characteristics of HCC and reveal important targets of molecular therapy.

  3. Carcinoma diferenciado de tiroides después de irradiación: a propósito de un caso Differentiated thyroid carcinoma after irradiation: apropos of a case

    Directory of Open Access Journals (Sweden)

    Caridad Verdecia Cañizares

    2007-12-01

    Full Text Available El carcinoma diferenciado de tiroides es una enfermedad rara en el niño. En pacientes de edad pediátrica y en adolescentes tiene un buen pronóstico y una elevada sobrevida. Presentamos el caso de un paciente diagnosticado en nuestro hospital quien había recibido, 6 años atrás, irradiación de cabeza y cuello a causa de un linfoma no Hodgkin de localización cervical derecha. En el seguimiento se detectó nódulo del lóbulo derecho del tiroides y mediante biopsia se realizó el diagnóstico de carcinoma papilar de tiroides. El resultado del tratamiento realizado (cirugía y aplicación de yodo radioactivo fue bueno, por lo que se concluye que el diagnóstico temprano y el tratamiento actual logran una remisión completa en el carcinoma diferenciado de tiroides.The differentiated thyroid carcinoma is a rare disease in children. In patients at pediatric ages and among adolescents, it has a good prognosis and a high survival rate. The case of a patient diagnosed in our hospital that received irradiation of the head and neck due to a non-Hodgkin lymphoma of right cervical localization 6 years before, was presented. A nodule in the right lobe of the thyroid was detected in the follow-up. The diagnosis of thyroid papillary carcinoma was made by biopsy. As the result of the treatment (surgery and radioiodine was good, it was concluded that the early diagnosis and the current treatment allowed a complete remission in the differentiated thyroid carcinoma.

  4. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wahid M

    2017-01-01

    Full Text Available Mohd Wahid, Arshad Jawed, Sajad Ahmad Dar, Raju K Mandal, Shafiul Haque Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia Abstract: Patients suffering from advanced basal cell carcinoma (BCC have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region. The primary efficacy analyses showed that 18 patients in the 200 mg group and 35 patients in the 800 mg group show an objective response (Central Review Committee that corresponds to 43% (95% confidence interval [CI]: 28–59 and 38% (95% CI: 28–48 in their respective categories. Disease control was found in 93% (39 patients and 80% (74 patients of the patients administered 200 and 800 mg sonidegib, respectively. The adverse events were assessed by the Central Review Committee as well as the investigator review team as per the guidelines of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The most frequently found adverse events reported in BOLT trials were muscle spasms, alopecia, dysgeusia (taste disturbance, nausea, elevated blood creatine kinase and fatigue. Comparatively, the patients administered 200 mg sonidegib showed fewer adverse events than those in the 800 mg sonidegib category. Thus, the benefit of using the 200 mg dose of sonidegib outweighs the associated risks and it can be inferred that it would be judicious to choose doses of lesser strength. Keywords: locally advanced basal cell carcinoma, metastatic basal

  5. Cytological diagnostic clues in poorly differentiated squamous cell carcinomas of the breast: Streaming arrangement, necrotic background, nucleolar enlargement and cannibalism of cancer cells.

    Science.gov (United States)

    Kinoshita, M; Matsuda, Y; Arai, T; Soejima, Y; Sawabe, M; Honma, N

    2018-02-01

    Squamous cell carcinoma (SCC) is a rare histological type of breast cancer. The cytological diagnosis of non-keratinising, poorly differentiated SCC is often difficult, and distinguishing it from invasive ductal carcinoma or apocrine carcinoma (AC) is especially challenging. We aimed to define the diagnostic cytological features of poorly differentiated SCC of the breast. We studied the cytological findings of poorly differentiated SCC (n=10) and compared them to those of IDC (n=15) and AC (n=14). The following six cytological features were evaluated: streaming arrangement, nucleolar enlargement, dense nuclei, cannibalism, atypical keratinocytes and necrotic background. SCC exhibited significantly higher frequencies of streaming arrangement (70% vs 6.7%, P=.002), nucleolar enlargement (80% vs 27%, P=.02), and necrotic background (80% vs 36%, P=.002) than invasive ductal carcinoma. The detection of two or three of these features yielded a higher sensitivity (80%) and specificity (93%) for the diagnosis of SCC. Streaming arrangement (70% vs 0%, Pstreaming arrangement, a necrotic background, nucleolar enlargement and cannibalism are useful indicators for the diagnosis of SCC of the breast. As such, greater attention should be paid to these morphological features in daily clinical practice. © 2017 John Wiley & Sons Ltd.

  6. Can video thermography improve differential diagnosis and therapy between basal cell carcinoma and actinic keratosis?

    Science.gov (United States)

    Di Carlo, Aldo; Elia, Fulvia; Desiderio, Flora; Catricalà, Caterina; Solivetti, Francesco M; Laino, Luigi

    2014-01-01

    Various noninvasive techniques (dermoscopy, confocal microscopy, etc.) have been introduced to help the clinical diagnosis in nonmelanoma skin cancer. Among them, the high definition video thermographic technique (VTG) has recently been proposed. The aim of this study is to define the VTG patterns, respectively of actinic keratosis (AK) and basal cell carcinoma (BCC), and to compare these data with them of dermoscopy. The study included 36 patients with a total number of 135 lesions who underwent clinical, VTG, and dermoscopic examination. The VTG showed the presence of a hyperthermic pattern in all the cases of AK, while in the case of the BCC, the pattern was hypothermic. Dermoscopy also showed distinct pattern for AK and for BCC, but in 22% of them the data were not conclusive. Our study permits us to define two specific VTG patterns, BCC and AK respectively. © 2014 Wiley Periodicals, Inc.

  7. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    Science.gov (United States)

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  8. Differentiation of focal-type autoimmune pancreatitis from pancreatic carcinoma: assessment by multiphase contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Furuhashi, Naohiro; Suzuki, Kojiro; Sakurai, Yusuke; Naganawa, Shinji [Nagoya University Graduate School of Medicine, Department of Radiology, Nagoya (Japan); Ikeda, Mitsuru [Nagoya University Graduate School of Medicine, Department of Radiological Technology, Nagoya (Japan); Kawai, Yuichi [Japanese Red Cross Nagoya Daiichi Hospital, Department of Diagnostic Radiology, Nagoya (Japan)

    2015-05-01

    To evaluate the utility of multiphase contrast-enhanced computed tomography (CT) findings alone and in combination for differentiating focal-type autoimmune pancreatitis (f-AIP) from pancreatic carcinoma (PC). The study group comprised 22 f-AIP lesions and 61 PC lesions. Two radiologists independently evaluated CT findings. Frequencies of findings were compared between f-AIP and PC. Statistical, univariate and multivariate analyses were performed. Homogeneous enhancement during the portal phase (AIP, 59 % vs. PC, 3 %; P < 0.001), dotted enhancement during the pancreatic phase (50 % vs. 7 %; P < 0.001), duct-penetrating sign (46 % vs. 2 %; P < 0.001), enhanced duct sign (36 % vs. 2 %; P < 0.001) and capsule-like rim (46 % vs. 3 %; P < 0.001) were more frequently observed in AIP. Ring-like enhancement during the delayed phase (5 % vs. 46 %; P < 0.001) and peripancreatic strands with a length of at least 10 mm (5 % vs. 39 %; P = 0.001) were more frequently observed in PC. AIP was identified with 82 % sensitivity and 98 % specificity using four of these seven findings. Multivariate analysis revealed significant differences in dotted enhancement (P = 0.004), duct-penetrating sign (P < 0.001) and capsule-like rim (P = 0.007). The combination of CT findings may allow improvements in differentiating f-AIP from PC. (orig.)

  9. Inhibition of miR-29c promotes proliferation, and inhibits apoptosis and differentiation in P19 embryonic carcinoma cells.

    Science.gov (United States)

    Chen, Bin; Song, Guixian; Liu, Ming; Qian, Lingmei; Wang, Lihua; Gu, Haitao; Shen, Yahui

    2016-03-01

    In our previous study, the upregulation of microRNA (miR)-29c was identified in the mother of a fetus with a congenital heart defect. However, the functional and regulatory mechanisms of miR‑29c in the development of the heart remain to be elucidated. In the present study, the role and mechanism of miR‑29c inhibition in heart development were investigated in an embryonic carcinoma cell model. Inhibition of miR‑29c promoted proliferation, and suppressed the apoptosis and differentiation of P19 cells. It was also demonstrated that Wingless‑related MMTV integration site 4 (Wnt4) was a target of miR‑29c, determined using bioinformatic analysis combined with luciferase assays. The inhibition of miR‑29c stimulated the WNT4/β‑catenin pathway, promoting proliferation of the P19 cells, but suppressing their differentiation into cardiomyocytes. Furthermore, the inhibition of miR‑29c promoted the expression of B cell lymphoma‑2 and inhibited cell apoptosis. These results demonstrate the significance of miR‑29c in the process of cardiac development and suggest that miR-29c dysregulation may be associated with the occurrence of CHD. Thus, miR-29c may have therapeutic potential in the future.

  10. Raman spectroscopy differentiates squamous cell carcinoma (SCC) from normal skin following treatment with a high-powered CO2 laser.

    Science.gov (United States)

    Fox, Sara A; Shanblatt, Ashley A; Beckman, Hugh; Strasswimmer, John; Terentis, Andrew C

    2014-12-01

    The number of cases of non-melanoma skin cancer (NMSC), which include squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), continues to rise as the aging population grows. Mohs micrographic surgery has become the treatment of choice in many cases but is not always necessary or feasible. Ablation with a high-powered CO2 laser offers the advantage of highly precise, hemostatic tissue removal. However, confirmation of complete cancer removal following ablation is difficult. In this study we tested for the first time the feasibility of using Raman spectroscopy as an in situ diagnostic method to differentiate NMSC from normal tissue following partial ablation with a high-powered CO2 laser. Twenty-five tissue samples were obtained from eleven patients undergoing Mohs micrographic surgery to remove NMSC tumors. Laser treatment was performed with a SmartXide DOT Fractional CO2 Laser (DEKA Laser Technologies, Inc.) emitting a wavelength of 10.6 μm. Treatment levels ranged from 20 mJ to 1200 mJ total energy delivered per laser treatment spot (350 μm spot size). Raman spectra were collected from both untreated and CO2 laser-treated samples using a 785 nm diode laser. Principal Component Analysis (PCA) and Binary Logistic Regression (LR) were used to classify spectra as originating from either normal or NMSC tissue, and from treated or untreated tissue. Partial laser ablation did not adversely affect the ability of Raman spectroscopy to differentiate normal from cancerous residual tissue, with the spectral classification model correctly identifying SCC tissue with 95% sensitivity and 100% specificity following partial laser ablation, compared with 92% sensitivity and 60% selectivity for untreated NMSC tissue. The main biochemical difference identified between normal and NMSC tissue was high levels of collagen in the normal tissue, which was lacking in the NMSC tissue. The feasibility of a combined high-powered CO2 laser ablation, Raman diagnostic procedure for the

  11. Correlation of metastasis characteristics with prognosis in gastric mixed adenoneuroendocrine carcinoma: Two case reports.

    Science.gov (United States)

    Tang, Qiang; Zhou, Zili; Chen, Jinhuang; Di, Maojun; Ji, Jintong; Yuan, Wenzheng; Liu, Zhengyi; Wu, Liang; Zhang, Xudan; Li, Kang; Shu, Xiaogang

    2017-12-01

    This article is aimed to retrospect the clinicopathological data of 2 cases of gastric MANENCs. MANEC is a rare biphasic tumor type that is coexistence of dual neuroendocrine and adenocarcinoma differentiation with each composing exceeding 30% volume. Gastric MANEC have just been reported anecdotally in the literature due to their rarity and heterogeneity. According to our study, these neoplasms have 3 different metastasis patterns: only adenocarcinomatous or neuroendocrine carcinoma and both of the 2 components. We first focus on the correlation of metastasis characteristics with prognosis in gastric MANEC, which may be potential implications for the choice of chemotherapy. The 2 cases of patient shared several symptoms: epigastric discomfort, weight loss, hematemesis, or melena. The 2 patients were diagnosis as MANEC based on the identification of histopathological analysis. In case 1, the poor differentiated adenocarcinoma accounted for 30%, the neuroendocrine part account for 70% and both of the 2 components metastasized to the lymph nodes, whereas in case 2, poorly differentiated adenocarcinoma accounted for 70%, the neuroendocrine part for 30% and only the glandular component invaded regional lymph nodes. The first patient underwent laparoscopic radical gastrectomy and underwent adjuvant chemotherapy, combination of cisplatin, and etoposide successfully. The second patient received radical gastronomy, and did not receive any chemotherapy due to general weakness. The first patient is alive with no evidence of recurrence, and the second patient died 6 months after the operation. The assessment of metastatic sites should be a routine pathological practice, which is crucial for clinical decision-making and the selection of management. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  12. Anaplastic carcinoma

    International Nuclear Information System (INIS)

    Parikh, D.M.; Agarwal, S.; Rao, R.S.

    1999-01-01

    Thyroid carcinoma (TC) is a slow growing tumor with an indolent course and has an excellent prognosis. However, a sharp contrast exists in the biological behavior of TC, which in its well-differentiated form is associated with long-term survival, but in its undifferentiated form is one of the most lethal neoplasms known. The anaplastic carcinoma (ANC) form has a fulminanat course with poor prognosis and almost invariably, a fatal outcome

  13. A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

    Science.gov (United States)

    Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

    1999-01-01

    We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

  14. Characterization of in vivo chemoresistant human hepatocellular carcinoma cells with transendothelial differentiation capacities

    International Nuclear Information System (INIS)

    Marfels, Christian; Hoehn, Miriam; Wagner, Ernst; Günther, Michael

    2013-01-01

    Chemotherapeutic treatment of hepatocellular carcinoma often leads to chemoresistance during therapy or upon relapse of tumors. For the development of better treatments a better understanding of biochemical changes in the resistant tumors is needed. In this study, we focus on the characterization of in vivo chemoresistant human hepatocellular carcinoma HUH-REISO established from a metronomically cyclophosphamide (CPA) treated HUH7 xenograft model. SCID mice bearing subcutaneous HUH7 tumors were treated i.p. with 75 mg/kg CPA every six days. Tumors were evaluated by immunohistochemistry, a functional blood-flow Hoechst dye assay, and qRT-PCR for ALDH-1, Notch-1, Notch-3, HES-1, Thy-1, Oct-4, Sox-2 and Nanog mRNA levels. Cell lines of these tumors were analyzed by qRT-PCR and in endothelial transdifferentiation studies on matrigel. HUH-REISO cells, although slightly more sensitive against activated CPA in vitro than parental HUH-7 cells, fully retained their in vivo CPA chemoresistance upon xenografting into SCID mice. Histochemical analysis of HUH-REISO tumors in comparison to parental HUH-7 cells and passaged HUH-PAS cells (in vivo passaged without chemotherapeutic pressure) revealed significant changes in host vascularization of tumors and especially in expression of the tumor-derived human endothelial marker gene PECAM-1/CD31 in HUH-REISO. In transdifferentiation studies with limited oxygen and metabolite diffusion, followed by a matrigel assay, only the chemoresistant HUH-REISO cells exhibited tube formation potential and expression of human endothelial markers ICAM-2 and PECAM-1/CD31. A comparative study on stemness and plasticity markers revealed upregulation of Thy-1, Oct-4, Sox-2 and Nanog in resistant xenografts. Under therapeutic pressure by CPA, tumors of HUH-PAS and HUH-REISO displayed regulations in Notch-1 and Notch-3 expression. Chemoresistance of HUH-REISO was not manifested under standard in vitro but under in vivo conditions. HUH-REISO cells showed

  15. Differentiating laryngeal carcinomas from precursor lesions by diffusion-weighted magnetic resonance imaging at 3.0 T: a preliminary study.

    Directory of Open Access Journals (Sweden)

    De-Sheng Shang

    Full Text Available BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI has been introduced in head and neck cancers. Due to limitations in the performance of laryngeal DWI, including the complex anatomical structure of the larynx leading to susceptibility effects, the value of DWI in differentiating benign from malignant laryngeal lesions has largely been ignored. We assessed whether a threshold for the apparent diffusion coefficient (ADC was useful in differentiating preoperative laryngeal carcinomas from precursor lesions by turbo spin-echo (TSE DWI and 3.0-T magnetic resonance. METHODS: We evaluated DWI and the ADC value in 33 pathologically proven laryngeal carcinomas and 17 precancerous lesions. RESULTS: The sensitivity, specificity, and accuracy were 81.8%, 64.7%, 76.0% by laryngostroboscopy, respectively. The sensitivity, specificity, and accuracy of conventional magnetic resonance imaging were 90.9%, 76.5%, 86.0%, respectively. Qualitative DWI analysis produced sensitivity, specificity, and accuracy values of 100.0, 88.2, and 96.0%, respectively. The ADC values were lower for patients with laryngeal carcinoma (mean 1.195±0.32×10(-3 mm(2/s versus those with laryngeal precancerous lesions (mean 1.780±0.32×10(-3 mm(2/s; P<0.001. ROC analysis showed that the area under the curve was 0.956 and the optimum threshold for the ADC was 1.455×10(-3 mm(2/s, resulting in a sensitivity of 94.1%, a specificity of 90.9%, and an accuracy of 92.9%. CONCLUSIONS: Despite some limitations, including the small number of laryngeal carcinomas included, DWI may detect changes in tumor size and shape before they are visible by laryngostroboscopy. The ADC values were lower for patients with laryngeal carcinoma than for those with laryngeal precancerous lesions. The proposed cutoff for the ADC may help distinguish laryngeal carcinomas from laryngeal precancerous lesions.

  16. 99mTc radio-guided completion thyroidectomy for differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Karyagar, Savas; Mulazimoglu, Mehmet; Oezpacaci, Tevfik; Uyanik, Ercan; Karyagar, Sevda S.; Oezdenkaya, Yasar; Karatape, Oguzhan; Bender, Oemer; Yalcin, Orhan

    2010-01-01

    The purpose of this study is to investigate whether or not radio-guided surgery has any beneficial effects on completion thyroidectomy (CT) and the associated complication rates. Twenty seven patients were scheduled for CT, for thyroid carcinoma, from December 2004 to June 2005, and were included in the study. All the patients had initial thyroid surgery in other centers and been referred to our clinic for CT. Operation findings and the effectiveness of 99m Tc radio-guided CT were analyzed. The intraoperative mean ratio of thyroid activity to background activity counted with a gamma probe was 1.3 ± 0.3. Average operation timing was 74 ± 9 minutes. Postoperatively, no residual tissue was detected in any of the patients with ultrasonography and thyroid scintigraphy. In the first postoperative month, serum TSH level was 61 ± 16.4 mlU/L, when preoperatively it was 7.3 ± 3.1 mlU/L (P < 0.001). In the postoperative period, one patient experienced temporary hypoparathyroidism (3.9%). Permanent hypoparathyroidism or recurrent laryngeal nerve damage was not detected in any patient. Tc-99 radio-guided CT is a reliable surgical method, which provides the detection and removal of residual thyroid tissues with minimal complications. (author)

  17. Practical recommendations for outpatients after differentiated thyroid carcinoma treatment with iodine-131

    International Nuclear Information System (INIS)

    Carlier, T.; Kraeber-Bodere, F.; Ansquer, C.; Couturier, O.; Lisbona, A.; Kraeber-Bodere, F.; Couturier, O.

    2004-01-01

    Few studies on radiation protection recommendation for patients leaving hospitalization area after thyroid carcinoma treatment with iodine-131 are based on experimental determination of effective half life. The aim of this work was to calculate times of adhesion to restrictions for patients using one dose rate measurement at 30 cm the last day, just before leaving hospital. Dose rate measurements were achieved every day at two localizations (abdomen mid trunk and neck) during hospitalization. Data were fitted by a monoexponential or a biexponential model in order to derive the effective half life. We considered 7 exposure states between patient and neighboring. We showed, according to our realistic scatter state, a dose rate variation inversely proportional to the distance from patient. Effective half life is equal to 16 ± 6 h whatever the measurement localization. Thus the times of adhesion to restrictions is never greater than 2 days after 3 days of hospitalization. A simple table is given to allow the computation of restrictions times according to the dose rate measurement before the patient is discharged. This protocol is applied in our institution and gives whole satisfaction as far as the ALARA principle and the patient information are concerned. (author)

  18. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Luis J. Jara

    2006-01-01

    Full Text Available The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.

  19. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Langer, Seppo W; Ringholm, Lene; Dali, Christine I

    2015-01-01

    Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may...... occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden...

  20. Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma.

    Science.gov (United States)

    Brose, Marcia S; Smit, Johannes; Capdevila, Jaume; Elisei, Rossella; Nutting, Christopher; Pitoia, Fabian; Robinson, Bruce; Schlumberger, Martin; Shong, Young Kee; Takami, Hiroshi

    2012-09-01

    For patients with advanced, radioactive iodine-refractory differentiated thyroid cancer, current treatment guidelines recommend clinical trial enrollment or small-molecule kinase inhibitor therapy. However, details of patient management vary between countries depending on trial availability and national regulatory policies. Insufficient clinical trial data and variable disease characteristics challenge the creation of universal guidelines, and treatment plans often reflect regional influences. A multidisciplinary, multiregional panel of experts met to discuss regional approaches to managing patients with advanced, radioactive iodine-refractory differentiated thyroid cancer and the potential impact of emerging therapies on current treatment strategies. Despite process-oriented regional differences, the decision-making strategies were similar. Multidisciplinary teams used to manage high-risk patients varied in composition across regions, particularly regarding the responsible physician's specialty. Cytotoxic chemotherapy was viewed as limited in clinical benefit, and targeted agents as attractive, based on promising data. Panel members support clinical trial enrollment as the preferred treatment strategy for managing these patients.

  1. The added value of SPECT/CT fusion imaging for differential diagnosis of bone metastases in patients with hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhang Yiqiu; Shi Hongcheng; Gu Yushen; Chen Shuguang; Zhu Weimin; Cai Liang; Xiu Yan; Li Beilei

    2011-01-01

    In this paper,the value of differentiating metastases from benign of bone lesions in patients with hepatocellular carcinoma using SPECT/ CT fusion imaging is evaluated. From patients with hepatocellular carcinoma (HCC) confirmed by pathology underwent bone scintigraphy, 97 patients were selected to undergo SPECT/CT scanning. The bone scintigraphy and SPECT/CT fusion images were analyzed by two experienced nuclear medicine physicians together. Each patient was rated using a 3-point diagnostic confidence scale: metastasis, benign and uncertainty. The analyzed items were divided into two groups, i.e. certainty to diagnose (metastasis and benign) and uncertainty to diagnose. The percentage and its 95% confidence intervals of each group were calculated. The coincidence rate of bone metastases compared with the final diagnosis and its 95% confidence interval were calculated. The degree of certainty to diagnose on bone scintigraphy was 36.1% (35/97), its 95% confidence intervals range from 26.5% to 45.6%. The degree of uncertainty to diagnose on bone scintigraphy was 63.9% (62/97), its 95% confidence intervals range from 54.4% to 73.5%. The coincidence rate of bone metastases was 50.0% (24/48), its 95% confidence intervals range from 35.9% to 64.1%. The degree of certainty to diagnose on SPECT/CT fusion images was 81.4% (79/97), its 95% confidence intervals range from 73.7 % to 89.1%. The degree of uncertainty to diagnose on SPECT/CT fusion images was 18.6% (18/97), its 95% confidence intervals range from 10.9% to 26.3%. The coincidence rate of bone metastases was 95.8% (46/48), its 95% confidence intervals range from 90.1% to 100%. SPECT/CT fusion images provide more information than bone scintigraphy in differentiating metastases from benign lesions in patients with HCC, increase the degree of certainty to diagnose, especially increase the diagnostic accuracy in some false-negative cases diagnosed by bone scintigraphy. (authors)

  2. Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Toumpanakis, Christos; Kim, Michelle K; Rinke, Anja; Bergestuen, Deidi S; Thirlwell, Christina; Khan, Mohid S; Salazar, Ramon; Oberg, Kjell

    2014-01-01

    Molecular imaging modalities exploit aspects of neuroendocrine tumors (NET) pathophysiology for both diagnostic imaging and therapeutic purposes. The characteristic metabolic pathways of NET determine which tracers are useful for their visualization. In this review, we summarize the diagnostic value of all available molecular imaging studies, present data about their use in daily practice in NET centers globally, and finally make recommendations about the appropriate use of those modalities in specific clinical scenarios. Somatostatin receptor scintigraphy (SRS) continues to have a central role in the diagnostic workup of patients with NET, as it is also widely available. However, and despite the lack of prospective randomized studies, many NET experts predict that Gallium-68 ((68)Ga)-DOTA positron emission tomography (PET) techniques may replace SRS in the future, not only because of their technical advantages, but also because they are superior in patients with small-volume disease, in patients with skeletal metastases, and in those with occult primary tumors. Carbon-11 ((11)C)-5-hydroxy-L-tryptophan (5-HTP) PET and (18)F-dihydroxyphenylalanine ((18)F-DOPA) PET are new molecular imaging techniques of limited availability, and based on retrospective data, their sensitivities seem to be inferior to that of (68)Ga-DOTA PET. Glucagon-like-peptide-1 (GLP-1) receptor imaging seems promising for localization of the primary in benign insulinomas, but is currently available only in a few centers. Fluorine-18 ((18)F)-fluorodeoxyglucose ((18)F-FDG) PET was initially thought to be of limited value in NET, due to their usually slow-growing nature. However, according to subsequent data, (18)F-FDG PET is particularly helpful for visualizing the more aggressive NET, such as poorly differentiated neuroendocrine carcinomas, and well-differentiated tumors with Ki67 values >10%. According to limited data, (18)F-FDG-avid tumor lesions, even in slow-growing NET, may indicate a more

  3. Neural differentiation of pluripotent mouse embryonal carcinoma cells by retinoic acid - inhibitory effect of serum

    Czech Academy of Sciences Publication Activity Database

    Pacherník, J.; Bryja, Vítězslav; Ešner, M.; Kubala, Lukáš; Dvořák, Petr; Hampl, Aleš

    2005-01-01

    Roč. 54, - (2005), s. 115-122 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GP524/03/P171; GA MŠk(CZ) LN00A065 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z5039906 Keywords : neural differentiation Subject RIV: FH - Neurology Impact factor: 1.806, year: 2005

  4. [Screening of differentially expressed genes in human renal cell carcinoma using suppression subtractive hybridization].

    Science.gov (United States)

    Wang, Ying; Chen, Wei; Li, Xu

    2008-01-01

    To suppress COL1A1 and COL3A1 gene expressions in human skin fibroblasts (HSFs) by means of RNA interference (RNAi). SSH was performed in two directions to isolate the differentially expressed genes between human a RCC cell line RLC-310 and a normal renal cell line HK-2 (ATCC). The cDNAs obtained from the final nested PCR were directly inserted into T/A cloning vector to establish a subtractive cDNA library of specifically or highly expressed genes in RCC. Reverse Northern dot blotting was performed to screen the truly differentially expressed genes, and 200 positive genes were randomly selected for sequencing. The two-directional subtractive libraries contained more than 1200 clones, and 213 positive clones were obtained using reverse Northern blotting. Sequence analysis of these clones identified 144 differentially expressed genes, including 67 up-regulated and 77 down-regulated genes, in which 14 novel ESTs and 21 functionally unknown genes were found. Cluster analysis indicated the involvement of the sequenced genes in cell growth, cell adhesion and apoptosis. Reliable subtractive cDNA libraries of human RCC have been constructed successfully with SSH. The identification of the gene expression profile in RCC may help clarify the mechanism of tumorigenesis and development of RCC, and also sheds light on new targets for prevention, diagnosis and therapy of this malignancy.

  5. The importance of clinical information in patients with gastroenteropancreatic neuroendocrine tumor.

    Science.gov (United States)

    Kudo, Atsushi; Akashi, Takumi; Kumagai, Jiro; Ban, Daisuke; Inokuchi, Mikito; Kojima, Kazuyuki; Kawano, Tatsuyuki; Tanaka, Shinji; Arii, Shigeki

    2012-01-01

    The WHO 2010 grading system for gastroenteropancreatic neuroendocrine tumors(GEP-NETs) is used to evaluate the malignant potential without clinicopathological information. This study was conducted to examine whether the new index is superior to the previous WHO 2004 classification, e.g.for well-differentiated endocrine carcinoma (WEC),involving clinical information. Between 2000 and 2011, 77 patients with sporadic GEP-NETs were treated at our institution and statistically estimated risk factors for overall survival (OS) were evaluated. Cox proportional hazards regression analyses were performed to estimate risk factors for OS. Overall 1-, 3- and 5-year survival rates were 92.8%, 78.4% and 76.0%, respectively. Median OS was 551 days in WEC-patients (odds ratio (OR)for OS=13.1, 95% confidence interval (CI)=2.90-59.5;p=0.001). The median OS was 813 days in G3-patients as compared with 1885 days in G1/G2-patients(OR for OS= 2.64, p=0.002). Multivariate analyses according to baseline characteristics revealed WEC as independent risk factor (OR=9.06, p=0.01). WEC was the only predictor of prognosis with an area under the receiver operating characteristic curves of 0.78(p=0.001). Clinical information was the best predictor for the prognosis of NETs.

  6. Differential requirement for de novo lipogenesis in cholangiocarcinoma and hepatocellular carcinoma of mice and humans.

    Science.gov (United States)

    Li, Lei; Che, Li; Tharp, Kevin M; Park, Hyo-Min; Pilo, Maria G; Cao, Dan; Cigliano, Antonio; Latte, Gavinella; Xu, Zhong; Ribback, Silvia; Dombrowski, Frank; Evert, Matthias; Gores, Gregory J; Stahl, Andreas; Calvisi, Diego F; Chen, Xin

    2016-06-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most prevalent types of primary liver cancer. These malignancies have limited treatment options, resulting in poor patient outcomes. Metabolism reprogramming, including increased de novo lipogenesis, is one of the hallmarks of cancer. Fatty acid synthase (FASN) catalyzes the de novo synthesis of long-chain fatty acids from acetyl-coenzyme A and malonyl-coenzyme A. Increased FASN expression has been reported in multiple tumor types, and inhibition of FASN expression has been shown to have tumor-suppressing activity. Intriguingly, we found that while FASN is up-regulated in human HCC samples, its expression is frequently low in human ICC specimens. Similar results were observed in mouse ICC models induced by different oncogenes. Ablating FASN in the mouse liver did not affect activated AKT and Notch (AKT/Notch intracellular domain 1) induced ICC formation in vivo. Furthermore, while both HCC and ICC lesions develop in mice following hydrodynamic injection of AKT and neuroblastoma Ras viral oncogene homolog oncogenes (AKT/Ras), deletion of FASN in AKT/Ras mice triggered the development almost exclusively of ICCs. In the absence of FASN, ICC cells might receive lipids for membrane synthesis through exogenous fatty acid uptake. In accordance with the latter hypothesis, ICC cells displayed high expression of fatty acid uptake-related proteins and robust long-chain fatty acid uptake. Our data demonstrate that FASN dependence is not a universal feature of liver tumors: while HCC development is highly dependent of FASN and its mediated lipogenesis, ICC tumorigenesis can be insensitive to FASN deprivation; our study supports novel therapeutic approaches to treat this pernicious tumor type with the inhibition of exogenous fatty acid uptake. (Hepatology 2016;63:1900-1913). © 2016 by the American Association for the Study of Liver Diseases.

  7. Differential expression of drug uptake and efflux transporters in Japanese patients with hepatocellular carcinoma.

    Science.gov (United States)

    Namisaki, Tadashi; Schaeffeler, Elke; Fukui, Hiroshi; Yoshiji, Hitoshi; Nakajima, Yoshiyuki; Fritz, Peter; Schwab, Matthias; Nies, Anne T

    2014-12-01

    Targeted chemotherapy for hepatocellular carcinoma (HCC) is impaired by intrinsic and/or acquired drug resistance. Because drugs used in HCC therapy (e.g., anthracyclines or the tyrosine kinase inhibitor sorafenib) are substrates of uptake and/or efflux transporters, variable expression of these transporters at the plasma membrane of tumor cells may contribute to drug resistance and subsequent clinical response. In this study, the variability of expression of uptake transporters [organic cation transporter (OCT) 1 and OCT3] and efflux transporters [multidrug resistance 1 (MDR1)/P-glycoprotein, multidrug resistance protein (MRP) 1, MRP2, and breast cancer resistance protein (BCRP)], selected for their implication in transporting drugs used in HCC therapy, was investigated. HCC and corresponding nontumor tissue samples were collected from 24 Japanese patients at the time of surgery. Protein expression was determined by immunohistochemistry. Expression data were correlated with clinicopathological characteristics and patients' outcome (median follow-up, 53 months). Generally, expression was highly variable among individual tumor samples. Yet median expression of OCT1, OCT3, and MDR1 in HCC was significantly lower (1.4-, 2.7-, and 2-fold, respectively) than in nontumor tissue, while expression of MRP2 persisted and BCRP showed a trend of increased levels in HCC. Patients with low BCRP expression had significantly shorter overall and recurrence-free survival times. Results suggest different expression patterns of drug transporters in HCC, which are associated only in part with clinicopathological characteristics. Detailed information on expression of drug transporters in HCC may be promising for individualization and optimization of drug therapy for liver cancer. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Dysregulation of the repressive H3K27 trimethylation mark in head and neck squamous cell carcinoma contributes to dysregulated squamous dif