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Sample records for anaplastic lymphoma kinase

  1. [A case of primary central nervous system anaplastic lymphoma kinase positive anaplastic large cell lymphoma manifested as a unilateral pachymeningits].

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    Fujisawa, Etsuco; Shibayama, Hidehiro; Mitobe, Fumi; Katada, Fumiaki; Sato, Susumu; Fukutake, Toshio

    2017-11-25

    There have been 23 reports of primary central nervous system anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma in the literature. Here we report the 24th case of a 40-year-old man who presented with occipital headache for one month. His contrast-enhanced brain MRI showed enhancement around the right temporal lobe, which suggested a diagnosis of hypertrophic pachymeningitis. He improved with steroid therapy. After discharge, however, he was readmitted with generalized convulsive seizures. Finally, he was diagnosed as primary central nervous system ALK-positive anaplastic large cell lymphoma by brain biopsy. Primary central nervous system lymphoma invading dura matter can rarely manifests as a unilateral pachymeningitis. Therefore, in case of pachymeningitis, we should pay attention to the possibility of infiltration of lymophoma with meticulous clinical follow-up.

  2. Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate as first clinical manifestation of acquired immune deficiency syndrome

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    Anjali Narwal

    2016-01-01

    Full Text Available Anaplastic large cell lymphoma (ALCL is an uncommon disease, accounting for <5% of all cases of non-Hodgkin's lymphoma. We report a case of 48-year-old male who presented a clinically benign swelling in the right anterior palatal region since last 2 months. Radiographic evaluation showed no bone loss in palatal area. Histological and radiological examination was in favor of a peripheral reactive lesion like pyogenic granuloma or a benign salivary gland tumor. Immunohistochemistry confirmed the diagnosis of anaplastic lymphoma kinase-negative (ALK(− ALCL. Further laboratory tests ELISA for human immunodeficiency virus (HIV and CD4 cell count was done which showed positivity for HIV. To the best of our knowledge, it is the first case of ALK(− ALCL in the hard palate presenting as the first clinical manifestation of acquired immune deficiency syndrome.

  3. Presence of anaplastic lymphoma kinase in inflammatory breast cancer.

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    Robertson, Fredika M; Petricoin Iii, Emanuel F; Van Laere, Steven J; Bertucci, Francois; Chu, Khoi; Fernandez, Sandra V; Mu, Zhaomei; Alpaugh, Katherine; Pei, Jianming; Circo, Rita; Wulfkuhle, Julia; Ye, Zaiming; Boley, Kimberly M; Liu, Hui; Moraes, Ricardo; Zhang, Xuejun; Demaria, Ruggero; Barsky, Sanford H; Sun, Guoxian; Cristofanilli, Massimo

    2013-01-01

    Although Inflammatory Breast Cancer (IBC) is recognized as the most metastatic variant of locally advanced breast cancer, the molecular basis for the distinct clinical presentation and accelerated program of metastasis of IBC is unknown. Reverse phase protein arrays revealed activation of the receptor tyrosine kinase, anaplastic lymphoma kinase (ALK) and biochemically-linked downstream signaling molecules including JAK1/STAT3, AKT, mTor, PDK1, and AMPKβ in pre-clinical models of IBC. To evaluate the clinical relevance of ALK in IBC, analysis of 25 IBC patient tumors using the FDA approved diagnostic test for ALK genetic abnormalities was performed. These studies revealed that 20/25 (80%) had either increased ALK copy number, low level ALK gene amplification, or ALK gene expression, with a prevalence of ALK alterations in basal-like IBC. One of 25 patients was identified as having an EML4-ALK translocation. The generality of gains in ALK copy number in basal-like breast tumors with IBC characteristics was demonstrated by analysis of 479 breast tumors using the TGCA data-base and our newly developed 79 IBC-like gene signature. The small molecule dual tyrosine kinase cMET/ALK inhibitor, Crizotinib (PF-02341066/Xalkori®, Pfizer Inc), induced both cytotoxicity (IC50 = 0.89 μM) and apoptosis, with abrogation of pALK signaling in IBC tumor cells and in FC-IBC01 tumor xenograft model, a new IBC model derived from pleural effusion cells isolated from an ALK(+) IBC patient. Based on these studies, IBC patients are currently being evaluated for the presence of ALK genetic abnormalities and when eligible, are being enrolled into clinical trials evaluating ALK targeted therapeutics.

  4. Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib

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    Huang, Qinhua; Johnson, Ted W.; Bailey, Simon; Brooun, Alexei; Bunker, Kevin D.; Burke, Benjamin J.; Collins, Michael R.; Cook, Andrew S.; Cui, J.Jean; Dack, Kevin N.; Deal, Judith G.; Deng, Ya-Li; Dinh, Dac; Engstrom, Lars D.; He, Mingying; Hoffman, Jacqui; Hoffman, Robert L.; Johnson, Patrick S.; Kania, Robert S.; Lam, Hieu; Lam, Justine L.; Le, Phuong T.; Li, Qiuhua; Lingardo, Laura; Liu, Wei; Lu, Melissa West; McTigue, Michele; Palmer, Cynthia L.; Richardson, Paul F.; Sach, Neal W.; Shen, Hong; Smeal, Tod; Smith, Graham L.; Stewart, Albert E.; Timofeevski, Sergei; Tsaparikos, Konstantinos; Wang, Hui; Zhu, Huichun; Zhu, Jinjiang; Zou, Helen Y.; Edwards, Martin P. (Pfizer)

    2014-02-27

    Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine 8e, which was potent across a broad panel of engineered ALK mutant cell lines and showed suitable preclinical pharmacokinetics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

  5. Combination therapy with brentuximab vedotin and cisplatin/cytarabine in a patient with primarily refractory anaplastic lymphoma kinase positive anaplastic large cell lymphoma

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    Heidegger S

    2014-06-01

    Full Text Available Simon Heidegger,1 Ambros Beer,2 Eva Geissinger,3 Andreas Rosenwald,3 Christian Peschel,1 Ingo Ringshausen,1 Ulrich Keller11III Medical Department, 2Nuclear Medicine Department, Technische Universität München, Munich, Germany; 3Institute of Pathology, University of Würzburg, Würzburg, GermanyAbstract: Anaplastic large cell lymphoma (ALCL is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone. However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis.Keywords: anaplastic large cell lymphoma (ALCL, refractory/relapsed lymphoma, anti-CD30 drug conjugate, DHAP

  6. Combination therapy with brentuximab vedotin and cisplatin/cytarabine in a patient with primarily refractory anaplastic lymphoma kinase positive anaplastic large cell lymphoma.

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    Heidegger, Simon; Beer, Ambros J; Geissinger, Eva; Rosenwald, Andreas; Peschel, Christian; Ringshausen, Ingo; Keller, Ulrich

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone) was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis.

  7. The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin\\'s lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3\\/4 (TMP3\\/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic

  8. Anaplastic lymphoma kinase inhibition in metastatic non-small cell lung cancer: clinical impact of alectinib

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    Muller IB

    2017-09-01

    Full Text Available Ittai B Muller,1 Adrianus J de Langen,2,3 Elisa Giovannetti,4,5 Godefridus J Peters4 1Department of Clinical Chemistry, 2Department of Pulmonology, VU University Medical Center, 3Department of Thoracic Oncology, Netherlands Cancer Institute, 4Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands; 5Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy Abstract: A subset of non-small cell lung cancer (NSCLC tumors (5% harbors an anaplastic lymphoma kinase (ALK translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS in treated and untreated patients by 4 months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS. Alectinib, a second-generation ALK inhibitor, has recently been approved for ALK-rearranged NSCLC after patients progressed on crizotinib. Alectinib is able to inhibit several crizotinib- and ceritinib-resistant ALK mutations in vitro. Furthermore, alectinib is a more potent tyrosine kinase inhibitor (TKI, with favorable safety profile, and has increased penetration into the central nervous system, inhibiting crizotinib-resistant brain metastases. The discovery of effective personalized therapies to combat ALK-rearranged NSCLC such as alectinib is an example of the importance of genomic profiling of NSCLC and provides an excellent template for future discoveries in managing these tumors. Keywords: crizotinib, acquired resistance, alectinib, anaplastic lymphoma kinase, tyrosine kinase inhibitors, non-small cell lung cancer

  9. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju

    2017-01-01

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refra...

  10. Prognostic significance and therapeutic potential of the activation of anaplastic lymphoma kinase/protein kinase B/mammalian target of rapamycin signaling pathway in anaplastic large cell lymphoma

    International Nuclear Information System (INIS)

    Gao, Ju; Yin, Minzhi; Zhu, Yiping; Gu, Ling; Zhang, Yanle; Li, Qiang; Jia, Cangsong; Ma, Zhigui

    2013-01-01

    Activation of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway has been demonstrated to be involved in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-mediated tumorigenesis in anaplastic large cell lymphoma (ALCL) and correlated with unfavorable outcome in certain types of other cancers. However, the prognostic value of AKT/mTOR activation in ALCL remains to be fully elucidated. In the present study, we aim to address this question from a clinical perspective by comparing the expressions of the AKT/mTOR signaling molecules in ALCL patients and exploring the therapeutic significance of targeting the AKT/mTOR pathway in ALCL. A cohort of 103 patients with ALCL was enrolled in the study. Expression of ALK fusion proteins and the AKT/mTOR signaling phosphoproteins was studied by immunohistochemical (IHC) staining. The pathogenic role of ALK fusion proteins and the therapeutic significance of targeting the ATK/mTOR signaling pathway were further investigated in vitro study with an ALK + ALCL cell line and the NPM-ALK transformed BaF3 cells. ALK expression was detected in 60% of ALCLs, of which 79% exhibited the presence of NPM-ALK, whereas the remaining 21% expressed variant-ALK fusions. Phosphorylation of AKT, mTOR, 4E-binding protein-1 (4E-BP1), and 70 kDa ribosomal protein S6 kinase polypeptide 1 (p70S6K1) was detected in 76%, 80%, 91%, and 93% of ALCL patients, respectively. Both phospho-AKT (p-AKT) and p-mTOR were correlated to ALK expression, and p-mTOR was closely correlated to p-AKT. Both p-4E-BP1 and p-p70S6K1 were correlated to p-mTOR, but were not correlated to the expression of ALK and p-AKT. Clinically, ALK + ALCL occurred more commonly in younger patients, and ALK + ALCL patients had a much better prognosis than ALK-ALCL cases. However, expression of p-AKT, p-mTOR, p-4E-BP1, or p-p70S6K1 did not have an impact on the clinical outcome. Overexpression of NPM-ALK in a nonmalignant murine pro-B lymphoid cell line, BaF3, induced the

  11. An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol.

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    Amy W Lasek

    Full Text Available Anaplastic lymphoma kinase (Alk is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs. These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention.

  12. Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population.

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    Jianming Ying

    Full Text Available Anaplastic lymphoma kinase (ALK rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.Tissue microarray (TMA was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH, real-time polymerase chain reaction (qRT-PCR, target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.Among the tested cases, 2 (0.44% CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1. One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.

  13. Role of anaplastic lymphoma kinase inhibition in the treatment of non-small-cell lung cancer.

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    Croegaert, Katie; Kolesar, Jill M

    2015-09-01

    Published data on the clinical efficacy, safety, dosage and administration, and costs of the anaplastic lymphoma kinase (ALK) inhibitors crizotinib and ceritinib in the treatment of non-small-cell lung cancer (NSCLC) are reviewed and compared. The ALK protein functions as a transmembrane receptor tyrosine kinase; rearrangements of the ALK gene are associated with the development of NSCLC with adenocarcinoma histology. Crizotinib is an oral tyrosine kinase inhibitor approved in 2011 as a first-line therapy for patients with metastatic ALK mutation-driven NSCLC. Significantly improved response rates and progression-free survival (PFS) have been reported with the use of crizotinib therapy versus standard chemotherapy, but mutations conferring resistance to treatment develop in most cases. The second-generation ALK inhibitor ceritinib was approved in 2014 for the treatment of ALK-mutated NSCLC in patients who are intolerant or develop resistance to crizotinib. In a clinical trial of ceritinib involving 130 patients with ALK-positive NSCLC, the majority of whom had experienced disease progression during crizotinib use, patients receiving at least 400 mg of ceritinib daily had an overall response rate of 56% and median PFS of seven months. Adverse effects commonly reported with the use of either drug include visual disturbances, gastrointestinal disorders (e.g., diarrhea), and liver enzyme abnormalities. The tyrosine kinase inhibitors crizotinib and ceritinib provide an effective treatment approach for patients with ALK-mutated NSCLC. Efficacy data for both crizotinib and ceritinib indicate improved response rates and PFS with the use of either drug as an alternative to standard chemotherapy. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  14. {sup 18}F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase

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    Lee, Dong Yun; Lee, Jong Jin; Park, Seol Hoon; Chae, Sunyoung; Kim, Shin; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung; Ryu, Jinsook [Univ. of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated {sup 18}F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) findings in primary systemic ALCL according to ALK expression. Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peak SUV, and interim and post-therapy PETs were visually analyzed. All cases were {sup 18}F-FDG-avid on baseline PET. The peak SUV of ALK-positive ALCL (n =16, 18.7±10.5) was higher than that of ALK-negative ALCL (n =21, 10.0±4.9) (P =0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100 % vs 37.5 %, P=0.02); however, there was no such difference in ALK-positive ALCL (100 % vs 75 %, P =0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7 % vs 47.6 %, P =0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3 % vs 25.0 %, P =0.06) and post-therapy PET patients (70.0%vs 20.0 %, P =0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results. On baseline PET, all cases showed {sup 18}F-FDG avidity, and ALK expression was related to higher {sup 18}F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group.

  15. Aberrant Expression of Anaplastic Lymphoma Kinase in Ovarian Carcinoma Independent of Gene Rearrangement.

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    Tang, Shaoxian; Yang, Fei; Du, Xiang; Lu, Yongming; Zhang, Ling; Zhou, Xiaoyan

    2016-07-01

    Ovarian carcinoma is the leading cause of death from gynecologic malignancies. The oncogenic role of anaplastic lymphoma kinase (ALK) is well characterized in many hematopoietic and solid tumors. ALK expression in ovarian carcinoma has been reported but the exact status of ALK protein and its association with clinicopathologic features requires further investigation. ALK expression was determined by immunohistochemistry in 110 primary ovarian carcinomas, including 85 cases of serous carcinoma and 25 cases of mucinous carcinoma. Fluorescence in situ hybridization (FISH) and real-time reverse transcription polymerase chain reaction (RT-PCR) were used for evaluating ALK translocation in ALK-positive ovarian carcinomas. Among 110 ovarian carcinomas, 23 (20.9%) cases were ALK positive by immunohistochemistry. All ALK-positive cases were ovarian high-grade serous carcinoma. ALK expression was detected in 23/85 (27.1%) ovarian serous carcinoma and 0/25 (0%) in ovarian mucinous carcinoma. None of the 23 ALK IHC-positive cases harbored ALK gene translocations by FISH or RT-PCR. ALK protein expression was associated with patient age, tumor stage, and histologic type. Specifically, the probability of ALK protein expression was significantly higher in high-grade serous carcinomas in older patients (above 50 y) with advanced disease (FIGO stage III and IV) compared with the low-grade serous and mucinous carcinomas in younger patients with relatively early disease. In conclusion, aberrant ALK expression is observed in ovarian serous carcinoma but not in mucinous carcinoma, is independent of gene translocation, and might be associated with progression and prognosis.

  16. [Expression of anaplastic lymphoma kinase fusion gene in patients with lung sarcomatoid carcinoma and treatment analysis].

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    Niu, H T; Dong, P; Wang, J N; Zeng, Y X; Yuan, W; Yuan, P

    2018-03-06

    Objective: To investigate the expression status of anaplastic lymphoma kinase (ALK) fusion gene in lung sarcomatoid carcinoma (LSC) and the role of ALK inhibitors for treatment. Methods: Total of 84 cases of LSC confirmed by histopathology were detected for ALK fusion gene from January 2011 to December 2014 in the Cancer Hospital of Chinese Academy of Medical Science&Peking Union Medical College and Shandong Zibo Wanjie Cancer Hospital. All patients were primarily treated by the multi-disciplinary mode in combination with chemotherapy or targeted therapy based on surgery. Postoperative adjuvant chemotherapy was given on platinum based two-drug combination regimen. In ALK fusion gene (+ ) patients with recurrence or metastasis, crizotinib target therapy was prefered. Chi-square test was applied for the comparison of 1, 3, 5-year survival rates between the two groups. Results: Eighty-two cases completed the follow-up. ALK fusion gene was found in 9(10.7%) patients. After application of crizotinib, 1 case was evaluated as complete remission, 6 cases as partial response, 2 cases as stable disease; the 1, 3, 5-year survival rate was 100% (9/9), 100% (9/9) and 88.9% (8/9) for the patients with ALK fusion gene, and it was 65.8% (48/73), 15.1% (11/73) and 6.8% (5/73) respectively for patients without ALK fusion gene. There was significant difference in the survival rate between the two groups (χ(2)=1.56, 1.56, 0.83, all P fusion gene maybe expressed in LSC patients. Compared with conventional chemotherapy, crizotinib can significantly prolong the survival time of patients with ALK fusion gene.

  17. An Immunohistochemical Study of Anaplastic Lymphoma Kinase and Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Carcinoma.

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    Verma, Sonal; Kumar, Madhu; Kumari, Malti; Mehrotra, Raj; Kushwaha, R A S; Goel, Madhumati; Kumar, Ashutosh; Kant, Surya

    2017-07-01

    Lung cancer is one of the leading causes of cancer related death. Targeted treatment for specific markers may help in reducing the cancer related morbidity and mortality. To study expression of Anaplastic Lymphoma Kinase (ALK)and Epidermal Growth Factor Receptor (EGFR) mutations in patients of Non-Small Cell Lung Cancer NSCLC, that are the targets for specific ALK inhibitors and EGFR tyrosine kinase inhibitors. Total 69 cases of histologically diagnosed NSCLC were examined retrospectively for immunohistochemical expression of EGFR and ALK, along with positive control of normal placental tissue and anaplastic large cell lymphoma respectively. Of the NSCLC, Squamous Cell Carcinoma (SCC) accounted for 71.0% and adenocarcinoma was 26.1%. ALK expression was seen in single case of 60-year-old female, non-smoker with adenocarcinoma histology. EGFR expression was seen in both SCC (59.18%) and adenocarcinoma in (77.78%) accounting for 63.77% of all cases. Both ALK and EGFR mutation were mutually exclusive. EGFR expression was seen in 63.77% of cases, highlighting the importance of its use in routine analysis, for targeted therapy and better treatment results. Although, ALK expression was seen in 1.45% of all cases, it is an important biomarker in targeted cancer therapy. Also, the mutually exclusive expression of these two markers need further studies to develop a diagnostic algorithm for NSCLC patients.

  18. Simultaneous targeting of insulin-like growth factor-1 receptor and anaplastic lymphoma kinase in embryonal and alveolar rhabdomyosarcoma : A rational choice

    NARCIS (Netherlands)

    van Gaal, J. Carlijn; Roeffen, Melissa H. S.; Flucke, Uta E.; van der Laak, Jeroen A. W. M.; van der Heijden, Gwen; de Bont, Eveline S. J. M.; Suurmeijer, Albert J. H.; Versleijen-Jonkers, Yvonne M. H.; van der Graaf, Winette T. A.

    2013-01-01

    Background: Rhabdomyosarcoma (RMS) is an aggressive soft tissue tumour mainly affecting children and adolescents. Since survival of high-risk patients remains poor, new treatment options are awaited. The aim of this study is to investigate anaplastic lymphoma kinase (ALK) and insulin-like growth

  19. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer

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    Ryohei Katayama

    2016-01-01

    Full Text Available The anaplastic lymphoma kinase (ALK fusion oncogene is observed in 3%–5% of non-small cell lung cancer (NSCLC. Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P-gp/ABCB1 overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression.

  20. Development of anaplastic lymphoma kinase (ALK inhibitors and molecular diagnosis in ALK rearrangement-positive lung cancer

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    Iwama E

    2014-03-01

    Full Text Available Eiji Iwama,1,2 Isamu Okamoto,3 Taishi Harada,2 Koichi Takayama,2 Yoichi Nakanishi2,3 1Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan Abstract: The fusion of echinoderm microtubule-associated protein-like 4 with anaplastic lymphoma kinase (ALK was identified as a transforming gene for lung cancer in 2007. This genetic rearrangement accounts for 2%–5% of non-small-cell lung cancer (NSCLC cases, occurring predominantly in younger individuals with adenocarcinoma who are never- or light smokers. A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC. Next-generation ALK inhibitors, such as alectinib, LDK378, and AP26113, are also being developed in ongoing clinical trials. In addition, the improvement and validation of methods for the detection of ALK rearrangement in NSCLC patients will be key to the optimal clinical use of ALK inhibitors. We here summarize recent progress in the development of new ALK inhibitors and in the molecular diagnosis of ALK rearrangement-positive NSCLC. Keywords: ALK, rearrangement, NSCLC, ALK inhibitor, targeted therapy, diagnosis

  1. Malignant transformation of mature T cells after gammaretrovirus mediated transfer of nucleophosmin-anaplastic lymphoma kinase oncogene

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    Ashok Kumar

    2015-01-01

    Full Text Available Background: Gene therapy has been in use to cure hereditary and acquired diseases by incorporating the desired gene into the cells with the help of gammaretroviral vectors. Despite the success of this therapy in X-linked severe combined immunodeficiency syndrome, few patients developed leukemia as a major adverse event due to retroviral insertional mutagenesis within stem cells. In experimental animals also, retroviral-mediated gene transfer technique resulted in the development of leukemia. On the other hand, evidence suggests that mature T cells (TC are relatively resistant to transformation even after retroviral-mediated transfer of potent oncogenes Tcl1, ΔTrkA and LMO2 with no reported side effects yet. Aims: To further address the safety issue for TC use in gene therapy, this study investigated susceptibility of mature polyclonal TC to malignant transformation by the retroviral-mediated transfer of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK oncogene. Materials and Methods: Wild-type mature TC, isolated from C57BL/6 donor mice (genetic background Ly5.1 were transduced with gamma-retroviral vectors encoding the potent TC oncogene NPM-ALK or the control vector enhanced green fluorescent protein eGFP. The cells were then transplanted into RAG-1 deficient recipient mice (genetic background Ly5.2. Results: Two out of five mice from NPM-ALK oncogene group developed leukemia/lymphoma after latency periods (153 and 250 days, respectively. None of the mice from the control group developed any malignancy throughout the observational period. Conclusion: Mature polyclonal TC are relatively susceptible to malignant transformation after gamma-retroviral mediated transfer of NPM-ALK oncogene; hence safety of TC use in gene therapy should be further investigated to avoid the possible side-effect of development of leukemia/lymphoma.

  2. Anaplastic Lymphoma Kinase Is a Regulator of Alcohol Consumption and Excitatory Synaptic Plasticity in the Nucleus Accumbens Shell

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    Regina A. Mangieri

    2017-08-01

    Full Text Available Anaplastic lymphoma kinase (ALK is a receptor tyrosine kinase recently implicated in biochemical, physiological, and behavioral responses to ethanol. Thus, manipulation of ALK signaling may represent a novel approach to treating alcohol use disorder (AUD. Ethanol induces adaptations in glutamatergic synapses onto nucleus accumbens shell (NAcSh medium spiny neurons (MSNs, and putative targets for treating AUD may be validated for further development by assessing how their manipulation modulates accumbal glutamatergic synaptic transmission and plasticity. Here, we report that Alk knockout (AlkKO mice consumed greater doses of ethanol, relative to wild-type (AlkWT mice, in an operant self-administration model. Using ex vivo electrophysiology to examine excitatory synaptic transmission and plasticity at NAcSh MSNs that express dopamine D1 receptors (D1MSNs, we found that the amplitude of spontaneous excitatory post-synaptic currents (EPSCs in NAcSh D1MSNs was elevated in AlkKO mice and in the presence of an ALK inhibitor, TAE684. Furthermore, when ALK was absent or inhibited, glutamatergic synaptic plasticity – long-term depression of evoked EPSCs – in D1MSNs was attenuated. Thus, loss of ALK activity in mice is associated with elevated ethanol consumption and enhanced excitatory transmission in NAcSh D1MSNs. These findings add to the mounting evidence of a relationship between excitatory synaptic transmission onto NAcSh D1MSNs and ethanol consumption, point toward ALK as one important molecular mediator of this interaction, and further validate ALK as a target for therapeutic intervention in the treatment of AUD.

  3. Anaplastic lymphoma kinase-positive large B-cell lymphoma: Clinico-pathological study of 17 cases with review of literature.

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    Xiang-Nan Jiang

    Full Text Available We retrospectively analysed 17 cases of anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+, LBCL according to the morphological, immunohistochemical, molecular and clinical features, using which we intend to elucidate the clinicopathological characteristics of this rare entity. In this study, all cases de facto share common features that defined them as a single entity, and various characteristics may expand the spectrum. Among 15 cases, 60% followed an aggressive clinical course with advanced stage and high IPI scores; the median survival of these patients was only 8 months. An analysis showed that both the IPI score and the Ann Arbor stage were significant prognostic factors. Most patients received a chemotherapy regimen including CHOP, CHOEP, EPOCH, and CVAD, and some also underwent localized radiotherapy. However, ALK+, LBCL cases display a dismal clinical outcome and can only be cured with conventional chemotherapy protocols at the stage of localized disease. Novel front-line intensive chemotherapy regimens should therefore be evaluated in this group of patients.

  4. The Molecular Mechanism Behind Resistance of the G1202R-Mutated Anaplastic Lymphoma Kinase to the Approved Drug Ceritinib.

    Science.gov (United States)

    Chen, Chaohong; He, Zhifeng; Xie, Deyao; Zheng, Liangcheng; Zhao, Tianhao; Zhang, Xinbo; Cheng, Dezhi

    2018-04-12

    Anaplastic lymphoma kinase (ALK) has been regarded as an essential target for the treatment of non-small cell lung cancer (NSCLC). However, the emergence of G1202R solvent front mutation that confer resistance to the drugs were reported for the first as well as the second generation ALK inhibitors. It was supposed that the G1202R solvent front mutation might hinder the drug binding. In this study, a different fact could be clarified by multiple molecular modeling methodologies through a structural analogue of ceritinib (compound 10, Cpd-10) that is reported to be a potent inhibitor against the G1202R mutation. Herein, molecular docking, accelerated molecular dynamics (aMD) simulations in conjunction with principal component analysis (PCA) and free energy map calculations were used to produce reasonable and representative initial conformations for the conventional MD simulations. Compared with Cpd-10, the binding specificity of ceritinib between ALK wild type (ALK WT ) and ALK G1202R (ALK G1202R ) are primarily controlled by conformational change of the P-loop and A-loop induced energetic re-distributions, and the variation is non-polar interactions as indicated by conventional MD simulations, PCA, dynamic cross-correlation map (DCCM) analysis and free energy calculations. Furthermore, the umbrella sampling (US) simulations were carried out to make clear the principle of the dissociation processes of ceritinib and Cpd-10 towards ALKWT and ALK G1202R . The calculation results suggest that Cpd-10 has similar dissociation processes from both ALK WT and ALK G1202R , but ceritinib is more easily dissociate from ALK G1202R than from ALK WT , thus less residence time is responsible for the ceritinib resistance. Our results suggest both of the binding specificity and the drug residence time should be emphasized in rational drug design to overcome the G1202R solvent front mutation of ALK resistance.

  5. Synchronous meningioma and anaplastic large cell lymphoma.

    Science.gov (United States)

    Colen, Chaim B; Rayes, Mahmoud; Kupsky, William J; Guthikonda, Murali

    2010-06-01

    Synchronous primary brain tumors are exceedingly rare. When they occur, most cases are associated with metastatic disease. To the best of our knowledge, we report the first case of an atypical meningioma infiltrated by a T-cell-primary central nervous system lymphoma (PCNSL), specifically anaplastic large cell lymphoma (ALCL). We present a novel, unifying, plausible mechanism for its origin based on theories in the current literature. A 65-year-old man with a history of near-total resection of atypical meningioma presented with a complaint of progressive headaches. Imaging revealed recurrent tumor. Left frontal-temporal craniotomy with near-total tumor resection followed by radiation was performed. Recurrent symptomatic tumor led to repeat left frontotemporal craniotomy with tumor resection and partial anterior temporal lobectomy. Part of the specimen showed predominantly fibrotic neoplasm composed of nests and whorls of meningothelial cells, highlighted by epithelial membrane antigen (EMA) staining. The remainder of the specimen consisted of densely cellular neoplasm centered in connective tissue, including areas involved by meningioma. This tumor was composed of moderately large lymphoid cells with large nuclei, prominent nucleoli, and amphophilic cytoplasm. These cells were strongly immunoreactive for CD3 and CD30 but remained unstained with EMA, anaplastic lymphoma kinase-1 (ALK-1), CD15 or cytotoxic associated antigen TIA-1. Smaller mature lymphocytes, chiefly T-cells, were intermixed. The morphologic and immunohistochemical features were considered typical of anaplastic large T-cell lymphoma. The pathogenesis of this association may have been due to radiation-mediated breakdown of the blood-brain barrier with subsequent T-cell infiltration and proliferation. We advocate aggressive resection and long-term surveillance for individuals with metastasis, especially higher-grade neoplasms that receive radiotherapy.

  6. Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Gregory N., E-mail: gregory.gan@ucdenver.edu [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Weickhardt, Andrew J.; Scheier, Benjamin; Doebele, Robert C. [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States); Gaspar, Laurie E.; Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Camidge, D. Ross [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States)

    2014-03-15

    Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.

  7. Identification of anaplastic lymphoma kinase as a potential therapeutic target in Basal Cell Carcinoma.

    Science.gov (United States)

    Ning, Hanna; Mitsui, Hiroshi; Wang, Claire Q F; Suárez-Fariñas, Mayte; Gonzalez, Juana; Shah, Kejal R; Chen, Jie; Coats, Israel; Felsen, Diane; Carucci, John A; Krueger, James G

    2013-12-01

    The pathogenesis of BCC is associated with sonic hedgehog (SHH) signaling. Vismodegib, a smoothened inhibitor that targets this pathway, is now in clinical use for advanced BCC patients, but its efficacy is limited. Therefore, new therapeutic options for this cancer are required. We studied gene expression profiling of BCC tumour tissues coupled with laser capture microdissection to identify tumour specific receptor tyrosine kinase expression that can be targeted by small molecule inhibitors. We found a >250 fold increase (FDRskin was observed by immunohistochemistry. Crizotinib, an FDA-approved ALK inhibitor, reduced keratinocyte proliferation in culture, whereas a c-Met inhibitor did not. Crizotinib significantly reduced the expression of GLI1 and CCND2 (members of SHH-pathway) mRNA by approximately 60% and 20%, respectively (p<0.01). Our data suggest that ALK may increase GLI1 expression in parallel with the conventional SHH-pathway and promote keratinocyte proliferation. Hence, an ALK inhibitor alone or in combination with targeting SHH-pathway molecules may be a potential treatment for BCC patients.

  8. High expression of Mcl-1 in ALK positive and negative anaplastic large cell lymphoma

    NARCIS (Netherlands)

    Rust, R; Harms, G; Blokzijl, T; Boot, M; Diepstra, A; Kluiver, J; Visser, L; Peh, SC; Lim, M; Kamps, WA; Poppema, S; van den Berg, Anke

    Aim: To gain more insight into the genes involved in the aetiology and pathogenesis of anaplastic large cell lymphoma (ALCL). Methods: Serial analysis of gene expression ( SAGE) was undertaken on the CD4+ALK+ ( anaplastic lymphoma kinase positive) ALCL derived cell line Karpas299 and as comparison

  9. Primary cutaneous anaplastic large-cell lymphoma.

    Science.gov (United States)

    Perry, Edward; Karajgikar, Jay; Tabbara, Imad A

    2013-10-01

    Since the recognition of the anaplastic large-cell lymphomas in the 1980s, much has been learned about the diagnosis, clinical presentation, and treatment of these malignant conditions. The systemic and primary cutaneous types of anaplastic large cell lymphomas have been differentiated on clinical and immunophenotypical findings, but further research is required to elucidate their exact etiologies and pathogeneses. Primary cutaneous anaplastic large-cell lymphoma has a 95% disease-specific 5-year survival, owing partly to the relatively benign course of the disease and partly to the variety of effective treatments that are available. As with many other oncological diseases, new drugs are continually being tested and developed, with immunotherapy and biological response modifiers showing promise.

  10. Real-world usage and clinical outcomes of alectinib among post-crizotinib progression anaplastic lymphoma kinase positive non-small-cell lung cancer patients in the USA

    Directory of Open Access Journals (Sweden)

    DiBonaventura MD

    2017-12-01

    Full Text Available Marco D DiBonaventura,1 William Wong,2 Bijal Shah-Manek,3,4 Mathias Schulz2 1Ipsos Healthcare, Global Evidence, Value & Access, New York, NY, 2Genentech, US Medical Affairs, San Francisco, CA, 3Ipsos Healthcare, Global Evidence, Value & Access, San Francisco, CA, 4College of Pharmacy, Touro University California, CA, USA Background: Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression. Methods: Participating oncologists (N=95 in the USA were recruited from an online physician panel to participate in a retrospective patient chart review. Physicians randomly selected eligible patients (ie, patients who progressed on crizotinib as their first ALK inhibitor and were treated with alectinib as their second ALK inhibitor, collected demographics and clinical history from their medical charts, and entered the data into an online data collection form. Results: A total of N=207 patient charts were included (age: 60.1±10.4 years; 53.6% male. The patients in our sample were older (median age of 60 vs 53 years, were more likely to be current smokers (12% vs 1%, had better performance status (45% vs 33% had an Eastern Cooperative Oncology Group [ECOG] of 0, and were less likely to have an adenocarcinoma histology (83% vs 96% relative to published clinical trials. The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively as was the disease control rate (89.9% vs 78.8%, respectively, though it varied by race/ethnicity, ECOG, and prior treatment history. Discontinuation (0.0% and dose reductions (3.4% due to adverse events were uncommon in alectinib.Conclusion: Patients using alectinib post-crizotinib in clinical practice are older, more racially/ethnically and histologically

  11. Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Shimada M

    2017-06-01

    Full Text Available Midori Shimada,1,2 Minoru Fukuda,2,3 Masaaki Fukuda,2 Takeshi Kitazaki,2 Kohji Hashiguchi,2 Takaya Ikeda,1 Hiroyuki Yamaguchi,1 Katsumi Nakatomi,1 Kazuto Ashizawa,3 Hiroshi Mukae1 1Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 2Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, 3Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan Abstract: A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK gene translocation was identified, the therapy was changed to crizotinib. However, the patient’s blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks. Keywords: lung cancer, ALK, renal dysfunction, alectinib

  12. Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Hamatani, K.; Mukai, M.; Takahashi, K.; Nakachi, K.; Kusunoki, Y. [Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima (Japan); Hayashi, Y. [Geriatric Health Service Facility Hidamari, Hiroshima (Japan)

    2012-07-01

    Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

  13. Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

    International Nuclear Information System (INIS)

    Hamatani, K.; Mukai, M.; Takahashi, K.; Nakachi, K.; Kusunoki, Y.; Hayashi, Y.

    2012-01-01

    Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

  14. Destaining of Diff-Quik stained cytologic smears is not necessary for the detection of anaplastic lymphoma kinase gene rearrangement in lung adenocarcinoma by fluorescence in situ hybridization

    Directory of Open Access Journals (Sweden)

    Weisheng Xu

    2016-01-01

    Full Text Available Background: Anaplastic lymphoma kinase (ALK gene rearrangement analysis by fluorescence in situ hybridization (FISH is one of the standard molecular tests for targeted therapy of lung adenocarcinoma. However, insufficient cell block cellularity may impede molecular testing. A recent study showed that Diff-Quik (DQ stained cytology smear is suitable for ALK by FISH. Aims: The aim of our study was to observe the impact of destaining intervals on the quality of FISH signals and determine if DQ smears without destaining would allow FISH analysis. Materials and Methods: Thirty-five DQ smears from 27 cases of lung adenocarcinoma were analyzed for ALK gene rearrangement by FISH. Twenty three DQ smears were destained for different intervals, including 30 s (13 cases, 1 min (6 cases, or 2 min (4 cases. Twelve DQ smears were not subjected to destaining. For further validation, FISH signals in 8 smears and 6 cell blocks were compared with the paired destained DQ smears. The signal quality was semi-quantified and analyzed with Chi-squared test. Results: Of the total 27 selected cases, three (11% were positive for ALK gene rearrangement, whereas 24 (89% were negative. FISH signal was satisfactory in all DQ smears. There was no significant difference in the quality of signal among smears with different destaining intervals (P = 0.55 or between smears with and without destaining (P = 0.41. DQ smears without destaining showed identical FISH results and similar or better signals as compared with paired destained smears and cell blocks in all cases. Conclusions: Duration of destaining intervals does not impact the quality of FISH signal on DQ smears. Destaining of DQ smears is not necessary for ALK by FISH.

  15. Anaplastic Lymphoma Kinase is Dynamically Expressed on Subsets of Motor Neurons and in the Peripheral Nervous System

    OpenAIRE

    Hurley, Shawn P.; Clary, Douglas O.; Copié, Valérie; Lefcort, Frances

    2006-01-01

    During embryonic development, complex events such as cellular proliferation, differentiation, survival, and guidance of axons are orchestrated and regulated by a variety of extracellular signals. Receptor tyrosine kinases mediate many of these events with several playing critical roles in neuronal survival and axonal guidance. It is evident that not all the receptor tyrosine kinases that play key roles in regulating neuronal development have been identified. In this study, we have characteriz...

  16. Cost-effectiveness of ceritinib in patients previously treated with crizotinib in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer in Canada.

    Science.gov (United States)

    Hurry, Manjusha; Zhou, Zheng-Yi; Zhang, Jie; Zhang, Chenxue; Fan, Liangyi; Rebeira, Mayvis; Xie, Jipan

    2016-10-01

    To assess the cost-effectiveness of ceritinib vs alternatives in patients who discontinue treatment with crizotinib in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) from a Canadian public healthcare perspective. A partitioned survival model with three health states (stable, progressive, and death) was developed. Comparators were chosen based on reported utilization from a retrospective Canadian chart study; comparators were pemetrexed, best supportive care (BSC), and historical control (HC). HC comprised of all treatment alternatives reported. Progression-free survival and overall survival for ceritinib were estimated using data reported from single-arm clinical trials (ASCEND-1 [NCT01283516] and ASCEND-2 [NCT01685060]). Survival data for comparators were obtained from published clinical trials in a NSCLC population and from a Canadian retrospective chart study. Parametric models were used to extrapolate outcomes beyond the trial period. Drug acquisition, administration, resource use, and adverse event (AE) costs were obtained from databases. Utilities for health states and disutilities for AEs based on EQ-5D were derived from literature. Incremental costs per quality-adjusted life year (QALY) gained were estimated. Univariate and probabilistic sensitivity analyses were performed. Over 4 years, ceritinib was associated with 0.86 QALYs and total direct costs of $89,740 for the post-ALK population. The incremental cost-effectiveness ratio (ICER) was $149,117 comparing ceritinib vs BSC, $80,100 vs pemetrexed, and $104,436 vs HC. Additional scenarios included comparison to docetaxel with an ICER of $149,780 and using utility scores reported from PROFILE 1007, with a reported ICER ranging from $67,311 vs pemetrexed to $119,926 vs BSC. Due to limitations in clinical efficacy input, extensive sensitivity analyses were carried out whereby results remained consistent with the base-case findings. Based on the willingness-to-pay threshold for

  17. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial.

    Science.gov (United States)

    Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju; Reckamp, Karen L; Hansen, Karin Holmskov; Kim, Sang-We; Huber, Rudolf M; West, Howard L; Groen, Harry J M; Hochmair, Maximilian J; Leighl, Natasha B; Gettinger, Scott N; Langer, Corey J; Paz-Ares Rodríguez, Luis G; Smit, Egbert F; Kim, Edward S; Reichmann, William; Haluska, Frank G; Kerstein, David; Camidge, D Ross

    2017-08-01

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%/27%), and cough (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed

  18. Pathobiology of Anaplastic Large Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Pier Paolo Piccaluga

    2010-01-01

    Full Text Available The authors revise the concept of anaplastic large cell lymphoma (ALCL in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented.

  19. Anaplastic lymphoma kinase inhibitors in phase I and phase II clinical trials for non-small cell lung cancer.

    Science.gov (United States)

    Karachaliou, Niki; Santarpia, Mariacarmela; Gonzalez Cao, Maria; Teixido, Cristina; Sosa, Aaron E; Berenguer, Jordi; Rodriguez Capote, Alejandra; Altavilla, Giuseppe; Rosell, Rafael

    2017-06-01

    Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients. The development of acquired resistance to crizotinib represents an ongoing challenge with the central nervous system being one of the most common sites of relapse. Ceritinib and alectinib are approved second-generation ALK TKIs. Several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib, are currently in development. Areas covered: This review will focus on new ALK inhibitors, currently in phase 1 or 2 clinical studies. We will also comment on the mechanisms of resistance to ALK inhibition and the strategies to delay or overcome resistance. Expert opinion: The therapeutic management of ALK-rearranged NSCLC has been greatly improved. Next-generation ALK inhibitors have shown differential potency against ALK rearrangements and ALK resistance mutations. The molecular profile of the tumor at the time of disease progression to crizotinib is crucial for the sequencing of novel ALK TKIs. Ongoing clinical studies will address key issues, including the optimal therapeutic algorithm and whether combinational approaches are more effective than single ALK inhibition for the outcome of ALK-rearranged NSCLC patients.

  20. MicroRNA Expression Profiling Identifies Molecular Diagnostic Signatures for Anaplastic Large Cell Lymphoma

    DEFF Research Database (Denmark)

    Liu, Cuiling; Iqbal, Javeed; Teruya-Feldstein, Julie

    2013-01-01

    Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[-]) ALCLs, 9......) that differentiates ALK(-) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, the miR-17∼92 cluster and its paralogues were also highly expressed in ALK(+) ALCL and may represent important downstream effectors of the ALK oncogenic pathway....... angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated...

  1. Dual anaplastic large cell lymphoma mimicking meningioma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keun Ho; Kim, Ki Hwan; Lee, Ghi Jai; Lee, Hye Kyung; Shim, Jae Chan; Lee, Kyoung Eun; Suh, Jung Ho [Seoul Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Lee, Chae Heuck [Dept. of Neurosurgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang (Korea, Republic of)

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) is a rare T cell lymphoma composed of CD30-positive lymphoid cells. Most ALCLs present as nodal disease, with skin, bone, soft tissue, lung, and liver as common extranodal sites. ALCL rarely occurs in the central nervous system and is even more infrequent in the dura of the brain. We report a case of dural-based ALCL secondary to systemic disease in a 17-year-old male that mimicked meningioma on magnetic resonance imaging and angiography.

  2. Change in the diagnosis from classical Hodgkin's lymphoma to anaplastic large cell lymphoma by 18F flourodeoxyglucose positron emission tomography/computed tomography: Importance of recognising disease pattern on imaging and immunohistochemistry

    International Nuclear Information System (INIS)

    Senthil, Raja; Mohapatra, Ranjan Kumar; Sampath, Mouleeswaran Koramadai; Sundaraiya, Sumati

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is a rare type of nonHodgkin's lymphoma (NHL), but one of the most common subtypes of T-cell lymphoma. It is an aggressive T-cell lymphoma, and some ALCL may mimic less aggressive classical HL histopathlogically. It may be misdiagnosed unless careful immunohistochemical examination is performed. As the prognosis and management of these two lymphomas vary significantly, it is important to make a correct diagnosis. We describe a case who was diagnosed as classical HL by histopathological examination of cervical lymph node, in whom 18 F-flouro deoxyglucose positron emission tomography/computed tomography appearances were unusual for HL and warranted review of histopathology that revealed anaplastic lymphoma kinase-1 negative anaplastic large T-cell lymphoma, Hodgkin-like variant, thereby changing the management

  3. Detection of Echinoderm Microtubule Associated Protein Like 4-Anaplastic Lymphoma Kinase Fusion Genes in Non-small Cell Lung Cancer Clinical Samples by a Real-time Quantitative Reverse Transcription Polymerase Chain Reaction Method.

    Science.gov (United States)

    Zhao, Jing; Zhao, Jin-Yin; Chen, Zhi-Xia; Zhong, Wei; Li, Long-Yun; Liu, Li-Cheng; Hu, Xiao-Xu; Chen, Wei-Jun; Wang, Meng-Zhao

    2016-12-20

    Objective To establish a real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) for the rapid, sensitive, and specific detection of echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion genes in non-small cell lung cancer. Methods The specific primers for the four variants of EML4-ALK fusion genes (V1, V2, V3a, and V3b) and Taqman fluorescence probes for the detection of the target sequences were carefully designed by the Primer Premier 5.0 software. Then, using pseudovirus containing EML4-ALK fusion genes variants (V1, V2, V3a, and V3b) as the study objects, we further analyzed the lower limit, sensitivity, and specificity of this method. Finally, 50 clinical samples, including 3 ALK-fluorescence in situ hybridization (FISH) positive specimens, were collected and used to detect EML4-ALK fusion genes using this method. Results The lower limit of this method for the detection of EML4-ALK fusion genes was 10 copies/μl if no interference of background RNA existed. Regarding the method's sensitivity, the detection resolution was as high as 1% and 0.5% in the background of 500 and 5000 copies/μl wild-type ALK gene, respectively. Regarding the method's specificity, no non-specific amplification was found when it was used to detect EML4-ALK fusion genes in leukocyte and plasma RNA samples from healthy volunteers. Among the 50 clinical samples, 47 ALK-FISH negative samples were also negative. Among 3 ALK-FISH positive samples, 2 cases were detected positive using this method, but another was not detected because of the failure of RNA extraction. Conclusion The proposed qRT-PCR assay for the detection of EML4-ALK fusion genes is rapid, simple, sensitive, and specific, which is deserved to be validated and widely used in clinical settings.

  4. Anaplastic large cell lymphoma ALK-negative clinically mimicking alcoholic hepatitis – a review

    Directory of Open Access Journals (Sweden)

    Fernando Peixoto Ferraz de Campos

    2013-10-01

    Full Text Available Anaplastic large cell lymphoma (ALCL, described less than 30 years ago by Karl Lennert and Herald Stein in Kiel, West Germany, is a T-cell or null non-Hodgkin lymphoma, with distinctive morphology (hallmark cells, prominent sinus and/or perivascular growth pattern, characteristic immunophenotype (CD30+, cytotoxic granules protein+, CD3–/+ and specific genetic features as translocations involving the receptor tyrosine kinase called anaplastic lymphoma kinase (ALK on 2p23 and variable partners genes, which results in the expression of ALK fusion protein. The absence of ALK expression is also observed and is associated with poorer prognosis that seen with ALK expression. ALK-negative ALCL is more frequent in adults, with both nodal and extra nodal clinical presentation and includes several differential diagnoses with other CD30+ lymphomas. Liver involvement by ALCL is rare and is generally seen as mass formation; the diffuse pattern of infiltration is even more unusual. The authors present a case of a 72-year-old man who presented clinical symptoms of acute hepatic failure. The patient had a long history of alcohol abuse and the diagnosis of alcoholic hepatitis was highly considered, although the serum lactic dehydrogenase (LDH value was highly elevated. The clinical course was fulminant leading to death on the fourth day of hospitalization. Autopsy demonstrated diffuse neoplastic hepatic infiltration as well as splenic, pulmonary, bone marrow, and minor abdominal lymph nodes involvement by the tumor. Based on morphological, immunophenotypical, and immunohistochemical features, a diagnosis of ALK- negative ALCL was concluded. When there is marked elevation of LDH the possibility of lymphoma, ALCL and other types, should be the principal diagnosis to be considered.

  5. Large anaplastic spinal B-cell lymphoma in a cat.

    Science.gov (United States)

    Flatland, Bente; Fry, Michael M; Newman, Shelley J; Moore, Peter F; Smith, Joanne R; Thomas, William B; Casimir, Roslyn H

    2008-12-01

    A 5-year-old female spayed domestic shorthair cat was presented for evaluation of tetraparesis. The neurologic lesion was localized to the cervical spinal segment (C1-C6). A left axillary mass was identified, and the results of fine needle aspiration cytology indicated malignant round cell neoplasia of possible histiocytic origin. The cells were large, had marked anisocytosis and anisokaryosis, occasional bi- and multinucleation, and cytoplasmic vacuolation. Euthanasia was performed due to the poor prognosis associated with severe, progressive neurologic signs and a malignant neoplasm. Postmortem examination revealed spinal cord compression and an extradural mass at the C1-C2 spinal segment, with neoplastic cells in the adjacent vertebral bodies, surrounding skeletal muscle, left axillary lymph node, and bone marrow from the right femur. The initial histologic diagnosis was anaplastic sarcoma, but immunohistochemical results indicated the cells were CD20+ and CD45R+ and CD3-, compatible with a diagnosis of B-cell lymphoma. CD79a staining was nonspecific and uninterpretable. Weak to moderate CD18 positivity and E-cadherin positivity were also observed. Clonality of the B-cell population could not be demonstrated using PCR testing for antigen receptor gene rearrangement. To the authors' knowledge, this is the first reported case of a feline spinal anaplastic B-cell lymphoma exhibiting bi- and multinucleated cells. The prognostic significance of this cell morphology and immunophenotype is unknown.

  6. Spinal cord compression caused by anaplastic large cell lymphoma in an HIV infected individual

    Directory of Open Access Journals (Sweden)

    Kumar Susheel

    2010-01-01

    Full Text Available Lymphomas occur with an increased frequency in patients with Human Immunodeficiency Virus (HIV infection. These are usually high-grade immunoblastic lymphomas and primary central nervous system lymphomas. Anaplastic large cell lymphoma (ALCL is a distinct type of non-Hodgkin′s lymphoma. It is uncommon in HIV infected individuals. We describe here an uncommon presentation of this relatively rare lymphoma in the form of spinal cord compression syndrome in a young HIV infected individual.

  7. ALK signaling and target therapy in anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Fabrizio eTabbo

    2012-05-01

    Full Text Available The discovery by Morris SW et al. in 1994 of the genes contributing to the t(2;5(p23;q35 translocation has put the foundation for a molecular based recognition of Anaplastic Large Cell Lymphoma (ALCL and pointed out the need for a further stratification of T-cell neoplasia. Likewise the detection of ALK genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

  8. High intratumoral macrophage content is an adverse prognostic feature in anaplastic large cell lymphoma

    DEFF Research Database (Denmark)

    Pedersen, Martin B; Danielsen, Allan V; Hamilton-Dutoit, Stephen J

    2014-01-01

    AIMS: Macrophage infiltration has been associated with prognosis in several cancers, including lymphoma, but has not been assessed systematically in anaplastic large cell lymphoma (ALCL). The aim of the study was to correlate expression of the macrophage-associated antigens CD68 and CD163 with pr...

  9. Clinical and laboratory characteristics of systemic anaplastic large cell lymphoma in Chinese patients

    Directory of Open Access Journals (Sweden)

    Wang Yan-Fang

    2012-07-01

    Full Text Available Abstract Background Systemic anaplastic large cell lymphoma (S-ALCL is a rare disease with a highly variable prognosis and no standard chemotherapy regimen. Anaplastic lymphoma kinase (ALK has been reported as an important prognostic factor correlated with S-ALCL in many but not all studies. In our study, we retrospectively analyzed 92 patients with S-ALCL from the Peking University Lymphoma Center for clinical and molecular prognostic factors to make clear the role of ALK and other prognostic factors in Han Chinese S-ALCL. Results The majority of Chinese S-ALCL patients were young male patients (median age 26, male/female ratio 1.7 and the median age was younger than previous reports regardless of ALK expression status. The only statistically significant different clinical characteristic in S-ALCL between ALK positive (ALK+ and ALK negative (ALK- was age, with a younger median age of 22 for ALK+ compared with 30 for ALK-. However, when pediatric patients (≤18 were excluded, there was no age difference between ALK+ and ALK-. The groups did not differ in the proportion of males, those with clinical stage III/IV (49 vs 51% or those with extranodal disease (53 vs 59%. Of 73 evaluable patients, the 3-year and 5-year survival rates were 60% and 47%, respectively. Univariate analysis showed that three factors: advanced stage III/IV, lack of expression of ALK, and high Ki-67 expression, were associated with treatment failure in patients with S-ALCL. However, ALK expression correlated with improved survival only in patients younger than 14 years, while not in adult patients. In multivariate analysis, only clinical stage was an independent prognostic factor for survival. Expressions of Wilms tumor 1 (WT1 and B-cell lymphoma 2 protein (BCL-2 correlated with the expression of ALK, but they did not have prognostic significance. High Ki-67 expression was also a poor prognostic factor. Conclusions Our results show that ALK expression alone is not

  10. Anaplastic large-cell lymphoma with florid granulomatous reaction: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Balamurugan S

    2009-01-01

    Full Text Available Granulomatous reactions have been reported in association with lymphomas, more often with Hodgkins disease than with Non-Hodgkins Lymphoma. Not many reports are available on the association of anaplastic large-cell lymphoma with sarcoid-type granuloma. Herein, we report a case of an elderly female with generalized lymphadenopathy who had a florid granulomatous reaction almost masking the lymphoma cells in the lymph node biopsy. A detailed clinical history, careful histological examination and immunohistochemistry helped in attaining the correct diagnosis.

  11. Primary cutaneous anaplastic large cell lymphoma masquerading as large pyogenic granuloma

    Directory of Open Access Journals (Sweden)

    Anupama Bains

    2016-01-01

    Full Text Available Primary cutaneous anaplastic large cell lymphoma (pcALCL forms 9% of the cutaneous T-cell lymphomas. It usually presents as solitary reddish brown ulcerating nodule or indurated plaque. Sometimes, it mimics other dermatological diseases such as eczema, pyoderma gangrenosum, pyogenic granuloma, morphea, and squamous cell carcinoma. Our case presented with large pyogenic granuloma like lesion with regional lymphadenopathy. Since pcALCL is rare, one can misdiagnose such cases and therefore high index of suspicion is necessary.

  12. The non-specific symptoms of breast implant-associated anaplastic large cell lymphoma resulting in delayed diagnosis: A case-based review

    Directory of Open Access Journals (Sweden)

    Reem Dina Jarjis

    2015-12-01

    Full Text Available Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL is a rare entity that has become known as a distinct clinical condition recently. In general, BIA-ALCL patients with a history of breast implants present with non-specific implant-related complications, resulting in delayed diagnosis and appropriate treatment because of the lack of awareness of BIA-ALCL. The cause and pathogenesis have still not been identified, and there are no evidence-based guidelines on how this condition should be detected, treated or followed up because of the rarity of available data. We present the first published Danish case of anaplastic lymphoma kinase negative BIA-ALCL, and review the current literature to raise awareness of and discuss management options for this rare clinical entity.

  13. Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience

    International Nuclear Information System (INIS)

    Million, Lynn; Yi, Esther J.; Wu, Frank; Von Eyben, Rie; Campbell, Belinda A.; Dabaja, Bouthaina; Tsang, Richard W.; Ng, Andrea; Wilson, Lynn D.; Ricardi, Umberto; Kirova, Youlia; Hoppe, Richard T.

    2016-01-01

    Purpose: To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome. Methods and Materials: The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide. Results: Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease. Conclusions: Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.

  14. Extreme neutrophil granulocytosis in a patient with anaplastic large cell lymphoma of T-cell lineage

    DEFF Research Database (Denmark)

    Engsig, Frederik Neess; Møller, Michael Boe; Hasselbalch, Hans K

    2007-01-01

    We describe a 47-year-old male admitted with fever and extreme neutrophil granulocytosis (up to 80 x 10(9)/L). All microbiology tests and test for autoimmune disease were negative. CT scan showed pulmonary infiltrates bilaterally, mediastinal lymphadenopathy and splenomegaly. Conventional...... led to a diagnosis of anaplastic large cell lymphoma (ALCL) of T-cell lineage. Involvement of peripheral blood with leukemoid reaction is a rare manifestation of ALCL. This case emphasizes the importance of immunophenotyping in unexplained extreme granulocytosis....

  15. A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Zu Youli

    2011-01-01

    Full Text Available Abstract Background Many in vitro studies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limited in vivo application for siRNA-mediated gene therapy. Results In this study, we tested a functional RNA nanocomplex which exclusively targets and affects human anaplastic large cell lymphoma (ALCL by taking advantage of the abnormal expression of CD30, a unique surface biomarker, and the anaplastic lymphoma kinase (ALK gene in lymphoma cells. The nanocomplexes were formulated by incorporating both ALK siRNA and a RNA-based CD30 aptamer probe onto nano-sized polyethyleneimine-citrate carriers. To minimize potential cytotoxicity, the individual components of the nanocomplexes were used at sub-cytotoxic concentrations. Dynamic light scattering showed that formed nanocomplexes were ~140 nm in diameter and remained stable for more than 24 hours in culture medium. Cell binding assays revealed that CD30 aptamer probes selectively targeted nanocomplexes to ALCL cells, and confocal fluorescence microscopy confirmed intracellular delivery of the nanocomplex. Cell transfection analysis showed that nanocomplexes silenced genes in an ALCL cell type-selective fashion. Moreover, exposure of ALCL cells to nanocomplexes carrying both ALK siRNAs and CD30 RNA aptamers specifically silenced ALK gene expression, leading to growth arrest and apoptosis. Conclusions Taken together, our findings indicate that this functional RNA nanocomplex is both tumor cell type-selective and cancer gene-specific for ALCL cells.

  16. Post transplant anaplastic large T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Azhir Afshin

    2009-01-01

    Full Text Available Post transplant lymphoproliferative disorders (PTLD are a heterogeneous group of lymphoid proliferation that ranges from polyclonal hyperplasia to monoclonal malignant lym-phoma. We report a 13-year-old boy who was diagnosed with PTLD in February 2007 after 3 1/2 years of deceased renal transplantation. We treated him with an adapted ACVBP (doxorubicin, cyclo-phosphamide, vincristine, bleomycin and prednisone regimen. He responded well to the chemo-therapy without deterioration of graft function.

  17. Cardiac Tamponade Associated with the Presentation of Anaplastic Large Cell Lymphoma in a 2-Year-Old Child

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    Gema Mira-Perceval Juan

    2015-01-01

    Full Text Available The anaplastic large cell lymphoma is a rare entity in pediatric patients. We present an unusual case of pericardial involvement, quite uncommon as extranodal presentation of this type of disorder, that provoked a life-risk situation requiring an urgent pericardiocentesis. To our knowledge, this is the first report on a child with pericardial involvement without an associated cardiac mass secondary to anaplastic large cell lymphoma in pediatric age. We report the case of a 21-month-old Caucasian male infant with cardiac tamponade associated with the presentation of anaplastic large cell lymphoma. Initially, the child presented with 24-day prolonged fever syndrome, cutaneous lesions associated with hepatomegaly, inguinal adenopathies, and pneumonia. After a 21-day asymptomatic period, polypnea and tachycardia were detected in a clinical check-up. Chest X-ray revealed a remarkable increase of the cardiothoracic index. The anaplastic large cell lymphoma has a high incidence of extranodal involvement but myocardial or pericardial involvements are rare. For this reason, we recommend a close monitoring of patients with a differential diagnosis of anaplastic large cell lymphoma.

  18. Discovery of (10 R )-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro- 2H -8,4-(metheno)pyrazolo[4,3- h ][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase (ALK) and c-ros Oncogene 1 (ROS1) with Preclinical Brain Exposure and Broad-Spectrum Potency against ALK-Resistant Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Ted W.; Richardson, Paul F.; Bailey, Simon; Brooun, Alexei; Burke, Benjamin J.; Collins, Michael R.; Cui, J.Jean; Deal, Judith G.; Deng, Ya-Li; Dinh, Dac; Engstrom, Lars D.; He, Mingying; Hoffman, Jacqui; Hoffman, Robert L.; Huang, Qinhua; Kania, Robert S.; Kath, John C.; Lam, Hieu; Lam, Justine L.; Le, Phuong T.; Lingardo, Laura; Liu, Wei; McTigue, Michele; Palmer, Cynthia L.; Sach, Neal W.; Smeal, Tod; Smith, Graham L.; Stewart, Albert E.; Timofeevski, Sergei; Zhu, Huichun; Zhu, Jinjiang; Zou, Helen Y.; Edwards, Martin P. (Pfizer)

    2014-06-12

    Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinoma patients, progression during treatment eventually develops. Resistant patient samples revealed a variety of point mutations in the kinase domain of ALK, including the L1196M gatekeeper mutation. In addition, some patients progress due to cancer metastasis in the brain. Using structure-based drug design, lipophilic efficiency, and physical-property-based optimization, highly potent macrocyclic ALK inhibitors were prepared with good absorption, distribution, metabolism, and excretion (ADME), low propensity for p-glycoprotein 1-mediated efflux, and good passive permeability. These structurally unusual macrocyclic inhibitors were potent against wild-type ALK and clinically reported ALK kinase domain mutations. Significant synthetic challenges were overcome, utilizing novel transformations to enable the use of these macrocycles in drug discovery paradigms. This work led to the discovery of 8k (PF-06463922), combining broad-spectrum potency, central nervous system ADME, and a high degree of kinase selectivity.

  19. Treatment of primary cutaneous anaplastic large cell lymphoma with superficial x-rays

    DEFF Research Database (Denmark)

    Jepsen, Malene E; Gniadecki, Robert

    2015-01-01

    The optimal radiation schedule for primary cutaneous anaplastic lymphoma (PCALCL) has not been investigated. We report here satisfactory outcomes of low-dose (16-20 Gy, 3-5 fractions), superficial X-ray radiation (40-50 kV) in a series of 10 patients with PCALCL. Only 1 patient developed a local ...... relapse during the median observation time of 25 months; complete remission was recorded in the other patients. This observation indicates that superficial, low dose X-ray therapy may provide a cost-effective alternative to the traditional 35-45 Gy schedules....

  20. Novel Technique for Sampling of Breast Implant–associated Seroma in Anaplastic Large Cell Lymphoma

    Science.gov (United States)

    T’Kindt, Johan; Mertens, Marianne; Colpaert, Steven D. M.

    2016-01-01

    Summary: We describe a novel technique for the sampling of breast implant–associated seroma. Using a blunt-tip lipofilling cannula, we have the freedom of movement to sample all fluid collections and prevent the misfortunes of damaging the implant. Also, we have demonstrated the inability of the Coleman style I lipofilling cannula to perforate a silicone breast implant. This practical and reliable technique will prove to be useful in managing the breast implant–associated seroma, especially with the rising incidence of the anaplastic large cell lymphoma, where the sampling of seroma is mandatory. PMID:27200250

  1. Primary CNS anaplastic diffuse large B-cell lymphoma mimicking undifferentiated metastatic tumors: a case report.

    Science.gov (United States)

    Yang, Tianyu; Belverud, Shawn; Yeh, Albert Y; Bandovic, Jela; Farmer, Peter; Woldenberg, Rona F; Demopoulos, Alexis; Schulder, Michael; Li, Jian Yi

    2010-02-01

    Primary central nervous system lymphoma (PCNSL) is a rare intracranial tumor, with an annual incidence of six per million population. Anaplastic variant of primary CNS diffuse large B-cell lymphoma is less common; to our knowledge, there is only one other case report in the world literature. We describe a 71 year old immunocompetent female without significant past medical history who presented with confusion and a homogeneously enhancing midline mass. The patient underwent craniotomy for tumor biopsy, followed by high-dose methotrexate-based chemotherapy despite a remarkably low performance status. Histologically, this tumor was composed of undifferentiated polymorphic tumor cells, multi-nucleated giant cells, extensive necrosis, and conspicuous mitotic activity, mimicking undifferentiated metastatic tumors. Immunohistochemical stains demonstrated immunopositivity of tumor cells for CD20, MUM-1, and BCL-6, and negative staining for CD3, CD10, and CD30. The clinical course, diagnostic workup, pathologic correlates, and treatment outcomes are described.

  2. Anaplastic Large-Cell Lymphoma in a Child with Type I Diabetes and Unrecognised Coeliac Disease

    Directory of Open Access Journals (Sweden)

    Jemima Sharp

    2012-01-01

    Full Text Available Screening for coeliac disease is recommended for children from certain risk groups, with implications for diagnostic procedures and dietetic management. The risk of a malignant complication in untreated coeliac disease is not considered high in children. We present the case of a girl with type I diabetes who developed weight loss, fatigue, and inguinal lymphadenopathy. Four years before, when she was asymptomatic, a screening coeliac tTG test was positive, but gluten was not eliminated from her diet. Based on clinical examination, a duodenal biopsy, and an inguinal lymph node biopsy were performed, which confirmed both coeliac disease and an anaplastic large-cell lymphoma. HLA-typing demonstrated that she was homozygous for HLA-DQ8, which is associated with higher risk for celiac disease, more severe gluten sensitivity, and diabetes susceptibility. She responded well to chemotherapy and has been in remission for over 4 years. She remains on a gluten-free diet. This is the first case reporting the association of coeliac disease, type I diabetes, and anaplastic large-cell lymphoma in childhood. The case highlights the malignancy risk in a genetically predisposed individual, and the possible role of a perpetuated immunologic response by prolonged gluten exposure.

  3. The HSP90 inhibitor 17-AAG synergizes with doxorubicin and U0126 in anaplastic large cell lymphoma irrespective of ALK expression.

    Science.gov (United States)

    Georgakis, Georgios V; Li, Yang; Rassidakis, Georgios Z; Medeiros, L Jeffrey; Younes, Anas

    2006-12-01

    Heat shock protein 90 (HSP90) chaperones and maintains the molecular integrity of a variety of signal transduction proteins, including the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncogenic protein, a genetic abnormality that is frequently observed in anaplastic large cell lymphoma (ALCL) cells. Here we demonstrate that HSP90 is overexpressed in primary and cultured ALK-positive and ALK-negative ALCL cells, and we evaluate the potential role of the small molecule inhibitor of HSP90, 17-allylamino-17-demethoxygeldanamycin (17-AAG) in treating ALCL. The antiproliferative effect of 17-AAG-cultured cells was determined by MTS assay. Apoptosis and cell-cycle arrest were determined by Annexin-V/propidium iodide and propidium iodide staining, respectively, and fluorescein-activated cell sorting analysis. Expression of HSP90 was evaluated by immunohistochemistry, and molecular changes were determined by Western blot. Treatment of cultured ALCL cells with 17-AAG induced cell-cycle arrest and apoptosis, irrespective of ALK expression. At the molecular level, 17-AAG induced degradation of ALK and Akt proteins, dephosphorylated extracellular signal-regulated kinase, and degraded the cell-cycle regulatory protein cyclin D1 and its cyclin-dependent kinases, CDK4 and CDK6, but had a differential effect on p27 and p53 proteins. Inhibition of extracellular signal-regulated kinase phosphorylation by the mitogen activated protein kinase inhibitor U0126 induced cell death in all ALCL cell lines, and sublethal concentration 17-AAG showed synergistic antiproliferative effects when combined with U0126 or doxorubicin. Our data demonstrate that targeting HSP90 function by 17-AAG may offer a novel therapeutic strategy for ALCL, either as single-agent activity or by combining 17-AAG with conventional or targeted therapeutic schemes.

  4. Leukaemic presentation of small cell variant anaplastic large cell lymphoma: report of four cases.

    Science.gov (United States)

    Bayle, C; Charpentier, A; Duchayne, E; Manel, A M; Pages, M P; Robert, A; Lamant, L; Dastugue, N; Bertrand, Y; Dijoud, F; Emile, J F; Machover, D; Brugiéres, L; Delsol, G

    1999-03-01

    We report four cases of a rare subtype of CD30-positive anaplastic large cell lymphoma (ALCL) with a predominant small cell component (small cell variant of ALCL) presenting with a leukaemic feature. Lymph node biopsy showed malignant cells of varying size with a predominant population of small to medium-sized malignant cells associated with large anaplastic cells strongly positive for CD30 and epithelial membrane antigen (EMA). Both large and small cells were reactive with antibody ALK1, which recognizes the chimaeric NPM-ALK protein associated with the t(2;5)(p23;q35). All patients presented with hyperleucocytosis with atypical small lymphocytes. Bone marrow involvement was detected on both aspirate and bone marrow trephine where scattered malignant cells were only demonstrated by immunostaining for CD30 and ALK protein. Atypical cells in peripheral blood, lymph node and skin biopsies showed a T or null cell phenotype. Cytogenetic analysis of blood, bone marrow and/or lymph node revealed the t(2:5)(p23;q35) characteristic of ALCL. The patients responded to chemotherapy but showed early relapse without abnormal cells in peripheral blood. This report shows that the small cell variant of ALCL may have a leukaemic presentation with peripheral blood involvement by atypical lymphocytes and provides evidence that, in the small cell variant of ALCL, the small cell component is a part of the malignant clone.

  5. Skin involvement as the first manifestation of breast implant-associated anaplastic large cell lymphoma.

    Science.gov (United States)

    Alcalá, Rebeca; Llombart, Beatriz; Lavernia, Javier; Traves, Víctor; Guillén, Carlos; Sanmartín, Onofre

    2016-07-01

    Breast implant-associated anaplastic large cell lymphoma (ALCL) is a newly described clinical and pathologic entity that typically presents as seroma in the fibrous scar around the implant. Less frequently, it presents as a solid peri-implant mass, and there have been no reports to date of cutaneous lesions as the presenting manifestation. We report the case of a 56-year-old woman with a history of bilateral breast reconstruction following breast cancer of the right breast who consulted with several papules on the right breast suggestive of metastasis. Histopathology showed a proliferation of large epithelioid lymphocytes with highly pleomorphic cells and nuclei. The neoplastic cells were CD15 and CD30 positive and ALK-1 negative. The epithelial markers were all negative except for epithelial membrane antigen (EMA), which was weakly positive. Molecular analysis showed monoclonal T-cell receptor γ gene rearrangement, confirming a diagnosis of breast implant-associated ALCL. The non-specific morphology of the skin lesions, the epithelioid nature of the neoplastic cells and the expression of EMA can lead to an erroneous diagnosis of skin metastases from a poorly differentiated adenocarcinoma of the breast. We recommend immunohistochemical staining for CD30 and ALK-1 for patients with breast implants who develop anaplastic lesions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. TARC, a CC chemokine, is frequently expressed in classic Hodgkin's lymphoma but not in NLP Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and most cases of anaplastic large cell lymphoma

    NARCIS (Netherlands)

    Peh, SC; Kim, LH; Poppema, S

    Thymus and activation-regulated chemokine (TARC) has been identified as a lymphocyte-directed CC chemokine that attracts activated T-helper type 2 (Th2) cells in humans. Recent studies showed that the T cells surrounding Reed-Sternberg cells in Hodgkin's lymphomas (HL) are Th2 type. Anaplastic large

  7. Successful Treatment in a Child with Anaplastic Large Cell Lymphoma and Coexistence of Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Margarita Baka

    2013-01-01

    Full Text Available A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL, whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months, pyrazinamide (the first 2 months, and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time.

  8. Crizotinib in Combination with Everolimus Synergistically Inhibits Proliferation of ALK-Positive Anaplastic Large Cell Lymphoma.

    Science.gov (United States)

    Xu, Wendan; Kim, Ji-Won; Jung, Woo June; Koh, Youngil; Yoon, Sung-Soo

    2017-06-19

    Anaplastic large cell lymphoma (ALCL) is a rare aggresive non-Hodgkin lymphoma, of which over 50% of cases have an aberrant NPM-ALK fusion protein. Both mTOR inhibitor everolimus and ALK inhibitor crizotinib have shown promising antitumor activity in ALK-positive cancer cell lines. However, their combined effect has not yet been investigated. We evaluated the anti-proliferative effects of everolimus and/or crizotinib in ALK-positive ALCL cell lines, Karpas 299 and SU-DHL-1, and lung adenocarcinoma cell line, NCI-H2228. We found that individually, both everolimus and crizotinib potently inhibited cell growth in a dose-dependent manner in both Karpas 299 and SU-DHL-1 cells. A combination of these agents synergistically inhibited proliferation in the two cell lines. Crizotinib down-regulated aberrant AKT and ERK phosphorylation induced by everolimus. Combination treatment also significantly increased G0/G1 cell-cycle arrest, DNA damage, and apoptosis compared with everolimus or crizotinib alone in ALK-positive ALCL cells. In the Karpas 299 xenograft model, the combination treatment exerted a stronger antitumor effect than monotherapies, without significant change in body weight. The synergistic effect of everolimus and crizotinib was also reproduced in the ALK-positive lung adenocarcinoma cell line NCI-H2228. The combination treatment abrogated PI3K/AKT and mTOR signaling pathways with little effect on the Ras/ERK pathway in NCI-H2228 cells. Crizotinib combined with everolimus synergistically inhibits proliferation of ALK-positive ALCL cells. Our results suggest that this novel combination is worthy of further clinical development in patients with ALK-positive ALCL.

  9. Comparison of primary thyroid lymphoma with anaplastic thyroid carcinoma on computed tomographic imaging

    International Nuclear Information System (INIS)

    Ishikawa, Hitoshi; Mitsuhashi, Norio; Niibe, Hideo

    2002-01-01

    Primary non-Hodgkin's lymphoma (LY) and anaplastic carcinoma (AC) of the thyroid gland are rare malignant tumors, and the initial symptoms of these diseases are very similar. The aim of our study was to compare the characteristics of the two diseases using computed tomographic (CT) scans in order to make an accurate differential diagnosis. Ten patients with LY and 10 with AC were analyzed. Differences in the CT findings of the two diseases were evaluated before treatment and statistically tested with either Student's t-test or the chi-square test. In the analysis of characteristics of CT imaging, the existence of calcification and necrosis, and heterogeneous tumor were dominant findings in AC, and there was a statistically significant difference in frequency between the two diseases (p<0.01). Calcification detected in AC was usually multiple and/or gross (mean size: φ8.2 mm). All lymphadenopathies were delineated as having the same homogeneous attenuation as the tumors in the thyroid gland in LY, but were shown as irregular rim enhancement in AC. The CT features of the two diseases are characteristic in terms of calcification, necrosis, and tumor composition. Evaluation by means of CT imaging is useful in distinguishing between LY and AC. (author)

  10. Infectious Mimicry Complicates Diagnosis in Hemophagocytic Syndrome Caused by Anaplastic Large-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Michael J. Peluso

    2012-01-01

    Full Text Available Hemophagocytic syndrome (HPS arises secondary to genetic, rheumatologic, neoplastic, and infectious causes. We discuss a patient whose presentation was consistent with systemic infection but was discovered to have HPS of unknown etiology. The presenting symptoms, as well as unremarkable malignancy and rheumatologic workups, led to the pursuit of an infectious cause, but the patient was ultimately discovered to have an occult anaplastic large-cell lymphoma (ALCL. This case demonstrates the diagnostic challenges that result from infectious mimicry in the context of HPS—first, in distinguishing noninfectious HPS from the systemic inflammation that can result from a widespread infectious process, second, in the identification of the precipitating cause of HPS. While evidence of these challenges has been suggested by the limited literature on HPS and ALCL, our case illustrates the diagnostic dilemma that arises when tissue biopsy does not quickly reveal an etiology. It is important that all physicians be aware that HPS can mimic infection and be prepared to redirect the workup when an infectious etiology for HPS cannot be identified.

  11. PIM kinases as potential therapeutic targets in a subset of peripheral T cell lymphoma cases.

    Directory of Open Access Journals (Sweden)

    Esperanza Martín-Sánchez

    Full Text Available Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL. The Proviral Integration site of Moloney murine leukemia virus (PIM kinases are important mediators of cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs and pharmacologically (mainly with the pan-PIM inhibitor (PIMi ETP-39010 in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.

  12. Bacterial Biofilm Infection Detected in Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

    Science.gov (United States)

    Hu, Honghua; Johani, Khalid; Almatroudi, Ahmad; Vickery, Karen; Van Natta, Bruce; Kadin, Marshall E; Brody, Garry; Clemens, Mark; Cheah, Chan Yoon; Lade, Stephen; Joshi, Preeti Avinash; Prince, H Miles; Deva, Anand K

    2016-06-01

    A recent association between breast implants and the development of anaplastic large-cell lymphoma (ALCL) has been observed. The purpose of this study was to identify whether bacterial biofilm is present in breast implant-associated ALCL and, if so, to compare the bacterial microbiome to nontumor capsule samples from breast implants with contracture. Twenty-six breast implant-associated ALCL samples were analyzed for the presence of biofilm by real-time quantitative polymerase chain reaction, next-generation sequencing, fluorescent in situ hybridization, and scanning electron microscopy, and compared to 62 nontumor capsule specimens. Both the breast implant-associated ALCL and nontumor capsule samples yielded high mean numbers of bacteria (breast implant-associated ALCL, 4.7 × 10 cells/mg of tissue; capsule, 4.9 × 10 cells/mg of tissue). Analysis of the microbiome in breast implant-associated ALCL specimens showed significant differences with species identified in nontumor capsule specimens. There was a significantly greater proportion of Ralstonia spp. present in ALCL specimens compared with nontumor capsule specimens (p capsule specimens compared with breast implant-associated ALCL specimens (p < 0.001). Bacterial biofilm was visualized both on scanning electron microscopy and fluorescent in situ hybridization. This novel finding of bacterial biofilm and a distinct microbiome in breast implant-associated ALCL samples points to a possible infectious contributing cause. Breast implants are widely used in both reconstructive and aesthetic surgery, and strategies to reduce their contamination should be more widely studied and practiced. Risk, V.

  13. A Case of an Unusually Aggressive Cutaneous Anaplastic Large T-Cell Lymphoma in an HIV Patient Treated with CHOP

    Directory of Open Access Journals (Sweden)

    Jorge Hurtado-Cordovi

    2011-01-01

    Full Text Available Anaplastic large cell lymphoma (ALCL is the second most common malignancy of T-cell phenotype. This case report describes an unusual rapidly progressing cutaneous anaplastic large T-cell lymphoma in an HIV patient. Our patient is a twenty-year-old African American male with perinatally acquired HIV who presented with a 2×2 centimeter necrotic lesion in the right 1st toe; however, 2-3 weeks later multiple smaller lesions appeared on the anterior aspect of the right foot, ankle, and thigh. Biopsy showed cells strongly positive for CD3 and CD30 and negative for CD56 and the ALK gene product. CT of the chest, abdomen, and pelvis was negative for extracutaneous involvement favoring cutaneous ALCL. Patient was treated with 6 cycles of CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone chemotherapy and went into complete remission. Due to the aggressive course that this malignancy follows in HIV patients we suggest prompt treatment with systemic therapy.

  14. TIMP-I expression in anaplastic large cell lymphoma is usually restricted to macrophages and only seldom observed in tumour cells

    NARCIS (Netherlands)

    Rust, R; Blokzijl, T; Harms, G; Lim, M; Visser, L; Kamps, WA; Poppema, S; van den Berg, Anke

    Anaplastic large cell lymphomas (ALCLs) can be subdivided into two subgroups on the basis of their expression of the ALK protein. ALK protein expression leads to activation of signal transducer and activator of transcription (STAT) 3, which is more commonly expressed in ALK-positive than in

  15. Tyrosine phosphorylation in human lymphomas

    NARCIS (Netherlands)

    Haralambieva, E; Jones, M.; Roncador, GM; Cerroni, L; Lamant, L; Ott, G; Rosenwald, A; Sherman, C; Thorner, P; Kusec, R; Wood, KM; Campo, E; Falini, B; Ramsay, A; Marafioti, T; Stein, H; Kluin, PM; Pulford, K; Mason, DY

    2002-01-01

    In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated

  16. Locally advanced breast implant associated anaplastic large cell lymphoma: A case report of successful treatment with radiation and chemotherapy

    Directory of Open Access Journals (Sweden)

    Christopher Fleighton Estes

    2015-02-01

    Full Text Available The development of breast implant associated anaplastic large cell lymphoma (ALCL is a rare phenomenon. A typical presentation is an effusion associated with a breast implant. Less commonly, disease can become more advanced locoregionally or distantly. The optimal treatment schema is a topic of debate: localized ALCL can potentially be cured with implant removal alone, while other cases in the literature, including those that are more advanced, have been treated with varying combinations of surgery, chemotherapy, and external beam radiotherapy. This is a case report of breast implant ALCL with pathologically proven lymph node involvement, the fifth such patient reported. Our patient experienced a favorable outcome with radiation therapy and chemotherapy.

  17. Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant–Associated Anaplastic Large-Cell Lymphoma

    Science.gov (United States)

    Clemens, Mark W.; Medeiros, L. Jeffrey; Butler, Charles E.; Hunt, Kelly K.; Fanale, Michelle A.; Horwitz, Steven; Weisenburger, Dennis D.; Liu, Jun; Morgan, Elizabeth A.; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R.; Ferry, Judith A.; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M.; Hanson, Summer E.; Nastoupil, Loretta J.; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H.

    2016-01-01

    Purpose Breast implant–associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. Patients and Methods In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. Results The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Conclusion Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. PMID:26628470

  18. Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

    Science.gov (United States)

    Clemens, Mark W; Medeiros, L Jeffrey; Butler, Charles E; Hunt, Kelly K; Fanale, Michelle A; Horwitz, Steven; Weisenburger, Dennis D; Liu, Jun; Morgan, Elizabeth A; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R; Ferry, Judith A; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; DiNapoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M; Hanson, Summer E; Nastoupil, Loretta J; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H; Miranda, Roberto N

    2016-01-10

    Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. © 2015 by American Society of Clinical Oncology.

  19. Extrinsic apoptotic pathways: A new potential "Target" for more sufficient therapy in a case of cutaneous anaplastic large CD30+ ALK-T--cell lymphoma

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2011-01-01

    Full Text Available The primary cutaneous T-cell lymphomas (CTCL represent a clonal T-lymphocyte proliferation infiltrating the skin. CD30+ T-cell lymphomas present clinically as nodules with a diameter between 1 and 15 cm, mostly in elderly patients. The role of the CD30 molecule in patients suffering from T-cell lymphomas is not completely clear yet. The signal transduction pathway which includes CD30 seems to play a key role in tumor progression. In certain forms of T-cellular lymphomas, the interaction between CD30/CD30-ligand is able to provoke apoptosis of the "tumor lymphocytes". The modern conceptions of the pathogenesis of T-cell lymphomas include disorders in the pathways involved in programmed cellular death and disregulation in the expression of certain of its regulatory molecules. We are presenting an unusual case of a female patient with a primary cutaneous form of CD30 + /ALK− anaplastic large T-cell lymphoma. Upon the introduction of systemic PUVA, (psoralen plus ultraviolet light radiation combined with beam therapy, a complete remission could be noticed. Eight months later, we observed a local recurrence, which was overcome by CHOP chemotherapy (Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin, Vincristin (Oncovin®, Predniso(lon. Six months later, new cutaneous lesions had been noticed again. A new therapeutic hope for the patients with anaplastic large CTCL is actually based on the influence of the activity of the different apoptotic pathways. Death ligands, including tumor necrosis factor (TNF-α, CD95L/FasL, and TRAIL, mediate also some important safeguard mechanisms against tumor growth in patients with CD30 + cutaneous anaplastic large T-cell lymphomas and critically contribute to lymphocyte homeostasis.

  20. Occurrence of anaplastic large cell lymphoma following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma.

    Science.gov (United States)

    Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Keiko; Kagotani, Akiko; Iwai, Muneo; Yoshii, Miyuki; Okuno, Hiroko; Horinouchi, Akiko; Nakanishi, Ryota; Harada, Ayumi; Yoshida, Takashi; Okabe, Hidetoshi

    2013-01-01

    IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Recently, the association between IgG4-related sclerosing disease and the risk of malignancies has been suggested. IgG4-related autoimmune pancreatitis with pancreatic cancer has been reported. Further, a few cases of extraocular malignant lymphoma in patients with IgG4-related sclerosing disease have also been documented. Herein, we describe the first documented case of anaplastic large cell lymphoma (ALCL) following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma (DLBCL). A 61-year-old Japanese male, with a past history of DLBCL, was detected with swelling of the pancreas and tumorous lesions in the gallbladder. Histopathological study of the resected gallbladder specimen revealed diffuse lymphoplasmacytic infiltration with fibrosclerosis in the entire gallbladder wall. Eosinophilic infiltration and obliterative phlebitis were also noted. Immunohistochemically, many IgG4-positive plasma cells had infiltrated into the lesion, and the ratio of IgG4/IgG-positive plasma cells was 71.6%. Accordingly, a diagnosis of IgG4-related cholecystitis was made. Seven months later, he presented with a painful tumor in his left parotid gland. Histopathological study demonstrated diffuse or cohesive sheet-like proliferation of large-sized lymphoid cells with rich slightly eosinophilic cytoplasm and irregular-shaped large nuclei. These lymphoid cells were positive for CD30, CD4, and cytotoxic markers, but negative for CD3 and ALK. Therefore, a diagnosis of ALK-negative ALCL was made. It has been suggested that the incidence of malignant lymphoma may be high in patients with IgG4-related sclerosing disease, therefore, intense medical follow-up is important in patients with this disorder.

  1. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children’s Oncology Group phase 1 consortium study

    Science.gov (United States)

    Mossé, Yael P; Lim, Megan S; Voss, Stephan D; Wilner, Keith; Ruffner, Katherine; Laliberte, Julie; Rolland, Delphine; Balis, Frank M; Maris, John M; Weigel, Brenda J; Ingle, Ashish M; Ahern, Charlotte; Adamson, Peter C; Blaney, Susan M

    2013-01-01

    Summary Background Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as anaplastic large-cell lymphoma, inflammatory myofibroblastic tumours, non-small-cell lung cancer (NSCLC), and neuroblastoma. Therefore, ALK inhibition could be a useful therapeutic strategy in children. We aimed to determine the safety, recommended phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma. Methods In this open-label, phase 1 dose-escalation trial, patients older than 12 months and younger than 22 years with measurable or evaluable solid or CNS tumours, or anaplastic large-cell lymphoma, refractory to therapy and for whom there was no known curative treatment were eligible. Crizotinib was given twice daily without interruption. Six dose levels (100, 130, 165, 215, 280, 365 mg/m2 per dose) were assessed in the dose-finding phase of the study (part A1), which is now completed. The primary endpoint was to estimate the maximum tolerated dose, to define the toxic effects of crizotinib, and to characterise the pharmacokinetics of crizotinib in children with refractory cancer. Additionally, patients with confirmed ALK translocations, mutations, or amplification (part A2 of the study) or neuroblastoma (part A3) could enrol at one dose level lower than was currently given in part A1. We assessed ALK genomic status in tumour tissue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood samples of patients with anaplastic large-cell lymphoma. All patients who received at least one dose of crizotinib were evaluable for response; patients completing at least one cycle of therapy or experiencing dose limiting toxicity before that were considered fully evaluable for toxicity. This study is registered with ClinicalTrials. gov, NCT00939770. Findings 79 patients were enrolled in the study from Oct 2, 2009, to May 31, 2012. The median age was 10

  2. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study.

    Science.gov (United States)

    Mossé, Yael P; Lim, Megan S; Voss, Stephan D; Wilner, Keith; Ruffner, Katherine; Laliberte, Julie; Rolland, Delphine; Balis, Frank M; Maris, John M; Weigel, Brenda J; Ingle, Ashish M; Ahern, Charlotte; Adamson, Peter C; Blaney, Susan M

    2013-05-01

    Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as anaplastic large-cell lymphoma, inflammatory myofibroblastic tumours, non-small-cell lung cancer (NSCLC), and neuroblastoma. Therefore, ALK inhibition could be a useful therapeutic strategy in children. We aimed to determine the safety, recommended phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma. In this open-label, phase 1 dose-escalation trial, patients older than 12 months and younger than 22 years with measurable or evaluable solid or CNS tumours, or anaplastic large-cell lymphoma, refractory to therapy and for whom there was no known curative treatment were eligible. Crizotinib was given twice daily without interruption. Six dose levels (100, 130, 165, 215, 280, 365 mg/m(2) per dose) were assessed in the dose-finding phase of the study (part A1), which is now completed. The primary endpoint was to estimate the maximum tolerated dose, to define the toxic effects of crizotinib, and to characterise the pharmacokinetics of crizotinib in children with refractory cancer. Additionally, patients with confirmed ALK translocations, mutations, or amplification (part A2 of the study) or neuroblastoma (part A3) could enrol at one dose level lower than was currently given in part A1. We assessed ALK genomic status in tumour tissue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood samples of patients with anaplastic large-cell lymphoma. All patients who received at least one dose of crizotinib were evaluable for response; patients completing at least one cycle of therapy or experiencing dose limiting toxicity before that were considered fully evaluable for toxicity. This study is registered with ClinicalTrials.gov, NCT00939770. 79 patients were enrolled in the study from Oct 2, 2009, to May 31, 2012. The median age was 10.1 years (range 1.1-21.4); 43

  3. Breast Implant–Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients

    Science.gov (United States)

    Miranda, Roberto N.; Aladily, Tariq N.; Prince, H. Miles; Kanagal-Shamanna, Rashmi; de Jong, Daphne; Fayad, Luis E.; Amin, Mitual B.; Haideri, Nisreen; Bhagat, Govind; Brooks, Glen S.; Shifrin, David A.; O'Malley, Dennis P.; Cheah, Chan Y.; Bacchi, Carlos E.; Gualco, Gabriela; Li, Shiyong; Keech, John A.; Hochberg, Ephram P.; Carty, Matthew J.; Hanson, Summer E.; Mustafa, Eid; Sanchez, Steven; Manning, John T.; Xu-Monette, Zijun Y.; Miranda, Alonso R.; Fox, Patricia; Bassett, Roland L.; Castillo, Jorge J.; Beltran, Brady E.; de Boer, Jan Paul; Chakhachiro, Zaher; Ye, Dongjiu; Clark, Douglas; Young, Ken H.; Medeiros, L. Jeffrey

    2014-01-01

    Purpose Breast implant–associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. Patients and Methods We reviewed the literature for all published cases of breast implant–associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. Results The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Conclusion Most patients with breast implant–associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants. PMID:24323027

  4. Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients.

    Science.gov (United States)

    Miranda, Roberto N; Aladily, Tariq N; Prince, H Miles; Kanagal-Shamanna, Rashmi; de Jong, Daphne; Fayad, Luis E; Amin, Mitual B; Haideri, Nisreen; Bhagat, Govind; Brooks, Glen S; Shifrin, David A; O'Malley, Dennis P; Cheah, Chan Y; Bacchi, Carlos E; Gualco, Gabriela; Li, Shiyong; Keech, John A; Hochberg, Ephram P; Carty, Matthew J; Hanson, Summer E; Mustafa, Eid; Sanchez, Steven; Manning, John T; Xu-Monette, Zijun Y; Miranda, Alonso R; Fox, Patricia; Bassett, Roland L; Castillo, Jorge J; Beltran, Brady E; de Boer, Jan Paul; Chakhachiro, Zaher; Ye, Dongjiu; Clark, Douglas; Young, Ken H; Medeiros, L Jeffrey

    2014-01-10

    Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.

  5. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration

    DEFF Research Database (Denmark)

    Voena, Claudia; Conte, Chiara; Ambrogio, Chiara

    2007-01-01

    , leading to increased cell growth, resistance to apoptosis, and changes in morphology and migration of transformed cells. To search for new NPM-ALK interacting molecules, we developed a mass spectrometry-based proteomic approach in HEK293 cells expressing an inducible NPM-ALK and identified the tyrosine......), formed a complex with Shp2, Gab2, and growth factor receptor binding protein 2 (Grb2), where Grb2 bound to the phosphorylated Shp2 through its SH2 domain. Shp2 knock down by specific shRNA decreased the phosphorylation of extracellular signal-regulated kinase 1/2 and of the tyrosine residue Y416...... in the activation loop of Src, resulting in impaired ALCL cell proliferation and growth disadvantage. Finally, migration of ALCL cells was reduced by Shp2 shRNA. These findings show a direct involvement of Shp2 in NPM-ALK lymphomagenesis, highlighting its critical role in lymphoma cell proliferation and migration....

  6. Anomalous constitutive Src kinase activity promotes B lymphoma survival and growth

    OpenAIRE

    Ke, Jiyuan; Chelvarajan, R Lakshman; Sindhava, Vishal; Robertson, Darrell A; Lekakis, Lazaros; Jennings, C Darrell; Bondada, Subbarao

    2009-01-01

    Abstract Background Previously we have shown that B cell receptor (BCR) expression and B cell receptor signaling pathways are important for the basal growth of B lymphoma cells. In particular we have shown that the activation of Syk, a non-src family protein tyrosine kinase and the mitogen activated protein kinases (MAPK), ERK and JNK that mediate BCR signals are required for the constitutive growth of B lymphoma cells. Since src family protein tyrosine kinases (SFKs) like Lyn are known to be...

  7. Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma

    DEFF Research Database (Denmark)

    Zhang, Qian; Raghunath, Puthryaveett N; Xue, Liquan

    2002-01-01

    , STAT3 was constitutively associated with NPM/ALK in the ALK+ TCL cell lines. Additional studies into the mechanisms of STAT3 activation revealed that the ALK+ TCL cells expressed a positive regulator of STAT3 activation, protein phosphatase 2A (PP2A), which was constitutively associated with STAT3....... Treatment with the PP2A inhibitor calyculin A abrogated tyrosine phosphorylation of STAT3. Finally, ALK+ T cells failed to express a negative regulator of activated STAT3, protein inhibitor of activated STAT3. These data indicate that NPM/ALK activates STAT3 and that PP2A and lack of protein inhibitor...

  8. Intravesicular taxane-induced dermatotoxicity in a 78-year-old man with urothelial carcinoma and primary cutaneous anaplastic large cell lymphoma.

    Science.gov (United States)

    Pelletier, Daniel; O'Donnell, Michael; Stone, Mary Seabury; Liu, Vincent

    2018-02-27

    Patients treated with intravesical bacillus Calmette-Guerin therapy for urothelial carcinoma often become refractory and experience recurrent disease, thus necessitating alternative intravesical treatment modalities if the patient is to be spared the morbidities associated with radical cystectomy. Intravesical treatment with taxane-based chemotherapy, such as docetaxel, has gained traction in urologic oncology, proving to be an effective salvage therapy in such patients. Systemic taxane-based chemotherapeutic regimens have long been used in several advanced malignancies, and their systemic side effects and associated histologic correlates have been extensively documented. In contrast to adverse effects associated with systemic administration, intravesical taxane administration has thus far proven to be well-tolerated, with little to no systemic absorption. To our knowledge, features of taxane-induced systemic effects have not been reported in this setting. Herein, we report a case of a patient with recurrent urothelial carcinoma treated with intravesical docetaxel, along with primary cutaneous anaplastic large cell lymphoma, who developed characteristic dermatotoxic histologic findings associated with intravenous taxane administration. As such histopathologic findings often represent close mimickers of neoplastic and infectious etiologies, knowledge of the potential for systemic manifestations of taxane therapy in patients treated topically may prevent potentially costly diagnostic pitfalls. This article is protected by copyright. All rights reserved.

  9. Epigenetic Silencing of the Proapoptotic Gene BIM in Anaplastic Large Cell Lymphoma through an MeCP2/SIN3a Deacetylating Complex12

    Science.gov (United States)

    Piazza, Rocco; Magistroni, Vera; Mogavero, Angela; Andreoni, Federica; Ambrogio, Chiara; Chiarle, Roberto; Mologni, Luca; Bachmann, Petra S; Lock, Richard B; Collini, Paola; Pelosi, Giuseppe; Gambacorti-Passerini, Carlo

    2013-01-01

    BIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL) cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2) corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation. PMID:23633923

  10. Epigenetic Silencing of the Proapoptotic Gene BIM in Anaplastic Large Cell Lymphoma through an MeCP2/SIN3a Deacetylating Complex

    Directory of Open Access Journals (Sweden)

    Rocco Piazza

    2013-05-01

    Full Text Available BIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2 corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation.

  11. Anomalous constitutive Src kinase activity promotes B lymphoma survival and growth

    Directory of Open Access Journals (Sweden)

    Robertson Darrell A

    2009-12-01

    Full Text Available Abstract Background Previously we have shown that B cell receptor (BCR expression and B cell receptor signaling pathways are important for the basal growth of B lymphoma cells. In particular we have shown that the activation of Syk, a non-src family protein tyrosine kinase and the mitogen activated protein kinases (MAPK, ERK and JNK that mediate BCR signals are required for the constitutive growth of B lymphoma cells. Since src family protein tyrosine kinases (SFKs like Lyn are known to be needed for the phosphorylation of BCR co-receptors, Ig-α and Ig-β, we hypothesized that one or more SFKs will be constitutively activated in B lymphoma cells and may be necessary for B lymphoma growth. Results Src kinase activity was found to be constitutively high in many murine and human B lymphoma cell lines and primary lymphoma samples. The specific pharmacological inhibitors of SFKs, PP1 and PP2 inhibited the proliferation of a number of both murine and human B lymphomas in a dose-dependent manner. Importantly, dasatinib (BMS-354825, an oral dual BCR-ABL and SFK specific inhibitor inhibited the growth of B lymphomas in the nanomolar range in vitro and strongly inhibited a mouse lymphoma growth in vivo. Among the SFKs, Lyn is predominantly phosphorylated and Lyn-specific small interfering RNA inhibited the growth of B lymphomas, supporting an important role for Lyn in B lymphoma growth. Suppression of SFK activity blocks BCR mediated signaling pathways. PMA or CpG can partially reverse the growth inhibition induced by SFK inhibition. Although blocking SFK activity inhibited the growth of a number of B lymphomas, some lymphomas such as SudHL-4, SudHL-6, OCI-Ly3 and OCI-Ly10 are more resistant due to an increased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL. Conclusions These studies further support our concept that BCR signaling pathways are important for the continued growth of established B lymphoma cells. Some of the intermediates in this

  12. Sub-megabase resolution tiling (SMRT array-based comparative genomic hybridization profiling reveals novel gains and losses of chromosomal regions in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma cell lines

    Directory of Open Access Journals (Sweden)

    Lam Wan L

    2008-01-01

    Full Text Available Abstract Background Hodgkin lymphoma (HL and Anaplastic Large Cell Lymphoma (ALCL, are forms of malignant lymphoma defined by unique morphologic, immunophenotypic, genotypic, and clinical characteristics, but both overexpress CD30. We used sub-megabase resolution tiling (SMRT array-based comparative genomic hybridization to screen HL-derived cell lines (KMH2 and L428 and ALCL cell lines (DEL and SR-786 in order to identify disease-associated gene copy number gains and losses. Results Significant copy number gains and losses were observed on several chromosomes in all four cell lines. Assessment of copy number alterations with 26,819 DNA segments identified an average of 20 genetic alterations. Of the recurrent minimally altered regions identified, 11 (55% were within previously published regions of chromosomal alterations in HL and ALCL cell lines while 9 (45% were novel alterations not previously reported. HL cell lines L428 and KMH2 shared gains in chromosome cytobands 2q23.1-q24.2, 7q32.2-q36.3, 9p21.3-p13.3, 12q13.13-q14.1, and losses in 13q12.13-q12.3, and 18q21.32-q23. ALCL cell lines SR-786 and DEL, showed gains in cytobands 5p15.32-p14.3, 20p12.3-q13.11, and 20q13.2-q13.32. Both pairs of HL and ALCL cell lines showed losses in 18q21.32-18q23. Conclusion This study is considered to be the first one describing HL and ALCL cell line genomes at sub-megabase resolution. This high-resolution analysis allowed us to propose novel candidate target genes that could potentially contribute to the pathogenesis of HL and ALCL. FISH was used to confirm the amplification of all three isoforms of the trypsin gene (PRSS1/PRSS2/PRSS3 in KMH2 and L428 (HL and DEL (ALCL cell lines. These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been previously associated with lymphoma biology. The findings raise interesting possibilities about the role of signaling

  13. ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK)

    Science.gov (United States)

    Morris, S W; Naeve, C; Mathew, P; James, P L; Kirstein, M N; Cui, X; Witte, D P

    1997-05-08

    Anaplastic Lymphoma Kinase (ALK) was originally identified as a member of the insulin receptor subfamily of receptor tyrosine kinases that acquires transforming capability when truncated and fused to nucleophosmin (NPM) in the t(2;5) chromosomal rearrangement associated with non-Hodgkin's lymphoma, but further insights into its normal structure and function are lacking. Here, we characterize a full-length normal human ALK cDNA and its product, and determine the pattern of expression of its murine homologue in embryonic and adult tissues as a first step toward the functional assessment of the receptor. Analysis of the 6226 bp ALK cDNA identified an open reading frame encoding a 1620-amino acid (aa) protein of predicted mass approximately 177 kDa that is most closely related to leukocyte tyrosine kinase (LTK), the two exhibiting 57% aa identity and 71% similarity over their region of overlap. Biochemical analysis demonstrated that the approximately 177 kDa ALK polypeptide core undergoes co-translational N-linked glycosylation, emerging in its mature form as a 200 kDa single chain receptor. Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane, consistent with the prediction that ALK serves as the receptor for an unidentified ligand(s). In situ hybridization studies revealed Alk expression beginning on embryonic day 11 and persisting into the neonatal and adult periods of development. Alk transcripts were confined to the nervous system and included several thalamic and hypothalamic nuclei; the trigeminal, facial, and acoustic cranial ganglia; the anterior horns of the spinal cord in the region of the developing motor neurons; the sympathetic chain; and the ganglion cells of the gut. Thus, ALK is a novel orphan receptor tyrosine kinase that appears to play an important role in the normal development and function of the nervous system.

  14. 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

  15. Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

    International Nuclear Information System (INIS)

    Colomba, A; Giuriato, S; Dejean, E; Thornber, K; Delsol, G; Tronchère, H; Meggetto, F; Payrastre, B; Gaits-Iacovoni, F

    2011-01-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas

  16. Anaplastic thyroid cancer

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000352.htm Anaplastic thyroid cancer To use the sharing features on this page, ... carcinoma is a rare and aggressive form of cancer of the thyroid gland. Causes Anaplastic thyroid cancer is an invasive ...

  17. Anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related human papillary thyroid carcinoma after the Chernobyl accident.

    Science.gov (United States)

    Arndt, Annette; Steinestel, Konrad; Rump, Alexis; Sroya, Manveer; Bogdanova, Tetiana; Kovgan, Leonila; Port, Matthias; Abend, Michael; Eder, Stefan

    2018-04-06

    Childhood radiation exposure has been associated with increased papillary thyroid carcinoma (PTC) risk. The role of ALK gene rearrangements in radiation-related PTC remains unclear, but STRN-ALK fusions have recently been detected in PTCs from radiation-exposed persons after Chernobyl using targeted next-generation sequencing and RNA-seq. We investigated ALK and RET gene rearrangements as well as known driver point mutations in PTCs from 77 radiation-exposed patients (mean age at surgery 22.4 years) and PTCs from 19 non-exposed individuals after the Chernobyl accident. ALK rearrangements were detected by fluorescence in situ hybridisation (FISH) and confirmed with immunohistochemistry (IHC); point mutations in the BRAF and RAS genes were detected by FISH and DNA pyrosequencing, respectively. Among the 77 tumours from exposed persons, we identified 7 ALK rearrangements and none in the unexposed group. When combining ALK and RET rearrangements, we found 10 in the exposed (31.2%) compared to two (10.5%) in the unexposed group. Odds ratios increased significantly in a dose-dependent manner up to 6.2 (95%CI: 1.1, 34.7; p=0.039) at Iodine-131 thyroid doses >500 mGy. In total, 27 cases carried point mutations of BRAF or RAS genes, yet logistic regression analysis failed to identify significant dose association. To our knowledge we are the first to describe ALK rearrangements in post-Chernobyl PTC samples using routine methods such as FISH and IHC. Our findings further support the hypothesis that gene rearrangements, but not oncogenic driver mutations, are associated with ionizing radiation-related tumour risk. IHC may represent an effective method for ALK-screening in PTCs with known radiation aetiology, which is of clinical value since ALK fusions might represent a valuable target for small molecule inhibitors. This article is protected by copyright. All rights reserved. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.

  18. Round cell anaplastic carcinoma of the pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Hoon; Lee, Dong Ho; Ko, Young Tae; Yang, Moon Ho [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1989-02-15

    Ultrasonography of the upper abdomen disclosed an oval well defined mass in the pancreas. Round cell anaplastic carcinoma is one of sarcomatoid pancreatic carcinoma, microscopically characterized by monotonous sheaths of small round plump cells with rare giant cells and thus more or less reminiscent of malignant lymphoma. Whether this tumor is of ductal or acinar cell origin remains to be determined. Clinically, this tumor does not differ significantly from ordinary adenocarcinoma of the pancreas. We report a cases of round cell anaplastic carcinoma and describe the CT and sonographic findings, and discuss the differential points from other solid pancreatic tumors.

  19. Panobinostat in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-03-21

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  20. Clinical significance of cyclin-dependent kinase inhibitor p27Kip1 expression and proliferation in non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Skjødt, Karsten; Mortensen, Leif Spange

    1999-01-01

    The cyclin-dependent kinase inhibitor p27Kip1 is a negative cell cycle regulator linking extracellular growth-regulatory signals to the cell cycle machinery in G1. We investigated the pattern and prognostic value of p27Kip1 expression in a population-based group of 203 non-Hodgkin's lymphoma (NHL...

  1. Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2015-06-03

    Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  2. Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  3. Controversies on Hodgkin's disease and anaplastic large cell lymphoma. Hematopathology Study Group of the Società Italiana di Anatomia Patologica.

    Science.gov (United States)

    Pileri, S

    1994-01-01

    Just one year ago the Italian Society of Pathology (S.I.A.P.) created a Study Group which included members of the most active Italian hematopathology teams. Prof. Pasquale Calapso was asked to chair the Group and Prof. Stefano Pileri to take care of secretarial duties. The aim of the Group is to spread hematopathologic knowledge among young pathologists and to promote activities that can contribute to updating Italian pathologists on topics of both speculative and diagnostic interest. The first Workshop of the S.I.A.P. Hematopathology Group was held at the Palazzo dei Congressi in Bologna, November 20, 1993. About 150 pathologists from all over Italy took part in the meeting, which consisted of two sections devoted to: a) discussion of the boundaries between Hodgkin's disease and non-Hodgkin's lymphomas, and b) a case seminar illustrating the impact of immunohistochemistry in the diagnosis of bone-marrow biopsy. The first section included 5 presentations and a Round Table chaired by Prof. Luciano Fiore-Donati. Below, the contributors to this section summarize the content of their presentations, which were aimed at answering specific questions the Organizers had put to them.

  4. Influence of cations on activity and distribution of protein kinase C in S49 lymphoma cells

    International Nuclear Information System (INIS)

    Brunton, L.; Watson, M.; Schultz, M.; Trejo, J.; Speizer, L.

    1987-01-01

    In S49 lymphoma cells, the distribution of protein kinase C (PKC) between soluble and membrane fractions can be regulated by the concentration of Ca ++ in the homogenization buffer. When cells are fractionated with 10μM Ca ++ and low Mg ++ (0.3mM), PKC is largely (56%) membrane-bound. Mg ++ inhibits this effect of Ca ++ by 75%; the EC 50 for Mg ++ reducing the translocation induced by 10μM Ca ++ is 1mM, as detected by binding of [ 3 H] phorbol dibutyrate ([ 3 H]PDB). Other divalent cations have different effects. When Cu ++ (1mM) is included in the homogenization buffer, both the enzymic activity of PKC and its capacity to bind [ 3 H]PDB are lost in both the cytosolic and membrane fractions. Cd ++ and Zn ++ (at 1mM) also inhibit the binding of [ 3 H]PDB to PKC in cytosolic fractions. K + , Li + , Co ++ and Mn ++ at 1mM do not mimic these effects. With Ca ++ at 500μM, the EC 50 for inhibition by Cu ++ of [ 3 H]PDB binding and enzymic activity of PKC are 25μM and 75μM, respectively. These effects of Cu ++ are also noticeable when the cation is added to intact S49 cells. The effect of Cu ++ on PKC is only relatively specific: [Cu ++ ] ≥ 100μM inhibits the activity of cyclic AMP-dependent protein kinase in vitro. Knowledge of these effects of heavy metals on PKC may prove helpful in manipulation of the enzyme pharmacologically as well as in determining the role of PKC in the cellular responses to heavy metals

  5. Phosphatidylinositol-3-kinase-dependent phosphorylation of SLP-76 by the lymphoma-associated ITK-SYK fusion-protein

    International Nuclear Information System (INIS)

    Hussain, Alamdar; Faryal, Rani; Nore, Beston F.; Mohamed, Abdalla J.; Smith, C.I. Edvard

    2009-01-01

    Recurrent chromosomal translocations have long been implicated in various types of lymphomas and other malignancies. Novel recurrent t(5;9)(q33;q22) has been recently discovered in un-specified peripheral T-cell lymphoma. To elucidate the role of this translocation, the corresponding fusion construct encoding the N-terminal portion of the ITK kinase and the C-terminal catalytic region of the SYK kinase was generated. We herein show that the ITK-SYK fusion-protein is constitutively active. Moreover, we demonstrate that ITK-SYK is phosphorylated on key tyrosine residues and is capable of potently phosphorylating the related adapter proteins BLNK and SLP-76. In transiently transfected cells, SYK was phosphorylated at Y352 but not detectably at the activation-loop tyrosines Y525/Y526. In contrast, ITK-SYK was phosphorylated both at Y212 and the activation-loop tyrosines Y385/Y386, corresponding to Y352 and Y525/Y526 in SYK, respectively. In resting primary lymphocytes, ITK-SYK predominantly localizes to the cell surface. In addition, we demonstrate that following stimulation, the ITK-SYK fusion-protein in cell lines translocates to the cell membrane and, moreover, that this phenomenon as well as SLP-76 phosphorylation are blocked upon phosphatidylinositol-3-kinase (PI3-kinase) inhibition.

  6. MHC-I-induced apoptosis in human B-lymphoma cells is dependent on protein tyrosine and serine/threonine kinases

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Bregenholt, S; Johansen, B

    1999-01-01

    B lymphoma cells, is dependent on protein tyrosine kinases and the phosphatidylinositol 3 (PI-3) kinase. Functional studies showed that MHC-I crosslinking induced almost complete inhibition of the spontaneous proliferation of the B lymphoma cells as early as 6 h post-crosslinking and apoptosis 24 h...... post-crosslinking. Preincubation with either protein tyrosine kinase or protein serine/threonine kinase inhibitors reduced the MHC-I-induced apoptosis to background levels, whereas inhibition of PI-3 kinase had no effect. These data demonstrate a pivotal role for protein tyrosine and serine....../threonine kinases in MHC-I-mediated apoptosis in human B-cells and suggest the presence of several MHC-I signaling pathways leading to diverse effects in these cells....

  7. A Case Report: an EML4-ALK Positive Lung Adenocarcinoma Diagnosed 
with Lymphoma Previously

    Directory of Open Access Journals (Sweden)

    Li LIU

    2015-02-01

    Full Text Available In recent years, with the deepening of the research of molecular biology, targeted therapy has become one of the trend of lung cancer treatment. The individualized treatment of lung cancer is attached great importance at present. Echinoderm microtubule associated protein like 4 anaplastic lymphoma kinase (EML4-ALK as a new biological marker is a hot topic in the field of lung cancer treatment. Meanwhile, with the improvement of anticancer treatment and survival, the incidence of multiple primary carcinomas (MPC has become increasingly. But the report that malignant lymphoma complicated with lung adenocarcinoma harboring EML4-ALK fusion gene in one individual is rare. Here, we report an EML4-ALK positive non-small cell lung cancer (NSCLC in a patient previously diagnosed with T cell lymphoma and review literature on metachronous lung cancer complicating with lymphoma.

  8. Salvia Hispanica Seed in Reducing Risk of Disease Recurrence in Patients With Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-05

    Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Adult T-Cell Leukemia/Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; B Lymphoblastic Leukemia/Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Burkitt Leukemia; Central Nervous System Lymphoma; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Diffuse Large B-Cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Hepatosplenic T-Cell Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Mycosis Fungoides; Nasal Type Extranodal NK/T-Cell Lymphoma; Nodal Marginal Zone Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Post-Transplant Lymphoproliferative Disorder; Primary Cutaneous Anaplastic Large Cell Lymphoma; Primary Effusion Lymphoma; Sezary Syndrome; Splenic Marginal Zone Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma; Systemic Anaplastic Large Cell Lymphoma; T Lymphoblastic Leukemia/Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  9. MHC-I-induced apoptosis in human B-lymphoma cells is dependent on protein tyrosine and serine/threonine kinases

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Bregenholt, S; Johansen, B

    1999-01-01

    In addition to providing the framework for peptide presentation, major histocompatibility complex class I (MHC-I) molecules can act as signal transducing molecules in lymphoid cells. Here we show that the mobilization of intracellular calcium, which follows crosslinking of MHC-I molecules on human...... B lymphoma cells, is dependent on protein tyrosine kinases and the phosphatidylinositol 3 (PI-3) kinase. Functional studies showed that MHC-I crosslinking induced almost complete inhibition of the spontaneous proliferation of the B lymphoma cells as early as 6 h post-crosslinking and apoptosis 24 h...... post-crosslinking. Preincubation with either protein tyrosine kinase or protein serine/threonine kinase inhibitors reduced the MHC-I-induced apoptosis to background levels, whereas inhibition of PI-3 kinase had no effect. These data demonstrate a pivotal role for protein tyrosine and serine...

  10. MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells.

    Science.gov (United States)

    Mukherjee, P; Tinder, T L; Basu, G D; Gendler, S J

    2005-01-01

    MUC1 (CD227) is a large transmembrane epithelial mucin glycoprotein, which is aberrantly overexpressed in most adenocarcinomas and is a target for immune therapy for epithelial tumors. Recently, MUC1 has been detected in a variety of hematopoietic cell malignancies including T and B cell lymphomas and myelomas; however, its function in these cells is not clearly defined. Using the Jurkat T cell lymphoma cell line and normal human T cells, we demonstrate that MUC1 is not only expressed in these cells but is also phosphorylated upon T cell receptor (TCR) ligation and associates with the Src-related T cell tyrosine kinase, p56lck. Upon TCR-mediated activation of Jurkat cells, MUC1 is found in the low-density membrane fractions, where linker of T cell activation is contained. Abrogation of MUC1 expression in Jurkat cells by MUC1-specific small interfering RNA resulted in defects in TCR-mediated downstream signaling events associated with T cell activation. These include reduction in Ca2+ influx and extracellular signal-regulated kinase 1/2 phosphorylation, leading to a decrease in CD69 expression, proliferation, and interleukin-2 production. These results suggest a regulatory role of MUC1 in modulating proximal signal transduction events through its interaction with proteins of the activation complex.

  11. Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

    Science.gov (United States)

    2017-04-17

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

  12. Evaluation of clinical trial eligibility and prognostic indices in a population-based cohort of systemic peripheral T-cell lymphomas from the Danish Lymphoma Registry

    DEFF Research Database (Denmark)

    Pedersen, Martin Bjerregård; Hamilton-Dutoit, Stephen Jacques; Bendix, Knud

    2014-01-01

    Clinical trials (CTs) are needed to improve the outcome for peripheral T-cell lymphomas (PTCL), and accrual into CTs is one of the main recommendations in international treatment guidelines. The use of risk-adapted strategies has been suggested as a way to optimize treatment outcome in PTCL......-ALAT and measurable tumour lesion), patients were subdivided into four groups: 'younger fit', 'elderly fit', 'frail' and 'not CT eligible'. International prognostic index (IPI), prognostic index for T-cell lymphoma (PIT) and anaplastic lymphoma kinase (ALK) protein expression were tested at subtype-specific level....... Overall, 41% of the patients were considered eligible for interventional CTs implicating curatively intended multiagent chemotherapy, including, if considered appropriate, consolidating stem cell transplantation (SCT), as part of the upfront management strategy. Moreover, 28% was elderly fit and eligible...

  13. Serum soluble CD27, but not thymidine kinase, is an independent prognostic factor for outcome in indolent non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Kok, Marleen; Bonfrer, Johannes M.; Korse, Catharina M.; de Jong, Daphne; Kersten, Marie José

    2003-01-01

    Non-Hodgkin's lymphoma (NHL) forms a heterogeneous group of diseases. Tumor markers may help to identify high-risk patients who might benefit from more aggressive therapy. Serum soluble CD27 (sCD27) and thymidine kinase (TK) are potentially valuable markers, since sCD27 has previously been shown to

  14. Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2015-05-06

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  15. Successful treatment of hepatic oligometastases with stereotactic ablative radiotherapy and radiofrequency ablation in an anaplastic lymphoma kinase fusion-positive lung cancer patient

    DEFF Research Database (Denmark)

    Weber, Britta; Liu, Mitchell; Sobkin, Paul

    2016-01-01

    Local ablative therapy with stereotactic ablative radiotherapy may improve survival in oncogene‐addicted lung cancer patients with extracranial oligometastatic disease treated with targeted therapies. There is limited data on the use of radiofrequency ablation (RFA) in this same setting. We present...

  16. Resistance to mTOR kinase inhibitors in lymphoma cells lacking 4EBP1.

    Directory of Open Access Journals (Sweden)

    Sharmila Mallya

    Full Text Available Inhibitors of the mechanistic target of rapamycin (mTOR hold promise for treatment of hematological malignancies. Analogs of the allosteric mTOR inhibitor rapamycin are approved for mantle cell lymphoma but have limited efficacy in other blood cancers. ATP-competitive "active-site" mTOR inhibitors produce more complete mTOR inhibition and are more effective than rapamycin in preclinical models of leukemia, lymphoma and multiple myeloma. In parallel to clinical trials of active-site mTOR inhibitors, it will be important to identify resistance mechanisms that might limit drug efficacy in certain patients. From a panel of diffuse large B-cell lymphoma cell lines, we found that the VAL cell line is particularly resistant to apoptosis in the presence of active-site mTOR inhibitors. Mechanistic investigation showed that VAL does not express eukaryotic initiation factor 4E-binding protein-1 (4EBP1, a key negative regulator of translation controlled by mTOR. Although VAL cells express the related protein 4EBP2, mTOR inhibitor treatment fails to displace eukaryotic initiation factor 4G from the mRNA cap-binding complex. Knockdown of eukaryotic initiation factor 4E, or re-expression of 4EBP1, sensitizes cells to apoptosis when treated with active-site mTOR inhibitors. These findings provide a naturally occurring example of 4EBP deficiency driving lymphoma cell resistance to active-site mTOR inhibitors.

  17. High incidence of Epstein-Barr virus (EBV)-positive Hodgkin lymphoma and Hodgkin lymphoma-like B-cell lymphoproliferations with EBV latency profile 2 in children with interleukin-2-inducible T-cell kinase deficiency.

    Science.gov (United States)

    Bienemann, Kirsten; Borkhardt, Arndt; Klapper, Wolfram; Oschlies, Ilske

    2015-11-01

    Interleukin-2-inducible T-cell kinase (ITK) deficiency is an inherited T-cell deficiency characterized by the development of Epstein-Barr virus (EBV)-associated lymphoproliferations. We aimed to describe the histopathological features of lymphoproliferative processes arising in ITK deficiency, and to compare them with lymphoproliferations in otherwise immunocompromised patients. We revised the histopathological diagnoses of 12 biopsies of lymphoproliferations from seven ITK-deficient children according to the World Health Organization criteria, and determined the EBV latency types and lytic activity by staining for EBV-encoded small RNA, latent membrane protein 1, EBV nuclear antigen 2, and ZEBRA. We found polymorphic and borderline polymorphic to monomorphic B-cell lymphoproliferations with variable contents in large cells (five cases), a Hodgkin-like B-cell proliferation (one case), and classic mixed-cellularity Hodgkin lymphoma (six cases). All cases (12/12) were EBV-positive. The Hodgkin lymphoma-like and Hodgkin lymphoma, and all but one polymorphic B-cell lymphoproliferation, showed EBV latency type 2, as observed in classic EBV-positive Hodgkin lymphoma. The 100% EBV association, the high percentage of EBV-positive classic Hodgkin lymphoma and Hodgkin-like B-cell proliferations and the predominance of EBV latency type 2 even in polymorphic lesions are the main features of lymphoproliferations in patients with ITK deficiency, and suggest a unique pathomechanism of lymphomagenesis in this T-cell immunodeficiency. © 2015 John Wiley & Sons Ltd.

  18. Protein tyrosine kinases p53/56lyn and p72syk in MHC class I-mediated signal transduction in B lymphoma cells

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Bregenholt, S; Skov, S

    1998-01-01

    Crosslinking of major histocompatibility complex class I (MHC-I) molecules on the surface of human B lymphoma cells was shown to induce protein tyrosine phosphorylation and mobilization of intracellular free calcium. Immunoprecipitations indicated that the protein tyrosine kinases p53/56lyn and p72......syk are among the tyrosine-phosphorylated proteins. The kinetics of phosphorylation of these kinases after MHC-I crosslinking differ from the kinetics observed after crosslinking of the B cell antigen receptor (BCR). Additional experiments were performed with chicken lyn- and syk-negative DT40 B cells...... and the results indicate that these two kinases have different substrate specificity and regulate intracellular free calcium differently in response to MHC-I crosslinking. In addition MHC-I crosslinking of a sIgM-negative DT40 chicken B cell variant results in less activity of tyrosine kinases and less...

  19. 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-01-24

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenstr

  20. Cross-talk between NFkB and the PI3-kinase/AKT pathway can be targeted in primary effusion lymphoma (PEL cell lines for efficient apoptosis.

    Directory of Open Access Journals (Sweden)

    Azhar R Hussain

    Full Text Available A number of constitutively activated signaling pathways play critical roles in the survival and growth of primary effusion lymphoma cells (PELs including NFkB and PI3/AKT kinase cascades. NFkBis constitutively activated in a number of malignancies, including multiple myeloma, Burkitt's lymphoma and diffuse large cell B-cell lymphoma. However, its role in primary effusion lymphoma has not been fully explored.We used pharmacological inhibition and gene silencing to define the role of NFkB in growth and survival of PEL cells. Inhibition of NFkB activity by Bay11-7085 resulted in decreased expression of p65 in the nuclear compartment as detected by EMSA assays. In addition, Bay11-7085 treatment caused de-phosphorylation of AKT and its downstream targets suggesting a cross-talk between NFkB and the PI3-kinase/AKT pathway. Importantly, treatment of PEL cells with Bay11-7085 led to inhibition of cell viability and induced apoptosis in a dose dependent manner. Similar apoptotic effects were found when p65 was knocked down using specific small interference RNA. Finally, co-treatment of PEL cells with suboptimal doses of Bay11-7085 and LY294002 led to synergistic apoptotic responses in PEL cells.These data support a strong biological-link between NFkB and the PI3-kinase/AKT pathway in the modulation of anti-apoptotic effects in PEL cells. Synergistic targeting of these pathways using NFKB- and PI3-kinase/AKT-inhibitors may have a therapeutic potential for the treatment of PEL and possibly other malignancies with constitutive activation of these pathways.

  1. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    Science.gov (United States)

    2018-04-10

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  2. CK1δ in lymphoma: gene expression and mutation analyses and validation of CK1δ kinase activity for therapeutic application

    Directory of Open Access Journals (Sweden)

    Brigitte Sophia Winkler

    2015-02-01

    Full Text Available The prognosis of lymphoid neoplasms has improved considerably during the last decades. However, treatment response for some lymphoid neoplasms is still poor, indicating the need for new therapeutic approaches. One promising new strategy is the inhibition of kinases regulating key signal transduction pathways, which are of central importance in tumorigenesis. Kinases of the CK1 family may represent an attractive drug target since CK1 expression and/or activity are associated with the pathogenesis of malignant diseases. Over the last years efforts were taken to develop highly potent and selective CK1-specific inhibitor compounds and their therapeutic potential has now to be proved in pre-clinical trials. Therefore, we analyzed expression and mutational status of CK1δ in several cell lines representing established lymphoma entities, and also measured the mRNA expression level in primary lymphoma tissue as well as non-neoplastic blood cells. For a selection of lymphoma cell lines we furthermore determined CK1δ kinase activity and demonstrated therapeutic potential of CK1-specific inhibitors as a putative therapeutic option in the treatment of lymphoid neoplasms.

  3. Mutation in the FGFR1 tyrosine kinase domain or inactivation of PTEN is associated with acquired resistance to FGFR inhibitors in FGFR1-driven leukemia/lymphomas.

    Science.gov (United States)

    Cowell, John K; Qin, Haiyan; Hu, Tianxiang; Wu, Qing; Bhole, Aaron; Ren, Mingqiang

    2017-11-01

    Stem cell leukemia/lymphoma syndrome (SCLL) is driven by constitutive activation of chimeric FGFR1 kinases generated by chromosome translocations. We have shown that FGFR inhibitors significantly suppress leukemia and lymphoma development in vivo, and cell viability in vitro. Since resistance to targeted therapies is a major reason for relapse, we developed FGFR1-overexpressing mouse and human cell lines that are resistant to the specific FGFR inhibitors AZD4547 and BGJ398, as well as non-specific inhibitors, such as ponatinib, TKI258 and E3810. Two mutually exclusive mechanisms for resistance were demonstrated; an activating V561M mutation in the FGFR1 kinase domain and mutational inactivation of PTEN resulting in increased PI3K/AKT activity. Ectopic expression of PTEN in the PTEN-mutant cells resensitizes them to FGFR inhibitors. Treatment of resistant cells with BGJ398, in combination with the BEZ235 PI3K inhibitor, shows an additive effect on growth in vitro and prolongs survival in xenograft models in vivo. These studies provide the first direct evidence for both the involvement of the FGFR1 V561M mutation and PTEN inactivation in the development of resistance in leukemias overexpressing chimeric FGFR1. These studies also provide a potential strategy to treat leukemias and lymphomas driven by FGFR1 activation that become resistant to FGFR1 inhibitors. © 2017 UICC.

  4. Pediatric lymphomas in Brazil

    Directory of Open Access Journals (Sweden)

    Gabriela Gualco

    2010-01-01

    Full Text Available OBJECTIVE: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. METHODS: A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. RESULTS: Non-Hodgkin lymphomas represented 68% of the cases, including those of precursor (36% and mature (64% cell origin. Mature cell lymphomas comprised 81% of the B-cell phenotype and 19% of the T-cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central-west region. The distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. Among mature B-cell lymphomas, most of the cases were Burkitt lymphomas (65%, followed by diffuse large B-cell lymphomas (24%. In the mature T-cell group, anaplastic large cell lymphoma, ALK-positive was the most prevalent (57%, followed by peripheral T-cell lymphoma, then not otherwise specified (25%. In the group of classic Hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%. Nodular lymphocyte predominance occurred more frequently than in other series. CONCLUSION: Some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the Brazilian population in different regions.

  5. Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction

    Science.gov (United States)

    2014-02-21

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage

  6. Workshop report on Hodgkin's disease and related diseases ('grey zone' lymphoma)

    NARCIS (Netherlands)

    Rudiger, T; Jaffe, ES; Delsol, G; deWolf-Peeters, C; Gascoyne, RD; Georgii, A; Harris, NL; Kadin, ME; MacLennan, KA; Poppema, S; Stein, H; Weiss, LE; Muller-Hermelink, HK

    1998-01-01

    Despite advances in immunohistochemistry and molecular biology, the distinction between classical Hodgkin's lymphoma and related diseases such as nodular lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or anaplastic large cell lymphoma has remained difficult in rare

  7. 3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma

    Science.gov (United States)

    2013-09-27

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T

  8. lymphoma - histopathology in changing clinical perspective

    African Journals Online (AJOL)

    Retrospectively it became clear that in 85% of the cases examined histopathology alone sufficed for reliable diagnosis;. Table IlL Oinical characteristics and laboratory data. Diffuse. Marginal. Mediastinal. Anaplastic large. Peripheral. Small zone diffuse large. Mantle-. Follicular. B-cell. T-eell. lymphocytiC lymphoma' large B- ...

  9. Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

    International Nuclear Information System (INIS)

    Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

    2006-01-01

    Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

  10. Constitutive activation of extracellular signal-regulated kinase predisposes diffuse large B-cell lymphoma cell lines to CD40-mediated cell death

    DEFF Research Database (Denmark)

    Hollmann, C Annette; Owens, Trevor; Nalbantoglu, Josephine

    2006-01-01

    , including LCK and VAV. In addition, CD40-sensitive DLBCL cell lines also displayed constitutive activation of extracellular signal-regulated kinase (ERK) and failed to undergo apoptosis when ERK phosphorylation was inhibited. In contrast, CD40-resistant lines showed no constitutive activation of ERK......CD40 promotes survival, proliferation, and differentiation of normal B cells but can cause activation-induced cell death in malignant B lymphocytes. CD40 ligand and anti-CD40 antibodies have been used successfully to induce apoptosis in lymphoma lines both in vitro and in xenograft tumor models....... Although this makes CD40 an attractive target for antitumor therapies, the response of malignant B cells to CD40 signaling is variable, and CD40 stimulation can enhance proliferation and can increase chemoresistance in some cell lines. It would therefore be useful to identify markers that predict whether...

  11. Ipilimumab and Local Radiation Therapy in Treating Patients With Recurrent Melanoma, Non-Hodgkin Lymphoma, Colon, or Rectal Cancer

    Science.gov (United States)

    2017-01-12

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Colon Cancer; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Melanoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Rectal Cancer; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  12. [Gene expression profiling by suppression subtractive hybridization (SSH): a example for its application to the study of lymphomas].

    Science.gov (United States)

    Villalva, C; Trempat, P; Zenou, R C; Delsol, G; Brousset, P

    2001-03-01

    Suppression subtractive hybridization (SSH) was used to isolate genes that were differentially expressed in anaplastic lymphoma kinase (ALK)-positive and ALK-negative anaplastic large cell lymphoma. In addition, this approach was applied to Hodgkin's disease cases with different clinical outcomes. SSH combines a normalization step that equalizes the abundance of cDNAs within the sequences to be tested and a subtraction step that excludes the common sequences between the target and the control. In a model system, the SSH technique enriches for rare sequences up to 5,000-fold in one round. We have isolated several genes whose expression varied significantly with regard to the tumour subtypes. There were different genes with known or unknown functions. We aim to compare the results of the SSH approach with those obtained with high density filters. In a near future, we would like to design DNA chips specific of each pathology that could be used for clinical purposes (evaluation of prognosis and therapeutic response).

  13. TGFbeta1-mediated inactivation of G1 phase cyclin-dependent kinases in malignant B lymphoma cells

    Czech Academy of Sciences Publication Activity Database

    Tvrdík, Daniel; Djaborkhel, Rashed; Raška, Ivan; Müller, Julius

    č. 8 (2001), s. 36 ISSN 1107-3756. [World Congress on Advances in Oncology /6./ and International Symposium on Molecular Medicine /4./. 18.10.2001-20.10.2001, Crete] R&D Projects: GA MŠk VS96130; GA ČR GA302/99/0587; GA ČR GA304/00/1481; GA ČR GA304/01/0564 Keywords : lymphoma lells * CDK * CDK-inhibitors Subject RIV: EB - Genetics ; Molecular Biology

  14. Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

    Energy Technology Data Exchange (ETDEWEB)

    Halasz, Lia M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Jacene, Heather A. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Van den Abbeele, Annick D. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); LaCasce, Ann [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Mauch, Peter M. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Ng, Andrea K., E-mail: ang@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2012-08-01

    Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.

  15. Combined modality treatment for PET-positive non-Hodgkin lymphoma: favorable outcomes of combined modality treatment for patients with non-Hodgkin lymphoma and positive interim or postchemotherapy FDG-PET.

    Science.gov (United States)

    Halasz, Lia M; Jacene, Heather A; Catalano, Paul J; Van den Abbeele, Annick D; Lacasce, Ann; Mauch, Peter M; Ng, Andrea K

    2012-08-01

    To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [(18)F]fluoro-2-deoxy-2-d-glucose positron emission tomography (FDG-PET) response. We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Anaplastic thyroid cancer, tumorigenesis and therapy.

    LENUS (Irish Health Repository)

    O'Neill, J P

    2010-03-01

    Anaplastic thyroid cancer (ATC) is a fatal endocrine malignancy. Current therapy fails to significantly improve survival. Recent insights into thyroid tumorigenesis, post-malignant dedifferentiation and mode of metastatic activity offer new therapeutic strategies.

  17. MicroRNA-26a/cyclin-dependent kinase 5 axis controls proliferation, apoptosis and in vivo tumor growth of diffuse large B-cell lymphoma cell lines.

    Science.gov (United States)

    Farina, Floriana Maria; Inguscio, Alessandra; Kunderfranco, Paolo; Cortesi, Alice; Elia, Leonardo; Quintavalle, Manuela

    2017-06-22

    Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. Despite a favorable therapeutic response to first-line chemo-immunotherapy, still 30-40% of patients is refractory, or relapse after this treatment. Thus, alternative strategies must be sought. Previous studies have indicated that cyclin-dependent kinase 5 (CDK5), a serine/threonine protein kinase, is involved in tumor development and progression, and it may represent a potential therapeutic target. However, its role in modulating DLBCL growth and progression remains largely unexplored. In this study, we show that CDK5 and its activator, cyclin-dependent kinase 5 activator 1 (CDK5R1 or p35), are overexpressed in DLBCL cell lines and that signal transducer and activator of transcription 3 (STAT3) phosphorylation and activity is dependent on CDK5 expression in DLBCL. Using public data sets, we also demonstrate that patients with DLBCL show a higher expression of CDK5 compared with healthy individuals. By using loss-of-function approaches, we demonstrate that CDK5's activity regulates proliferation and survival of DLBCL cells. MicroRNAs (miRNAs or miRs) are small noncoding RNAs that negatively regulating gene expression and are involved in cancer initiation and progression. We identify miR-26a as direct regulator of p35 expression and CDK5 activity. We show that miR-26a expression is lower in DLBCL cell lines compared to B lymphocytes and that its ectopic expression leads to a drastic reduction of DLBCL tumor growth in vivo and decreased proliferation, cell-cycle progression, and survival in vitro. Remarkably, concomitant overexpression of a 3'-UTR-truncated form of p35 promoted tumor growth in vivo and cell proliferation, cell-cycle progression, and cell survival in vitro. In conclusion, these results demonstrate an important role for miR-26a and CDK5 together in the survival and growth of DLBCL cells, suggesting the existence of potential novel therapeutic targets for the

  18. Postoperative radiotherapy of supratentorial anaplastic gliomas

    International Nuclear Information System (INIS)

    Wendt, T.G.; Bacherler, B.; Baumer, K.; Rohloff, R.; Willich, N.

    1986-01-01

    Between 1970 and 1983, 149 patients with high grade anaplastic supratentorial gliomas received a postoperative irradiation during primary treatment. 118 out of these patients had an anaplastic astrocytoma, 18 an anaplastic oligodendroglioma, and 13 an anaplastic ependymoma. Most of these patients were treated by irradiation of a great volume with 50 Gy within five weeks, the others by irradiation of the total brain with 50 Gy within five weeks and saturation with 10 Gy within one week. The one-year survival of the total group was 35.5% and the two-year survival 10.6%. Patients at an age of less than 40 years show a significantly longer survival than older patients (one-year survival rates 40% and 30.7%, respectively). Patients suffering from anaplastic tumors with astrocytic and oligodendrocytic differentiation have a comparable prognosis. Patients suffering from anaplastic tumors with ependymal differentiation, however, have prolonged survival times. The therapy results of different treatment methods are discussed using the communications of literature. (orig.) [de

  19. Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease – a combined tissue microarray, in vitro and in vivo study

    International Nuclear Information System (INIS)

    Márk, Ágnes; Kopper, László; Sebestyén, Anna; Hajdu, Melinda; Váradi, Zsófia; Sticz, Tamás Béla; Nagy, Noémi; Csomor, Judit; Berczi, Lajos; Varga, Viktória; Csóka, Monika

    2013-01-01

    Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic

  20. Pleomorphic xanthoastrocytoma with anaplastic features

    Directory of Open Access Journals (Sweden)

    Cheng ZHI

    2015-08-01

    Full Text Available Objective  To explore the clinical pathological characteristics, immunophenotyping, diagnosis and differential diagnosis and prognosis of pleomorphic xanthoastrocytoma (PXA with anaplastic features.  Methods  HE staining was used for histological observation. The expressions of glial fibrillary acidic protein (GFAP, vimentin (Vim, CD34, epithelial membrane antigen (EMA, progestrone receptor (PR, neurofilment protein (NF, neuronal nuclei (NeuN, synaptophysin (Syn, Nestin (Nes, S-100 protein (S-100, P53 and Ki-67 labeling index were detected by immunohistochemical method. BRAF mutation was detected by polymerase chain reaction (PCR amplification.  Results  A 43-year-old male patient presented with repeatedly paroxysmal tic of limbs and disturbance of consciousness. Cranial MRI revealed multiple abnormal signals in left temporo-occipito-parietal lobe and posterior horn of lateral ventricle, with unclear borderline and cystic degeneration. Surgical removal of the lesion was performed. Histologically, the tumor was biphasic. One part was composed of spindle cells arranged in fascicles or as running water, with weird multinuclear giant cells. Abundant vacuolated lipidized cytoplasm could be seen. Mitosis and "map"-like necrosis were noted. Another part revealed the tumor cells were consistent in size and uniform in distribution, with loose background tissue. Immunohistochemistry showed tumor cells were diffusely positive for GFAP, Vim, S-100, Nes, CD34 and P53, and negative for EMA, Syn, NeuN and NF. Ki-67 labeling index was about 15%. Reticular fiber staining showed abundant reticular fibers in the tumor tissue. BRAF mutation detected by PCR amplification was not found.  Conclusions  Classified as grade Ⅱ in the World Health Organization (WHO classification, the prognosis of PXA is good. A diagnosis of PXA with anaplastic features should be considered when the tumor demonstrates mitotic activity > 5/10 high power field (HPF and/or areas of

  1. Malignant transformation of CD4+ T lymphocytes mediated by oncogenic kinase NPM/ALK recapitulates IL-2-induced cell signaling and gene expression reprogramming

    DEFF Research Database (Denmark)

    Marzec, Michal; Halasa, Krzysztof; Liu, Xiaobin

    2013-01-01

    expressed in T cell lymphomas (TCLs), closely resembles cell activation induced by IL-2, the key cytokine supporting growth and survival of normal CD4(+) T lymphocytes. Direct comparison of gene expression by ALK(+) TCL cells treated with an ALK inhibitor and IL-2-dependent ALK(-) TCL cells stimulated......Anaplastic lymphoma kinase (ALK), physiologically expressed only by nervous system cells, displays a remarkable capacity to transform CD4(+) T lymphocytes and other types of nonneural cells. In this study, we report that activity of nucleophosmin (NPM)/ALK chimeric protein, the dominant form of ALK...... the target CD4(+) T lymphocytes, at least in part, by using the pre-existing, IL-2-dependent signaling pathways....

  2. The importance of Notch signaling in peripheral T-cell lymphomas

    DEFF Research Database (Denmark)

    Kamstrup, Maria Rørbæk; Biskup, Edyta; Gjerdrum, Lise Mette Rahbek

    2014-01-01

    Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PT...

  3. Small-molecule inhibitors of Ataxia Telangiectasia and Rad3 related kinase (ATR) sensitize lymphoma cells to UVA radiation

    DEFF Research Database (Denmark)

    Biskup, Edyta; Naym, David Gram; Gniadecki, Robert

    2016-01-01

    and require more aggressive therapies. OBJECTIVE: The aim of this project was to investigate whether inhibition of Ataxia Telangiectasia and Rad3 related kinase (ATR) may enhance efficacy of phototherapy. METHODS: CTCL cell lines (MyLa2000, SeAx and Mac2a) served as in vitro cell models. ATR and Chk1 were...

  4. Hodgkin's Lymphoma

    Science.gov (United States)

    Hodgkin's lymphoma (Hodgkin's disease) Overview Hodgkin's lymphoma — formerly known as Hodgkin's disease — is a cancer of the lymphatic system, which ... prognosis continues to improve for people with Hodgkin's lymphoma. Hodgkin's lymphoma care at Mayo Clinic Symptoms Signs and ...

  5. Cerebral oligodendroglioma: MR features indicating anaplastic changes

    International Nuclear Information System (INIS)

    Choi, Choong Gon; Chang, Kee Hyun; Han, Moon Hee; Chi, Je Geun; Yoon, Hyun Ki

    1995-01-01

    The purpose of this study is to find helpful MR findings for predicting anaplastic oligodendrogliomas. Retrospective analysis of 46 MR images and 37 CT scans was performed for 46 patients with pathologically-proven cerebral oligodendrogliomas. A neuropathologist graded the tumors as one of low-grade (n = 16), intermediate-grade (n = 12), or anaplastic oligodendroglioma (n 18). MR imaging features were retrospectively analysed with respect to histologic grading of the tumors. Contrast enhancement was observed always in anaplastic group (17/17), in a portion of intermediate-grade group (4/10) but not in low-grade group (0/4). Peritumoral edema was observed infrequently in anaplastic group (4/18) or intermediate-grade group (1/12). Cystic changes (25/46) or calcifications on CT Scans (14/37) were not related with histologic grading. Grossly identifiable hemorrhage was rare in this series (2/46). Among the various imaging features, only tumor enhancement and peritumoral edema were statistically significant for trend test (ρ < 0.05). When considering the diagnosis of oligodendrogliomas, the presence of contrast enhancement or peritumoral edema is a helpful features suggesting anaplastic oligodendrogliomas

  6. Reversion of apoptotic resistance of TP53-mutated Burkitt lymphoma B-cells to spindle poisons by exogenous activation of JNK and p38 MAP kinases.

    Science.gov (United States)

    Farhat, M; Poissonnier, A; Hamze, A; Ouk-Martin, C; Brion, J-D; Alami, M; Feuillard, J; Jayat-Vignoles, C

    2014-05-01

    Defects in apoptosis are frequently the cause of cancer emergence, as well as cellular resistance to chemotherapy. These phenotypes may be due to mutations of the tumor suppressor TP53 gene. In this study, we examined the effect of various mitotic spindle poisons, including the new isocombretastatin derivative isoNH2CA-4 (a tubulin-destabilizing molecule, considered to bind to the colchicine site by analogy with combretastatin A-4), on BL (Burkitt lymphoma) cells. We found that resistance to spindle poison-induced apoptosis could be reverted in tumor protein p53 (TP53)-mutated cells by EBV (Epstein Barr virus) infection. This reversion was due to restoration of the intrinsic apoptotic pathway, as assessed by relocation of the pro-apoptotic molecule Bax to mitochondria, loss of mitochondrial integrity and activation of the caspase cascade with PARP (poly ADP ribose polymerase) cleavage. EBV sensitized TP53-mutated BL cells to all spindle poisons tested, including vincristine and taxol, an effect that was systematically downmodulated by pretreatment of cells with inhibitors of p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases. Exogenous activation of p38 and JNK pathways by dihydrosphingosine reverted resistance of TP53-mutated BL cells to spindle poisons. Dihydrosphingosine treatment of TP53-deficient Jurkat and K562 cell lines was also able to induce cell death. We conclude that activation of p38 and JNK pathways may revert resistance of TP53-mutated cells to spindle poisons. This opens new perspectives for developing alternative therapeutic strategies when the TP53 gene is inactivated.

  7. Anaplastic meningioma: The dark side of meningiomas

    Directory of Open Access Journals (Sweden)

    Andreea Cioca

    2017-06-01

    Full Text Available Anaplastic meningioma is a rare malignant tumor of the meninges, with a very aggressive behavior and a grim prognosis. Here we report a case of a 64-year old man which presented to the neurosurgery department with motor deficit in the right hemi–body, loss of speech and disorientation. Magnetic resonance imaging detected a mass located in the left frontal lobe that measured 7/8/7 cm, leading to the conclusion that surgery is necessary. Microscopic examination of the tumor showed great number of hypercellular areas with a high mitotic index, and focal necrosis with psammoma bodies. Using a panel of antibodies such as EMA, vimentin, CD34 GFAP, pancytokeratin and Ki67, we concluded that he final diagnosis was anaplastic meningioma, WHO grade III. Due to its morphological similarity with other tumors, the diagnosis of anaplastic meningioma may be challenging.

  8. Anaplastic hemangiopericytoma of eyelid: An unusual location

    Directory of Open Access Journals (Sweden)

    Pradeep Ventrapati

    2017-01-01

    Full Text Available Hemangiopericytomas (HPCs are rare soft tissue tumors. The eyelid is a very uncommon site for these tumors, and an anaplastic variant of HPC in the eyelid has not been reported before. A 44-year-old male presented with complaints of slowly progressive, painless swelling on the inner aspect of the left upper eyelid for 9 months. He underwent local excision of the swelling and histopathology revealed a WHO Grade III anaplastic HPC. Whole body 18 F-fluorodeoxyglucose positron emission tomography-computed tomography done postoperatively did not show any evidence of local or distant disease. The patient was planned for adjuvant radiotherapy of 60 Gy in 30 fractions over 6 weeks in view of high grade of histopathology and doubtful margins. He is disease free at the time of the last follow-up. To the best of our knowledge, this is the first case of anaplastic HPC of eyelid being reported in English literature.

  9. Primary and Secondary T-cell Lymphomas of the Breast: Clinico-pathologic Features of 11 Cases

    Science.gov (United States)

    Gualco, Gabriela; Chioato, Lucimara; Harrington, William J.; Weiss, Lawrence M.; Bacchi, Carlos E.

    2009-01-01

    Breast involvement by non-Hodgkin lymphomas is rare, and exceptional for T-cell lymphomas; we studied the morphologic, immunophenotypic, and clinical features of 11 patients with T-cell non-Hodgkin lymphomas involving the breast. Four cases fulfilled the definition criteria for primary breast lymphomas, 3 females and 1 male, with a median age of 51 years. One primary breast lymphomas was T-cell lymphoma unspecified, other was subcutaneous panniculitis-like T-cell lymphoma, and 2 cases were anaplastic large cell lymphomas. One of the anaplastic large cell lymphoma cases was found surrounding a silicone breast implant and presented as clinically as mastitis; whereas the other case occurred in a man. T-cell lymphoma secondarily involved the breast in 7 patients, all women and 1 bilateral, with a median age of 29 years. These secondary breast lymphomas occurred as part of widespread nodal or leukemic disease. Three patients had adult T-cell leukemia/lymphoma, including the patient with bilateral lesions, 3 others had precursor T-lymphoblastic lymphoma/leukemia, and the other presented with a peripheral-T-cell lymphoma nonotherwise specified type. Breast T-cell lymphomas are very infrequent and are morphologically and clinically heterogeneous. PMID:19318917

  10. P276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in vitro and in vivo in mantle cell lymphoma cell lines

    Directory of Open Access Journals (Sweden)

    Shirsath Nitesh P

    2012-10-01

    Full Text Available Abstract Background Mantle cell lymphoma (MCL is a well-defined aggressive lymphoid neoplasm characterized by proliferation of mature B-lymphocytes that have a remarkable tendency to disseminate. This tumor is considered as one of the most aggressive lymphoid neoplasms with poor responses to conventional chemotherapy and relatively short survival. Since cyclin D1 and cell cycle control appears as a natural target, small-molecule inhibitors of cyclin-dependent kinases (Cdks and cyclins may play important role in the therapy of this disorder. We explored P276-00, a novel selective potent Cdk4-D1, Cdk1-B and Cdk9-T1 inhibitor discovered by us against MCL and elucidated its potential mechanism of action. Methods The cytotoxic effect of P276-00 in three human MCL cell lines was evaluated in vitro. The effect of P276-00 on the regulation of cell cycle, apoptosis and transcription was assessed, which are implied in the pathogenesis of MCL. Flow cytometry, western blot, immunoflourescence and siRNA studies were performed. The in vivo efficacy and effect on survival of P276-00 was evaluated in a Jeko-1 xenograft model developed in SCID mice. PK/PD analysis of tumors were performed using LC-MS and western blot analysis. Results P276-00 showed a potent cytotoxic effect against MCL cell lines. Mechanistic studies confirmed down regulation of cell cycle regulatory proteins with apoptosis. P276-00 causes time and dose dependent increase in the sub G1 population as early as from 24 h. Reverse transcription PCR studies provide evidence that P276-00 treatment down regulated transcription of antiapoptotic protein Mcl-1 which is a potential pathogenic protein for MCL. Most importantly, in vivo studies have revealed significant efficacy as a single agent with increased survival period compared to vehicle treated. Further, preliminary combination studies of P276-00 with doxorubicin and bortezomib showed in vitro synergism. Conclusion Our studies thus provide

  11. Clinicopathological study of primary gastric lymphoma

    International Nuclear Information System (INIS)

    Al-Shehabi, Zubeir A.; Saleh, Rana S.; Zezafon, Hassan B.

    2007-01-01

    Objective was to present a histopathologic and immunohistochemical analysis of primary gastric lymphomas that was reclassified according to the new World Health Organization classification of lymphoid neoplasms. We reviewed the morphological and immunohistochemical features of 28 patients with gastric lymphomas, diagnosed in the Department of pathology at the University Hospital of Tishreen University, Lattakia, Syria, during the period 1994-2003. Specimens were obtained from endoscopic and surgical biopsies. The immunohistochemical study was performed to analyze the immunophenotype of these lymphomas. Patients were aged 17-71 years. There was a slight predominance of females (male to female ratio, 13:15). Seventeen of the patients had tumors mainly located in the gastric antrum. Histologically, the most common lymphoma was of mucosa-associated lymphoid tissue (MALT) type (20 patients), also with diffuse large B-cell lymphoma (7 patients) and anaplastic large cell lymphoma (one patient). Our study demonstrates the different patterns of gastric lymphomas in Lattakia, Syria during a 10-year period in 28 Syrian patients, and reveals that the most primary gastric lymphomas are B-cell MALT lymphomas. (author)

  12. Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma.

    Science.gov (United States)

    Shahid, Ruqaiya; Gulzar, Rubina; Avesi, Lubna; Hassan, Saba; Danish, Farheen; Mirza, Talat

    2016-02-01

    To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Cross-sectional analytical study. Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Out of the 318 cases, 79 (25%) were Hodgkin Lymphomas (HL) and 239 (75%) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95%) were B cell lymphomas and 24 (10.05%) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95% of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HLwas significantly higher in the younger age group and that of NHLwas higher in the older age group (p Hodgkin lymphoma comprises 25% and non-Hodgkin lymphoma comprises 75% of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHLis three times more common than T-cell lymphoma. DLBCLis the most frequent lymphoma. ALCLis the most common T-cell, and mixed cellularity is the most common Hodgkin lymphoma.

  13. Proteomic and Metabolic Analyses of S49 Lymphoma Cells Reveal Novel Regulation of Mitochondria by cAMP and Protein Kinase A.

    Science.gov (United States)

    Wilderman, Andrea; Guo, Yurong; Divakaruni, Ajit S; Perkins, Guy; Zhang, Lingzhi; Murphy, Anne N; Taylor, Susan S; Insel, Paul A

    2015-09-04

    Cyclic AMP (cAMP), acting via protein kinase A (PKA), regulates many cellular responses, but the role of mitochondria in such responses is poorly understood. To define such roles, we used quantitative proteomic analysis of mitochondria-enriched fractions and performed functional and morphologic studies of wild-type (WT) and kin(-) (PKA-null) murine S49 lymphoma cells. Basally, 75 proteins significantly differed in abundance between WT and kin(-) S49 cells. WT, but not kin(-), S49 cells incubated with the cAMP analog 8-(4-chlorophenylthio)adenosine cAMP (CPT-cAMP) for 16 h have (a) increased expression of mitochondria-related genes and proteins, including ones in pathways of branched-chain amino acid and fatty acid metabolism and (b) increased maximal capacity of respiration on branched-chain keto acids and fatty acids. CPT-cAMP also regulates the cellular rate of ATP-utilization, as the rates of both ATP-linked respiration and proton efflux are decreased in WT but not kin(-) cells. CPT-cAMP protected WT S49 cells from glucose or glutamine deprivation, In contrast, CPT-cAMP did not protect kin(-) cells or WT cells treated with the PKA inhibitor H89 from glutamine deprivation. Under basal conditions, the mitochondrial structure of WT and kin(-) S49 cells is similar. Treatment with CPT-cAMP produced apoptotic changes (i.e. decreased mitochondrial density and size and loss of cristae) in WT, but not kin(-) cells. Together, these findings show that cAMP acts via PKA to regulate multiple aspects of mitochondrial function and structure. Mitochondrial perturbation thus likely contributes to cAMP/PKA-mediated cellular responses. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas

    Science.gov (United States)

    2015-04-28

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Epstein-Barr Virus Infection; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis

  15. Aggressive primary thyroid lymphoma: imaging features of two elderly patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eu Hyun; Kim, Jee Young; Kim, Tae Jung [Yeouido St. Mary' s Hospital, The Catholic University College of Medicine, Seoul (Korea, Republic of)

    2014-12-15

    We report two cases of aggressive thyroid lymphoma in elderly patients that presented as Epub ahead of print large infiltrative thyroid masses with extensive invasion to adjacent structures including trachea, esophagus, and common carotid artery. Ultrasonography displayed irregular shaped, heterogeneous hypoechoic mass, mimicking anaplastic carcinoma. Computed tomography showed heterogeneously enhancing mass compared to surrounding muscles without calcification and hemorrhage. After biopsy, the masses were histopathologically diagnosed as lymphoma. Aggressive primary thyroid lymphoma is rare; therefore, here we report its image features, with emphasis on ultrasonographic findings, and discuss its differential diagnosis.

  16. Extensive Growth of an Anaplastic Meningioma

    Directory of Open Access Journals (Sweden)

    Hajrullah Ahmeti

    2013-01-01

    Full Text Available We present the case of a 30-year-old male patient with an almost complete destruction of the calvarial bone through an anaplastic meningioma diagnosed in line with dizziness. Neuroimaging revealed an extensive growing, contrast enhancing lesion expanding at the supra- and infratentorial convexity, infiltrating and destroying large parts of the skull, and infiltrating the skin. Due to progressive ataxia and dysarthria with proven tumor growth in the posterior fossa in the continuing course, parts of the tumor were resected. A surgical procedure with the aim of complete tumor resection in a curative manner was not possible. Six months after the first operation, due to a new tumor progression, most extensive tumor resection was performed. Due to the aggressive and destructive growth with a high rate of recurrence and tendency of metastases, anaplastic meningiomas can be termed as malignant tumors. The extrinsic growth masks the tumor until they reach a size, which makes these tumors almost unresectable. In the best case scenarios, the five-year survival is about 50%. With the presented case, we would like to show the aggressive behavior of anaplastic meningiomas in a very illustrative way. Chemotherapy, radiotherapy, and surgery reach their limits in this tumor entity.

  17. Primary Ki-1-positive T-cell lymphoma of the brain--an aggressive subtype of lymphoma: case report and review of the literature.

    Science.gov (United States)

    Goldbrunner, R; Warmuth-Metz, M; Tonn, J C; Vince, G H; Roosen, K

    1996-07-01

    By detection of the Ki-1 antigen, Stein (1985) defined a new entity of anaplastic large cell lymphoma [24]. Apart from our case, only four further cases of Ki-1 positive primary central nervous system lymphoma (PCNSL) have been reported in the literature to date. A 63-year-old man presented with two frontal and parietal mass lesions and one ring lesion on computed tomography scan. Clinically, no evidence of brain metastases or abscesses could be found. Immunohistochemical investigations of biopsy specimens revealed a large cell anaplastic T-cell lymphoma positive to Ki-1 antigen. In spite of all therapeutic efforts, the patient died less than 3 months after the onset of symptoms. In all cases the clinical course was very rapid, suggesting that Ki-1 positive PCNSL might form an aggressive subtype of lymphomas. Since the radiologic appearance was atypical and clinical diagnosis was not possible, diagnostic biopsy for immunohistochemical diagnosis should be performed.

  18. Hodgkin Lymphoma (For Teens)

    Science.gov (United States)

    ... check for disease, including lymphoma. What Is Hodgkin Lymphoma? Hodgkin lymphoma is a type of cancer called a ... they are divided into two broad categories: Hodgkin lymphoma and non-Hodgkin lymphoma. Lymphomas that involve a particular type of ...

  19. Conjunctival Lymphoma

    DEFF Research Database (Denmark)

    Kirkegaard, Marina M; Rasmussen, Peter K; Coupland, Sarah E

    2016-01-01

    AND RELEVANCE: Conjunctival lymphoma consists of mainly 4 subtypes of B-cell non-Hodgkin lymphoma: EMZL, FL, MCL, and DLBCL. Mantle cell lymphoma is characterized by a particularly high frequency of secondary disease of stage IVE and bilateral manifestation. The histological subtype is the main outcome......IMPORTANCE: To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize subtype-specific clinical features of CL and their effect on patient outcome. DESIGN, SETTING, AND PARTICIPANTS...... age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse...

  20. Malignant clinical features of anaplastic gliomas without IDH mutation.

    Science.gov (United States)

    Shibahara, Ichiyo; Sonoda, Yukihiko; Shoji, Takuhiro; Kanamori, Masayuki; Saito, Ryuta; Inoue, Tomoo; Kawaguchi, Tomohiro; Yamashita, Yoji; Watanabe, Takashi; Kumabe, Toshihiro; Watanabe, Mika; Suzuki, Hiroyoshi; Tominaga, Teiji

    2015-01-01

    Diagnosis of WHO grade III anaplastic gliomas does not always correspond to its clinical outcome because of the isocitrate dehydrogenase (IDH) gene status. Anaplastic gliomas without IDH mutation result in a poor prognosis, similar to grade IV glioblastomas. However, the malignant features of anaplastic gliomas without IDH mutation are not well understood. The aim of this study was to examine anaplastic gliomas, in particular those without IDH mutation, with regard to their malignant features, recurrence patterns, and association with glioma stem cells. We retrospectively analyzed 86 cases of WHO grade III anaplastic gliomas. Data regarding patient characteristics, recurrence pattern, and prognosis were obtained from medical records. We examined molecular alterations such as IDH mutation, 1p19q loss, TP53 mutation, MGMT promoter methylation, Ki67 labeling index, and CD133, SOX2, and NESTIN expression. Of the 86 patients with anaplastic gliomas, 58 carried IDH mutation, and 40 experienced recurrence. The first recurrence was local in 25 patients and distant in 15. Patients without IDH mutation exhibited significantly higher CD133 and SOX2 expression (P = .025 and .020, respectively) and more frequent distant recurrence than those with IDH mutation (P = .022). Patients with anaplastic gliomas without IDH mutation experienced distant recurrence and exhibited glioma stem cell markers, indicating that this subset may share some malignant characteristics with glioblastomas. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma

    Science.gov (United States)

    Stenson, Mary J.; Maurer, Matthew J.; Wellik, Linda E.; Link, Brian; Hege, Kristen; Dogan, Ahmet; Sotomayor, Eduardo; Witzig, Thomas; Gupta, Mamta

    2015-01-01

    Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4EWT) but not cap-mutant eIF4E (eIF4Ecap mutant) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor CC214-1 reduced the level of the eIF4F complex by decreasing the cap bound fraction of eIF4G and increasing the levels of 4E-BP1. CC214-1 inhibited both the cap dependent and global protein translation. CC214-1 inhibited c-Myc, and cyclin D3 translation by decreasing polysomal fractions from lymphoma cells. Inhibition of eIF4E with shRNA further decreased the CC214-1 induced inhibition of the eIF4F complex, c-Myc, cyclin D3 translation, and colony formation. These studies demonstrate that the eIF4F complex is deregulated in aggressive lymphoma and that dual mTOR therapy has therapeutic potential in these patients. PMID:25839159

  2. Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma.

    Science.gov (United States)

    Demosthenous, Christos; Han, Jing Jing; Stenson, Mary J; Maurer, Matthew J; Wellik, Linda E; Link, Brian; Hege, Kristen; Dogan, Ahmet; Sotomayor, Eduardo; Witzig, Thomas; Gupta, Mamta

    2015-04-20

    Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4E(WT)) but not cap-mutant eIF4E (eIF4E(cap mutant)) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor CC214-1 reduced the level of the eIF4F complex by decreasing the cap bound fraction of eIF4G and increasing the levels of 4E-BP1. CC214-1 inhibited both the cap dependent and global protein translation. CC214-1 inhibited c-Myc, and cyclin D3 translation by decreasing polysomal fractions from lymphoma cells. Inhibition of eIF4E with shRNA further decreased the CC214-1 induced inhibition of the eIF4F complex, c-Myc, cyclin D3 translation, and colony formation. These studies demonstrate that the eIF4F complex is deregulated in aggressive lymphoma and that dual mTOR therapy has therapeutic potential in these patients.

  3. Discrepancy between low levels of mTOR activity and high levels of p-S6 in primary central nervous system lymphoma may be explained by PAS domain-containing serine/threonine-protein kinase-mediated phosphorylation

    DEFF Research Database (Denmark)

    Marosvari, Dora; Nagy, Noemi; Kriston, Csilla

    2018-01-01

    The primary aim of this study was to determine mTOR-pathway activity in primary central nervous system lymphoma (PCNSL), which could be a potential target for therapy. After demonstrating that p-S6 positivity largely exceeded mTOR activity, we aimed to identify other pathways that may lead to S6...... phosphorylation. We measured mTOR activity with immunohistochemistry for p-mTOR and its downstream effectors p(T389)-p70S6K1, p-S6, and p-4EBP1 in 31 cases of PCNSL and 51 cases of systemic diffuse large B-cell lymphoma (DLBCL) and evaluated alternative S6 phosphorylation pathways with p-RSK, p(T229)-p70S6K1......, and PASK antibodies. Finally, we examined the impact of PASK inhibition on S6 phosphorylation on BHD1 cell line. mTOR-pathway activity was significantly less frequent in PCNSL compared with DLBCL. p-S6 positivity was related to mTOR-pathway in DLBCL, but not in PCNSL. Among the other kinases potentially...

  4. Redundant and nonredundant roles for Cdc42 and Rac1 in lymphomas developed in NPM-ALK transgenic mice

    DEFF Research Database (Denmark)

    Choudhari, Ramesh; Minero, Valerio Giacomo; Menotti, Matteo

    2016-01-01

    Increasing evidence suggests that Rho family GTPases could have a critical role in the biology of T-cell lymphoma. In ALK-rearranged anaplastic large cell lymphoma (ALCL), a specific subtype of T-cell lymphoma, the Rho family GTPases Cdc42 and Rac1 are activated by the ALK oncogenic activity....... In vitro studies have shown that Cdc42 and Rac1 control rather similar phenotypes of ALCL biology such as the proliferation, survival, and migration of lymphoma cells. However, their role and possible redundancy in ALK-driven lymphoma development in vivo are still undetermined. We genetically deleted Cdc42...... or Rac1 in a mouse model of ALK-rearranged ALCL to show that either Cdc42 or Rac1 deletion impaired lymphoma development, modified lymphoma morphology, actin filament distribution, and migration properties of lymphoma cells. Cdc42 or Rac1 deletion primarily affected survival rather than proliferation...

  5. Anaplastic Medullary Ependymoma Presenting as Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Nicolas Nicastro

    2013-01-01

    Full Text Available A-41-year old man presented with violent thunderclap headache and a bilateral proprioceptive sensibility deficit of the upper limbs. Cerebral CT scan and MRI were negative. Lumbar puncture confirmed subarachnoid hemorrhage (SAH, but cerebral angiography was negative. Three months later, the patient presented with paraparesis, and a thorough work-up revealed a diffuse, anaplastic extramedullary C7-D10 ependymoma with meningeal carcinomatosis considered the source of hemorrhage. The patient went through a D5-D8 laminectomy, temozolomide chemotherapy, and radiotherapy. The situation remained stable for a few months. In this paper, we would like to emphasize that spinal masses should be considered in cases of SAH with negative diagnostic findings for aneurysms or arteriovenous malformation.

  6. [Mediastinal lymphomas].

    Science.gov (United States)

    Rauthe, S; Rosenwald, A

    2016-09-01

    Lymphomas infiltrating the mediastinum are a challenge for the treating physician as well as for the pathological diagnostics. The clinical scenario is often an emergency situation, while the pathologist is usually confronted only with small biopsy samples. Classical Hodgkin's lymphoma is by far the most frequently occurring lymphoma in the mediastinum and predominantly the nodular sclerosis subtype. In small and very sclerotic specimens it can be difficult to morphologically detect Hodgkin and Reed-Sternberg cells and to identify the characteristic phenotype by immunohistochemistry. Primary mediastinal large B‑cell lymphomas should be distinguished from classical Hodgkin's lymphomas as the treatment is different. This is characterized by the detection of sheets of blast cells, which immunohistochemically show a strong B‑cell phenotype (positivity for CD20 and CD79a), while CD30 can also often be expressed. The intimate biological relationship between classical Hodgkin's lymphomas and mediastinal large B‑cell lymphomas is illustrated by the existence of B‑cell lymphomas with intermediate features (so-called mediastinal grey zone lymphomas). It is important to recognize and diagnose these lymphomas as they are associated with a slightly inferior prognosis. Extranodal thymic marginal zone lymphomas of the mucosa-associated lymphoid tissue (MALT) type are a rare form of lymphoma encountered in the mediastinum, which can be associated with autoimmune diseases. T‑lymphoblastic lymphomas and leukemia, which occur predominantly in children and young adults, represent a rapidly growing precursor cell neoplasia and must be distinguished from thymomas in the differential diagnostics as well as from normal and hyperplastic thymus glands.

  7. Non-Hodgkin's Lymphoma

    Science.gov (United States)

    ... more common than the other general type of lymphoma — Hodgkin lymphoma. Many different subtypes of non-Hodgkin's lymphoma ... helps to determine your treatment options. Where non-Hodgkin's lymphoma occurs Non-Hodgkin's lymphoma generally involves the presence ...

  8. Non-Small Cell Lung Cancer Cells Acquire Resistance to the ALK Inhibitor Alectinib by Activating Alternative Receptor Tyrosine Kinases.

    Science.gov (United States)

    Isozaki, Hideko; Ichihara, Eiki; Takigawa, Nagio; Ohashi, Kadoaki; Ochi, Nobuaki; Yasugi, Masayuki; Ninomiya, Takashi; Yamane, Hiromichi; Hotta, Katsuyuki; Sakai, Katsuya; Matsumoto, Kunio; Hosokawa, Shinobu; Bessho, Akihiro; Sendo, Toshiaki; Tanimoto, Mitsune; Kiura, Katsuyuki

    2016-03-15

    Crizotinib is the standard of care for advanced non-small cell lung cancer (NSCLC) patients harboring the anaplastic lymphoma kinase (ALK) fusion gene, but resistance invariably develops. Unlike crizotinib, alectinib is a selective ALK tyrosine kinase inhibitor (TKI) with more potent antitumor effects and a favorable toxicity profile, even in crizotinib-resistant cases. However, acquired resistance to alectinib, as for other TKIs, remains a limitation of its efficacy. Therefore, we investigated the mechanisms by which human NSCLC cells acquire resistance to alectinib. We established two alectinib-resistant cell lines that did not harbor the secondary ALK mutations frequently occurring in crizotinib-resistant cells. One cell line lost the EML4-ALK fusion gene, but exhibited increased activation of insulin-like growth factor-1 receptor (IGF1R) and human epidermal growth factor receptor 3 (HER3), and overexpressed the HER3 ligand neuregulin 1. Accordingly, pharmacologic inhibition of IGF1R and HER3 signaling overcame resistance to alectinib in this cell line. The second alectinib-resistant cell line displayed stimulated HGF autocrine signaling that promoted MET activation and remained sensitive to crizotinib treatment. Taken together, our findings reveal two novel mechanisms underlying alectinib resistance that are caused by the activation of alternative tyrosine kinase receptors rather than by secondary ALK mutations. These studies may guide the development of comprehensive treatment strategies that take into consideration the various approaches ALK-positive lung tumors use to withstand therapeutic insult. ©2015 American Association for Cancer Research.

  9. Salvage Lenvatinib Therapy in Metastatic Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Iñiguez-Ariza, Nicole M; Ryder, Mabel M; Hilger, Crystal R; Bible, Keith C

    2017-07-01

    Historical anaplastic thyroid cancer (ATC) outcomes have been terrible, with a median survival of only five months and <20% one-year survival. Improved outcomes are now achieved with aggressive initial therapy in stages IVA and IVB disease, but patients with distant metastatic disease (stage IVC) still do poorly; improved therapies are sorely needed. Kinase inhibitors have emerged as promising agents in the therapy of advanced medullary and differentiated thyroid cancer, but there are limited data regarding the use of lenvatinib in ATC. The aim of this study was to delineate clinical outcomes in a series of patients with advanced ATC in response to lenvatinib therapy. A retrospective analysis was conducted involving all lenvatinib-treated Mayo Clinic ATC patients in 2015. Of 28 distinct ATC patients seen in 2015, three (11%) with metastatic disease of ECOG performance status 2-3 were treated with lenvatinib. Two patients were male; age range at ATC diagnosis was 57-84 years. All three patients attained successful local control of their disease with surgery and/or combined chemoradiotherapy. Lenvatinib was offered as the second, third, or fourth line of therapy at the time of metastatic disease progression. Two patients incurred minor responses to therapy, with structural regression of distant metastatic tumor disease soon after starting lenvatinib treatment (at one to two months), while one patient achieved stable disease, but no Response Evaluation Criteria In Solid Tumors partial responses resulted. Overall survival after starting lenvatinib was two, six, and seven months. Fatigue and hypertension were prominent, and one patient developed pulmonary emboli while on lenvatinib. This initial single-institution experience suggests that lenvatinib may have some disease-modifying activity in metastatic ATC that is otherwise refractory to cytotoxic chemotherapy. Unfortunately, observed benefits were transient, and toxicities were prominent. Clinical trials are required

  10. Ginkgo biloba extract prevents acute myocardial infarction and suppresses the inflammation‑ and apoptosis‑regulating p38 mitogen‑activated protein kinases, nuclear factor‑κB and B‑cell lymphoma 2 signaling pathways.

    Science.gov (United States)

    Li, Yanping; Zhang, Ya; Wen, Min; Zhang, Ju; Zhao, Xia; Zhao, Yuan; Deng, Jiagang

    2017-09-01

    Ginkgo biloba is a plant known from the Mesozoic and has been regarded as one of the first to be used in traditional Chinese medicine (TCM). The plant extract has attracted a great deal of attention in recent years. The Ginkgo biloba leaf contains flavones and diterpenes. In addition, Ginkgo biloba performs certain pharmacologic actions, including antioxidant and anti‑aging activities. The aim of the present study was to examine whether Ginkgo biloba extract prevents acute myocardial infarction (AMI). The results demonstrated that Ginkgo biloba extract significantly inhibited infarct size, increased serum histamine levels and weakened creatine kinase (CK)‑MB activity in AMI mice. Ginkgo biloba extract significantly inhibited serum interleukin (IL)‑6 and IL‑1β levels, and caspase‑3/9 activity. In addition, it suppressed matrix metallopeptidase‑9, transforming growth factor‑β, p38 mitogen‑activated protein kinases (MAPK) and nuclear factor (NF)‑κB protein expression, and promoted B‑cell lymphoma 2 (Bcl‑2) protein expression in AMI mice. The results of in vivo assays demonstrated that Ginkgo biloba extract prevents AMI and suppresses inflammation‑ and apoptosis‑regulating p38 MAPK, NF‑κB and Bcl‑2 signaling pathways.

  11. A 16-gene signature distinguishes anaplastic astrocytoma from glioblastoma.

    Directory of Open Access Journals (Sweden)

    Soumya Alige Mahabala Rao

    Full Text Available Anaplastic astrocytoma (AA; Grade III and glioblastoma (GBM; Grade IV are diffusely infiltrating tumors and are called malignant astrocytomas. The treatment regimen and prognosis are distinctly different between anaplastic astrocytoma and glioblastoma patients. Although histopathology based current grading system is well accepted and largely reproducible, intratumoral histologic variations often lead to difficulties in classification of malignant astrocytoma samples. In order to obtain a more robust molecular classifier, we analysed RT-qPCR expression data of 175 differentially regulated genes across astrocytoma using Prediction Analysis of Microarrays (PAM and found the most discriminatory 16-gene expression signature for the classification of anaplastic astrocytoma and glioblastoma. The 16-gene signature obtained in the training set was validated in the test set with diagnostic accuracy of 89%. Additionally, validation of the 16-gene signature in multiple independent cohorts revealed that the signature predicted anaplastic astrocytoma and glioblastoma samples with accuracy rates of 99%, 88%, and 92% in TCGA, GSE1993 and GSE4422 datasets, respectively. The protein-protein interaction network and pathway analysis suggested that the 16-genes of the signature identified epithelial-mesenchymal transition (EMT pathway as the most differentially regulated pathway in glioblastoma compared to anaplastic astrocytoma. In addition to identifying 16 gene classification signature, we also demonstrated that genes involved in epithelial-mesenchymal transition may play an important role in distinguishing glioblastoma from anaplastic astrocytoma.

  12. Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus.

    Science.gov (United States)

    Gonzalez Malagon, Sandra G; Lopez Muñoz, Anna M; Doro, Daniel; Bolger, Triòna G; Poon, Evon; Tucker, Elizabeth R; Adel Al-Lami, Hadeel; Krause, Matthias; Phiel, Christopher J; Chesler, Louis; Liu, Karen J

    2018-03-19

    Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest in Xenopus and mouse models. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in mouse neural crest cells and that loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK3 results in failure of migration. We find that pY-GSK3 phosphorylation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with increased ALK activity express high levels of pY-GSK3, and blockade of GSK3 or ALK can affect migration of these cells. Altogether, this work identifies a role for GSK3 in cell migration during neural crest development and cancer.

  13. Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Shahid, R.; Gulzar, R.; Avesi, L.; Hassan, S.; Danish, F.; Mirza, T.

    2016-01-01

    Objective: To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Study Design: Cross-sectional analytical study. Place and Duration of Study: Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Methodology: Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Results: Out of the 318 cases, 79 (25 percentage) were Hodgkin Lymphomas (HL) and 239 (75 percentage) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95 percentage) were B cell lymphomas and 24 (10.05percentage) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95 percentage of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HL was significantly higher in the younger age group and that of NHL was higher in the older age group (p < 0.001). Primary lymph node involvement was reported in 175 (55 percentage) and cervical lymph node was the most frequent site. Extra nodal involvement was seen in 93 (29 percentage) of all cases and was reported in 87 (36.4 percentage) of NHL and 6 (7.5 percentage) of HL. The most common extra nodal site was the gastrointestinal tract. Conclusion: Hodgkin lymphoma comprises 25 percentage and non-Hodgkin lymphoma comprises 75 percentage of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHL is three times more common than T-cell lymphoma. DLBCL is the most frequent lymphoma. ALCL is the most common T-cell, and mixed

  14. Breast lymphoma

    African Journals Online (AJOL)

    Sixteen patients presenting with lymphoma involving the breast are described. Seven fulfilled the criteria for primary breast lymphoma, while the other 9 had evidence. (sometimes only detected after extensive staging procedures) of concurrent lymphomatous involvement outside the breast. Histological diagnoses of the so- ...

  15. Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas

    Science.gov (United States)

    Kondratiev, Svetlana; Duraisamy, Sekhar; Unitt, Christine L.; Green, Michael R.; Pinkus, Geraldine; Shipp, Margaret A.; Kutok, Jeffery L.; Drapkin, Ronny I.; Rodig, Scott J.

    2011-01-01

    TNFAIP2 is a protein upregulated in response to TNF signaling but its cellular expression and function in normal and neoplastic tissues remains largely unknown. Here we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of tumor cells in 4/4 cases (100%) of follicular dendritic cell sarcoma and in 3/3 cases (100%) of histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-size neoplastic B-cells comprising follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, or marginal zone lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells, in 31/31 cases (100%) of classical Hodgkin lymphoma, 12/12 cases (100%) of nodular lymphocyte predominant Hodgkin lymphoma, and 27/31 cases (87%) of primary mediastinal (thymic) large B cell lymphoma. In contrast, TNFAIP2 was expressed by the malignant cells in only 2/45 cases (4%) of diffuse large B cell lymphoma, not otherwise specified, 2/18 cases (11%) of Burkitt lymphoma, and 1/19 cases (5%) of anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity= 87%) and specific (specificity= 96%) than TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B-cells of primary mediastinal (thymic) large B cell lymphoma from those of its morphologic and immunophenotypic mimic, diffuse large B cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and histiocytic sarcomas whose aberrant expression in the malignant cells of classical Hodgkin lymphoma and primary mediastinal (thymic) large B cell lymphoma serves to distinguish these tumors from other large cell lymphomas in routine clinical practice. PMID

  16. A phase i study of the cyclin-dependent kinase 4/6 inhibitor ribociclib (LEE011) in patients with advanced solid tumors and lymphomas

    NARCIS (Netherlands)

    Infante, Jeffrey R.; Cassier, Philippe A.; Gerecitano, John F.; Witteveen, Petronella O.; Chugh, Rashmi; Ribrag, Vincent; Chakraborty, Abhijit; Matano, Alessandro; Dobson, Jason R.; Crystal, Adam S.; Parasuraman, Sudha; Shapiro, Geoffrey I.

    2016-01-01

    Purpose: Ribociclib (an oral, highly specific cyclin-dependent kinase 4/6 inhibitor) inhibits tumor growth in preclinical models with intact retinoblastoma protein (Rb+). This first-in-human study investigated the MTD, recommended dose for expansion (RDE), safety, preliminary activity,

  17. Musculosceletal lymphomas

    International Nuclear Information System (INIS)

    Ludwig, K.

    2002-01-01

    Primary lymphomas of bone or skeletal muscle are rare entities. The most frequent among these diseases are primary non-Hodgkin's lymphomas of bone. They account for 3-5% of all bone tumors and 5% of all primary extranodal non-Hodgkin's lymphomas. Primary manifestations of Hodgkin's disease in bone or skeletal muscle are rarities. Primary non-Hodgkin's lymphomas of skeletal muscle are rarities as well.Primary non-Hodgkin's lymphomas of bone can be found in any patient age. A preference exists for the 3.-6. decade of life. The radiographic appearance of these entities resembles other aggressive bone tumors.Their differential diagnosis includes - depending on the patient's age - Ewing's sarcoma,malignant fibrous histiocytoma,metastases of small cell tumors and osteomyelitis.Further differential diagnoses are the peripheral primitiv neuroektodermal tumor (PNET), osteosarcoma, eosinophilic granuloma and fibrosarcoma.Treatment of primary non-Hodgkin's lymphomas uses combinations of chemotherapy and radiation therapy.Operative treatment is reserved for the treatment of complications.The prognosis of primary non-Hodgkin's lymphomas is reflected by 10-year-survival-rates without recurrence of more than 80% in unifocal manifestations. (orig.) [de

  18. Anaplastic Thyroid Cancer with Uncommon Long-term Survival

    Directory of Open Access Journals (Sweden)

    Ai-Hung Liu

    2006-10-01

    Full Text Available In general, most thyroid cancers are indolent and have a slowly progressive course. The exception is anaplastic thyroid cancer. It is one of the most fatal neoplasms in humans, with median survival of 4-12 months. Here, we present a patient with anaplastic thyroid cancer who survived for more than 10 years after diagnosis. A 68-year-old man was incidentally found to have anaplastic thyroid cancer during operation for follicular neoplasm. Total thyroidectomy was performed and hyperfractionated radiotherapy was carried out. After operation, annual follow-up examinations were negative for residual tumor or metastatic lesions. The patient also had chronic obstructive pulmonary disease and unfortunately died of pneumonia in a local hospital 10 years after thyroid operation.

  19. The spectral karyotype of L5178Y TK⁺/⁻ mouse lymphoma cells clone 3.7.2C and factors affecting mutant frequency at the thymidine kinase (tk) locus in the microtitre mouse lymphoma assay.

    Science.gov (United States)

    Fellows, Mick D; McDermott, Angela; Clare, Katie R; Doherty, Ann; Aardema, Marilyn J

    2014-01-01

    There has been much discussion on acceptable spontaneous mutant frequencies in the mouse lymphoma assay (MLA). This culminated in the International Workshop on Genotoxicity Testing (IWGT) recommended control limits for the microtitre version of 50-170 mutants/10(6) viable cells, which has now been included in the draft Organization for Economic Co-Operation and Development guideline for assays investigating mammalian cell gene mutation at the tk locus. Some of the factors affecting mutant frequency have been investigated. It was shown that when culturing methotrexate cleansed TK⁺/⁻ cells, a spontaneous mutant frequency of ∼100 mutants/10⁶ viable cells was achieved after only 26 doublings. However, after further culturing for ∼6 months the spontaneous mutant frequency only gradually increased. Culturing for this time did not affect the karyotype of the cell in so much as the modal chromosome number remained stable. The spontaneous mutant frequency could effectively be manipulated by cleansing with various concentrations of methotrexate. The necessity for using appropriately heat-inactivated horse serum was confirmed. Finally, following treatment with 4-nitroquinoline-N-oxide, cells did not preferentially survive when plated at high cell densities (1.6 cells plus 2,000 feeder cells/well) versus cells at low density (1.6 cells/well). It was considered that these findings confirm that the dynamics of spontaneous mutant formation in the MLA are complex. However, the karyotype of L5178Y cells is remarkably stable and assuming investigators are using cells with appropriate provenance and good culturing technique, it is clear that the IWGT recommendations are achievable. Copyright © 2013 Wiley Periodicals, Inc.

  20. [Analysis of long-term survivors in anaplastic thyroid carcinoma].

    Science.gov (United States)

    Yoshida, Akira; Matuzu, Kenichi

    2012-07-01

    We analyzed the clinicopathologic and therapeutic factors associated with long-term survival in 449 patients with anaplastic carcinoma registered with the Anaplastic Thyroid Carcinoma Consortium of Japan. Univariate analysis showed a significant relationship between long-term survival of more than 1 year and the following factors: the appearance of acute symptom; WBC thyroid gland after surgery; no distant metastasis at initial diagnosi; complete resection of gross tumor; and administration of external irradiation (40 Gy) and chemotherapy. In multivariate analysis, only tumor diameter (disease.

  1. Peripheral T-cell lymphomas: an evaluation of reproducibility of the updated Kiel classification.

    Science.gov (United States)

    Hastrup, N; Hamilton-Dutoit, S; Ralfkiaer, E; Pallesen, G

    1991-02-01

    Haematoxylin and eosin, and Giemsa stained sections from 100 peripheral T-cell lymphomas were examined blind on two occasions by four experienced haematopathologists in order to evaluate the inter- and intra-observer reproducibility of the updated Kiel classification for these malignancies. In all cases, the T-cell phenotype had been established previously in frozen section using a panel of monoclonal antibodies. Analysis by kappa statistics showed poor reproducibility, both overall and for most subtypes, with the exception of large cell anaplastic lymphoma. The distinction between low- and high-grade lymphomas was also unsatisfactory. These results indicate the need for improved precision in the definition of histological categories of peripheral T-cell lymphoma. The reproducibility of the update Kiel classification for peripheral T-cell lymphomas in its present form is inadequate.

  2. Targeted therapies in non-small cell lung cancer: a focus on ALK/ROS1 tyrosine kinase inhibitors.

    Science.gov (United States)

    Sgambato, Assunta; Casaluce, Francesca; Maione, Paolo; Gridelli, Cesare

    2018-01-01

    Anaplastic lymphoma kinase (ALK) and ROS1 rearrangements define important molecular subgroups of advanced non-small cell lung cancer (NSCLC). The identification of these genetic driver alterations created new potential for highly active therapeutic interventions. After discovery of ALK rearrangements in NSCLC, it was recognized that these confer sensitivity to ALK inhibition. Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC. After initial response to crizotinib, tumors inevitably relapse. Next-generation ALK inhibitors, more potent and brain-penetrable than crizotinib, may be effective in re-inducing remissions when cancers are still addicted to ALK. Ceritinib and alectinib are approved for metastatic ALK positive NSCLC patients, while brigatinib received granted accelerated approval by the United States Food and Drug Administration. Regarding ROS1 rearrangement, to date crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as treatment of ROS1 positive advanced NSCLC. Expert commentary: Although novel ALK-inhibitors are under clinical investigation compared to crizotinib as front-line treatment for ALK-positive NSCLC, nowadays the current standard first-line therapy for these patients is crizotinib. Further research will clarify the best management of ALK-positive NSCLC, above all who progress on first-line crizotinib.

  3. Protein tyrosine kinases p53/56lyn and p72syk in MHC class I-mediated signal transduction in B lymphoma cells

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Bregenholt, S; Skov, S

    1998-01-01

    syk are among the tyrosine-phosphorylated proteins. The kinetics of phosphorylation of these kinases after MHC-I crosslinking differ from the kinetics observed after crosslinking of the B cell antigen receptor (BCR). Additional experiments were performed with chicken lyn- and syk-negative DT40 B cells...... mobilization of intracellular free calcium compared with MHC-I crosslinking of wild-type DT40 cells. Thus, expression of BCR at the cell surface is likely to be important for the signal cascade initiated by MHC-I crosslinking. Our data suggest that signal transduction initiated through ligation of the MHC...

  4. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  5. Anaplastic Thyroid Cancer: A Review of Epidemiology, Pathogenesis, and Treatment

    Directory of Open Access Journals (Sweden)

    Govardhanan Nagaiah

    2011-01-01

    Full Text Available Anaplastic thyroid cancer (ATC is an uncommon malignancy of the thyroid. Only 1-2% of thyroid cancers are anaplastic, but the disease contributes to 14–50% of the mortality with a median survival of 3 to 5 months. Most patients diagnosed with this disease are 65 years of age or older. The incidence of anaplastic thyroid cancer is decreasing worldwide. Most patients present with a rapidly growing neck mass, dysphagia, or voice change. We performed a comprehensive literature search using PubMed focusing on the treatment of anaplastic thyroid cancer including historical review of treatment and outcomes and investigations of new agents and approaches. A total of sixteen chart review and retrospective studies and eleven prospective studies and/or clinical trials were reviewed. The current standard therapeutic approach is to consider the disease as systemic at time of diagnosis and pursue combined modality therapy incorporating cytoreductive surgical resection where feasible and/or chemoradiation either concurrently or sequentially. Doxorubicin is the most commonly used agent, with a response rate of 22%. Several new agents are currently under investigation. Referral of patients for participation in clinical trials is needed.

  6. Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

    International Nuclear Information System (INIS)

    Sabet, Amir; Ahmadzadehfar, Hojjat; Herrlinger, Ulrich; Wilinek, Winfried; Biersack, Hans-Jürgen; Ezziddin, Samer

    2011-01-01

    A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition

  7. Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

    Directory of Open Access Journals (Sweden)

    Biersack Hans-Jürgen

    2011-08-01

    Full Text Available Abstract A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition.

  8. Anaplastic ependymoma of the fourth ventricle causing obstrictive ...

    African Journals Online (AJOL)

    The case of fourth ventricular anaplastic epednymoma in a four-year-old child is reported in which the initial presentation was deterioration of the level of consciousness secondary to acute obstructive hydrocephalus. An initial insertion of a ventriculo-peritoneal shunt (V-P) to deal with the acute intracranial hypertension was ...

  9. Loss of function mutations in PTPN6 promote STAT3 deregulation via JAK3 kinase in diffuse large B-cell lymphoma

    Science.gov (United States)

    Demosthenous, Christos; Han, Jing Jing; Hu, Guangzhen; Stenson, Mary; Gupta, Mamta

    2015-01-01

    PTPN6 (SHP1) is a tyrosine phosphatase that negatively controls the activity of multiple signaling pathways including STAT signaling, however role of mutated PTPN6 is not much known. Here we investigated whether PTPN6 might also be a potential target for diffuse large B cell lymphoma (DLBCL) and performed Sanger sequencing of the PTPN6 gene. We have identified missense mutations within PTPN6 (N225K and A550V) in 5% (2/38) of DLBCL tumors. Site directed mutagenesis was performed to mutate wild type (WT) PTPN6 and stable cell lines were generated by lentiviral transduction of PTPN6WT, PTPN6N225K and PTPN6A550V constructs, and effects of WT or mutated PTPN6 on STAT3 signaling were analyzed. WT PTPN6 dephosphorylated STAT3, but had no effect on STAT1, STAT5 or STAT6 phosphorylation. Both PTPN6 mutants were unable to inhibit constitutive, as well as cytokines induced STAT3 activation. Both PTPN6 mutants also demonstrated reduced tyrosine phosphatase activity and exhibited enhanced STAT3 transactivation activity. Intriguingly, a lack of direct binding between STAT3 and WT or mutated PTPN6 was observed. However, compared to WT PTPN6, cells expressing PTPN6 mutants exhibited increased binding between JAK3 and PTPN6 suggesting a more dynamic interaction of PTPN6 with upstream regulators of STAT3. Consistent with this notion, both the mutants demonstrated increased resistance to JAK3 inhibitor, WHIP-154 relative to WT PTPN6. Overall, this is the first study, which demonstrates that N225K and A550V PTPN6 mutations cause loss-of-function leading to JAK3 mediated deregulation of STAT3 pathway and uncovers a mechanism that tumor cells can use to control PTPN6 substrate specificity. PMID:26565811

  10. Co-targeting aurora kinase with PD-L1 and PI3K abrogates immune checkpoint mediated proliferation in peripheral T-cell lymphoma: a novel therapeutic strategy.

    Science.gov (United States)

    Islam, Shariful; Vick, Eric; Huber, Bryan; Morales, Carla; Spier, Catherine; Cooke, Laurence; Weterings, Eric; Mahadevan, Daruka

    2017-11-21

    Peripheral T-cell non-Hodgkin lymphoma (PTCL) are heterogeneous, rare, and aggressive diseases mostly incurable with current cell cycle therapies. Aurora kinases (AKs) are key regulators of mitosis that drive PTCL proliferation. Alisertib (AK inhibitor) has a response rate ∼30% in relapsed and refractory PTCL (SWOG1108). Since PTCL are derived from CD4 + /CD8 + cells, we hypothesized that Program Death Ligand-1 (PD-L1) expression is essential for uncontrolled proliferation. Combination of alisertib with PI3Kα (MLN1117) or pan-PI3K inhibition (PF-04691502) or vincristine (VCR) was highly synergistic in PTCL cells. Expression of PD-L1 relative to PD-1 is high in PTCL biopsies (∼9-fold higher) and cell lines. Combination of alisertib with pan-PI3K inhibition or VCR significantly reduced PD-L1, NF-κB expression and inhibited phosphorylation of AKT, ERK1/2 and AK with enhanced apoptosis. In a SCID PTCL xenograft mouse model, alisertib displayed high synergism with MLN1117. In a syngeneic PTCL mouse xenograft model alisertib demonstrated tumor growth inhibition (TGI) ∼30%, whilst anti-PD-L1 therapy alone was ineffective. Alisertib + anti-PD-L1 resulted in TGI >90% indicative of a synthetic lethal interaction. PF-04691502 + alisertib + anti-PD-L1 + VCR resulted in TGI 100%. Overall, mice tolerated the treatments well. Co-targeting AK, PI3K and PD-L1 is a rational and novel therapeutic strategy for PTCL.

  11. Lymphoma cytogenetics.

    Science.gov (United States)

    Dave, Bhavana J; Nelson, Marilu; Sanger, Warren G

    2011-12-01

    Lymphomas are a heterogeneous group of neoplasms with distinct morphologic, immunologic, and cytogenetic characteristics. Overlapping morphologic and immunophenotypic features often makes accurate diagnosis difficult. Cytogenetics helps simplify the diagnostic complexities presented in transforming and progressive lymphoid malignancies. Genetic studies using technical advances such as fluorescence in situ hybridization and the newer approaches of array comparative genomic hybridization and gene expression profiling play a critical and often defining role in the diagnosis, progression, prognosis, and therapeutic stratification. This article reviews characteristic cytogenetic abnormalities in specific subtypes of lymphomas at diagnosis, disease progression, and prognosis.

  12. Clinico-hematological Profile of 184 Patients with Non-Hodgkin's Lymphoma: An Experience from Southern Pakistan.

    Science.gov (United States)

    Sultan, Sadia; Irfan, Syed Mohammed; Rashid, Anila; Parveen, Saira; Nawaz, Neesha

    2017-09-01

    Non-Hodgkin lymphoma (NHL) is a diverse group of lymphoma comprises of divergent tumors with paradoxical clinical behaviors and potential difference in response to therapy. We conducted a data-base analysis on NHL patients to evaluate the clinico-epidemiological features and WHO spectrum of NHL in Pakistani patients. This descriptive study was conducted over a period of 5 years from January 2011 to December 2015 at Hematology department of Liaquat National Hospital. All NHL cases were diagnosed by morphology on H&E sections and Immunohistochemical profile according to WHO classification of lymphoid neoplasms. 184 histopathologically confirmed cases of NHL were identified. There were 139 males and 45 females, with a male to female ratio of 3: 1. The mean age was 48.5±16.0 years with the median age of 50 years. B symptoms were present in 80.4% of patients. Lymph node enlargement was present in 71.1% of the cases. 168 patients ad B-cell lymphoma (91.3%) and 16 patients had T-cell (8.6%) lymphoma. Overall 158 (85.8%) patients had aggressive lymphoma. Histopathologically, Diffuse large B-cell lymphoma constituted major subtype in 67.9%, followed by follicular lymphoma in 7.6% patients. Marginal lymphoma in 3.8%patients, 3.2% patients had mantle cell, 2.7% patients of anaplastic large cell and 2.1% patients each for Burkitt's lymphoma and T-cell rich lymphoma. In T cell neoplasm, peripheral T cell lymphoma and adult T cell lymphoma are the main variants accountable in 4.3% and 3.2% respectively. B cell lymphoma is more frequent than T cell lymphoma with diffuse large B-cell lymphoma being the commonest NHL. Our analysis shows that clinicopathological features of NHL are comparable to published data. However, aggressive lymphoma and predominance of B symptoms are more frequently seen.

  13. Testicular lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; d'Amore, F; Christensen, Bjarne Egelund

    1994-01-01

    In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases...

  14. Diversity of imaging and pathological features at different stages of primary central nervous system lymphoma

    Directory of Open Access Journals (Sweden)

    Jing LIU

    2018-01-01

    Full Text Available Objective The clinical, imaging and pathological manifestations of one patient at different stages of primary central nervous system lymphoma (PCNSL have been analyzed to disclose its pathogenesis. Methods and Results A 29-year-old female patient showed recurrent onsets. On the first onset, the main clinical manifestation was blurred vision and visual field defect. Cranial MRI showed a patchy lesion in the right parietal and occipital lobes without obvious occupying sign. T1WI showed slight low-intensity sign, T2WI and FLAIR showed high-intensity signs. Enhanced scanning showed heterogeneous punctate enhancement. The lesion disappeared gradually after glucocorticoid impact therapy. Headache, vomiting and left limb paralysis were the main clinical manifestations on the second onset, and MRI showed a lesion in the right frontal and parietal lobes with obvious occupying sign and solid enhancement, low-intensity on T1WI, high-intensity on T2WI and FLAIR. The tumor was totally removed under microscope. Histological findings showed large tumor cells, rich cytoplasm, nuclei with various sizes and shapes, conspicuous mitosis, patchy necrosis, and interstitial small vessel hyperplasia. Immunohistochemical staining showed that membrane of tumor cells was positive for CD20, and nuclei were positive for paired box gene 5 (PAX5 and multiple myeloma oncogene 1 (MUM1. In a few tumor cells, membrane was positive for CD10 and CD30, and nuclei were positive for cyclin D1. Besides, tumor cells were negative for CD3, anaplastic lymphoma kinase (ALK and glial fibrillary acidic protein (GFAP. Ki?67 labeling index was about 80%. EBER in situ hybridization (ISH assay showed that mRNA coded by Epstein?Barr (EB virus was negative. The tumor showed angiotropic characteristics, and the walls of involved blood vessels were wrapped and destructed. The final diagnosis was confirmed as diffuse large B cell lymphoma. Conclusions PCNSL has various imaging features, revealing as

  15. Stages of Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... and skin. There are two general types of lymphoma : Hodgkin lymphoma and non-Hodgkin lymphoma . (See the PDQ ... more information.) There are two types of childhood Hodgkin lymphoma. The two types of childhood Hodgkin lymphoma are: ...

  16. Plasma cytokine profiles at diagnosis in pediatric patients with non-hodgkin lymphoma

    DEFF Research Database (Denmark)

    Mellgren, Karin; Hedegaard, Chris Juul; Schmiegelow, Kjeld

    2012-01-01

    Non-Hodgkin lymphoma (NHL) has been associated with elevated levels of inflammatory and immune-regulating cytokines, and polymorphisms in the genes encoding interleukin (IL)-10 and tumor necrosis factor (TNF)-α have been associated with increased incidence of certain subtypes of NHL. The aim......, between 1995 and 2008. Cytokines and growth factors were measured in serum using the Luminex platform by application of a 30-plex kit. Levels of IL-6, IL-2R, IL-10, TNF-RI, and macrophage inflammatory protein-1α were significantly higher in patients with anaplastic large-cell lymphoma compared...... with patients diagnosed with B-cell lymphomas and lymphoblastic lymphomas. High levels of IL-4, IL-13, TNF-RI, and epidermal growth factor were associated with a poorer general condition at diagnosis. The present study suggests that NHL subgrouping and the general condition of pediatric patients at diagnosis...

  17. Use of tracheal stenting in the palliation of anaplastic thyroid carcinoma: tertiary centre experience.

    Science.gov (United States)

    Varadharajan, K; Mathew, R; Odutoye, B; Williamson, P; Madden, B

    2015-06-01

    Anaplastic thyroid carcinoma is rare but carries a poor prognosis. Anaplastic thyroid carcinoma leads to tracheal compression, airway compromise and eventually death. Airway compromise, a particularly distressing symptom, can be palliated with tracheal stenting. A retrospective case note analysis was conducted of patients diagnosed with anaplastic thyroid carcinoma between July 2003 and July 2013. Twelve patients with anaplastic thyroid carcinoma were identified. Four patients underwent palliative tracheal stenting. Three patients had no dyspnoea at the time of stenting. Two stented patients subsequently developed dyspnoea secondary to stent migration; this was managed successfully with stent exchange. The other stented patient remained asymptomatic with regards to dyspnoea. All non-stented patients died with or from airway compromise. Tracheal stenting is a relatively safe and effective method for palliation of distressing airway symptoms in patients with anaplastic thyroid carcinoma. Early prophylactic tracheal stenting in anaplastic thyroid carcinoma may be an effective option to prevent development of airway compromise as the disease progresses.

  18. Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

    Science.gov (United States)

    2018-03-02

    Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

  19. Plasma Cell-Free DNA in Paediatric Lymphomas

    Science.gov (United States)

    Mussolin, Lara; Burnelli, Roberta; Pillon, Marta; Carraro, Elisa; Farruggia, Piero; Todesco, Alessandra; Mascarin, Maurizio; Rosolen, Angelo

    2013-01-01

    Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells. Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics. Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among different patient subgroups and controls and to analyze relationship between levels of cfDNA and clinical characteristics. Results: Levels of cfDNA in lymphoma patients were significantly higher compared with controls (p<0.0001). CfDNA was associated with median age (p=0.01) in HL, and with stage in ALCL (p=0.01). In HL patients high cfDNA levels were correlated with poor prognosis (p=0.03). In ALCL we found that most of the cfDNA (77%) was non-tumor DNA. Conclusion: level of plasma cfDNA might constitute an important non-invasive tool at diagnosis in lymphoma patients' management; in particular in patients with HL, cfDNA seems to be a promising prognostic biomarker. PMID:23678368

  20. Lymphoma of the eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik Holm; Heegaard, Steffen

    2017-01-01

    lymphomatoid papulosis has a female predominance. Signs of B-cell and T-cell lymphomas are tumor and swelling of the eyelid. Ulceration and erythema occur frequently among patients with T-cell lymphoma. Radiotherapy with or without surgery is the treatment of choice for low-grade, solitary lymphomas, whereas......Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B...

  1. [Plasmablastic lymphoma].

    Science.gov (United States)

    Fernández-Álvarez, Rubén; Sancho, Juan-Manuel; Ribera, Josep-María

    2016-11-04

    Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin lymphoma that commonly occurs in human immunodeficiency virus (HIV)-positive individuals, and affects oral sites. Occasionally, it has been described in HIV-negative patients and involving non-oral sites. Pathologically, PBL is a high-grade B-cell lymphoma that displays the immunophenotype of a terminally differentiated B-lymphocyte with loss of B-cell markers (CD20) and expression of plasma-cell antigens. Epstein-Barr virus infection and MYC rearrangements are frequently observed. Treatment of PBL is challenging because of the lack of established treatment and poor outcomes, with median survival times shorter than one year. In this review, we discuss the clinical and epidemiologic spectrum of PBL as well as its distinct pathological features. Finally, we summarize the currently available approaches for the treatment of patients with PBL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  2. Breast Implant–associated Anaplastic Large Cell Lymphoma: Updated Results from a Structured Expert Consultation Process

    Directory of Open Access Journals (Sweden)

    Benjamin Kim, MD, MPhil

    2015-01-01

    Conclusions: Our assessment yielded consistent results on a number of key, incompletely addressed issues regarding BIA-ALCL, but additional research is needed to support these statement ratings and enhance our understanding of the biology, treatment, and outcomes associated with this disease.

  3. Epigenetic regulation of CD44 in Hodgkin and non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Eberth, Sonja; Schneider, Björn; Rosenwald, Andreas; Hartmann, Elena M; Romani, Julia; Zaborski, Margarete; Siebert, Reiner; Drexler, Hans G; Quentmeier, Hilmar

    2010-01-01

    Epigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples. We screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 lymphoma-derived cell lines representing anaplastic large cell lymphoma, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Hodgkin lymphoma and mantle cell lymphoma (MCL) as well as in 50 primary lymphoma samples. The methylation status of differentially methylated CD44 was verified by methylation-specific PCR and bisulfite sequencing. Gene expression of CD44 and its reactivation by DNA demethylation was determined by quantitative real-time PCR and on the protein level by flow cytometry. Induction of apoptosis by anti-CD44 antibody was analyzed by annexin-V/PI staining and flow cytometry. On average 8 ± 2.8 of 24 TSG were methylated per lymphoma cell line and 2.4 ± 2 of 24 TSG in primary lymphomas, whereas 0/24 TSG were methylated in tonsils and blood mononuclear cells from healthy donors. Notably, we identified that CD44 was hypermethylated and transcriptionally silenced in all BL and most FL and DLBCL cell lines, but was usually unmethylated and expressed in MCL cell lines. Concordant results were obtained from primary lymphoma material: CD44 was not methylated in MCL patients (0/11) whereas CD44 was frequently hypermethylated in BL patients (18/29). In cell lines with CD44 hypermethylation, expression was re-inducible at mRNA and protein levels by treatment with the DNA demethylating agent 5-Aza-2'-deoxycytidine, confirming epigenetic regulation of CD44. CD44 ligation assays with a monoclonal anti-CD44 antibody showed that CD44 can mediate apoptosis in CD44 + lymphoma cells. CD44 hypermethylated, CD44 - lymphoma cell lines were consistently

  4. Hodgkin Lymphoma (For Kids)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hodgkin Lymphoma KidsHealth / For Kids / Hodgkin Lymphoma What's in this ... of the cool things he's missed. What Is Hodgkin Lymphoma? Lymphoma (say: lim-FOH-mah) is cancer of ...

  5. Radiotherapy in anaplastic thyroid carcinoma: An Australian experience

    International Nuclear Information System (INIS)

    So, Kevin; Smith, Robin E.; Davis, Sidney R.

    2017-01-01

    Anaplastic thyroid cancer is a rare and fatal malignancy, associated with significant local tumour and often treatment related morbidity. We report our experience in treating this cancer over a 20-year period. A retrospective review of prospectively collected data from a single Australian Institution (Alfred Health Radiation Oncology) was carried out on patients referred with anaplastic thyroid carcinoma between 1992 and 2013. Thirty patients (17 females and 13 males) were identified with a median age at presentation of 72 years. At presentation, six (20%), 14 (47%) and 10 (33%) patients had stage IVA, IVB and IVC disease respectively. Thirteen patients underwent radical surgical resection with five having microscopic residual (R1) and eight having macroscopic residual (R2) disease. Twenty-eight patients were offered radiotherapy with 27 proceeding with treatment. Of those who received radiotherapy, three, six and 18 were treated with adjuvant, definitive and palliative intent respectively. Six patients had concomitant chemotherapy of which three received trimodality therapy. Only one patient experienced a grade 3 toxicity (oesophagitis). Median survival was 5.3 months and at last follow-up or time of death, 19 of 27 (70.4%) maintained loco-regional control. All patients who had R1 surgical resections and radiotherapy had loco-regional control. Seven of nine (77.8%) and 12 of 18 (66.7%) achieved loco-regional control after receiving definitive or palliative radiotherapy, respectively. Our study suggests that radiotherapy with or without surgery or chemotherapy is well-tolerated and results in durable loco-regional control in a high proportion of patients with anaplastic thyroid carcinoma.

  6. The effect of low level laser on anaplastic thyroid cancer

    Science.gov (United States)

    Rhee, Yun-Hee; Moon, Jeon-Hwan; Ahn, Jin-Chul; Chung, Phil-Sang

    2015-02-01

    Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Here we report that the effects of laser irradiation on anaplastic thyroid cancer cells leads to hyperplasia. 650nm of laser diode was performed with a different time interval (0, 15, 30, 60J/cm2 , 25mW) on anaplastic thyroid cancer cell line FRO in vivo. FRO was orthotopically injected into the thyroid gland of nude mice and the irradiation was performed with the same method described previously. After irradiation, the xenograft evaluation was followed for one month. The thyroid tissues from sacrificed mice were undergone to H&E staining and immunohistochemical staining with HIF-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.

  7. 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

  8. Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas.

    Science.gov (United States)

    Kondratiev, Svetlana; Duraisamy, Sekhar; Unitt, Christine L; Green, Michael R; Pinkus, Geraldine S; Shipp, Margaret A; Kutok, Jeffery L; Drapkin, Ronny I; Rodig, Scott J

    2011-10-01

    Tumor necrosis factor-α-inducible protein-2 (TNFAIP2) is a protein upregulated in cultured cells treated with tumor necrosis factor α (TNF), but its expression in normal and neoplastic tissues remains largely unknown. Here, we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of tumor cells in 4 of 4 cases (100%) of follicular dendritic cell sarcoma and in 3 of 3 cases (100%) of histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-sized neoplastic B cells comprising follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, or marginal zone lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells in 31 of 31 cases (100%) of classical Hodgkin lymphoma, in 12 of 12 cases (100%) of nodular lymphocyte-predominant Hodgkin lymphoma, and in 27 of 31 cases (87%) of primary mediastinal (thymic) large B-cell lymphoma. In contrast, TNFAIP2 was expressed by malignant cells in only 2 of 45 cases (4%) of diffuse large B-cell lymphoma, not otherwise specified, in 2 of 18 cases (11%) of Burkitt lymphoma, and in 1 of 19 cases (5%) of anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity=87%) and specific (specificity=96%) than TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B cells of primary mediastinal (thymic) large B-cell lymphoma from those of its morphologic and immunophenotypic mimic, diffuse large B-cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and histiocytic sarcomas, the aberrant expression of which in the malignant cells of classical Hodgkin lymphoma and primary mediastinal (thymic) large B-cell lymphoma

  9. Clinicopathological study of anaplastic carcinoma of the thyroid gland

    International Nuclear Information System (INIS)

    Maeda, Akiteru; Umeno, Hirohito; Chijiwa, Hideki; Mihashi, Hiroyuki; Chitose, Shunichi; Nakashima, Tadashi

    2010-01-01

    Seventeen cases (5 males and 12 females) of anaplastic carcinoma of the thyroid gland treated at the Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, between January 1999 and January 2009 were reviewed. Ages of the patients ranged from 54 to 94 years. Six cases were treated by radical surgery. All cases were treated by radiotherapy and 5 cases received additional chemotherapy. The 6 cases treated by radical surgery were able to experience home life. Survival time of the radical surgery cases ranged from 8 to 36 months, with a median of 17 months. In cases without surgery, the survival time ranged from 1 to 8 months, with a median of 4 months. As the final outcome, only 1 case is alive after 36 months; 8 cases died by primary tumor, 7 by lung metastasis and 1 by suicide. Although the prognosis of anaplastic carcinoma of the thyroid gland is generally poor, radical surgery, if possible, may provide better survival results. (author)

  10. Malignant lymphoma of the conjunctiva

    DEFF Research Database (Denmark)

    Kirkegaard, Marina M.; Coupland, Sarah E.; Prause, Jan U.

    2015-01-01

    Conjunctival lymphomas constitute 25% of all ocular adnexal lymphomas. The majority are B-cell non-Hodgkin lymphomas (NHLs) (98%), whereas conjunctival T-cell NHLs are rare (2%). The most frequent subtype of conjunctival B-cell lymphoma is extranodal marginal zone lymphoma (EMZL; 81%), followed...... by follicular lymphoma (8%), diffuse large B-cell lymphoma (3%), and mantle cell lymphoma (3%). Extranodal marginal zone lymphoma occurs slightly more often in women and, along with follicular lymphoma, presents late in the seventh decade of life, whereas diffuse large B-cell lymphoma and especially mantle cell...... lymphoma have a predilection for the male gender and typically present in the eighth decade. Extranodal marginal zone lymphoma and follicular lymphoma present most frequently in the forniceal and bulbar conjunctiva. Conjunctival diffuse large B-cell lymphoma, mantle cell lymphoma and T-cell NHLs...

  11. Tec family kinases in inflammation and disease.

    Science.gov (United States)

    Horwood, Nicole J; Urbaniak, Ania M; Danks, Lynett

    2012-04-01

    Over the last decade, the Tec family of nonreceptor tyrosine kinases (Btk, Tec, Bmx, Itk, and Rlk) have been shown to play a key role in inflammation and bone destruction. Bruton's tyrosine kinase (Btk) has been the most widely studied due to the critical role of this kinase in B-cell development and recent evidence showing that blocking Btk signaling is effective in ameliorating lymphoma progression and experimental arthritis. This review will examine the role of TFK in myeloid cell function and the potential of targeting these kinases as a therapeutic intervention in autoimmune disorders such as rheumatoid arthritis.

  12. Lymphoma of the Eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik Holm; Rasmussen, Peter Kristian; Coupland, Sarah E.

    2017-01-01

    . The cases included primary and secondary lymphomas affecting the eyelid. Overall survival, disease-specific survival (DSS), and progression-free survival were the primary endpoints. Results Eighty-six patients were included. Mean age was 63 years and 47 (55%) were male. Non-Hodgkin B-cell lymphomas......Purpose To document subtype-specific clinical features of lymphoma of the eyelid, and their effect on patient outcome. Design Retrospective observational case series. Methods Patient data were collected from 7 international eye cancer centers from January 1, 1980 through December 31, 2015...... constituted 83% (n = 71) and T-cell lymphomas constituted 17% (n = 15). The most common subtypes were extranodal marginal-zone lymphoma (EMZL) (37% [n = 32]), follicular lymphoma (FL) (23% [n = 20]), diffuse large B-cell lymphoma (DLBCL) (10% [n = 9]), mantle cell lymphoma (MCL) (8% [n = 7]), and mycosis...

  13. Hodgkin lymphoma - children

    Science.gov (United States)

    ... children; Hodgkin disease - children; Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... of cancer is unknown. But, certain factors may play a role in ... Common early childhood infections also may increase the risk.

  14. T-Cell Lymphoma

    Science.gov (United States)

    ... Cell Lymphoma (AITL) is a rare, aggressive type accounting for about seven percent of all patients with ... 100 Buildings Worldwide Will Join the Lymphoma Research Foundation to Light Red to Raise Awareness for Blood ...

  15. Marginal Zone Lymphoma

    Science.gov (United States)

    ... MALT) is the most common form of MZL, accounting for about two-thirds of all MZL cases ... Your Story Become an Advocate The Lymphoma Research Foundation’s mission is to eradicate lymphoma and serve those ...

  16. International Lymphoma Epidemiology Consortium

    Science.gov (United States)

    The InterLymph Consortium, or formally the International Consortium of Investigators Working on Non-Hodgkin's Lymphoma Epidemiologic Studies, is an open scientific forum for epidemiologic research in non-Hodgkin's lymphoma.

  17. Anaplastic thyroid carcinoma in Denmark 1996-2012

    DEFF Research Database (Denmark)

    Hvilsom, Gitte Bjørn; Londero, Stefano Christian; Hahn, Christoffer Holst

    2018-01-01

    BACKGROUND: Anaplastic thyroid carcinoma (ATC) is the least common but most malignant thyroid cancer. We aimed to examine the characteristics as well as evaluate the incidence, prognostic factors, and if introduction of a fast track cancer program might influence survival in a cohort of ATC...... patients. METHODS: A cohort study based on prospective data from the national Danish thyroid cancer database DATHYRCA and the national Danish Pathology Register including 219 patients diagnosed from 1996 to 2012, whom were followed until death or through September 2014. RESULTS: We found the median age...... in the 7th decade, the majority of patients being women presenting with a growing mass at the neck, diagnosed with stage T4b disease. At diagnosis, 56% of the patients had lymph node metastasis and 38% distant metastasis. We observed one- and five-year survival of 20.7% and 11.0%, respectively. Both...

  18. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

    International Nuclear Information System (INIS)

    Junor, E.J.; Paul, J.; Reed, N.S.

    1992-01-01

    Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dyspnagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. (Author)

  19. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Junor, E.J.; Paul, J.; Reed, N.S. (Beatson Oncology Centre, Glasgow (United Kingdom))

    1992-04-01

    Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dyspnagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. (Author).

  20. Recent Progress of Genome Study for Anaplastic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Jieun Lee

    2013-06-01

    Full Text Available Anaplastic thyroid cancer (ATC belongs to the most malignant and rapidly progressive human thyroid cancers and its prognosis is very poor. Also, it shows high resistance to cancer treatments, so that effective treatment for ATC has not been found to date, and virtually all patients terminate their life rapidly after diagnosis. Although targeted treatment of genetic alterations has emerged as an extremely promising approach to human cancers, such as BRAF in metastatic melanoma, it remains unclear that how commonly genomic alterations are influenced in ATC tumorigenesis. In recent years, genome wide approaches have been exploited to find genetic alterations associated with complex diseases, including cancer. Here, we reviewed the comprehensive genetic alterations in ATC and recent approaches in the context of identifying genomic alterations associated with ATC. Since surprisingly few reports have been published on the genome wide study of ATC, this review puts emphasis on the urgent needs of genomic research for the prevention and treatment of ATC.

  1. Lymphoma Research Foundation

    Science.gov (United States)

    ... Follow LRF Watch LRF Contact Us National Headquarters Wall Street Plaza 88 Pine Street, Suite 2400 | New York, NY 10005 212-349-2910 | 212-349-2886 Fax LRF@lymphoma.org LRF Helpline 800-500-9976 Helpline@lymphoma.org © 2012 Lymphoma Research Foundation | Privacy Policy

  2. [Oral lymphomas in AIDS].

    Science.gov (United States)

    Llanes, F; López, G; Asenjo, J A; Martín, C

    1989-05-01

    We present two cases of AIDS in drug-addicts, with mouth lymphoma. The diagnosis was established by a gum biopsy which gave high-grade non-Hodgkin lymphoma lymphoblastic "B" type. It is very rare that the oral mucous is affected by lymphomas, but in AIDS and immunodeficiencies it is more common.

  3. Pegfilgrastim and Rituximab in Treating Patients With Untreated, Relapsed, or Refractory Follicular Lymphoma, Small Lymphocytic Lymphoma, or Marginal Zone Lymphoma

    Science.gov (United States)

    2017-09-08

    Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  4. Effects of BP-14, a novel cyclin-dependent kinase inhibitor, on anaplastic thyroid cancer cells

    Czech Academy of Sciences Publication Activity Database

    Allegri, L.; Baldan, F.; Mio, F.; Puppin, C.; Russo, D.; Kryštof, Vladimír; Damante, G.

    2016-01-01

    Roč. 35, č. 4 (2016), s. 2413-2418 ISSN 1021-335X R&D Projects: GA ČR(CZ) GA15-15264S Institutional support: RVO:61389030 Keywords : mTOR * thyroid cancer * cell proliferation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.662, year: 2016

  5. Imaging of MALT lymphomas

    International Nuclear Information System (INIS)

    Rodallec, M.; Guermazi, A.; Attal, P.; Zagdanski, A.M.; Frija, J.; De Kerviler, E.; Brice, P.

    2002-01-01

    The broad category of non-Hodgkin's lymphoma includes a large variety of different diseases including indolent as well as aggressive lymphomas. Mucosa-associated lymphoid tissue (MALT) lymphoma arises in the extranodal mucosal lymphoid tissue and has only been recognised as a distinct entity in recent years. It affects one or several extranodal structures such as the stomach, the lung, the eye and salivary glands. The lymphoma is generally of low grade and has indolent course. The aim of this article is to exemplify the most common radiological patterns of MALT lymphoma. (orig.)

  6. Prognostic implication of clinical, radiologic, and pathologic features in patients with anaplastic gliomas.

    Science.gov (United States)

    Tortosa, Avelina; Viñolas, Núria; Villà, Salvador; Verger, Eugènia; Gil, Juan M; Brell, Marta; Caral, Lluís; Pujol, Teresa; Acebes, Juan J; Ribalta, Teresa; Ferrer, Isidre; Graus, Francesc

    2003-02-15

    The clinical evolution of anaplastic glioma (anaplastic astrocytoma, oligodendroglioma, and oligoastrocytoma) is variable. Previous studies merged patients with anaplastic glioma and the much more common glioblastoma multiforme. Therefore, the conclusions on prognostic factors reflected in part the consequences of an analysis in a heterogeneous population. To identify clinical, neuroradiologic, pathologic, and molecular factors with prognostic significance, we analyzed 95 treated patients with a histologic diagnosis of anaplastic glioma. Variables included age, gender, clinical manifestations at diagnosis (seizures, focal neurologic deficit, and cognitive changes), computed tomographic (CT) scan characteristics (diffuse, ring, and no enhancement), tumor location, extent of resection, histopathology, postoperative Karnofsky performance status (KPS) score, adjuvant chemotherapy, tumor response, proliferation index (Ki-67 expression), and p53, p16, pRb, and epidermal growth factor receptor immunohistochemical expression. Ninety-five patients with a histologic diagnosis of anaplastic astrocytoma (73%), anaplastic oligoastrocytoma (16.6%), or anaplastic oligodendroglioma (10.4%) constituted the basis of this study. Median overall survival was 29 months. Multivariate analysis revealed that an age of 49 years or younger (P < 0.03), postoperative KPS score of 80 or higher (P < 0.007), absence of ring enhancement (P = 0.03), and a proliferation index of 5.1% or lower (P = 0.044) were independently associated with longer survival. The presence of an oligodendroglial component was associated with better prognosis in the univariate analysis (P = 0.009), although this lost power in the multivariate analysis. In addition to previously recognized prognostic variables such as age and KPS score, CT ring enhancement and tumor proliferation index were identified as independent predictors of survival in a homogeneous series of patients with anaplastic gliomas. Copyright 2003 American

  7. Lymphoma-clinical questions

    International Nuclear Information System (INIS)

    Kim, H. C.

    2002-01-01

    Lymphoma is a group of neoplastic disease of lymphoid tissues, which can be classified into categories of Hodgkin's disease and non-Hodgkin's lymphoma(NHL). Prognosis of lymphoma depends on the extent of disease (staging) especially in Hodgkin's disease, but also depends on the histologic make up in non-Hodgkin's lymphoma. Although non-Hodgkin's lymphoma is a neoplastic transformation of lymphoid cell it is a collection of disease with morphologically and immunologically diverse make up. Consequently the classification of NHL has changed frequently and evolved according to the progress of immunologic and molecular knowledge added to the original morphologic classification. Lymphoma is a disorder sensitive to chemotherapy which often leads to cure of the disease even in advanced stage, while many other patients die from the progression of disease. Therefore, better understanding in newer classification and sensitive imaging technique, such as PET, in lymphoma will likely lead to the improvement of survival rate

  8. CD30(+) cutaneous lymphoma in association with atopic eczema.

    Science.gov (United States)

    Fletcher, Clair L; Orchard, Guy E; Hubbard, Virginia; Whittaker, Sean J; Edelson, Richard L; Russell-Jones, Robin

    2004-04-01

    Chronic atopic eczema is not regarded as a precursor of malignancy, and, to our knowledge, there has been only one previous case report of CD30(+) cutaneous lymphoma in association with atopic dermatitis. We report 4 cases of CD30(+) lymphoproliferative disease in young adult patients with active atopic eczema dating from early childhood. Three patients developed primary cutaneous anaplastic large cell lymphoma, of whom 2 developed systemic disease and 1 died. The other patient developed lymphomatoid papulosis type A, which resolved after withdrawal of cyclosporine therapy. No other patient had received immunosuppressive therapy. Three had been treated with phototherapy, and 2 of these patients exhibited positive immunostaining for p53 within a proportion of the tumor cell population. Although we have not been able to establish a causative link, we believe that the association of these 2 conditions has not occurred by chance. Biopsies of lesional skin from subjects with atopic eczema exhibit a proportion of CD30 cells, and clonal transformation of this subpopulation might account for the CD30(+) lymphomas in our patients.

  9. General Information about Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... and skin. There are two general types of lymphoma : Hodgkin lymphoma and non-Hodgkin lymphoma . (See the PDQ ... more information.) There are two types of childhood Hodgkin lymphoma. The two types of childhood Hodgkin lymphoma are: ...

  10. Treatment Option Overview (Childhood Hodgkin Lymphoma)

    Science.gov (United States)

    ... and skin. There are two general types of lymphoma : Hodgkin lymphoma and non-Hodgkin lymphoma . (See the PDQ ... more information.) There are two types of childhood Hodgkin lymphoma. The two types of childhood Hodgkin lymphoma are: ...

  11. Treatment Options for Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... and skin. There are two general types of lymphoma : Hodgkin lymphoma and non-Hodgkin lymphoma . (See the PDQ ... more information.) There are two types of childhood Hodgkin lymphoma. The two types of childhood Hodgkin lymphoma are: ...

  12. Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    He, Xiayun; Li, Duanshu; Hu, Chaosu; Wang, Zhuoying; Ying, Hongmei; Wu, Yi

    2014-01-01

    Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC. 13 patients with ATC who were treated by IMRT in our institution between October 2008 and February 2011, have been analyzed. The target volume for IMRT was planned to include Gross tumor volume (GTV): primary tumor plus any N + disease (66 Gy/33 F/6.6 W), with elective irradiation of thyroid bed, bilateral level II through VI and mediastinal lymph nodes to the level of the carina (54-60 Gy). Seven patients received surgical intervention and eleven patients had chemotherapy. The median radiotherapy dose to GTV was 60 Gy/30 fractions/6 weeks. The median survival time of the 13 patients was 9 months. The direct causes of death were distant metastases (75%) and progression of the locoregional disease (25%). Ten patients were spared dyspnea and tracheostomy because their primary neck lesion did not progress. The results showed that IMRT combined by surgery and chemotherapy for ATC might be beneficial to improve locoregional control. Further new therapies are needed to control metastases

  13. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro (Gunma Univ., Maebashi (Japan). School of Medicine)

    1992-04-01

    A case of anaplastic astrocytoma following radiotherapy for growth hormone secreting pituitary adenoma is presented with a review of the literature. A 43 year old female was admitted with signs of acromegaly and hypertension. An eosinophilic pituitary adenoma was subtotally removed by transsphenoidal approach, followed by 60 Gy irradiation using a 2x2 cm lateral field. Fourteen years later at the age of 57, she suffered from headache, recent-memory disturbance and uncinate fits. CT scan and MRI disclosed ring-like enhanced mass lesion in the left temporal lobe, corresponding to the previous irradiated field. {sup 18}F-FDG PET showed hypermetabolism at the lesion. Left frontotemporal craniotomy was performed, and a reddish gray gelatinous tumor containing necrotic center and cyst was partially removed. Histologically, the tumor consisted of hypercellular astrocytic cells with perivascular pseudorosette. Coagulation necrosis at the center of the tumor, and hyalinosis and fibrosis of the blood vessels in and around the tumor, which might have been caused by the antecedent radiotherapy, were recognized. Postoperative radiotherapy and chemotherapy, were given, however, she expired 13 months after the operation. Seven cases, including ours, of malignant glioma following radiotherapy for pituitary adenoma were reported in the literature. A total dose of irradiation varies from 45 to 95 Gy with a mean of 50 Gy. The period of latency before tumor occurrence ranges from 5 to 22 years with a mean of 10 years. The differentiation of radiation-induced gliomas from radionecrosis of the brain is also discussed. (author).

  14. Membrane-associated signaling in human B-lymphoma lines

    Energy Technology Data Exchange (ETDEWEB)

    Tauzin, Sebastien; Ding, Heidrun; Burdevet, Dimitri [Department of Pathology and Immunology, Centre medical universitaire, 1, rue Michel-Servet, 1211 Geneva 11 (Switzerland); Borisch, Bettina [Department of Social and Preventive Medicine, Centre medical universitaire, 1, rue Michel-Servet, 1211 Geneva 11 (Switzerland); Hoessli, Daniel C., E-mail: danielhoessli@gmail.com [Department of Pathology and Immunology, Centre medical universitaire, 1, rue Michel-Servet, 1211 Geneva 11 (Switzerland)

    2011-01-15

    In B-non-Hodgkin lymphomas, Lyn and Cbp/PAG constitute the core of an oncogenic signalosome that captures the Phosphatidylinositol-3-kinase, the Spleen tyrosine kinase and the Signal transducer and activator of transcription-3 to generate pro-survival and proliferative signals. Lymphoma lines corresponding to follicular, mantle-cell and Burkitt-derived lymphomas display type-specific signalosome organizations that differentially activate PI3K, Syk and STAT3. In the follicular lymphoma line, PI3K, Syk and STAT3 were optimally activated upon association with the Lyn-Cbp/PAG signalosome, while in the Burkitt lymphoma-derived line, the association with Cbp/PAG and activation of PI3K were interfered with by the latent membrane proteins encoded by the Epstein-Barr virus. In the Jeko-1 mantle-cell line, a weak association of Syk with the Lyn-Cbp/PAG signalosome resulted in poor activation of Syk, but in those cells, as in the follicular and Burkitt-derived lines, efficient apoptosis induction by the Syk inhibitor R406 indicated that Syk is nonetheless an important prosurvival element and therefore a valuable therapeutic target. In all configurations described herein is the Lyn-Cbp/PAG signalosome independent of external signals and provides efficient means of activation for its associated lipid and protein kinases. In follicular and Burkitt-derived lines, Syk appears to be activated following binding to Cbp/PAG and no longer requires B-cell receptor-associated activation motifs for activation. Assessment of the different modalities of Lyn-Cbp/PAG signalosome organization could help in selecting the appropriate combination of kinase inhibitors to eliminate a particular type of lymphoma cells.

  15. Involvement of Cot activity in the proliferation of ALCL lymphoma cells.

    Science.gov (United States)

    Fernández, Margarita; Manso, Rebeca; Bernaldo de Quirós, Flavia; Bernáldez, Flavia; López, Pilar; Martín-Duce, Antonio; Alemany, Susana

    2011-08-12

    Anaplastic large-cell lymphoma (ALCL) cells overexpress CD30 on their cell surface, show increased levels of activated Erk1/2 and of JunB; participating JunB in the proliferative capacity of these lymphomas. Here, we show that ALCL lymphoma cells also present high expression levels of the proto-oncogenic Cot (MAP3K8). Using pharmacological drugs as well as the RNA interference technique we show that Cot protein is responsible for the constitutive Erk1/2 activation in the ALCL lymphoma cells, SUDHL-1. Besides, inhibition of Cot activity reduces the number of cell divisions which is achieved, at least in part, by the control that Cot exercises on the activation state of p70 S6K and on the expression levels of JunB. Since Cot represents an alternative mode, independently of RAF, to activate Erk1/2, all these data strongly suggest that molecular targeting of Cot may be a potential new specific strategy for ALCL lymphomas therapy, without the fully disturbance of the Erk1/2 function. Copyright © 2011. Published by Elsevier Inc.

  16. Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

    International Nuclear Information System (INIS)

    Eberhart, Charles G; Chaudhry, Aneeka; Daniel, Richard W; Khaki, Leila; Shah, Keerti V; Gravitt, Patti E

    2005-01-01

    p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein

  17. World Health Organisation Classification of Lymphoid Tumours in Veterinary and Human Medicine: a Comparative Evaluation of Gastrointestinal Lymphomas in 61 Cats.

    Science.gov (United States)

    Wolfesberger, B; Fuchs-Baumgartinger, A; Greß, V; Hammer, S E; Gradner, G; Knödl, K; Tichy, A; Rütgen, B C; Beham-Schmid, C

    2018-02-01

    To diagnose and classify the various entities of lymphomas, the World Health Organisation (WHO) classification is applied in human as well as in veterinary medicine. We validated the concordance of these classification systems by having a veterinary and human pathologist evaluate gastrointestinal lymphoma tissue from 61 cats. In 59% of all cases, there was a match between their respective diagnoses of the lymphoma subtype. A complete consensus between the two evaluators was obtained for all samples with a diagnosis of diffuse large B-cell lymphoma, T-cell anaplastic large cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. A corresponding diagnosis was also made in the majority of samples with enteropathy associated T-cell lymphoma (EATL) type II, although this subtype in cats has similarities to the 'indolent T-cell lymphoproliferative disorder of the gastrointestinal tract', a provisional entity newly added to the revised human WHO classification in 2016. Very little consensus has been found with cases of EATL type I due to the fact that most did not meet all of the criteria of human EATL I. Hence, the human pathologist assigned them to the heterogeneous group of peripheral T-cell lymphomas (not otherwise specified). Consequently, concrete guidelines and advanced immunophenotyping based on the model of human medicine are essential to differentiate these challenging entities in veterinary medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. TrkAIII Promotes Microtubule Nucleation and Assembly at the Centrosome in SH-SY5Y Neuroblastoma Cells, Contributing to an Undifferentiated Anaplastic Phenotype

    Science.gov (United States)

    Farina, Antonietta R.; Di Ianni, Natalia; Cappabianca, Lucia; Ruggeri, Pierdomenico; Ragone, Marzia; Ianni, Giulia; Gulino, Alberto; Mackay, Andrew R.

    2013-01-01

    The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs) and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α-tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC. PMID:23841091

  19. TrkAIII Promotes Microtubule Nucleation and Assembly at the Centrosome in SH-SY5Y Neuroblastoma Cells, Contributing to an Undifferentiated Anaplastic Phenotype

    Directory of Open Access Journals (Sweden)

    Antonietta R. Farina

    2013-01-01

    Full Text Available The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α-tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC.

  20. Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Prasongsook, Naiyarat; Kumar, Aditi; Chintakuntlawar, Ashish V; Foote, Robert L; Kasperbauer, Jan; Molina, Julian; Garces, Yolanda; Ma, Daniel; Wittich, Michelle A Neben; Rubin, Joseph; Richardson, Ronald; Morris, John; Hay, Ian; Fatourechi, Vahab; McIver, Bryan; Ryder, Mabel; Thompson, Geoffrey; Grant, Clive; Richards, Melanie; Sebo, Thomas J; Rivera, Michael; Suman, Vera; Jenkins, Sarah M; Smallridge, Robert C; Bible, Keith C

    2017-12-01

    Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. MMT appears to convey longer survival in ATC among patients with stage IVA/B disease. Copyright © 2017 Endocrine Society

  1. Anaplastic Thyroid Cancer: Experience of the Philippine General Hospital.

    Science.gov (United States)

    Lo, Tom Edward; Jimeno, Cecilia Alegado; Paz-Pacheco, Elizabeth

    2015-06-01

    Anaplastic thyroid cancer (ATC) is a rare type of thyroid malignancy and one of the most aggressive solid tumors, responsible for between 14% and 50% of the total annual mortality associated with thyroid cancer. A retrospective study was made of all ATC cases diagnosed by biopsy in the Philippine General Hospital between 2008 and 2013. A total of 15 patients were identified, with a median age at diagnosis of 63 years. All tumors were at least 6 cm in size upon diagnosis. All patients had a previous history of thyroid pathology, presenting with an average duration of 11 years. Eleven patients presented with cervical lymphadenopathies, whereas seven exhibited signs of distant metastases, for which the lungs appeared to be the most common site. More than 70% of the patients presented with a rapidly growing neck mass, leading to airway obstruction. Only three patients were treated using curative surgery; the majority received palliative and supportive forms of treatment. In addition, only three patients were offered radiotherapy. Chemotherapy was not offered to any patient. Only two patients were confirmed to still be alive during the study period. The median survival time for the other patients was 3 months; in the majority of cases the patient died within the first year following diagnosis. Our experience with ATC demonstrated concordance with other institutions with respect to current clinical profile, presentation, and prognosis. An absence of distant metastases and lymph node involvement was associated with improved survival outcomes, whereas age at diagnosis and tumor size did not affect survival. Curative surgery offers the most effective means of prolonging survival. Radiotherapy and chemotherapy in combination with surgery represents a promising treatment strategy.

  2. PET CT and lymphomas

    International Nuclear Information System (INIS)

    Castro, R.

    2012-01-01

    This presentation is about Tc and lymphomas. Classification and clinical cases of various cancer such as gastro duodenal or ulcer, mama, medullary, lymph and neck, leukemia, nodular sclerosis. Metabolic information, anatomical nature of lymphoma and its clinical presentation determine the extent that PET should be used in the patient.

  3. Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient

    Directory of Open Access Journals (Sweden)

    Zeliha Esin Celik

    2016-01-01

    Full Text Available Kaposi sarcoma (KS, a vascular tumor caused by infection with human herpesvirus 8 (HHV8, is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence and metastatic potential. We report here a 47-year-old HIV negative male presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenal KS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS without mucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient.

  4. Novel Bruton's tyrosine kinase inhibitors currently in development

    Directory of Open Access Journals (Sweden)

    D'Cruz OJ

    2013-03-01

    Full Text Available Osmond J D'Cruz,1 Fatih M Uckun1,21Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA; 2Department of Pediatrics, University of Southern California, Los Angeles, CA, USAAbstract: Bruton's tyrosine kinase (Btk is intimately involved in multiple signal-transduction pathways regulating survival, activation, proliferation, and differentiation of B-lineage lymphoid cells. Btk is overexpressed and constitutively active in several B-lineage lymphoid malignancies. Btk has emerged as a new antiapoptotic molecular target for treatment of B-lineage leukemias and lymphomas. Preclinical and early clinical results indicate that Btk inhibitors may be useful in the treatment of leukemias and lymphomas.Keywords: tyrosine kinase, personalized therapy, kinase inhibitors, Btk, leukemia, lymphoma

  5. Large B-cell lymphoma arising in cardiac myxoma or intracardiac fibrinous mass: a localized lymphoma usually associated with Epstein-Barr virus?

    Science.gov (United States)

    Aguilar, Cristian; Beltran, Brady; Quiñones, Pilar; Carbajal, Tomas; Vilcapaza, Jorge; Yabar, Alejandro; Segura, Pedro; Quintanilla-Martinez, Leticia; Miranda, Roberto N; Castillo, Jorge J

    2015-01-01

    Primary cardiac neoplasms are rare. However, among them, cardiac myxoma is the most common tumor. In contrast, primary cardiac lymphoma within a cardiac myxoma is extremely rare and might be difficult to diagnose because of non-specific clinical manifestations. We report the case of a previously healthy 52-year-old man who presented with acute onset of transient dysarthria and left hemiplegia. A transthoracic echocardiography showed a 6×2.5-cm solid mass in the left atrium, which was subsequently resected. Histological, immunohistochemical, and molecular analyses revealed an EBV-associated CD30-positive large B-cell lymphoma with anaplastic morphology within a cardiac myxoma and fibrinous material. Staging studies showed no evidence of lymphoma elsewhere. The patient achieved complete remission and is alive 42 months after diagnosis, and did not receive chemotherapy. We discuss the clinical and pathologic features of lymphoma arising in cardiac myxoma or in intra-atrial fibrinoid mass and the potential role of IL-6 in its pathogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Hodgkin Lymphoma Mimicking Osteomyelitis

    Directory of Open Access Journals (Sweden)

    Aneela Majeed

    2017-06-01

    Full Text Available Hodgkin lymphoma with symptomatic osseous involvement can have a similar presentation to osteomyelitis. Common findings in symptoms, laboratory workup, and imaging can make it very difficult to distinguish between the two diseases. Excisional biopsy should be pursued if fine-needle biopsy is equivocal and suspicion of lymphoma is high. We report a case of a 40-year-old man who presented with a history of marine animal sting on his neck and later developed erythema in the area, chest pain, constitutional symptoms, adenopathy, and imaging classic for sternal osteomyelitis. Fortunately, initial biopsy prompted the possibility of lymphoma, and further workup was initiated, which confirmed Hodgkin lymphoma. This case is a good reminder that malignancies and infections can share many common features, and keeping a broad differential diagnosis can be lifesaving. Proper staging and risk stratification of Hodgkin lymphoma help determine the optimal treatment.

  7. [Secondary orbital lymphoma].

    Science.gov (United States)

    Basanta, I; Sevillano, C; Álvarez, M D

    2015-09-01

    A case is presented of an 85 year-old Caucasian female with lymphoma that recurred in the orbit (secondary ocular adnexal lymphoma). The orbital tumour was a diffuse large B-cell lymphoma according to the REAL classification (Revised European-American Lymphoma Classification). Orbital lymphomas are predominantly B-cell proliferations of a variety of histological types, and most are low-grade tumours. Patients are usually middle-aged or elderly, and it is slightly more common in women. A palpable mass, proptosis and blepharoptosis are the most common signs of presentation. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  8. What's the Difference between Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma?

    Science.gov (United States)

    ... What's the difference? What's the difference between Hodgkin's lymphoma and non-Hodgkin's lymphoma? Answers from Rajiv K. Pruthi, M.B.B.S. Both Hodgkin's lymphoma and non-Hodgkin's lymphoma are lymphomas — a type of cancer that ...

  9. Primary extra nodal non Hodgkin lymphoma: a 5 year retrospective analysis.

    Science.gov (United States)

    Padhi, Somanath; Paul, Tara Roshni; Challa, Sundaram; Prayaga, Aruna K; Rajappa, Senthil; Raghunadharao, D; Sarangi, Rajlaxmi

    2012-01-01

    The incidence of extra nodal non Hodgkin lymphoma (ENL) is rising throughout the world. However, data regarding ENL as a group is limited. The aim was to study the epidemiological and histomorphological trends of primary ENL (pENL) in India. The biopsy materials from sixty eight patients with pENL (45 male, 23 female, M:F= 1.9:1), diagnosed over a five year period (2005-2009), were analysed and pathologically reclassified according to the World Health Organization (WHO) classification, 2008 criteria. Primary extra nodal non Hodgkin lymphomas constituted 22.0% (68/308) of all non Hodgkin lymphomas (NHL). The mean age at presentation for pENL and primary nodal NHL was 43 years and 58 years, respectively with a male predilection (M: F=2:1). Central nervous system (CNS) constituted the most common extranodal site (20/68, 29.5%) followed by gastrointestinal tract (17/68, 25%), and nose/nasopharynx (8/68, 11.8%). Diffuse large B-cell lymphoma (DLBCL, not otherwise specified), extranodal marginal lymphoma of mucosa associated lymphoid tissue (MALT) type, and B cell NHL unclassified (U) were the three most common histological types observed. T-cell phenotype was rarely noted (4%). Follicular lymphomas and anaplastic large cell lymphoma, seen among nodal NHL, were absent at extra nodal sites. Majority (41/68, 60%) of the patients with pENL were immunocompetent and 55% were in stage I-II with favorable prognosis. Central nervous system was the most common site of ENL, followed by gastrointestinal tract. Majority of pENL occurred in immunocompetent hosts with a favorable prognosis.

  10. Anaplastic Thyroid Cancer in Sicily: The Role of Environmental Characteristics

    Directory of Open Access Journals (Sweden)

    Martina Tavarelli

    2017-10-01

    Full Text Available BackgroundAnaplastic thyroid cancer (ATC is a rare but extremely aggressive cancer of the thyroid, contributing up to 30–40% of thyroid cancer-specific mortality. We analyzed ATC characteristics and survival rates in Sicily to evaluate the possible influence of environmental factors. With this aim, data regarding ATC incidences in urban/rural and industrial, iodine-deficient, and volcanic vs control areas were compared in Sicily as well as ATC data from Sicily and USA.MethodsUsing the Sicilian Register of Thyroid Cancer (SRTC database incidence, age, gender, tumor size and histotype, extrathyroidal extension, stage, and coexistence with pre-existing differentiated thyroid cancer (DTC were evaluated in different areas of Sicily and also compared with Surveillance Epidemiology and End Results data in USA.ResultsForty-three ATCs were identified in Sicily in the period 2002–2009. In our series only age <70 years at diagnosis (p = 0.01, coexistence with DTC (p = 0.027 and tumor size ≤6 cm (p = 0.012 were significant factors for increased survival at univariate analysis (only age at multivariate analysis. No difference in ATC incidence was found in urban vs rural areas and in iodine-deficient and industrial vs control areas. By contrast, in the volcanic area of Sicily, where DTC incidence is doubled relative to the rest of the island, also ATC incidence was increased. ATC data in Sicily were similar to those reported in the same period in the USA where overall survival rate at 6 and 12 months, however, was smaller.ConclusionThe similar ATC data observed in Sicily and USA (having different genetic background and lifestyle and the increased ATC incidence in the volcanic area of Sicily paralleling the increased incidence of papillary thyroid cancer are compatible with the possibility that casual additional mutations, more frequent in a background of increased cell replication like DCT, are the major causes of ATC rather than

  11. Lymphoma-clinical questions

    Energy Technology Data Exchange (ETDEWEB)

    Kim, H. C. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    2002-07-01

    Lymphoma is a group of neoplastic disease of lymphoid tissues, which can be classified into categories of Hodgkin's disease and non-Hodgkin's lymphoma(NHL). Prognosis of lymphoma depends on the extent of disease (staging) especially in Hodgkin's disease, but also depends on the histologic make up in non-Hodgkin's lymphoma. Although non-Hodgkin's lymphoma is a neoplastic transformation of lymphoid cell it is a collection of disease with morphologically and immunologically diverse make up. Consequently the classification of NHL has changed frequently and evolved according to the progress of immunologic and molecular knowledge added to the original morphologic classification. Lymphoma is a disorder sensitive to chemotherapy which often leads to cure of the disease even in advanced stage, while many other patients die from the progression of disease. Therefore, better understanding in newer classification and sensitive imaging technique, such as PET, in lymphoma will likely lead to the improvement of survival rate.

  12. Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-23

    Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  13. Radiotherapy for Hodgkin lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Specht, Lena [Rigshospitalet Copenhagen Univ. (Denmark). Depts. of Oncology and Haematology; Yahalom, Joachim (eds.) [Memorial Sloan-Kettering Cancer, New York, NY (United States). Dept. of Radiation Oncology

    2011-07-01

    This book deals in detail with all aspects of the best practice in modern radiotherapy for Hodgkin lymphoma. It provides the background and rationale for the inclusion of radiotherapy in today's combined-modality approach, including special clinical situations such as Hodgkin lymphoma in children, in the pregnant patient, and in the elderly. Radiotherapy planning using state-of-the-art imaging, target definition, planning software, and treatment equipment is expounded in detail. Acute and long-term side effects of radiotherapy are analyzed, and the implications for modern radiotherapy approaches in Hodgkin lymphomas are explained. (orig.)

  14. Radiotherapy for Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Specht, Lena; Yahalom, Joachim

    2011-01-01

    This book deals in detail with all aspects of the best practice in modern radiotherapy for Hodgkin lymphoma. It provides the background and rationale for the inclusion of radiotherapy in today's combined-modality approach, including special clinical situations such as Hodgkin lymphoma in children, in the pregnant patient, and in the elderly. Radiotherapy planning using state-of-the-art imaging, target definition, planning software, and treatment equipment is expounded in detail. Acute and long-term side effects of radiotherapy are analyzed, and the implications for modern radiotherapy approaches in Hodgkin lymphomas are explained. (orig.)

  15. Hemangioendothelioma of the thyroid gland--true endothelioma or anaplastic carcinoma?

    Science.gov (United States)

    Krisch, K; Holzner, J H; Kokoschka, R; Jakesz, R; Niederle, B; Roka, R

    1980-12-01

    After a critical histological re-examination of 26 cases of malignant hemangioendothelioma of the thyroid, and a comparison with 51 cases of anaplastic spindle and giant cell carcinoma, it becomes obvious that traumatic and shrinkage artefacts due to fixation, as well as superimposition of neoplastic and repair processes due to regressive changes--almost always seen in malignant hemangioendothelioma associated nodular goiter--may be misinterpreted as neoplastic vascular spaces (and therefore angioblastic tumour differentiation). Focal epithelial arrangements of tumour cells often observed in these malignant hemangioendotheliomas and the lack of objective light microscopic differential diagnostic criteria of anaplastic spindle and giant cell carcinoma make the high incidence of endotheliomas of the thyroid in European endemic goiter regions very questionable. Compared with anaplastic spindle and giant cell carcinoma, the incidence for (1) extrathyroid tumours that infiltrate into the trachea or the oesophagus, (2) lymph node metastases and (3) distant metastases is not statistically different in malignant hemangioendothelioma. Therefore we conclude that the tumours classified as malignant hemangioendothelioma in goitrous areas represent a special growth pattern of anaplastic spindle and giant cell carcinoma within adenomatous glands rather than a distinct tumour type.

  16. Primary bony non-Hodgkin lymphoma of the cervical spine: a case report

    Directory of Open Access Journals (Sweden)

    Sedrak Mark F

    2010-02-01

    Full Text Available Abstract Introduction Non-Hodgkin lymphoma primarily originating from the bone is exceedingly rare. To our knowledge, this is the first report of primary bone lymphoma presenting with progressive cord compression from an origin in the cervical spine. Herein, we discuss the unusual location in this case, the presenting symptoms, and the management of this disease. Case presentation We report on a 23-year-old Caucasian-American man who presented with two months of night sweats, fatigue, parasthesias, and progressive weakness that had progressed to near quadriplegia. Magnetic resonance (MR imaging demonstrated significant cord compression seen primarily at C7. Surgical management, with corpectomy and dorsal segmental fusion, in combination with adjuvant chemotherapy and radiation therapy, halted the progression of the primary disease and preserved neurological function. Histological analysis demonstrated an aggressive anaplastic large cell lymphoma. Conclusion Isolated primary bony lymphoma of the spine is exceedingly rare. As in our case, the initial symptoms may be the result of progressive cervical cord compression. Anterior corpectomy with posterolateral decompression and fusion succeeded in preventing progressive neurologic decline and maintaining quality of life. The reader should be aware of the unique presentation of this disease and that surgical management is a successful treatment strategy.

  17. Non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Glatstein, E.; Wasserman, T.H.

    1987-01-01

    Non-Hodgkin's lymphomas are a varied and complex group of diseases that must be distinguished from Hodgkin's disease. The latter almost always begins in lymph nodes and spreads primarily in an axial fashion; non-Hodgkin's lymphomas may begin either in lymph nodes or in extranodal tissue and can spread both in an axial fashion and centrifugally. Because of changes in pathology terminology and the introduction of a classification using cell surface markers, many prognostic groups of patients with lymphomas have evolved. Therapeutic choices and prognosis are greatly influenced by variations in anatomic sites and extent of disease. Currently, the decisions on management require a balancing of radiation therapy with systemic chemotherapy. In some cases, radiation therapy alone may be sufficient; however, because most patients with non-Hodgkins's lymphomas tend to have advanced disease, a large percentage of patients will be managed with chemotherapy alone or in combination with radiation therapy

  18. Leukemia & Lymphoma Society

    Science.gov (United States)

    ... Light The Night Man & Woman of the Year Leukemia Cup Regatta Student Series Lifestyle Community Careers at ... Special Projects Beat AML Patients & caregivers Disease Information Leukemia Lymphoma Myeloma Myelodysplastic Syndromes Myeloproliferative Neoplasms Childhood Blood ...

  19. Targeted therapy in lymphoma

    Directory of Open Access Journals (Sweden)

    Cavalli Franco

    2010-11-01

    Full Text Available Abstract Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma.

  20. Primary breast lymphomas.

    Science.gov (United States)

    Julen, Olivier; Dellacasa, Ilaria; Pelte, Marie-Françoise; Borish, Bettina; Bouchardy, Christine; Capanna, Federica; Vlastos, Georges; Dubuisson, Jean-Bernard; Vlastos, Anne-Thérèse

    2009-07-22

    The diagnosis, prognostic factors, and optimal management of primary breast lymphomas (PBL) is difficult. Seven patients recorded at the Geneva Cancer Registry between 1973-1998 were reviewed. Five patient had diffuse large B-cell lymphoma, one a follicular lymphoma and one a MALT-lymphoma. All patients had clinical and radiological findings consistent with breast cancer and underwent mastectomy, which is not indicated in PBL. Diagnosis should be established prior to operative interventions, as fine needle aspiration missed the diagnosis for one patient and intra-operative frozen sections for 3 patients in our study. Five-year and 10-year overall survivals were 57% and 15%, respectively. Of the 3 patients who died from PBL, 2 had tumors that were Bcl-2 positive but Bcl-6 negative. All 3 surviving patients have positive Bcl-2 and Bcl-6 immunostaining, which could be important prognostic factors if confirmed by a larger study.

  1. Primary breast lymphomas

    Directory of Open Access Journals (Sweden)

    Anne-Thérèse Vlastos

    2009-07-01

    Full Text Available The diagnosis, prognostic factors, and optimal management of primary breast lymphomas (PBL is difficult. Seven patients recorded at the Geneva Cancer Registry between 1973-1998 were reviewed. Five patient had diffuse large B-cell lymphoma, one a follicular lymphoma and one a MALT-lymphoma. All patients had clinical and radiological findings consistent with breast cancer and underwent mastectomy, which is not indicated in PBL. Diagnosis should be established prior to operative interventions, as fine needle aspiration missed the diagnosis for one patient and intra-operative frozen sections for 3 patients in our study. Five-year and 10-year overall survivals were 57% and 15%, respectively. Of the 3 patients who died from PBL, 2 had tumors that were Bcl-2 positive but Bcl-6 negative. All 3 surviving patients have positive Bcl-2 and Bcl-6 immunostaining, which could be important prognostic factors if confirmed by a larger study.

  2. Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Teens For Kids For Parents MORE ON THIS TOPIC Dealing With Cancer Cancer Center Cancer: Readjusting to Home and School Blood Transfusions Stem Cell Transplants Hodgkin Lymphoma Types of Cancer ...

  3. Primary thyroid lymphomas

    International Nuclear Information System (INIS)

    Mazur-Roszak, M.; Litwiniuk, M.; Lacka, K.

    2007-01-01

    Primary thyroid lymphoma (PTL) is a rare disease with heterogeneous histological and clinical characteristics. As a result, diagnosis and subsequent management of the disease is difficult. PTL occurs most commonly in the thyroid glands with a background of Hashimotos thyroiditis. The clinical presentation was usually an enlarging neck mass squeezing the surrounding structures. Most patients can be diagnosed by fine-needle aspiration (FNA) followed by immuno phenotypic analysis, obviating the need for open surgical biopsy. Main histopathologic subtypes are either diffuse large B cell lymphomas (DLBCL) or mucosa-associated lymphoid tissue (MALT). Patients with localised, low-grade MALT lymphomas may be treated with surgery. Postoperative chemotherapy or radiotherapy is necessary in some patients. Systemic chemotherapy is the optimal treatment for DLBCL. In this group surgery may be used for palliative debulking to alleviate obstructive symptoms. Prognosis for MALT lymphoma is good. Diffuse large B cell lymphoma patients have poor prognosis (5-yr survival <50%). What should be stressed here is that patients with rapidly growing nodular goitre with or without cervical adenopathy should always be examined for primary thyroid lymphoma. (authors)

  4. [Primary vitreoretinal lymphoma].

    Science.gov (United States)

    Jaehne, D; Coupland, S E

    2018-04-01

    Primary vitreoretinal lymphoma (PVRL) is the most common intraocular lymphoma. It is a high grade malignant B‑cell lymphoma, which is thought to arise in the retina. It often infiltrates the central nervous system (CNS) and is therefore associated with a poor prognosis. The PVRL must be differentiated from other forms of intraocular lymphoma, such as the low-grade B‑cell lymphoma that rarely arises in the choroid. The choroidal lymphomas do not spread to the brain, they can be treated with low-dose external beam radiotherapy and the patients have a good prognosis. Since PVRL is a relatively rare tumor, there is little information with respect to its true incidence, to any geographical or ethnic variability and to the main risk factors apart from an association with immunosuppression, as a result of HIV or Epstein-Barr virus infections. The treatment of PVRL is very variable between oncology centres and is also dependent on the unilaterality or bilaterality of disease and whether there is any concomitant CNS involvement. Further studies and research projects in this field are necessary in order to diagnose PVRL at an early stage and to develop new targeted individualized treatment.

  5. Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead.

    Science.gov (United States)

    Minard-Colin, Véronique; Brugières, Laurence; Reiter, Alfred; Cairo, Mitchell S; Gross, Thomas G; Woessmann, Wilhelm; Burkhardt, Birgit; Sandlund, John T; Williams, Denise; Pillon, Marta; Horibe, Keizo; Auperin, Anne; Le Deley, Marie-Cécile; Zimmerman, Martin; Perkins, Sherrie L; Raphael, Martine; Lamant, Laurence; Klapper, Wolfram; Mussolin, Lara; Poirel, Hélène A; Macintyre, Elizabeth; Damm-Welk, Christine; Rosolen, Angelo; Patte, Catherine

    2015-09-20

    Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse. © 2015 by American Society of Clinical Oncology.

  6. Management of mantle cell lymphoma in the elderly: current and potential strategies.

    Science.gov (United States)

    Vignon, Marguerite; Venon, Marie-Dominique; Hermine, Olivier; Delarue, Richard

    2013-12-01

    Mantle cell lymphoma is a distinct subtype of B-cell non-Hodgkin lymphoma, accounting for 3-10 % of all non-Hodgkin lymphoma cases. The median age at diagnosis is nearly 70 years. The prognosis of patients is based on the Mantle Cell Lymphoma International Prognostic Index, which is calculated on the basis of four independent prognostic factors (age, performance status, serum lactate dehydrogenase and leukocyte count). Treatment of elderly patients with de novo untreated mantle cell lymphoma is based on rituximab combined with chemotherapy. The most commonly used regimen is the classical CHOP21 (cyclophosphamide, doxorubicin, vincristine and prednisone) regimen. Bendamustine is also an option, especially for patients with cardiac comorbidities. In elderly patients who are relatively young and fit, an approach based on treatment usually used for younger patients, with cytarabine-based induction followed by autologous stem cell transplantation, should be discussed. Treatment of relapsing patients is based on the use of newer effective drugs, including bortezomib, lenalidomide and thalidomide, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus. These drugs are often combined with rituximab and can be prescribed in combination with chemotherapy. Promising new drugs are Bruton tyrosine kinase inhibitors and other inhibitors of the phosphoinositide 3-kinase (PI3K)-mTOR-protein kinase B (AKT) pathway. Despite these new advances, mantle cell lymphoma remains an incurable disease, and further basic and clinical research is warranted.

  7. Lymphoma risk in systemic lupus

    DEFF Research Database (Denmark)

    Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Joseph, Lawrence

    2014-01-01

    to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. CONCLUSIONS: In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma......OBJECTIVE: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). METHODS: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated...... (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. RESULTS: We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma...

  8. The Danish National Lymphoma Registry

    DEFF Research Database (Denmark)

    Arboe, Bente; El-Galaly, Tarec Christoffer; Clausen, Michael Roost

    2016-01-01

    of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000-2012 were included. The positive predictive......BACKGROUND: The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically assessed. AIM: To test the coverage and data...... was good with high PPVs (87% to 100%), and high completeness (92% to 100%). CONCLUSION: The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research....

  9. Immunohistochemical Characterization of Canine Lymphomas

    Directory of Open Access Journals (Sweden)

    Roxana CORA

    2017-11-01

    Full Text Available Lymphomas occur by clonal expansion of lymphoid cells and have distinctive morphological and immunophenotypic features. Determination of canine lymphoma immunophenotype is useful for accurate prognosis and further therapy. In the suggested study, we performed an immunohistochemical evaluation of some cases with canine lymphoma diagnosed in the Department of Pathology (Faculty of Veterinary Medicine, Cluj-Napoca, Romania, in order to characterize them. The investigation included 39 dogs diagnosed with different anatomical forms of lymphoma, following necropsy analysis or assessment of biopsies. The diagnosis of lymphoma was confirmed by necropsy and histopathology (Hematoxylin-eosin stain examinations. The collected specimens were analyzed by immunohistochemistry technique (automatic method using the following antibodies: CD3, CD20, CD21 and CD79a. The analyzed neoplasms were characterized as follows: about 64.10% of cases were diagnosed as B-cell lymphomas, 33.34% of cases as T-cell lymphomas, whereas 2.56% of cases were null cell type lymphomas (neither B nor T. Most of multicentric (80%, mediastinal (60% and primary central nervous system lymphomas (100% had B immunophenotype, while the majority of cutaneous (80% and digestive (100% lymphomas had T immunophenotype. Immunohistochemical description of canine lymphomas can deliver some major details concerning their behavior and malignancy. Additionally, vital prognosis and efficacy of some therapeutic protocols are relying on the immunohistochemical features of canine lymphoma.

  10. Nodular breast lymphoma

    International Nuclear Information System (INIS)

    Rodriguez, M.; Sahagun, E.; Pena, J.; Mendez, J.

    1996-01-01

    We attempt to correlate the histological types [in three cases of B-cell non-Hodgkin's lymphoma (NHL), one case of T-cell NHL and one of Hodgkin's disease] with the radiological presentation and compare our findings with the literature reviewed. Among the mammographic studies, performed over and 18-month period, we have assessed five patients (four women and one man, aged as having lymphoma. the man presented bilateral involvement. Both mammography and a broader study with ultrasound and chest and abdominal CT scan were performed in every case. Four patients underwent breast ultrasound. The definitive diagnosis was based on biopsy in all cases. Three of the five cases involved primary lymphomas and the other two were secondary. Four patients presented NHL and the remaining patient had Hodgkin's disease. In mammography, the nodules showed different degrees of margin definition. In ultrasound, all the lesion were hypoechoic. The radiological diagnosis of breast lymphoma is difficult in the absence of a previous diagnosis of lymphoma. This lesion should be included in the differential diagnosis in the presence of a breast nodule associated with axillary lymph nodes, especially when the latter are bilateral. (Author)

  11. p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

    Science.gov (United States)

    McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

    2014-01-01

    Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

  12. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Moira Ragazzi

    2014-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

  13. Targeting of slug sensitizes anaplastic thyroid carcinoma SW1736 cells to doxorubicin via PUMA upregulation

    OpenAIRE

    Dong, Anbing; Jiao, Xuelong; Chen, Dong; Hao, Fengyun; Zhang, Kejun

    2016-01-01

    Objective: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers and often shows resistance to multimodal therapeutic approaches. It has been shown that the transcriptional repressor Slug inhibits the chemotherapeutic agent-induced apoptosis of cancer cells. We evaluated whether targeting of Slug could augment doxorubicin (DOX)-induced apoptosis of ATC cells. We also determined changes in PUMA (p53-upregulated modulator of apoptosis) expression levels to identify poss...

  14. Mediastinal Gray Zone Lymphoma.

    Science.gov (United States)

    Bhardwaj, Mukesh; Saha, Rajat; Misra, Deepti Shuklia; Malhotra, Veena

    2015-01-01

    A 50-year-old male presented with cough and breathlessness. A positron emissoin tomography scan revealed FDG (Fluorodeoxyglucose) avid mediastinal mass. Tru-cut biopsy showed fibrotic stromal tissue with cellular infiltrate consisting of abnormal lymphoid cells and few large cells with smudged nucleus. Immunohistochemistry revealed diffuse positivity with CD20, focal positivity for CD30 and rare CD15 positive cells. Histological picture and immune profile showed overlaping features of non-Hodgkin's as well as Hodgkin's lymphoma. A diagnosis of mediastinal gray zone lymphoma was made. The patient showed a complete metabolic response to six cycles of chemotherapy.

  15. Lymphoma of the Cervix

    Directory of Open Access Journals (Sweden)

    Juanita Parnis

    2012-01-01

    Full Text Available Primary non-Hodgkins lymphoma of the uterine cervix is a very rare diagnosis. A 54-year-old woman presented with a 3-month history of postmenopausal bleeding per vaginum. On examination, a friable, fungating lesion was seen on the cervix. Histology revealed a CD 20 positive high-grade non-Hodgkin’s diffuse large B cell lymphoma from cervical biopsies and endometrial curettage. She was diagnosed as stage IE after workup and subsequently treated with six cycles of R-CHOP chemotherapy followed by radiotherapy of the involved field.

  16. Kinases and Cancer.

    Science.gov (United States)

    Cicenas, Jonas; Zalyte, Egle; Bairoch, Amos; Gaudet, Pascale

    2018-03-01

    Protein kinases are a large family of enzymes catalyzing protein phosphorylation. The human genome contains 518 protein kinase genes, 478 of which belong to the classical protein kinase family and 40 are atypical protein kinases [...].

  17. Kinases and Cancer

    OpenAIRE

    Jonas Cicenas; Egle Zalyte; Amos Bairoch; Pascale Gaudet

    2018-01-01

    Protein kinases are a large family of enzymes catalyzing protein phosphorylation. The human genome contains 518 protein kinase genes, 478 of which belong to the classical protein kinase family and 40 are atypical protein kinases [...

  18. Anaplastic transformation of metastatic papillary thyroid carcinoma at shoulder mimicking soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Seema Kaushal

    2011-01-01

    Full Text Available A 52-year-old woman presented with fracture upper end of the left humerus after trivial trauma and aspiration cytology from the lytic lesion in the upper humerus seen on X-ray revealed a metastatic papillary carcinoma from the thyroid. Total thyroidectomy confirmed the papillary carcinoma thyroid. Post-operatively, she was given radioactive iodine (I-131 ablation therapy for 8 years and was asymptomatic during this period; however, for the last 1 year, she has been complaining of swelling in the shoulder, which did not respond to palliative radiotherapy and rapidly increased in size. Disarticulation of the shoulder joint was performed, which showed anaplastic carcinoma on histopathological examination. Anaplastic transformation of papillary carcinoma at the metastatic sites is well documented in the literature and is rare. However, the same has not been reported at the shoulder and from India before. Although soft tissue sarcomas are most common at this site, however, the possibility of anaplastic transformation should be kept in the differential diagnosis of rapidly enlarging painful mass in a known case of metastatic thyroid carcinoma to prevent misdiagnosis.

  19. Renal Cell Carcinoma Metastatic to Thyroid Gland, Presenting Like Anaplastic Carcinoma of Thyroid

    Directory of Open Access Journals (Sweden)

    Khalid Riaz

    2013-01-01

    Full Text Available Background. Renal cell carcinoma (RCC has unpredictable and diverse behavior. The classic triad of hematuria, loin pain, and abdominal mass is uncommon. At time of diagnosis, 25%–30% of patients are found to have metastases. Bones, lungs, liver, and brain are the frequent sites of metastases. RCC with metastasis to the head and neck region and thyroid gland is the rarest manifestation and anaplastic carcinoma behaving metastatic thyroid mass is an extremely rare presentation of RCC. Case Presentation. A 56-year-old Saudi man with past history of right radical nephrectomy 5 years back presented with 3 months history of rapid increasing neck mass with dysphagia, presenting like anaplastic thyroid carcinoma. Tru-cut biopsy turned out to be metastatic renal cell carcinoma. Patient was treated with radiation therapy 30 Gy in 10 fractions to mass. Patient died 4 months after the discovery of anaplastic thyroid looking metastasis. Conclusion. Rapidly progressing thyroid metastases secondary to RCC are rare and found often unresectable which are not amenable to surgery. Palliative radiotherapy can be considered for such patients.

  20. A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma.

    Science.gov (United States)

    Kreisl, Teri N; Zhang, Weiting; Odia, Yazmin; Shih, Joanna H; Butman, John A; Hammoud, Dima; Iwamoto, Fabio M; Sul, Joohee; Fine, Howard A

    2011-10-01

    The purpose of this study was to evaluate the activity of single-agent bevacizumab in patients with recurrent anaplastic glioma and assess correlative advanced imaging parameters. Patients with recurrent anaplastic glioma were treated with bevacizumab 10 mg/kg every 2 weeks. Complete patient evaluations were repeated every 4 weeks. Correlative dynamic contrast-enhanced MR and (18)fluorodeoxyglucose PET imaging studies were obtained to evaluate physiologic changes in tumor and tumor vasculature at time points including baseline, 96 h after the first dose, and after the first 4 weeks of therapy. Median overall survival was 12 months (95% confidence interval [CI]: 6.08-22.8). Median progression-free survival was 2.93 months (95% CI: 2.01-4.93), and 6-month progression-free survival was 20.9% (95% CI: 10.3%-42.5%). Thirteen (43%) patients achieved a partial response. The most common grade ≥ 3 treatment-related toxicities were hypertension, hypophosphatemia, and thromboembolism. Single-agent bevacizumab produces significant radiographic response in patients with recurrent anaplastic glioma but did not meet the 6-month progression-free survival endpoint. Early change in enhancing tumor volume at 4 days after start of therapy was the most significant prognostic factor for overall and progression-free survival.

  1. Glycerol as a chemical chaperone enhances radiation-induced apoptosis in anaplastic thyroid carcinoma cells

    Directory of Open Access Journals (Sweden)

    Emoto Mie

    2002-10-01

    Full Text Available Abstract Introduction Anaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cells (8305c cells. To examine the effectiveness of glycerol in radiation induced lethality for anaplastic thyroid carcinoma 8305c cells, we performed colony formation assay and apoptosis analysis. Results Apoptosis was analyzed with Hoechst 33342 staining and DNA ladder formation assay. 8305c cells became radiosensitive when glycerol was added to culture medium before X-ray irradiation. Apoptosis was induced by X-rays in the presence of glycerol. However, there was little apoptosis induced by X-ray irradiation or glycerol alone. The binding activity of whole cell extracts to bax promoter region was induced by X-rays in the presence of glycerol but not by X-rays alone. Conclusion These findings suggest that glycerol is effective against radiotherapy of p53-mutant thyroid carcinomas.

  2. Second-generation inhibitors of Bruton tyrosine kinase

    Directory of Open Access Journals (Sweden)

    Jingjing Wu

    2016-09-01

    Full Text Available Abstract Bruton tyrosine kinase (BTK is a critical effector molecule for B cell development and plays a major role in lymphoma genesis. Ibrutinib is the first-generation BTK inhibitor. Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib. Resistance to ibrutinib was also reported. The C481S mutation in the BTK kinase domain was reported to be a major mechanism of resistance to ibrutinib. This review summarizes the clinical development of novel BTK inhibitors, ACP-196 (acalabrutinib, ONO/GS-4059, and BGB-3111.

  3. Second-generation inhibitors of Bruton tyrosine kinase.

    Science.gov (United States)

    Wu, Jingjing; Liu, Christina; Tsui, Stella T; Liu, Delong

    2016-09-02

    Bruton tyrosine kinase (BTK) is a critical effector molecule for B cell development and plays a major role in lymphoma genesis. Ibrutinib is the first-generation BTK inhibitor. Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib. Resistance to ibrutinib was also reported. The C481S mutation in the BTK kinase domain was reported to be a major mechanism of resistance to ibrutinib. This review summarizes the clinical development of novel BTK inhibitors, ACP-196 (acalabrutinib), ONO/GS-4059, and BGB-3111.

  4. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Société Francaise de Greffe de Moëlle et de Thérapie Cellulaire.

    Science.gov (United States)

    Le Gouill, Steven; Milpied, Noel; Buzyn, Agnès; De Latour, Régis Peffault; Vernant, Jean-Paul; Mohty, Mohamad; Moles, Marie-Pierre; Bouabdallah, Krimo; Bulabois, Claude-Eric; Dupuis, Jehan; Rio, Bernard; Gratecos, Nicole; Yakoub-Agha, Ibrahim; Attal, Michel; Tournilhac, Olivier; Decaudin, Didier; Bourhis, Jean-Henry; Blaise, Didier; Volteau, Christelle; Michallet, Mauricette

    2008-05-10

    Aggressive T-cell lymphomas (ATCLs) represent 10% to 15% of non-Hodgkin's lymphomas (NHLs) in adults. ATCLs show a worse prognosis than B-cell lymphomas. On behalf of the Société Française de Greffe de Moëlle et de Thérapie Cellulaire, we conducted a retrospective analysis including 77 ATCL patients who underwent allogeneic stem-cell transplantation (alloSCT). The different diagnosis included anaplastic large-cell lymphoma (ALCL; n = 27), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n = 27), angioimmunoblastic T-cell lymphoma (AITL; n = 11), hepatosplenic gamma/delta lymphoma (HSL; n = 3), T-cell granular lymphocytic leukemia (T-GLL; n = 1), nasal natural killer (NK)/T-cell lymphoma (nasal-NK/L; n = 3) or non-nasal NK/T-cell lymphoma (non-nasal-NK/L; n = 2), enteropathy-type T-cell (n = 1), and human T-lymphotropic virus (HTLV)-1 lymphoma (n = 2). Fifty-seven patients received a myeloablative conditioning regimen. Donors were human leukocyte antigen (HLA)-matched in 70 cases and related in 60 cases. Thirty-one patients were in complete remission (CR) at the time of alloSCT, whereas 26 were in partial response (PR). Five-year toxicity-related mortality (TRM) incidence was 33% (95% CI, 24% to 46%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57% (95% CI, 45% to 68%) and 53% (95% CI, 41% to 64%), respectively. In multivariate analysis, chemoresistant disease (stable, refractory, or progressing disease) at the time of alloSCT and the occurrence of severe grade 3 to 4 acute graft-versus-host disease (aGVHD) were the strongest adverse prognostic factors for OS (P = .03 and .03, respectively). Disease status at transplantation significantly influenced the 5-year EFS (P = .003), and an HLA-mismatched donor increased TRM (P = .04). We conclude that alloSCT is a potentially efficient therapy for NK/T lymphomas and is worth further investigation through prospective clinical trials.

  5. Lymphoma classification update: B-cell non-Hodgkin lymphomas.

    Science.gov (United States)

    Jiang, Manli; Bennani, N Nora; Feldman, Andrew L

    2017-05-01

    Lymphomas are classified based on the normal counterpart, or cell of origin, from which they arise. Because lymphocytes have physiologic immune functions that vary both by lineage and by stage of differentiation, the classification of lymphomas arising from these normal lymphoid populations is complex. Recent genomic data have contributed additional complexity. Areas covered: Lymphoma classification follows the World Health Organization (WHO) system, which reflects international consensus and is based on pathological, genetic, and clinical factors. A 2016 revision to the WHO classification of lymphoid neoplasms recently was reported. The present review focuses on B-cell non-Hodgkin lymphomas, the most common group of lymphomas, and summarizes recent changes most relevant to hematologists and other clinicians who care for lymphoma patients. Expert commentary: Lymphoma classification is a continually evolving field that needs to be responsive to new clinical, pathological, and molecular understanding of lymphoid neoplasia. Among the entities covered in this review, the 2016 revision of the WHO classification particularly impact the subclassification and genetic stratification of diffuse large B-cell lymphoma and high-grade B-cell lymphomas, and reflect evolving criteria and nomenclature for indolent B-cell lymphomas and lymphoproliferative disorders.

  6. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  7. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  8. Craniocerebral involvement in lymphoma

    Directory of Open Access Journals (Sweden)

    Jorge D. Correale

    1990-09-01

    Full Text Available Nine-hundred-eighty-nine patients with lymphoma were studied. Fifty-three cases (5.3% had lymphomatous craniocerebral infiltration. The principal factors of risk for this complication were: advanced stage of the lymphoma (III or IV, diffuse histiocytic, diffuse poorly differentiated lymphocytic, or mixed cellularity lymphoma histological type, bone marrow involvement, and previous systemic chemotherapy. Thirty-two per cent of the cases of meningeal lymphomatous infiltration were asymptomatic and represented autopsy findings. CT-scan was an useful test to detect brain focal parenchymatous infiltration, as opposed to meningeal infiltration. Mean survival time in patients with lymphomatous meningeal infiltration was 4.3 months, following the combined use of systemic chemotherapy, radiation therapy and intrathecal methotrexate. Two cases had primary cerebral lymphoma, although without associated immunodeficiency Twenty patients (2% had intracranial hemorrhage, in clear relationship with platelet alterations. Fifteen patients (1.5% had CNS infection, caused by common bacteriae or opportunistic agents. In 7 cases, the diagnosis was made at autopsy. Thirty-six autopsies were performed. In 8 cases (22%, pathologic findings such as, demyelination, microcalcificat ons, coagulative necrosis, or gliosis, suggested complications from treatment.

  9. Ocular Adnexal Follicular Lymphoma

    DEFF Research Database (Denmark)

    Rasmussen, Peter K; Coupland, Sarah E; Finger, Paul T

    2014-01-01

    IMPORTANCE The clinical features of the follicular subtype of ocular adnexal lymphoma (OAL) have not been previously evaluated in a large cohort. OBJECTIVE To characterize the clinical features of follicular OAL. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective multicenter study tha...

  10. Primary splenic lymphoma

    International Nuclear Information System (INIS)

    Aslam, M.; Salamat, N.; Mamoon, N.; Ahmed, M.

    2006-01-01

    A middle-aged lady presented with fever and splenomegaly and had been provisionally treated for malaria, typhoid and tuberculosis. Diagnostic splenectomy was performed which revealed diffuse large cell lymphoma, B type, localized to spleen. Patient had remission of disease after splenectomy. (author)

  11. Lenalidomide and Blinatumomab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-19

    CD19 Positive; Mediastinal Lymphoma; Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma

  12. Musculosceletal lymphomas; Muskuloskelettale Lymphome

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, K. [Institut fuer Klinische Radiologie, Universitaetsklinikum Muenster (Germany)

    2002-12-01

    Primary lymphomas of bone or skeletal muscle are rare entities. The most frequent among these diseases are primary non-Hodgkin's lymphomas of bone. They account for 3-5% of all bone tumors and 5% of all primary extranodal non-Hodgkin's lymphomas. Primary manifestations of Hodgkin's disease in bone or skeletal muscle are rarities. Primary non-Hodgkin's lymphomas of skeletal muscle are rarities as well.Primary non-Hodgkin's lymphomas of bone can be found in any patient age. A preference exists for the 3.-6. decade of life. The radiographic appearance of these entities resembles other aggressive bone tumors.Their differential diagnosis includes - depending on the patient's age - Ewing's sarcoma,malignant fibrous histiocytoma,metastases of small cell tumors and osteomyelitis.Further differential diagnoses are the peripheral primitiv neuroektodermal tumor (PNET), osteosarcoma, eosinophilic granuloma and fibrosarcoma.Treatment of primary non-Hodgkin's lymphomas uses combinations of chemotherapy and radiation therapy.Operative treatment is reserved for the treatment of complications.The prognosis of primary non-Hodgkin's lymphomas is reflected by 10-year-survival-rates without recurrence of more than 80% in unifocal manifestations. (orig.) [German] Primaere Lymphome des Knochens oder der Skelettmuskulatur sind seltene Erkrankungen. Unter ihnen am haeufigsten sind primaere Non-Hodgkin-Lymphome des Knochens. Sie machen 3-5% aller Knochentumoren und 5% aller primaer extranodalen Non-Hodgkin-Lymphome aus. Primaere Manifestationen des Morbus Hodgkin in Knochen oder Muskulatur sind Raritaeten, genauso wie primaere Non-Hodgkin-Lymphome der Skelettmuskulatur.Primaere Non-Hodgkin-Lymphome des Knochens koennen in jedem Lebensalter vorkommen. Eine Bevorzugung besteht fuer die 3.-6.Lebensdekade. Ihr radiographisches Erscheinungsbild aehnelt dem anderer aggressiv wachsender Knochentumoren. Differenzialdiagnostisch abzugrenzen sind sie - in

  13. Four Lymphomas in 1 Patient: A Unique Case of Triple Composite Non-Hodgkin Lymphoma Followed by Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Tennese, Alysa; Skrabek, Pamela J; Nasr, Michel R; Sekiguchi, Debora R; Morales, Carmen; Brown, Theresa C; Weisenburger, Dennis D; Perry, Anamarija M

    2017-05-01

    Composite lymphomas consist of 2 or more distinct lymphomas occurring in a single anatomical site or simultaneously in different sites and can be composed of any combination of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, or Hodgkin lymphoma (HL). Cases of composite lymphomas with more than 2 lymphomas are extremely rare, with only 4 reports in the literature. We report the case of a 49-year-old man with a triple composite lymphoma in a single lymph node, consisting of small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma in situ. The patient received multiple courses of chemotherapy and an autologous stem cell transplant, which resulted in complete remission. Then, 6 years after the stem cell transplant, he developed classical HL. This unique case is, to our knowledge, the first report of a patient with triple composite lymphoma consisting of 3 small mature B-cell NHLs, who subsequently developed a fourth lymphoma.

  14. The Pim kinases: new targets for drug development.

    Science.gov (United States)

    Swords, Ronan; Kelly, Kevin; Carew, Jennifer; Nawrocki, Stefan; Mahalingam, Devalingam; Sarantopoulos, John; Bearss, David; Giles, Francis

    2011-12-01

    The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to cancer development and progression. They were first recognized as pro-viral integration sites for the Moloney Murine Leukemia virus. Unlike other kinases, they possess a hinge region which creates a unique binding pocket for ATP. Absence of a regulatory domain means that these proteins are constitutively active once transcribed. Pim kinases are critical downstream effectors of the ABL (ableson), JAK2 (janus kinase 2), and Flt-3 (FMS related tyrosine kinase 1) oncogenes and are required by them to drive tumorigenesis. Recent investigations have established that the Pim kinases function as effective inhibitors of apoptosis and when overexpressed, produce resistance to the mTOR (mammalian target of rapamycin) inhibitor, rapamycin . Overexpression of the PIM kinases has been reported in several hematological and solid tumors (PIM 1), myeloma, lymphoma, leukemia (PIM 2) and adenocarcinomas (PIM 3). As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Novel small molecule inhibitors of the human Pim kinases have been designed and are currently undergoing preclinical evaluation.

  15. In this issue: Tec kinases in the crosshairs.

    Science.gov (United States)

    Faris, Mary; Bot, Adrian

    2012-04-01

    Tec family kinases are the second largest family of non-receptor tyrosine kinases, of critical importance to the biology of cells derived from the bone marrow. Significant progress in this area during the last decade revealed a role for several of these kinases in inflammatory and oncologic disorders. This led to the discovery and development of molecular targeted therapies against Tec kinases, most notably to date Btk, already showing promising clinical activity in B cell lymphoma and autoimmunity. As Btk does not carry oncogenic modifications, this also establishes a novel therapeutic paradigm, based on targeting ancillary pathways recruited by the pathogenic process to become pivotal to cancer cell's biology. This issue focuses on biology and translation of Tec kinases, at the cross-roads between immunology and cancer.

  16. Pembrolizumab and Ibrutinib in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-01-25

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Mediastinal Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

  17. Multimodality imaging of cardiothoracic lymphoma

    International Nuclear Information System (INIS)

    Carter, Brett W.; Wu, Carol C.; Khorashadi, Leila; Godoy, Myrna C.B.; Groot, Patricia M. de; Abbott, Gerald F.; Lichtenberger III, John P.

    2014-01-01

    Lymphoma is the most common hematologic malignancy and represents approximately 5.3% of all cancers. The World Health Organization published a revised classification scheme in 2008 that groups lymphomas by cell type and molecular, cytogenetic, and phenotypic characteristics. Most lymphomas affect the thorax at some stage during the course of the disease. Affected structures within the chest may include the lungs, mediastinum, pleura, and chest wall, and lymphomas may originate from these sites as primary malignancies or secondarily involve these structures after arising from other intrathoracic or extrathoracic sources. Pulmonary lymphomas are classified into one of four types: primary pulmonary lymphoma, secondary pulmonary lymphoma, acquired immunodeficiency syndrome-related lymphoma, and post-transplantation lymphoproliferative disorders. Although pulmonary lymphomas may produce a myriad of diverse findings within the lungs, specific individual features or combinations of features can be used, in combination with secondary manifestations of the disease such as involvement of the mediastinum, pleura, and chest wall, to narrow the differential diagnosis. While findings of thoracic lymphoma may be evident on chest radiography, computed tomography has traditionally been the imaging modality used to evaluate the disease and effectively demonstrates the extent of intrathoracic involvement and the presence and extent of extrathoracic spread. However, additional modalities such as magnetic resonance imaging of the thorax and 18 F-FDG PET/CT have emerged in recent years and are complementary to CT in the evaluation of patients with lymphoma. Thoracic MRI is useful in assessing vascular, cardiac, and chest wall involvement, and PET/CT is more accurate in the overall staging of lymphoma than CT and can be used to evaluate treatment response

  18. Multimodality imaging of cardiothoracic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Brett W., E-mail: bcarter2@mdanderson.org [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Wu, Carol C. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Khorashadi, Leila [Department of Radiology, Mount Auburn Hospital, Cambridge, MA 02138 (United States); Godoy, Myrna C.B.; Groot, Patricia M. de [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Abbott, Gerald F. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Lichtenberger III, John P. [Department of Radiology, David Grant Medical Center, Travis AFB, CA 94535 (United States)

    2014-08-15

    Lymphoma is the most common hematologic malignancy and represents approximately 5.3% of all cancers. The World Health Organization published a revised classification scheme in 2008 that groups lymphomas by cell type and molecular, cytogenetic, and phenotypic characteristics. Most lymphomas affect the thorax at some stage during the course of the disease. Affected structures within the chest may include the lungs, mediastinum, pleura, and chest wall, and lymphomas may originate from these sites as primary malignancies or secondarily involve these structures after arising from other intrathoracic or extrathoracic sources. Pulmonary lymphomas are classified into one of four types: primary pulmonary lymphoma, secondary pulmonary lymphoma, acquired immunodeficiency syndrome-related lymphoma, and post-transplantation lymphoproliferative disorders. Although pulmonary lymphomas may produce a myriad of diverse findings within the lungs, specific individual features or combinations of features can be used, in combination with secondary manifestations of the disease such as involvement of the mediastinum, pleura, and chest wall, to narrow the differential diagnosis. While findings of thoracic lymphoma may be evident on chest radiography, computed tomography has traditionally been the imaging modality used to evaluate the disease and effectively demonstrates the extent of intrathoracic involvement and the presence and extent of extrathoracic spread. However, additional modalities such as magnetic resonance imaging of the thorax and {sup 18}F-FDG PET/CT have emerged in recent years and are complementary to CT in the evaluation of patients with lymphoma. Thoracic MRI is useful in assessing vascular, cardiac, and chest wall involvement, and PET/CT is more accurate in the overall staging of lymphoma than CT and can be used to evaluate treatment response.

  19. Malignant lymphomas of the stomach

    International Nuclear Information System (INIS)

    Drgona, L.

    2011-01-01

    Primary gastric lymphomas are the most common extra nodal lymphomas. They can be presented as aggressive or indolent, majority of indolent lymphomas are associated to H. pylori infection. The basic diagnostic procedures are endoscopy, endo sonography and biopsy of gastric tissue. Therapy is related to the histological subtype, stage, H. pylori positivity, clinical symptoms and condition of patient. The aim of the treatment is remission as well as good quality of life. The prognosis of patients with primary gastric lymphomas is relatively good. (author)

  20. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    Science.gov (United States)

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  1. Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-05

    Chronic Lymphocytic Leukemia; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

  2. Identification of novel therapeutic targets in anaplastic thyroid carcinoma using functional genomic mRNA-profiling : Paving the way for new avenues?

    NARCIS (Netherlands)

    Jonker, Pascal K. C.; van Dam, Gooitzen M.; Oosting, Sjoukje E.; Kruijff, Schelto; Fehrmann, Rudolf S. N.

    Background. Currently, anaplastic thyroid carcinoma has a very poor prognosis and there is an unmet need for new therapeutic options. Therefore, this study aims to identify upregulated genes in anaplastic thyroid carcinoma with known drug interactions that could serve as new therapeutic targets.

  3. Identification of novel therapeutic targets in anaplastic thyroid carcinoma using functional genomic mRNA-profiling: Paving the way for new avenues?

    Science.gov (United States)

    Jonker, Pascal K C; van Dam, Gooitzen M; Oosting, Sjoukje F; Kruijff, Schelto; Fehrmann, Rudolf S N

    2017-01-01

    Currently, anaplastic thyroid carcinoma has a very poor prognosis and there is an unmet need for new therapeutic options. Therefore, this study aims to identify upregulated genes in anaplastic thyroid carcinoma with known drug interactions that could serve as new therapeutic targets. Publicly available microarray expression profiles of anaplastic thyroid carcinoma and normal thyroid tissue were collected. FGmRNA-profiling was applied, which is a recently developed method that enhances the ability to capture the downstream effects of genomic alterations on gene expression levels. Next, a comparison between FGmRNA-profiles of anaplastic thyroid carcinoma and normal thyroid samples was performed. Significantly upregulated genes in ATC were prioritized based on: 1) known interaction with antineoplastic drugs, 2) current drug development status in human, and 3) association with biologic pathways known to be involved in anaplastic thyroid carcinoma carcinogenesis. In the study, 25 anaplastic thyroid carcinoma and 80 normal thyroid samples were included for FGmRNA-profiling. Class comparison identified 301 significantly upregulated genes. Following prioritization, MTOR, MET, WEE1, PSMD1, MERTK, FGFR3, RARG, and ESR2 were identified as potential therapeutic targets. We prioritized 8 potential therapeutic druggable targets in anaplastic thyroid carcinoma. Ultimately, inhibition of these therapeutic targets might improve patient outcome in anaplastic thyroid carcinoma by reducing locoregional disease and distant metastases. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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

  5. Imatinib disrupts lymphoma angiogenesis by targeting vascular pericytes.

    Science.gov (United States)

    Ruan, Jia; Luo, Min; Wang, Chunjie; Fan, Lei; Yang, Shao Ning; Cardenas, Mariano; Geng, Huimin; Leonard, John P; Melnick, Ari; Cerchietti, Leandro; Hajjar, Katherine A

    2013-06-27

    Pericytes and vascular smooth muscle cells (VSMCs), which are recruited to developing blood vessels by platelet-derived growth factor BB, support endothelial cell survival and vascular stability. Here, we report that imatinib, a tyrosine kinase inhibitor of platelet-derived growth factor receptor β (PDGFRβ), impaired growth of lymphoma in both human xenograft and murine allograft models. Lymphoma cells themselves neither expressed PDGFRβ nor were growth inhibited by imatinib. Tumor growth inhibition was associated with decreased microvascular density and increased vascular leakage. In vivo, imatinib induced apoptosis of tumor-associated PDGFRβ(+) pericytes and loss of perivascular integrity. In vitro, imatinib inhibited PDGFRβ(+) VSMC proliferation and PDGF-BB signaling, whereas small interfering RNA knockdown of PDGFRβ in pericytes protected them against imatinib-mediated growth inhibition. Fluorescence-activated cell sorter analysis of tumor tissue revealed depletion of pericytes, endothelial cells, and their progenitors following imatinib treatment. Compared with imatinib, treatment with an anti-PDGFRβ monoclonal antibody partially inhibited lymphoma growth. Last, microarray analysis (Gene Expression Omnibus database accession number GSE30752) of PDGFRβ(+) VSMCs following imatinib treatment showed down-regulation of genes implicated in vascular cell proliferation, survival, and assembly, including those representing multiple pathways downstream of PDGFRβ. Taken together, these data indicate that PDGFRβ(+) pericytes may represent a novel, nonendothelial, antiangiogenic target for lymphoma therapy.

  6. Investigation of the results of therapy of anaplastic thyroid gland carcinomas

    International Nuclear Information System (INIS)

    Ooijen, M. van.

    1979-01-01

    The results of the treatment of 28 patients with an anaplastic thyroid gland carcinoma are investigated, to see whether an optimal therapy is indicated. The execution of an operation before radiotherapy does not appear to improve the prognosis (statistically this conclusion is not wholly justified). The presence of metastases at the beginning of the therapy gave rise to a worse prognosis than the absence of metastases. The combination treatment of chemotherapy and either surgery or radiotherapy was only applied to two patients so no conclusions can be made about its benefit. (C.F.)

  7. [Incidence of anaplastic tumor in structure of other histologic forms of the thyroid gland cancer].

    Science.gov (United States)

    Vinnik, Iu A; Gorbenko, V N; Vas'ko, A R; Kikhtenko, E V; Gargin, V V

    2014-01-01

    The degrees of invasiveness, proliferative activity, morphofunctional activity of nuclei in the thyroidal gland tumors were studied, while analyzing material, obtained in 1343 patients, suffering thyroidal gland cancer (THGC) and operated on in 2000-2013 yrs. Morphological point quantity of malignancy (as a criterion of the tumor progression grade) and mitotic activity in cellular population were determined in various kinds of THGC. Undifferentiated (anaplastic carcinoma) type of THGC is the most malignant one. There were determined a spindle-like, giant-cell and squamous-cell forms of undifferentiated THGC. The presence of sites of differentiated cancer in 33% of histological preparations witnesses the interrelationship with the earlier existed pathological process.

  8. Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2015-12-01

    Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

  9. Emergency total thyroidectomy for bleeding anaplastic thyroid carcinoma: A viable option for palliation

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2011-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is a rare and highly aggressive thyroid neoplasm. Bleeding from tumor is an uncommon, but potentially life-threatening complication requiring sophisticated intervention facilities which are not usually available at odd hours in emergency. We report the case of a 45-year-old woman who presented with exsanguinating hemorrhage from ATC and was treated by emergency total thyroidectomy. The patient is well three months postoperatively. Emergency total thyroidectomy is a viable option for palliation in ATC presenting with bleeding.

  10. President's categorical course on lymphoma

    International Nuclear Information System (INIS)

    Hoppe, Richard T.

    1997-01-01

    Improvements in the classification, staging, and treatment of the lymphomas, complemented by an improved understanding of the biology of these diseases, has led to an improved outcome of therapy for both Hodgkin's disease and many of the non-Hodgkin's lymphomas. The rapid changes that have occurred in this field in the last decade make it timely to review this subject for radiation oncologists in a comprehensive fashion. This course is designed to meet broad educational needs required for understanding these diseases and providing effective care for patients with lymphoma. The faculty includes many leaders from both laboratory and clinical disciplines dealing with lymphomas, who will address a variety of scientific and clinical topics. The morning session will be devoted to Hodgkin's disease, including new concepts in its biology, a review of clinical trials for early stage disease, a discussion of the role of high dose therapy, and description of long term complications of treatment. The afternoon sessions will be devoted to the non-Hodgkin's lymphomas, including new concepts in pathology and biology, a description of specific entities including the low grade lymphomas, MALT lymphomas, extranodal lymphomas, intermediate grade lymphomas, mantle cell lymphomas, and summary discussions of the role of radioimmuno-therapy and high dose therapy. Although the role of radiation therapy in the management of patients with lymphoma has changed dramatically in the past two decades, radiation remains the most effective single agent for the treatment of these diseases and it is especially important for radiation onologists to keep abreast of these new concepts. This course has been designed to achieve that goal

  11. Danish National Lymphoma Registry

    Directory of Open Access Journals (Sweden)

    Arboe B

    2016-10-01

    Full Text Available Bente Arboe,1 Pär Josefsson,2 Judit Jørgensen,3 Jacob Haaber,4 Paw Jensen,5 Christian Poulsen,6 Dorthe Rønnov-Jessen,7 Robert S Pedersen,8 Per Pedersen,9 Mikael Frederiksen,10 Michael Pedersen,1 Peter de Nully Brown1 1Department of Hematology, Copenhagen University Hospital, Rigshospitalet, 2Department of Hematology, Copenhagen University Hospital, Herlev Hospital, Copenhagen, 3Department of Hematology, Aarhus University Hospital, Aarhus, 4Department of Hematology, Odense University Hospital, Odense, 5Department of Hematology, Aalborg University Hospital, Aalborg, 6Department of Hematology, Roskilde Hospital, Roskilde, 7Department of Hematology, Vejle Hospital, Vejle, 8Department of Hematology, Holstebro Hospital, Holstebro, 9Department of Hematology, Esbjerg Hospital, Esbjerg, 10Department of Hematology, Haderslev Hospital, Haderslev, Denmark Aim of database: The Danish National Lymphoma Registry (LYFO was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in Denmark. Study population: The LYFO database was established in 1982 as a seminational database including all lymphoma patients referred to the departments of hematology. The database became nationwide on January 1, 2000. Main variables: The main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation. Up to four forms are completed for each patient: a primary registration form, a treatment form, a relapse form, and a follow-up form. Variables are used to calculate six result quality indicators (mortality 30 and 180 days after diagnosis, response to first-line treatment, and survival estimates 1, 3, and 5 years after the time of diagnosis, and three process quality indicators (time from diagnosis until the start of treatment, the presence of relevant diagnostic markers, and inclusion rate in clinical protocols. Descriptive data: Approximately 23

  12. Doxorubicin fails to eradicate cancer stem cells derived from anaplastic thyroid carcinoma cells: characterization of resistant cells.

    Science.gov (United States)

    Zheng, Xuqin; Cui, Dai; Xu, Shuhang; Brabant, Georg; Derwahl, Michael

    2010-08-01

    Current chemotherapy with doxorubicin fails to eradicate anaplastic thyroid cancer or even to stop tumor progress which may be due to the failure of these drugs to effectively target putative cancer stem cells. To test this hypothesis, anaplastic thyroid cell lines were characterized by FACS for their content of cancer stem cells, their in vitro sphere-forming capacity and their expression of multidrug resistance transporters of the ABC gene family which may confer drug resistance to the cells. Cells were treated with doxorubicin in short-term and long-term culture up to 6 months to establish a resistant cell line. The survival of cancer and cancer stem cells and the differential expression of transporters were analyzed. Anaplastic thyroid cancer cell lines that consisted of 0.4-0.8% side population cells, expressed ABCG2 and multi-drug-resistant 1 (MDR1) transporters. Treatment with doxorubicin gradually killed the non-side population of cancer cells derived from anaplastic thyroid carcinoma cells. This conferred a growth advantage to cancer stem cells which in turn overgrew the culture. Resistant cell line consisted of a 70% side population fraction enriched with Oct4-positive cancer stem cells. Inhibition of ABCG2 and/or MDR1 revealed that resistance of cancer stem cells to doxorubicin may be mainly due to the expression of these ABC transporters that were highly up-regulated in the resistant subline. The poor outcome of chemotherapy with doxorubicin in anaplastic thyroid carcinoma may be partly explained by up-regulation of ABCG2 and MDR1 transporters that confers resistance to cancer stem cells. Thus an effective treatment of anaplastic thyroid cancer has not only to destroy cancer cells that represent the bulk of tumor cell population but also cancer stem cells that may drive tumor progression.

  13. Oncogenically active MYD88 mutations in human lymphoma

    Science.gov (United States)

    Ngo, Vu N.; Young, Ryan M.; Schmitz, Roland; Jhavar, Sameer; Xiao, Wenming; Lim, Kian-Huat; Kohlhammer, Holger; Xu, Weihong; Yang, Yandan; Zhao, Hong; Shaffer, Arthur L.; Romesser, Paul; Wright, George; Powell, John; Rosenwald, Andreas; Muller-Hermelink, Hans Konrad; Ott, German; Gascoyne, Randy D.; Connors, Joseph M.; Rimsza, Lisa M.; Campo, Elias; Jaffe, Elaine S.; Delabie, Jan; Smeland, Erlend B.; Fisher, Richard I.; Braziel, Rita M.; Tubbs, Raymond R.; Cook, J. R.; Weisenburger, Denny D.; Chan, Wing C.; Staudt, Louis M.

    2016-01-01

    The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy1. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling2,3, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt’s lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, theMYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations

  14. Lobatin B inhibits NPM/ALK and NF-κB attenuating anaplastic-large-cell-lymphomagenesis and lymphendothelial tumour intravasation.

    Science.gov (United States)

    Kiss, Izabella; Unger, Christine; Huu, Chi Nguyen; Atanasov, Atanas Georgiev; Kramer, Nina; Chatruphonprasert, Waranya; Brenner, Stefan; McKinnon, Ruxandra; Peschel, Andrea; Vasas, Andrea; Lajter, Ildiko; Kain, Renate; Saiko, Philipp; Szekeres, Thomas; Kenner, Lukas; Hassler, Melanie R; Diaz, Rene; Frisch, Richard; Dirsch, Verena M; Jäger, Walter; de Martin, Rainer; Bochkov, Valery N; Passreiter, Claus M; Peter-Vörösmarty, Barbara; Mader, Robert M; Grusch, Michael; Dolznig, Helmut; Kopp, Brigitte; Zupko, Istvan; Hohmann, Judit; Krupitza, Georg

    2015-01-28

    An apolar extract of the traditional medicinal plant Neurolaena lobata inhibited the expression of the NPM/ALK chimera, which is causal for the majority of anaplastic large cell lymphomas (ALCLs). Therefore, an active principle of the extract, the furanoheliangolide sesquiterpene lactone lobatin B, was isolated and tested regarding the inhibition of ALCL expansion and tumour cell intravasation through the lymphendothelium. ALCL cell lines, HL-60 cells and PBMCs were treated with plant compounds and the ALK inhibitor TAE-684 to measure mitochondrial activity, proliferation and cell cycle progression and to correlate the results with protein- and mRNA-expression of selected gene products. Several endpoints indicative for cell death were analysed after lobatin B treatment. Tumour cell intravasation through lymphendothelial monolayers was measured and potential causal mechanisms were investigated analysing NF-κB- and cytochrome P450 activity, and 12(S)-HETE production. Lobatin B inhibited the expression of NPM/ALK, JunB and PDGF-Rβ, and attenuated proliferation of ALCL cells by arresting them in late M phase. Mitochondrial activity remained largely unaffected upon lobatin B treatment. Nevertheless, caspase 3 became activated in ALCL cells. Also HL-60 cell proliferation was attenuated whereas PBMCs of healthy donors were not affected by lobatin B. Additionally, tumour cell intravasation, which partly depends on NF-κB, was significantly suppressed by lobatin B most likely due to its NF-κB-inhibitory property. Lobatin B, which was isolated from a plant used in ethnomedicine, targets malignant cells by at least two properties: I) inhibition of NPM/ALK, thereby providing high specificity in combating this most prevalent fusion protein occurring in ALCL; II) inhibition of NF-κB, thereby not affecting normal cells with low constitutive NF-κB activity. This property also inhibits tumour cell intravasation into the lymphatic system and may provide an option to manage this

  15. MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

    Science.gov (United States)

    2014-05-22

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  16. Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2013-12-13

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

  17. Lymphoma of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2014-01-01

    Full Text Available Background. Lymphoma of the urinary bladder (LUB is rare. Aims. To review the literature on LUB. Methods. Various internet databases were used. Results. LUB can be either primary or secondary. The tumour has female predominance; most cases occur in middle-age women. Secondary LUB occurs in 10% to 25% of leukemias/lymphomas and in advanced-stage systemic lymphoma. Less than 100 cases have been reported. MALT typically affects adults older than 60 years; 75% are female. Diffuse large B-cell lymphoma is also common and may arise from transformation of MALT. LUB presents with haematuria, dysuria, urinary frequency, nocturia, and abdominal or back pain. Macroscopic examination of LUBs show large discrete tumours centred in the dome or lateral walls of the bladder. Positive staining of LUB varies by the subtype of lymphoma; B-cell lymphomas are CD20 positive. MALT lymphoma is positively stained for CD20, CD19, and FMC7 and negatively stained for CD5, CD10, and CD11c. LUB stains negatively with Pan-keratin, vimentin, CK20, and CK7. MALT lymphoma exhibits t(11; 18(q21: 21. Radiotherapy is an effective treatment for the MALT type of LUB with no recurrence. Conclusions. LUB is diagnosed by its characteristic morphology and immunohistochemical characteristics. Radiotherapy is a useful treatment.

  18. Bilateral Primary Lacrimal Gland Lymphoma

    Directory of Open Access Journals (Sweden)

    Kürşad Ramazan Zor

    2016-12-01

    Full Text Available Lymphoma involving the lacrimal gland is rare. Most of the cases are unilateral at presentation. In this case, we present the diagnostic evaluation of a patient with bilateral lacrimal gland lymphoma. At presentation, the patient had inferomedial eccentric proptosis of the right eye. The patient also had limitation in the upper and lateral gaze in this eye. On magnetic resonance imaging, a mass was detected not only in the right but also in the left eye corresponding to the area of the lacrimal gland. Excisional biopsy was performed in the right eye with lateral orbitotomy approach. Histopathological examination revealed extranodal marginal zone lymphoma involving the lacrimal gland. No concurrent systemic lymphoma was detected during systemic evaluation of the patient. The patient was directed to the oncology department for systemic treatment planning. In conclusion, bilateral involvement is rare in lacrimal gland diseases but it can show severe diseases like lymphoma.

  19. Non-Hodgkin Lymphoma (For Parents)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Non-Hodgkin Lymphoma KidsHealth / For Parents / Non-Hodgkin Lymphoma What's in ... harmful things out of the body. About Non-Hodgkin Lymphoma No n-Hodgkin lymphoma is a disease in ...

  20. Anaplastic carcinoma of thyroid gland with widespread soft tissue metastasis: an unusual presentation.

    Science.gov (United States)

    Hassan, Muhammad; Janjua, Taimoor Khalid; Afridi, Hira Khan; Zahid, Naila Anjum

    2017-07-13

    Anaplastic thyroid cancer is the rarest tumour of the thyroid gland, representing only 2% of clinically recognised thyroid cancers. The most common metastatic sites are lungs, followed by the intrathoracic and neck lymph nodes. We report the case of a 62-year-old woman who presented to our setting with multiple soft tissue nodules, thyroid mass, head swelling and weight loss. Radiological investigation showed a large thyroid mass with widespread metastasis in subcutaneous tissues of both upper limbs, chest and abdomen. Metastasis was also found in lungs, skull and adrenal glands after which the patient was diagnosed with stage IVc anaplastic thyroid carcinoma (ATC). After careful consideration of patient's clinical condition with multiple poor prognostic factors, medical therapy was withheld and she was discharged on hospice care. The patient expired after 1 month. In ATC, metastasis to subcutaneous tissue is an extremely rare occurrence of which there is hardly any evidence in literature. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Prognostic Factors for Survival in Patients Treated with Multimodal Therapy for Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Käsmann, Lukas; Bolm, Louisa; Janssen, Stefan; Rades, Dirk

    2016-09-01

    To identify predictors of survival after multimodal treatment including surgery plus postoperative radio(chemo)therapy) for anaplastic thyroid cancer. Nine potential factors were evaluated in nine patients regarding survival after 6, 12 and 24 months. These factors were age, gender, Karnofsky performance score, tumour stage, nodal stage, resection margin status, radiation dose, concurrent chemotherapy administered with irradiation and symptom control at the end of radiotherapy. Survival rates were 67% at 6 months, 56% at 12 months and 22% at 24 months. On univariate survival analysis, concurrent radiochemotherapy (p=0.018) and controlled symptoms at the end of radiotherapy (p=0.03) were associated with improved survival. A trend for better survival was seen in patients with microscopically (R1) versus macroscopically (R2) residual disease (p=0.058). Prognostic factors for survival after multimodal treatment for anaplastic thyroid cancer were identified. Concurrent radio-chemotherapy resulted in significantly better survival and should be recommended. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. [Anaplastic Thyroid Carcinoma in a 17-Year-Old Female Patient].

    Science.gov (United States)

    Ivanišević, P; Čolović, Z; Pešutić-Pisac, V; Škrabić, V; Kontić, M; Kljajić, Z

    2016-04-01

    Anaplastic carcinoma of thyroid gland is one of the four most malignant tumors in humans. It appears in one or two patients per million per year. It is very rare in children. A 17-year-old female patient was admitted to the Clinical Department of ENT and Head and Neck Surgery, Split University Hospital Center, for thyroid gland surgery due to rapid growth of a node in the thyroid gland left lobe. Preoperative examination indicated benign nature of changes. Total thyroidectomy with levels VI and VII neck dissection was done. Intraoperative slide of the left lobe was malignant. Positron emission tomography and computed tomography were also done. The finding was negative. The patient was examined by an ENT-oncology team and juvenile radiotherapy was administered. It was found to be carcinoma stage IVa according to TNM classification. One year after the operation, the patient was well and had no signs of illness. This case report is a contribution to the existing but scarce knowledge of anaplastic carcinoma of thyroid gland in young patients in the world.

  3. A comparative evaluation of supervised and unsupervised representation learning approaches for anaplastic medulloblastoma differentiation

    Science.gov (United States)

    Cruz-Roa, Angel; Arevalo, John; Basavanhally, Ajay; Madabhushi, Anant; González, Fabio

    2015-01-01

    Learning data representations directly from the data itself is an approach that has shown great success in different pattern recognition problems, outperforming state-of-the-art feature extraction schemes for different tasks in computer vision, speech recognition and natural language processing. Representation learning applies unsupervised and supervised machine learning methods to large amounts of data to find building-blocks that better represent the information in it. Digitized histopathology images represents a very good testbed for representation learning since it involves large amounts of high complex, visual data. This paper presents a comparative evaluation of different supervised and unsupervised representation learning architectures to specifically address open questions on what type of learning architectures (deep or shallow), type of learning (unsupervised or supervised) is optimal. In this paper we limit ourselves to addressing these questions in the context of distinguishing between anaplastic and non-anaplastic medulloblastomas from routine haematoxylin and eosin stained images. The unsupervised approaches evaluated were sparse autoencoders and topographic reconstruct independent component analysis, and the supervised approach was convolutional neural networks. Experimental results show that shallow architectures with more neurons are better than deeper architectures without taking into account local space invariances and that topographic constraints provide useful invariant features in scale and rotations for efficient tumor differentiation.

  4. Demographics and outcome in paediatric non-hodgkin lymphoma: single centre experience at the children hospital, lahore, pakistan

    International Nuclear Information System (INIS)

    Faizan, M.; Khan, S.

    2018-01-01

    To describe the patient demographics and outcome analysis in paediatric non-Hodgkin lymphoma (NHL) patients. Study Design:An observational study. Place and Duration of Study:The Hematology/Oncology Unit of The Children's Hospital and Institute of Child Health, Lahore, from January 2012 till December 2014. Methodology:Demographics including age, gender, histopathology, stage and outcome data, in biopsy proven NHL patients were analyzed. Burkitts/B Cell and Diffuse Large B Cell lymphoma patients were treated with MCP 842 Protocol while T/B-cell lymphoblastic lymphoma (LL) patients were treated with EURO-LB 02 protocol. Results:Ninety-one patients were treated during the study period at CHL. Data was insufficient in 18 patients, so they were excluded from the study. Patients included were 73. Males were 53 (72.6%). Thirty-seven (50.7%) were 5-10 years of age, and 22 (30.1%) 10-16 years old. Abdominal mass was the commonest presentation seen in 32 (43.8%), lymphadenopathy in 27 (37%), intussusception in 5 (6.8%), while intestinal obstruction, obstructive uropathy, nasopharyngeal mass, gastric mass, primary bone lymphoma, pericardial effusion, jaw swelling, cheek swelling and paraspinal mass present in one (1%) each. Histopathological subtypes consist of Burkitt's lymphoma (BL) in 32 (43.8%), B cell NHL in 10 (13.7%), lymphoblastic lymphoma (LL) in 26 (35.6%), diffuse large B cell lymphoma (DLBCL) in 2 (2.8%), and anaplastic large cell lymphoma (ALCL) in 1 (1.4%). Sixty-seven (91%) presented in stage III, and six (8.4%) in stage IV. Forty-eight (65.8%) patients had completed treatment and are well to date, 16 (21.9%) died, 5 (6.8%) left against medical advice (LAMA), and 4 (5.5%) patients relapsed. Conclusion:Burkitt's lymphoma was the commonest type of NHL seen in this cohort that predominantly presented with an abdominal mass. Children usually presented in advanced stage with delayed diagnosis. Better supportive care can improve the prognosis

  5. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia.

    Science.gov (United States)

    Friedberg, Jonathan W; Sharman, Jeff; Sweetenham, John; Johnston, Patrick B; Vose, Julie M; Lacasce, Ann; Schaefer-Cutillo, Julia; De Vos, Sven; Sinha, Rajni; Leonard, John P; Cripe, Larry D; Gregory, Stephanie A; Sterba, Michael P; Lowe, Ann M; Levy, Ronald; Shipp, Margaret A

    2010-04-01

    Certain malignant B cells rely on B-cell receptor (BCR)-mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095.

  6. Gastric Lymphoma with Secondary Trigeminal Nerve Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Warissara Rongthong

    2017-05-01

    Full Text Available Data supporting the role of radiotherapy in secondary trigeminal nerve lymphoma is scarce. Here, I report the case of 64-year-old Thai male diagnosed as gastric diffuse large B cell lymphoma with secondary trigeminal nerve lymphoma. He had previously received one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, followed by five cycles of rituximab plus CHOP (R-CHOP with intrathecal methotrexate (MTX and cytarabine (Ara-C. One month after the last cycle of R-CHOP, he developed a headache and numbness on the left side of his face. MRI revealed thickening of the left trigeminal nerve. He received one intrathecal injection of MTX and Ara-C, followed by systemic chemotherapy. After receiving intrathecal chemotherapy, his symptoms disappeared. Clinical response and MRI studies suggested secondary trigeminal nerve lymphoma. Two months later, our patient’s secondary trigeminal nerve lymphoma had progressed. Salvage whole brain irradiation (36 Gy with boost dose (50 Gy along the left trigeminal nerve was given. Unfortunately, our patient developed heart failure and expired during the radiotherapy session. In conclusion and specific to secondary central nervous system lymphoma (SCNSL, radiotherapy may benefit patients who fail to respond to systemic chemotherapy and palliative treatment. The results this report fail to support the role of radiotherapy in secondary trigeminal nerve lymphoma.

  7. Sarcoidosis-lymphoma syndrome.

    Science.gov (United States)

    Brandy-García, Anahy M; Caminal-Montero, Luis; Fernández-García, María Soledad; Saiz Ayala, Angel; Cabezas-Rodríguez, Ivan; Morante-Bolado, Isla

    A 65 year-old female with a history of sarcoidosis with pulmonary and joint involvement, who after 5 years of diagnosis begins with central nervous system involvement manifesting as diplopia. She presents normal analysis results. In imaging results, a mass is identified in the right intraconal space; it depends of right optic nerve, and shows multiple lymph node involvement. Biopsy was performed diagnosed with large B-cell lymphoma, an atypical form of tumor associated with sarcoidosis. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  8. Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-05

    Aggressive Non-Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Small Lymphocytic Lymphoma

  9. Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

    Science.gov (United States)

    2018-01-02

    HIV Infection; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Plasmablastic Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Follicular Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  10. Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma

    DEFF Research Database (Denmark)

    Malmström, Annika; Poulsen, Hans Skovgaard; Grønberg, Bjørn Henning

    2017-01-01

    INTRODUCTION: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. Duri...

  11. Lymphoma Caused by Intestinal Microbiota

    Directory of Open Access Journals (Sweden)

    Mitsuko L. Yamamoto

    2014-09-01

    Full Text Available The intestinal microbiota and gut immune system must constantly communicate to maintain a balance between tolerance and activation: on the one hand, our immune system should protect us from pathogenic microbes and on the other hand, most of the millions of microbes in and on our body are innocuous symbionts and some can even be beneficial. Since there is such a close interaction between the immune system and the intestinal microbiota, it is not surprising that some lymphomas such as mucosal-associated lymphoid tissue (MALT lymphoma have been shown to be caused by the presence of certain bacteria. Animal models played an important role in establishing causation and mechanism of bacteria-induced MALT lymphoma. In this review we discuss different ways that animal models have been applied to establish a link between the gut microbiota and lymphoma and how animal models have helped to elucidate mechanisms of microbiota-induced lymphoma. While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.

  12. Primary gastric Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Koak Yashwant

    2007-10-01

    Full Text Available Abstract Background Primary Hodgkin's disease of the stomach is an extremely rare entity. Nearly all cases of primary gastric lymphoma are of the non-Hodgkin's variety. Diagnoses in such cases are difficult due to considerable histological similarities between the 2 disease entities. Case presentation We report the case of a 77 year old lady with a 1 year history of weight loss and poor appetite. Physical examination was unremarkable. Subsequent multiple upper GI endoscopies revealed a large malignant looking ulcer which was deemed to be histologically benign. Following CT imaging the patient underwent a radical gastrectomy. Postoperatively histology and immunohistochemistry failed to confirm a diagnosis. As such a second opinion was sought. Employing an extended array of immunohistological staining a diagnosis of 'Classical Hodgkin's' disease of the stomach was achieved. Conclusion Our case illustrates the significant difficulties in achieving a rare diagnosis of primary Hodgkin's lymphoma of the stomach. The non-specific nature of symptoms and a lack of histological features make a preoperative diagnosis extremely difficult. While immunohistochemistry is widely employed in aiding the evaluation of such cases, one should be wary of the considerable overlap in differentiating between Hodgkin's and non-Hodgkin's disease entities using this technique.

  13. Haemorrhage and intestinal lymphoma

    Directory of Open Access Journals (Sweden)

    Attilia M. Pizzini

    2013-04-01

    Full Text Available Background: The prevalence of coeliac disease is around 1% in general population but this is often unrecognised. The classical presentation of adult coeliac disease is characterized by diarrhoea and malabsorption syndrome, but atypical presentations are probably more common and are characterized by iron deficiency anaemia, weight loss, fatigue, infertility, arthralgia, peripheral neuropathy and osteoporosis. Unusual are the coagulation disorders (prevalence 20% and these are due to vitamin K malabsorption (prolonged prothrombin time. Clinical case: A 64-year-old man was admitted to our Department for an extensive spontaneous haematoma of the right leg. He had a history of a small bowel resection for T-cell lymphoma, with a negative follow-up and he didn’t report any personal or familiar history of bleeding. Laboratory tests showed markedly prolonged prothrombin (PT and partial-thromboplastin time (PTT, corrected by mixing studies, and whereas platelet count and liver tests was normal. A single dose (10 mg of intravenous vitamin K normalized the PT. Several days before the patient had been exposed to a superwarfarin pesticide, but diagnostic tests for brodifacoum, bromadiolone or difenacoum were negative. Diagnosis of multiple vitamin K-dependent coagulationfactor deficiencies (II, VII, IX, X due to intestinal malabsorption was made and coeliac disease was detected. Therefore the previous lymphoma diagnosis might be closely related to coeliac disease. Conclusions: A gluten free diet improves quality of life and restores normal nutritional and biochemical status and protects against these complications.

  14. Hodgkin Lymphoma: Diagnosis and Treatment.

    Science.gov (United States)

    Ansell, Stephen M

    2015-11-01

    Hodgkin lymphoma is a rare B-cell malignant neoplasm affecting approximately 9000 new patients annually. This disease represents approximately 11% of all lymphomas seen in the United States and comprises 2 discrete disease entities--classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Within the subcategorization of classical Hodgkin lymphoma are defined subgroups: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich Hodgkin lymphoma. Staging of this disease is essential for the choice of optimal therapy. Prognostic models to identify patients at high or low risk for recurrence have been developed, and these models, along with positron emission tomography, are used to provide optimal therapy. The initial treatment for patients with Hodgkin lymphoma is based on the histologic characteristics of the disease, the stage at presentation, and the presence or absence of prognostic factors associated with poor outcome. Patients with early-stage Hodgkin lymphoma commonly receive combined-modality therapies that include abbreviated courses of chemotherapy followed by involved-field radiation treatment. In contrast, patients with advanced-stage Hodgkin lymphoma commonly receive a more prolonged course of combination chemotherapy, with radiation therapy used only in selected cases. For patients with relapse or refractory disease, salvage chemotherapy followed by high-dose treatment and an autologous stem cell transplant is the standard of care. For patients who are ineligible for this therapy or those in whom high-dose therapy and autologous stem cell transplant have failed, treatment with brentuximab vedotin is a standard approach. Additional options include palliative chemotherapy, immune checkpoint inhibitors, nonmyeloablative allogeneic stem cell transplant, or participation in a clinical trial testing novel agents. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All

  15. Malignant lymphoma in african lions (panthera leo).

    Science.gov (United States)

    Harrison, T M; McKnight, C A; Sikarskie, J G; Kitchell, B E; Garner, M M; Raymond, J T; Fitzgerald, S D; Valli, V E; Agnew, D; Kiupel, M

    2010-09-01

    Malignant lymphoma has become an increasingly recognized problem in African lions (Panthera leo). Eleven African lions (9 male and 2 female) with clinical signs and gross and microscopic lesions of malignant lymphoma were evaluated in this study. All animals were older adults, ranging in age from 14 to 19 years. Immunohistochemically, 10 of the 11 lions had T-cell lymphomas (CD3(+), CD79a(-)), and 1 lion was diagnosed with a B-cell lymphoma (CD3(-), CD79a(+)). The spleen appeared to be the primary site of neoplastic growth in all T-cell lymphomas, with involvement of the liver (6/11) and regional lymph nodes (5/11) also commonly observed. The B-cell lymphoma affected the peripheral lymph nodes, liver, and spleen. According to the current veterinary and human World Health Organization classification of hematopoietic neoplasms, T-cell lymphoma subtypes included peripheral T-cell lymphoma (4/11), precursor (acute) T-cell lymphoblastic lymphoma/leukemia (2/11), chronic T-cell lymphocytic lymphoma/leukemia (3/11), and T-zone lymphoma (1/11). The single B-cell lymphoma subtype was consistent with diffuse large B-cell lymphoma. Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) testing by immunohistochemistry on sections of malignant lymphoma was negative for all 11 lions. One lion was seropositive for FeLV. In contrast to domestic and exotic cats, in which B-cell lymphomas are more common than T-cell lymphomas, African lions in this study had malignant lymphomas that were primarily of T-cell origin. Neither FeLV nor FIV, important causes of malignant lymphoma in domestic cats, seems to be significant in the pathogenesis of malignant lymphoma in African lions.

  16. What You Need to Know about Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Reports What You Need To Know About™ Non-Hodgkin Lymphoma This booklet is about non-Hodgkin lymphoma, a ... doctor visit. This booklet is not about Hodgkin lymphoma (also called Hodgkin disease). Hodgkin lymphoma is a different type of ...

  17. What You Need to Know about Hodgkin Lymphoma

    Science.gov (United States)

    ... Publications Reports What You Need To Know About™ Hodgkin Lymphoma This booklet is about Hodgkin lymphoma. This type ... visit. This booklet is not about non-Hodgkin lymphoma. Non-Hodgkin lymphoma is a different disease with different treatments ...

  18. Non-Hodgkin’s lymphoma with bone involvement: a single center experience with 18 patients

    Directory of Open Access Journals (Sweden)

    Filiz Vural

    2010-03-01

    Full Text Available Objective: Non-Hodgkin’s lymphoma (NHL of bone is a rare entity. The most common histological subtype is diffuse large B cell lymphoma (DLBCL. The major presenting symptoms are soft tissue swelling, bone pain and pathological fracture. Treatment options are chemotherapy, radiotherapy, surgery, or a combination of these modalities. Materials and Methods: We retrospectively analyzed the 18 patients (11 females, 7 males with NHL of bone who were diagnosed and treated between 1995-2005. The median age was 56.5 years. The median duration of symptoms was 4.5 months. The bone pain was the first symptom in all patients. Tru-cut biopsy was performed for diagnosis in most of the cases. Diagnosis in five patients (27.8% required open biopsy. Results: DLBCL (77.8% was the most common histological type among all patients. Other histological subtypes were anaplastic large cell lymphoma (11.1%, Burkitt-like lymphoma (5.6% and marginal zone lymphoma (5.6%. According to Ann Arbor staging system, 44.4% of patients were Stage I, 11.1% were Stage II and 44.4% were Stage IV. Bone marrow involvement was determined in four patients (22.2%. All patients except one were treated with anthracycline-containing regimens and eight patients (44.4% received rituximab combination with chemotherapy. Radiation therapy was performed as the first-line therapy in 9 (50% patients. The median follow-up was 37 months (range, 2-124 months. Among the 17 patients who achieved complete remission, five (27.8% relapsed. All patients were still alive. The five-year relapse-free survival was 73.5%.Conclusion: The treatment of bone lymphoma can be planned according to the stage and location of the disease. Although we had a relatively low number of patients, it could be concluded that whether or not radiation therapy is performed, rituximab in combination with systemic chemotherapy has been proven beneficial on survival.

  19. Radiographically Negative, Asymptomatic, Sentinel Lymph Node Positive Cutaneous T-Cell Lymphoma in a 3-Year-Old Male: A Case Report

    Directory of Open Access Journals (Sweden)

    Jeffrey Carson

    2012-01-01

    Full Text Available We present a case of a 3-year-old male originally diagnosed with a CD30+ anaplastic cutaneous T-cell lymphoma with no evidence of systemic disease after CT scan, PET scan, and bone marrow aspiration. Sentinel lymph node biopsy (SLNB was performed as an additional step in the workup and showed microscopic disease. Current management/recommendations for cutaneous T-cell lymphoma do not include SLNB. Medical and surgical management of cutaneous malignancies is dramatically different for local versus advanced disease. Therefore adequate evaluation is necessary to properly stage patients for specific treatment. Such distinction in extent of disease suggests more extensive therapy including locoregional radiation and systemic chemotherapy versus local excision only. Two international case reports have described SLNB in cutaneous T-cell lymphoma with one demonstrating evidence of node positive microscopic disease despite a negative metastatic disease workup. This case is being presented as a novel case in a child with implications including lymphoscintigraphy and SLNB as a routine procedure for evaluation and staging of cutaneous T-cell lymphoma if the patient does not demonstrate evidence of metastatic disease on routine workup.

  20. Hodgkin's Lymphoma with Cutaneous Involvement

    Directory of Open Access Journals (Sweden)

    Ahmad Ameri

    2016-10-01

    Full Text Available Cutaneous Hodgkin’s lymphoma is a rare disease (0.5% to 3.4% which tends to be in the setting of an advanced disease and has a poor prognosis. Treatment of patients with cutaneous involvement of Hodgkin’s lymphoma is according to dissemination of disease (systemic or localized therapy. The majority of data in this context are based on individual case reports or literature reviews. We have reported a case of Hodgkin’s lymphoma that relapsed with isolated cutaneous involvement two years after completion of his first treatment. Our case had no response to systemic chemotherapy but obtained a complete remission to radiation therapy and had longterm disease-free survival. Radiotherapy might be considered a good salvage treatment in patients with cutaneous Hodgkin’s lymphoma with long-term disease-free survival.

  1. [Pulmonary alterations in Hodgkin lymphoma].

    Science.gov (United States)

    Jóna, Ádám; Illés, Árpád; Szemes, Katalin; Miltényi, Zsófia

    2016-01-31

    Most of Hodgkin lymphoma patients survive due to combined chemo/radiotherapy. Improved survival brings long-term side effects to the front, which may determine the patients' subsequent quality of life and expected lifetime. This manuscript aims to analyze lung manifestations of Hodgkin lymphoma and treatment related pulmonary complications, demonstrated with own cases. The lung involvement in Hodgkin lymphoma is often secondary, and primary pulmonary involvement is very rare. The authors found 8-12% of lung involvement among their patients. Side effects of treatment consist of pulmonary infections in conjuction with immunosuppression, while on the other hand bleomycin and chest irradiation as part of current standard of care induced pneumonitis and fibrosis are reported. The pulmonary involvement in Hodgkin lymphoma may cause differential diagnostic difficulty. Lung involvement could modify stage and consequently treatment, and the development of side effects might determine later quality of life and expected lifetime. Therefore, identification of lung involvement is crucial.

  2. Gastrointestinal non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Makepeace, A.R.; Fermont, D.C.; Bennett, M.H.

    1987-01-01

    Seventy-two patients with gastrointestinal non-Hodgkin's lymphoma treated between 1952 and 1980 are reviewed. The small intestine was involved in 49% of cases and the stomach in 29%. Surgical resection of the tumour was performed whenever feasible. Radiotherapy was used either adjuvantly or for incompletely excised tumours and chemotherapy was more often reserved for advanced, unresected disease. The overall 5 year survival was 36% and the 5 year relapse free survival was 22%. Forty-one (57%) patients relapsed of whom 33 (80%) subsequently died of non-Hodgkin's lymphoma. The histology in each case was reviewed using the British National Lymphoma Investigation criteria and 94% of cases were reclassified as Grade 2 non-Hodgkin's lymphoma. (author)

  3. Primary intracerebral lymphoma: Case report

    Directory of Open Access Journals (Sweden)

    Olcay Eser

    2012-09-01

    Full Text Available We describe a case of primary central nervous lymphoma (PCNSL that may be confused with magnetic resonance imaging (MRI findings of high grade glioma. Primary central nervous lymphoma is a rare tumour and it account for 0.3-3% of intracranial tumours. A 61 year’s old woman was admitted to our clinic with a severe headache, vomiting, left hemiparesia and transient loss of consciousness. Primary central nervous lymphoma may show various biological and radiological characteristics. We herein emphasized being confused with MRI findings of PCNSL and high grade glioma. J Clin Exp Invest 2012; 3 (3: 409-411Key words: Primary central nervous lymphoma, high grade glioma, B-cell, diagnosis

  4. Endometrioid Adenocarcinoma Metastatic to the Thyroid, Presenting Like Anaplastic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Natasha Pollak

    2011-01-01

    Full Text Available Metastasis of uterine cancer to the head and neck is extremely rare. We report what we believe to be the first documented case of endometrioid adenocarcinoma metastasizing to the thyroid gland. An 80-year-old woman was referred to the otolaryngology service with a rapidly growing neck mass. The mass appeared to originate from the thyroid gland. Her clinical presentation was consistent with anaplastic thyroid carcinoma. A tracheostomy was performed. An open biopsy established the diagnosis of moderately differentiated adenocarcinoma, consistent with a gynecologic primary. The patient had undergone a hysterectomy 5 years prior for endometrioid adenocarcinoma. The thyroid tumor histology and immunophenotype corresponded well with her prior endometrial carcinoma, indicating that the thyroid mass was a metastasis from the endometrial primary. Radiotherapy appears to offer good local disease control in this rare case of endometrioid adenocarcinoma metastatic to the thyroid.

  5. Metronomic chemotherapy in anaplastic thyroid carcinoma: A potentially feasible alternative to therapeutic nihilism

    Directory of Open Access Journals (Sweden)

    Swaroop Revannasiddaiah

    2015-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT, and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC.

  6. Small cell anaplastic carcinoma of primary lung tumor in a miniature schnauzer dog

    International Nuclear Information System (INIS)

    Kim, J.M.; Han, H.J.; Ku, B.; Kim, G.; Shim, K.M.; Kang, S.S.; Choi, S.H.

    2011-01-01

    A seven-year-old male, an intact miniature Schnauzer dog with history of vomiting, abdominal distention, anorexia, and dyspnea was referred for further evaluation and treatment. Thoracic radiographs showed the well marginated solitary mass with soft density in the right caudal lung field, and abdominal radiographs showed signs of ascites, such as abdominal distention and moderate serosal detail loss. On ultrasonograph and computed tomograph, it was observed that the mass compressed the caudal vena cava (CVC) and adhered to the heart. Exploratory thoracotomy was performed, and then it was showed that mass adhered heart, CVC, and diaphragm. The mass was fully rejected although adhered part of CVC could not be completely rejected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma

  7. Metronomic chemotherapy in anaplastic thyroid carcinoma: a potentially feasible alternative to therapeutic nihilism.

    Science.gov (United States)

    Revannasiddaiah, Swaroop; Madabhavi, Irappa; Bodh, Anita; Thakur, Priyanka; Sharma, Mukesh

    2015-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT), and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC.

  8. Acute exacerbation of Hashimoto thyroiditis mimicking anaplastic carcinoma of the thyroid: A complicated case.

    Science.gov (United States)

    Kanaya, Hiroaki; Konno, Wataru; Fukami, Satoru; Hirabayashi, Hideki; Haruna, Shin-ichi

    2014-12-01

    The fibrous variant of Hashimoto thyroiditis is uncommon, accounting for approximately 10% of all cases of Hashimoto thyroiditis. We report a case of this variant that behaved like a malignant neoplasm. The patient was a 69-year-old man who presented with a right-sided anterior neck mass that had been rapidly growing for 2 weeks. Fine-needle aspiration cytology revealed clusters of large multinucleated cells suggestive of an anaplastic carcinoma. A week after presentation, we ruled out that possibility when the mass had shrunk slightly. Instead, we diagnosed the patient with an acute exacerbation of Hashimoto thyroiditis on the basis of laboratory findings. We performed a right thyroid lobectomy, including removal of the isthmus, to clarify the pathology and alleviate pressure symptoms. The final diagnosis was the fibrous variant of Hashimoto thyroiditis, with no evidence of malignant changes. Physicians should keep in mind that on rare occasions, Hashimoto thyroiditis mimics a malignant neoplasm.

  9. Cyclin D-cdk6 complex is targeted by p21WAF in growth-arrested lymphoma cells

    Czech Academy of Sciences Publication Activity Database

    Tvrdík, Daniel; Djaborkhel, Rashed; Nagy, Alexandr; Eckschlager, T.; Raška, Ivan; Müller, Julius

    2002-01-01

    Roč. 140, - (2002), s. 49-56 ISSN 1047-8477 R&D Projects: GA ČR GA304/01/0564 Institutional research plan: CEZ:AV0Z5039906; CEZ:MSM 111100003 Keywords : cyclin-dependent kinase * follicular lymphoma * retinoblastoma protein Subject RIV: EA - Cell Biology Impact factor: 4.194, year: 2002

  10. Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report

    International Nuclear Information System (INIS)

    Santoro, Claudia; Apicella, Andrea; Casale, Fiorina; La Manna, Angela; Di Martino, Martina; Di Pinto, Daniela; Indolfi, Cristiana; Perrotta, Silverio

    2016-01-01

    Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child’s kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15–20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance

  11. Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report.

    Science.gov (United States)

    Santoro, Claudia; Apicella, Andrea; Casale, Fiorina; La Manna, Angela; Di Martino, Martina; Di Pinto, Daniela; Indolfi, Cristiana; Perrotta, Silverio

    2016-06-13

    Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child's kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15-20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance.

  12. Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Ballova, V.

    2008-01-01

    The treatment of Hodgkin's lymphoma has changed considerably in the last decades. This entity is now one of the most curable human malignancies. With improved survival and extended follow-up, relevance of treatment induced late effects became more evident. Therefore modern therapeutic strategies must maximize chance of cure and minimize the risk of therapy associated toxicity. Here we review the pathology of Hodgkin’s lymphoma, clinical presentation, risk stratification, current treatment approaches and toxicity of the treatment. (author)

  13. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  14. Burkitt's lymphoma in South Ethiopia.

    Science.gov (United States)

    Lindtjørn, B; Olafsson, J

    1985-01-01

    In a retrospective study eleven cases with Burkitt's lymphoma have been diagnosed at three rural hospitals in the Sidamo and Gamu Gofa Regions of South Ethiopia. The clinical picture is heterogeneous with an abdominal mode of presentation being most frequently observed. It is concluded that South Ethiopia has an incidence of Burkitt's lymphoma between that of endemic countries (e.g. Uganda) and non-endemic countries such as the USA.

  15. Localized folicular lymphomas

    International Nuclear Information System (INIS)

    Soubeyran, P.; Eghbali, H.; Bonichon, F.; Coindre, J.M.; Richaud, P.; Hoerni, B.

    1988-01-01

    From 1966 to 1985, 103 patients with a localized follicular lymphoma were treated at the Fondation Bergonie. Clinical staging was performed using, after physical examination, chest X-rays, bipedal lymphangiography and unilateral bone marrow biopsy (BMB). The patients were then treated by radiotherapy with or without chemotherapy. Overall survival (OS) at 5 and 10 years is 69 and 56.3%, respectively. Relapse-free survival (RFS) is 53.7 and 49%. Unifactorial analysis shows three prognostic parameters to be independently significant in terms of OS: age, stage and B symptons. In terms of RFS, only 2 factors are significant: age and B symptons. Multivariate analysis (Cox model) shows that age is a more important prognostic factor than stage. 40 refs.; 3 figs.; 3 tabs

  16. Lymphoma in pregnancy

    International Nuclear Information System (INIS)

    Ballova, V.

    2016-01-01

    The diagnosis of malignant lymphoma during pregnancy is always a challenging situation, as for the patient a her family as well as for the whole medical team. Medical and communication skills are crucial in this situation. Interdisciplinary approach and a close cooperation between oncologist, obstetrician and neonatologist are equally important. The diagnosis of malignant potentially lethal disease and the need of treatment during pregnancy raise concerns about the life of mother if treatment was delayed and at the same time concerns about adverse fetal outcomes. This gives raise dilemmas at the therapeutical, ethical, moral and social levels. The patient must be included in the decisional process and the cultural as well as the religious aspects must be taken into account. (author)

  17. Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar.

    NARCIS (Netherlands)

    Tang, S.C.; Nguyen, L.N.; Sparidans, R.W.; Wagenaar, E.; Beijnen, J.H.; Schinkel, A.H.

    2014-01-01

    Crizotinib is an oral tyrosine kinase inhibitor approved for treating patients with non-small cell lung cancer (NSCLC) containing an anaplastic lymphoma kinase (ALK) rearrangement. We used knockout mice to study the roles of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) in

  18. Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    Science.gov (United States)

    2018-04-02

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  19. A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    Science.gov (United States)

    2017-11-09

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  20. Ascorbic Acid and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Lymphoma

    Science.gov (United States)

    2018-01-25

    High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Lymphoma

  1. Primary Cardiac Lymphoma

    Directory of Open Access Journals (Sweden)

    Shu-Ching Hsueh

    2006-04-01

    Full Text Available Primary cardiac lymphoma (PCL has rarely been reported in Chinese populations. PCL mostly occurs in the right atrium. The clinical manifestations may be variable and are attributed to its location, the presence of congestive heart failure, pericardial effusion, arrhythmia, and cardiomegaly. The prognosis is usually poor because it is usually found too late and therefore, clinicians should be aware of PCL. Imaging examinations are the best methods for initial diagnosis and include echocardiography, computed tomography (CT scan, magnetic resonance imaging (MRI, and radioisotope scan. However, the final diagnosis is made by pathology, such as cytologic examination of the effusive fluid and tissue biopsy. Because the tumors are difficult to resect, the main treatment for the disease is chemotherapy, which can be successful. Here, we report a 58-year-old man who had a tumor measuring 8 × 5 cm in the right atrium. By clinical staging, including chest X-ray, echocardiography, CT scan of the abdomen, MRI of the heart, whole body tumor Gallium scan, and gastrointestinal series, no metastatic lesion or involvement was found in other parts of the body. Pathologic findings including cytology of pericardial effusion and heart tumor biopsy revealed the case as a diffuse large B-cell lymphoma. After chemotherapy with COP (cyclophosphamide + vincristine + prednisone and CHOPBE (COP + doxorubicin + bleomycin + etoposide regimens, the intracardiac tumor had disappeared, but the patient survived for 12 months in total, despite additional radiotherapy over the pericardial lesions. It was presumed that because the tumor was very large and involved all 3 layers of the heart, it did not respond as well to the therapy as expected.

  2. Treatment results of localized gastric lymphoma

    International Nuclear Information System (INIS)

    Abe, Tatsuyuki; Gomi, Hiromichi; Sakaino, Shinjiro; Nakajima, Yasuo

    2008-01-01

    Between 2000 and 2007, 17 patients with localized gastric lymphoma (10 mucosa-associated lymphoid tissue lymphomas and 7 diffuse large B-cell lymphomas) were treated with radiotherapy alone or doxorubicin-based chemotherapy followed by radiotherapy. Radiation dose of mucosa-associated lymphoid tissue (MALT) lymphoma was 30 Gy with a daily fraction size of 1.5 Gy. Sixteen patients achieved complete remission and the 5-year overall survival of MALT lymphoma and diffuse large B-cell lymphoma (DLBCL) were 100% and 87%, respectively. No gastric perforation and hemorrhage were noticed. Using AP/LR 2-port radiotherapy markedly decreased the liver dose. (author)

  3. Molecular Pathogenesis of MALT Lymphoma

    Directory of Open Access Journals (Sweden)

    Katharina Troppan

    2015-01-01

    Full Text Available Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT, also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis.

  4. Molecular Pathogenesis of MALT Lymphoma

    Science.gov (United States)

    Troppan, Katharina; Wenzl, Kerstin; Neumeister, Peter; Deutsch, Alexander

    2015-01-01

    Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT), also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis. PMID:25922601

  5. [Malignant lymphomas of the eye].

    Science.gov (United States)

    Fend, F; Süsskind, D; Deuter, C; Coupland, S E

    2017-11-01

    The eye and the ocular adnexae are rare sites for malignant non-Hodgkin lymphoma (NHL). Based on their anatomical location, intraocular lymphomas must be discerned from NHL of adnexal structures including conjunctiva, lacrimal gland, and orbit. Whereas the latter group mostly consists of indolent extranodal marginal zone B‑cell lymphomas of mucosa-associated lymphoid tissue (MALT) type or secondary manifestations of systemic NHL, most primary intraocular lymphomas are classified as diffuse large B‑cell lymphomas (DLBCL) and are considered a variant of primary DLBCL of the central nervous system. The most common form is primary vitreoretinal lymphoma (PVRL), which presents with nonspecific symptoms and is difficult to discern from uveitis. Diagnosis of PVRL is usually made by cytological, immunocytochemical, and molecular analysis of vitreous aspirates. Degenerative changes, limited material, and the occurrence of pseudoclonality in the molecular analysis of B‑cell clonality can hamper diagnostic assessment. Novel techniques such as detection of MYD88 mutations common in PVRL can increase diagnostic sensitivity. Close cooperation with clinical colleagues and rapid specimen processing are fundamental for successful diagnosis.

  6. PET-Directed Therapy With Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Classical Hodgkin Lymphoma

    Science.gov (United States)

    2017-10-18

    Classical Hodgkin Lymphoma; Lymphocyte-Depleted Classical Hodgkin Lymphoma; Lymphocyte-Rich Classical Hodgkin Lymphoma; Mixed Cellularity Classical Hodgkin Lymphoma; Nodular Sclerosis Classical Hodgkin Lymphoma

  7. A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma

    Directory of Open Access Journals (Sweden)

    Daisuke Usuda

    2017-11-01

    Full Text Available A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

  8. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Bonnie K Harrington

    Full Text Available Acalabrutinib (ACP-196 is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL. First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR was 25% (5/20 with a median progression free survival (PFS of 22.5 days. Clinical benefit was observed in 30% (6/20 of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL.

  9. KSHV/HHV-8 associated lymph node based lymphomas in HIV seronegative subjects. Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Quyen Nguyen, MD

    2016-12-01

    Full Text Available Extracavitary primary effusion lymphoma (ExPEL is a rare, high-grade lymphoproliferative disorder that displays immunoblastic, plasmablastic, or anaplastic morphology. It usually lacks expression of B-cell and T-cell markers, but often expresses the plasma cell markers CD138 and MUM1, and the activation marker CD30, along with EMA. ExPEL, similar to classic PEL occurring as lymphomatous effusions in serous body cavities without an associated tumor mass, is consistently associated with human herpes virus-8 (HHV8 infection, while a majority of cases also exhibits Epstein–Barr virus (EBV co-infection. Clinically, it is characterized by an almost exclusive male predominance (98% male, HIV-positivity (96% of patients are HIV+, acute presentation with B symptoms, and unfavorable overall survival (40% of patients die within 2 months. We report an asymptomatic HIV-negative female patient with incidentally found splenomegaly and extensive PET FDG-avid retroperitoneal, pelvic, and mediastinal lymphadenopathy. A core biopsy of her right pelvic lymph node showed aggregates of atypical cells with anaplastic features. Immunohistochemistry revealed that the neoplastic cells were positive for CD45, CD20, CD30, MUM1, CD138, EMA, CD3, HHV-8 and EBER. The diagnosis of ExPEL was established. Against medical advice and given the absence of significant symptoms, the patient refused to start treatment. Four months after the diagnosis, the patient remains asymptomatic, and follow-up CT scan demonstrates stability of her lymphadenopathy. We present here a case of ExPEL in which the patient's presentation defies the clinical norms, illustrating that ExPEL should also be included in the differential diagnosis of lymphomas occurring in asymptomatic HIV-negative patients.

  10. Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases

    DEFF Research Database (Denmark)

    Miletic, Ana V; Anzelon-Mills, Amy N; Mills, David M

    2010-01-01

    The inositol phosphatases phosphatase and tensin homologue (PTEN) and Src homology 2 domain-containing inositol phosphatase (SHIP) negatively regulate phosphatidylinositol-3-kinase (PI3K)-mediated growth, survival, and proliferation of hematopoietic cells. Although deletion of PTEN in mouse T cells...... results in lethal T cell lymphomas, we find that animals lacking PTEN or SHIP in B cells show no evidence of malignancy. However, concomitant deletion of PTEN and SHIP (bPTEN/SHIP(-/-)) results in spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma or, less frequently......, follicular or centroblastic lymphoma. bPTEN/SHIP(-/-) B cells exhibit enhanced survival and express more MCL1 and less Bim. These cells also express low amounts of p27(kip1) and high amounts of cyclin D3 and thus appear poised to undergo proliferative expansion. Unlike normal B cells, bPTEN/SHIP(-/-) B cells...

  11. Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-01-04

    Adult Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  12. Composite Lymphoma : EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma A Case Report

    NARCIS (Netherlands)

    Gualco, Gabriela; Chioato, Lucimara; Van Den Berg, Anke; Weiss, Lawrence M.; Bacchi, Carlos E.

    Composite lymphomas are rare and defined as hematopoietic neoplasms with more than I malignant lymphomatous clone showing different phenotypic features. Of all possible combinations between non-Hodgkin lymphomas, B cell or T cell, and Hodgkin lymphoma, the least frequent are the ones combining

  13. Drugs Approved for Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... about Your Treatment Research Drugs Approved for Non-Hodgkin Lymphoma This page lists cancer drugs approved by the ... are not listed here. Drugs Approved for Non-Hodgkin Lymphoma Abitrexate (Methotrexate) Acalabrutinib Adcetris (Brentuximab Vedotin) Aliqopa (Copanlisib ...

  14. Psoriasis and risk of malignant lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, M R; Skov, L; Zachariae, C

    2018-01-01

    In patients with psoriasis, the risk of lymphoma has been a subject of controversy and data from larger studies are limited1-4 . We therefore investigated the 5-year risk of new-onset Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) (excluding cutaneous T-cell lymphoma [CTCL]), and CTCL, respect......In patients with psoriasis, the risk of lymphoma has been a subject of controversy and data from larger studies are limited1-4 . We therefore investigated the 5-year risk of new-onset Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) (excluding cutaneous T-cell lymphoma [CTCL]), and CTCL......, respectively, in patients with psoriasis. This article is protected by copyright. All rights reserved....

  15. B-cell leukemia/lymphoma panel

    Science.gov (United States)

    ... ency/article/003518.htm B-cell leukemia/lymphoma panel To use the sharing features on this page, please enable JavaScript. B-cell leukemia/lymphoma panel is a blood test that looks for certain ...

  16. The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.

    LENUS (Irish Health Repository)

    Kavanagh, Dara O

    2012-02-01

    Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.

  17. Primary Lymphoma of the Gall Bladder

    African Journals Online (AJOL)

    1974-06-29

    Jun 29, 1974 ... A patient with primary lymphocytic lymphoma of the gall bladder is presented, and cases of primary lymphoma of this organ reported in the English literature are reviewed. Primary lymphoma of the extrahepatic biliary drainage system is a rare cause of obstructive jaundice and has a poor prognosis. S. Air.

  18. Case presentation – thyroid lymphoma

    Directory of Open Access Journals (Sweden)

    Belkisa Izić

    2011-11-01

    Full Text Available Malignant tumors of the thyroid gland account for about 1% of thenewly diagnosed malignant tumors each year, and their incidence inwomen is twice the incidence in men. According to the WHO classification (2004 thyroid tumors are divided into: carcinoma of the thyroid, adenoma and similar tumors, and other thyroid tumors which include: teratomas, angiosarcomas, paragangliomas and others, as well as primary lymphomas and plasmacytomas. Primary thyroid lymphomasare defined as lymphomas which originate in the thyroid gland. This study presents the case of a 68-year-old patient with a thyroid lymphoma, which caused compression of the airways. In the patientpresented there was reduced activity of the thyroid gland. The dominant symptoms were: breathing difficulties, hoarse voice and the enlargement of the thyroid. An ultrasound examination was performedbefore surgery on the neck, which showed a multinodular thyroid,with compromised and compressed trachea to the right and rear. Anemergency surgical procedure was performed to reduce the tumor.Pathohistological diagnosis confirmed diffuse large B cell lymphoma.The aim of the study was to present a patient with a thyroid lymphoma, who had previously not had any immunological changes to the gland,that is, she had not had any chronic lymphocyte thyroiditis, but due to the compressive syndrome it was necessary to perform an emergencysurgical procedure to reduce the tumor.

  19. Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas.

    Science.gov (United States)

    Brell, Marta; Tortosa, Avelina; Verger, Eugenia; Gil, Juan Miguel; Viñolas, Nuria; Villá, Salvador; Acebes, Juan José; Caral, Lluis; Pujol, Teresa; Ferrer, Isidro; Ribalta, Teresa; Graus, Francesc

    2005-07-15

    Anaplastic gliomas constitute a heterogeneous group of tumors with different therapeutic responses to adjuvant chemotherapy with alkylating agents. O6-Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, is one of the implicated factors in glioma chemoresistance. The prognostic value of MGMT remains controversial due in part to the fact that previous published studies included heterogeneous groups of patients with different tumor grades. The aim of this study was to evaluate the prognostic significance of MGMT in patients with anaplastic glioma. Ninety-three patients with anaplastic glioma were analyzed for MGMT protein expression by immunohistochemistry. In addition, for those patients from whom a good yield of DNA was obtained (n = 40), MGMT promoter methylation profile was analyzed by methylation-specific PCR. MGMT prognostic significance was evaluated together with other well-known prognostic factors. Fifty-one tumors (54.8%) showed nuclear staining of MGMT. There was a trend towards longer overall survival for those patients with negative MGMT immunostaining (hazard ratio, 1.66; P = 0.066). In a secondary analysis including those patients who actually received chemotherapy (n = 72), the absence of MGMT expression was independently associated with better survival (hazard ratio, 2.12; P = 0.027). MGMT promoter methylation was observed in 50% of the analyzed tumors. No statistical correlation between MGMT expression and MGMT promoter hypermethylation was observed. Unlike previous studies, we did not find a correlation between MGMT promoter methylation and survival. However, we observed a correlation between MGMT protein expression and survival in those patients who received chemotherapy thus suggesting that the absence of MGMT expression is a positive predictive marker in patients with anaplastic glioma.

  20. Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK

    OpenAIRE

    Fontana, Diletta; Ceccon, Monica; Gambacorti-Passerini, Carlo; Mologni, Luca

    2015-01-01

    Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor involved in both solid and hematological tumors. About 80% of ALK-positive anaplastic large-cell lymphoma (ALCL) cases are characterized by the t(2;5)(p23;q35) translocation, encoding for the aberrant fusion protein nucleophosmin (NPM)-ALK, whereas 5% of non-small-cell lung cancer (NSCLC) patients carry the inv(2)(p21;p23) rearrangement, encoding for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion. The ALK/c...

  1. Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

    Directory of Open Access Journals (Sweden)

    Maher Kurdi

    2014-01-01

    Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

  2. Outcome of residual mediastinal masses of thoracic lymphomas in children: impact on management and radiological follow-up strategy

    International Nuclear Information System (INIS)

    Brisse, H.; Pacquement, H.; Burdairon, E.; Plancher, C.; Neuenschwander, S.

    1998-01-01

    Background. Following treatment with chemotherapy and radiotherapy, patients with thoracic lymphomas may demonstrate benign residual mediastinal masses, composed of inflammatory, fibrous or necrotic tissue. Because of the potential risk of viable tumour cells within the mass, histological verification of the nature of these masses may be requested. Objective. To study the outcome of thoracic lymphomas in children in order to optimise the radiological follow-up strategy of residual mediastinal masses (RMM). Materials and methods. A retrospective study of 39 children [24 with Hodgkin's disease (HD), 10 with non-Hodgkin's lymphoma (NHL), and 5 with anaplastic lymphoma (AL)]. The results of chest X-rays (CXR) and thoracic CT performed at the time of re-assessment were compared with the histology of the residual masses (n = 11) or the clinical course (n = 28). Results. At the time of re-evaluation, 16/39 patients had residual mediastinal enlargement (RME) on CXR, and 18/39 patients had RMM on CT. Good concordance was observed between the two imaging modalities (K = 0.69). Two children with a RMM died from extra-mediastinal progression. Two children with NHL had active residual mediastinal lesions but neither had RMM. Sixteen cases of RMM were observed in the remaining 35 children and 9 of these masses were histologically verified as benign. A favourable course was observed in these 35 cases. Conclusions. RMM are frequent and generally benign. They are well shown on CXR and have a non-specific appearance on CT. Except when required by a treatment protocol, they could be submitted to further radiological follow-up before contemplating surgical verification. (orig.)

  3. Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Margaret M. Briehl

    2012-08-01

    Full Text Available Acquired resistance to drugs commonly used for lymphoma treatment poses a significant barrier to improving lymphoma patient survival. Previous work with a lymphoma tissue culture model indicates that selection for resistance to oxidative stress confers resistance to chemotherapy-induced apoptosis. This suggests that adaptation to chronic oxidative stress can contribute to chemoresistance seen in lymphoma patients. Oxidative stress-resistant WEHI7.2 cell variants in a lymphoma tissue culture model exhibit a range of apoptosis sensitivities. We exploited this phenotype to test for mitochondrial changes affecting sensitivity to apoptosis in cells made resistant to oxidative stress. We identified impaired release of cytochrome c, and the intermembrane proteins adenylate kinase 2 and Smac/DIABLO, indicating inhibition of the pathway leading to permeabilization of the outer mitochondrial membrane. Blunting of a glucocorticoid-induced signal and intrinsic mitochondrial resistance to cytochrome c release contributed to both points of resistance. The level of Bcl-2 family members or a difference in Bim induction were not contributing factors. The extent of cardiolipin oxidation following dexamethasone treatment, however, did correlate with apoptosis resistance. The differences found in the variants were all proportionate to the degree of resistance to glucocorticoid treatment. We conclude that tolerance to oxidative stress leads to mitochondrial changes that confer resistance to apoptosis.

  4. The current state of clinical application of serum biomarkers for canine lymphoma.

    Directory of Open Access Journals (Sweden)

    Jeffrey N Bryan

    2016-09-01

    Full Text Available Serum biomarkers of canine lymphoma activity for diagnosis, prognosis, and therapy monitoring have been of clinical interest for more than a decade. Tumor products, biochemical enzymes, cytokines, metabolic profiling, leakage enzymes, as well as serum proteins have been studied as biomarkers for lymphoma. Multiple biomarkers combined have been shown to be most sensitive and specific. C-reactive protein, thymidine kinase 1, and haptoglobin have been most extensively studied and commercialized in diagnostic tests, the TK Canine Cancer Panel and the Canine Lymphoma Blood Test. These tests have been evaluated either in cohorts of diseased and healthy dogs or in prospective studies of ill dogs, respectively, for application to clinical decision making. Some evidence exists for application of these tests, but large-scale studies are lacking in a broad range of lymphoma forms. These biomarkers are commonly elevated at diagnosis and at relapse. Further study is necessary to determine if early intervention guided by biomarker elevation will improve quantity or quality of life for dogs with lymphoma.

  5. Malignant lymphomas (including myeloproliferative disorders)

    International Nuclear Information System (INIS)

    Todd, I.D.H.

    1985-01-01

    This chapter deals with the radiotherapy and cytotoxic chemotherapy of the malignant lymphomas. Included within this group are Hodgkin's disease, non-Hodgkin's lymphoma, mycosis fungoides, and chronic lymphatic leukaemia. A further section deals with the myeloproliferative disorders, including granulocytic leukaemia, polycythaemia vera, and primary thrombocythaemia. Excluded are myeloma and reticulum cell sarcoma of bone and acute leukaemia. With regard to Hodgkin's disease, the past 25 years have seen general recognition of the curative potential of radiotherapy, at least in the local stages, and, more recently, awareness of the ability to achieve long-term survival after combination chemotherapy in generalised or in recurrent disease. At the same time the importance of staging has become appreciated and the introduction of procedures such as lymphography, staging laparotomy, and computer tomography (CT) has enormously increased its reliability. Advances have not been so dramatic in the complex group of non-Hodgkins's lymphomas, but are still very real

  6. Interleukin-12 in Treating Patients With Previously Treated Non-Hodgkin's Lymphoma or Hodgkin's Disease

    Science.gov (United States)

    2015-04-14

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  7. Nodular lymphocyte predominant Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Siddiqui, Neelam; Al-Diab, Abdulrahman I.

    2005-01-01

    To describe the clinicopathological features, treatment, treatment outcome and sequelae of patients with nodular lymphocyte, predominant Hodgkin's lymphoma (NLPHL) in Saudi population. This is a retrospective review of 29 patients with lymphocyte predominant Hodgkin's lymphoma treated at two major hospitals (King Khalid University Hospital and Security Forces Hospital) in Riyadh, Kingdom of Saudi Arabia from 1985 to 2000. Histological subtypes were confirmed by review of hematoxylin and eosin paraffin sections and immunochemistry. Details of clinical presentation, stage, treatment and results of treatment were analyzed. On pathological reappraisal of the 29 cases, 3 patients had nodular sclerosis Hodgkin's lymphoma and 4 patients were reclassified as lymphocyte rich classical Hodgkin's lymphoma. Twenty-two patients were identified to have nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). These patients comprised of 18 mails and 4 female patients with a median age at presentation of 25 years. Nineteen (86%) patients had an early stage (Ann Arbor stage I and II) disease, 2 had stage III and one patient had stage IV. The majority of patients presented with peripheral lymphadenopathy and long duration of symptoms. For 16 patients, details of treatment and follow-up were available. All of these achieved a complete response to initial treatment. Four patients relapsed following the primary therapy. Our results are consistent with the previous series reported from Western countries and confirmed that the patients with NLPHL have characteristic clinical and pathological profile that distinguish it from other types of Hodgkin's lymphoma. The disease tends to run an unusual course and although most patients achieve an excellent response to therapy there is a tendency to replace. treatment remains controversial; however, recent understanding of the molecular pathogenesis of NLPHL could lead to modification of current therapeutic approach to this disease. (author)

  8. Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma

    Science.gov (United States)

    Smedby, K E; Åkerman, M; Hildebrand, H; Glimelius, B; Ekbom, A; Askling, J

    2005-01-01

    Background: Numerous studies have reported on the association between coeliac disease and the otherwise uncommon enteropathy-type T cell lymphoma (ETTL). A systematic risk assessment of more prevalent lymphoma entities, such as B cell and non-intestinal lymphomas, in coeliac disease has not been performed. Aims: In light of the increasing number of patients diagnosed with coeliac disease and the unknown aetiology of malignant lymphomas, we aimed to estimate the distribution and risk of lymphoma subtypes in coeliac disease. Methods: We reviewed and reclassified 56 cases of incident malignant lymphomas occurring in a Swedish population based cohort of 11 650 patients hospitalised with coeliac disease. The observed numbers of lymphoma subtypes were compared with those expected in the Swedish population. Results: The majority (n = 32, 57%) of lymphomas in the cohort were not intestinal T cell lymphomas. Significantly increased risks were observed for B cell non-Hodgkin lymphoma (NHL) (standardised incidence ratio (SIR) 2.2 (95% confidence interval (CI) 1.2–3.6); 11 non-intestinal and five intestinal) and for lymphomas of non-intestinal origin (SIR 3.6 (95% CI 2.3–5.2), 11 B and 14 T cell). Furthermore, 44% of patients with B cell NHL had a history of other autoimmune/inflammatory diseases. The relative risks for T cell NHL (SIR 51 (95% CI 35–68); n = 37) and for primary gastrointestinal lymphomas (SIR 24 (95% CI 16–34); five B and 25 T cell) were markedly increased, as anticipated. Conclusion: Most lymphomas complicating coeliac disease are indeed related to the disease and are not of the ETTL-type. There was a remarkable aggregation of autoimmune/inflammatory disorders, female sex, coeliac disease, and B cell lymphoma. PMID:15591504

  9. Tissue enzyme changes in parabiotic rats with subcutaneous lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Herzfeld, A; Greengard, O; Warren, S

    1977-01-01

    A solid lymphoma was implanted into normal rats and into one partner of parabiotic pairs. Appreciable decreases in hepatic ornithine aminotransferase and arginase occurred about a week earlier (4 to 6 days after implantation) in single than in parabiotic hosts. By 18 to 21 days significant decreases in both enzymes were also apparent in the host partner. The hepatic thymidine kinase showed a 5-fold elevation in single hosts 4 days after implantation; by 14 days its levels were about 200 times above normal and had also risen in the parabiotic hosts (20-fold) and the host partners (4-fold). Implantation of fibrosarcoma caused qualitatively similar but generally less pronounced changes in the above 3 enzymes in livers of single hosts, parabiotic hosts, and host partners. The splenic thymidine kinase, 14 days after implantation, was increased from control levels of about 3 units/g to 50.6, 44.8, and 13.5 units/g in single hosts, parabiotic hosts, and host partners, respectively. At later stages, 17 to 20 days after implantation of the lymphoma, appreciable amounts of thymidine kinase appeared in the plasma: the units of activity per ml were 6.2 in single hosts, 0.79 in parabolic hosts, and 0.55 in host partners (control <0.05). The observations on the hepatic and splenic enzyme changes in parabiotic rats suggest that effects of neoplasms on distant host tissues are mediated by humoral factors. The less pronounced responses in parabiotic than in single hosts indicate that the tumor-free partner affords some protection against these systemic effects.

  10. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

    Energy Technology Data Exchange (ETDEWEB)

    Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

    2014-08-15

    Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

  11. Hodgkin Lymphomas epidemiology

    International Nuclear Information System (INIS)

    Diaz, Carlos; Barroso, Maria; Alvarez, Julio; Sarmiento, Sofia; Diaz, Jose

    2003-01-01

    The interest of this study has been to learn the bio demographic characteristics of the Hodgkin lymphoma in our surrounding in accord with different clinical statistics that are considered of interest taken as references the results obtained in each on them. The clinical histories of the patients were evaluated retrospectively with diagnosis of Hodgkin, and registered in the national Institute of Oncology in Havana during the years 1980-1985 (group1) and the 1990-1995 (group 2). The sample was constituted by 242 patients (156 group 1, 86 group 2). The disease was slightly more frequent in males (1.3:1) in both groups. The biggest incidence fell upon the patients under 30 year of age with 74 (31%) in the group 1, and 41 (17%) group 2; followed by the group of patients between 30 and 49 years old with 24% in group 1 and 12 in group 2. The histological subtype most frequently found was the mixed cellularity 55% of the patients followed by nodular sclerosis in 32% clinical stage III was the most frequent with 138 patients (55%) the cervical adenopathy was the most consulted symptom referred by 199 (82%) of the patients. The ionizing radiation as only treatment were used in 115 patients (48%) while 80 (33%) were treated in conjunction with polychemotherapy, and in 40 (17%) polychemotherapy was used alone. A total of 204 (84%) patients showed complete remission when ended the initial treatment while 96 (40.9%) showed a relapse and 55 (62%) of them obtained a second CR. Until the last news, there are 196 (81%) alive patients and 43 (18%) dead. (The author)

  12. Imaging of non-hodgkin lymphomas

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Hutchings, Martin

    2015-01-01

    interim PET imaging has high prognostic value in lymphoma, a number of trials investigate PET-based, response-adapted therapy for non-Hodgkin lymphomas (NHL). PET response is the main determinant of response according to the new response criteria, but PET/CT has little or no role in routine surveillance......Optimal lymphoma management requires accurate pretreatment staging and reliable assessment of response, both during and after therapy. Positron emission tomography with computerized tomography (PET/CT) combines functional and anatomical imaging and provides the most sensitive and accurate methods...... for lymphoma imaging. New guidelines for lymphoma imaging and recently revised criteria for lymphoma staging and response assessment recommend PET/CT staging, treatment monitoring, and response evaluation in all FDG-avid lymphomas, while CT remains the method of choice for non-FDG-avid histologies. Since...

  13. Treatment options for ocular adnexal lymphoma (OAL

    Directory of Open Access Journals (Sweden)

    Victoria Mary Lendrum Cohen

    2009-11-01

    Full Text Available Victoria Mary Lendrum CohenSt. Bartholomew’s and Moorfields Eye Hospital, London UKAbstract: Most lymphomas that involve the ocular adnexal structure are low grade, B cell, non-Hodgkin’s lymphomas. The treatment depends upon the grade and stage of the disease. High grade lymhoma requires treatment with systemic chemotherapy whereas the localized low grade (extranodal marginal zone lymphoma can be successfully managed with local radiotherapy. Chlamydia psittaci infection is associated with low grade ocular lymphoma; however there is wide geographic variation in the strength of this association. Blanket antibiotic therapy is not advised unless there is proof of an infective agent. The monoclonal antibody, rituximab, may be successful for CD20 positive lymphoma, although it is likely that rituximab will have better long-term results when used in combination with systemic chemotherapy.Keywords: ocular adnexal lymphoma, mucosa associated lymphoid tissue, extranodal marginal zone lymphoma, Chlamydia psittaci, rituximab, radiotherapy, chemotherapy

  14. Immunological monitoring of patients affected by anaplastic glioma concerning the effects of surgery, radio-, and chemotherapy

    International Nuclear Information System (INIS)

    Servadei, F.; Gaist, G.; Padovani, R.; Parente, R.; Bucci, M.; Spagnolli, F.; Steiner, L.

    1982-01-01

    The authors studied 24 patients affected by anaplastic gliomas as regards immunology. In all of them the authors evaluated the lymphocyte subpopulation (B and T), firstly by simple lymphocyte count, secondly by studying the rosettes E-total and EAC, thirdly by stimulating the lymphocytes with mitogenes phytohaemoagglutinin-P (PHA), concanavalin A (Con A), and poke-weed mitogen (PWM), and lastly by counting the release of Cr 51 in Chang liver cells culture in order to obtain antibody dependent cellular cytotoxicity (ADCC). The parameters were also evaluated after surgery and during conventional radio-chemotherapy with BCNU. Whereas the so-called B-pool seems to be unaffected, the preliminary results show that the T-pool (identified by the E-t rosettes and by responses to PHA, PWM and ConA) is depressed to a statistically significant degree, if compared with a control group. This depression seems to be related to the tumoral mass and it is not increased by radio-chemotherapy. In addition, ADCC also seems to be depressed in our glioma patients in comparison with a control group and with a group of bladder cancer patients. (author)

  15. Anaplastic carcinoma of the pancreas: Is there a role for palliative surgical procedure?

    Directory of Open Access Journals (Sweden)

    Rajan Vaithianathan

    2014-01-01

    Full Text Available Anaplastic carcinoma (AC or undifferentiated carcinoma of the pancreas is a rare variant among the malignant pancreatic neoplasms. These tumors have a poor prognosis with survival measured in months. The role of surgical palliation to improve the quality of life is not well defined in these patients. We report a case of AC of pancreas in a 65-year-old male patient. Patient had upper abdominal pain with frequent bilious vomiting. Computed tomography scan of the abdomen showed a mass in the body of pancreas with possible infiltration of duodenojejunal flexure (DJF. Laparotomy revealed an inoperable mass with posterior fixity and involvement of the DJF. Patient underwent a palliative duodenojejunostomy. Tissue biopsy from the tumor showed pleomorphic type AC with giant cells. Patient had good symptomatic relief from profuse vomiting and progressed well at follow up. AC of pancreas is a rare and aggressive malignancy with dismal outlook. If obstructive symptoms are present due to duodenal involvement, a palliative bypass may be a worthwhile surgical option in selected cases.

  16. Lipoamino acid prodrugs of paclitaxel: synthesis and cytotoxicity evaluation on human anaplastic thyroid carcinoma cells.

    Science.gov (United States)

    Pignatello, R; Paolino, D; Pantò, V; Pistară, V; Calvagno, M G; Russo, D; Puglisi, G; Fresta, M

    2009-03-01

    Lipophilic derivatives of the anticancer drug paclitaxel (PTX) were prepared by means of its conjugation to lipoamino acid (LAA) residues, with the aim of increasing drug accumulation in tumor cells. PTX was linked to the methyl esters of norleucine (C6) or 2-aminodecanoic acid (C10). A succinic acid group was used as a spacer to link the 2'-hydroxyl group of PTX and the LAA residue, respectively by means of an ester and an amide bond. The in vitro anticancer activity of the prodrugs was tested on a human thyroid anaplastic cancer cell line (ARO). The intracellular uptake kinetics of free PTX and its prodrugs was assessed by HPLC. PTX-LAA prodrugs showed a noticeable cytotoxic activity against ARO cells at shorter incubation time (12 h) and lower doses (0.01-0.1 microM) than PTX. Intracellular accumulation experiments indicated an improvement of drug concentration inside these cells, related to the block of the cellular expulsion by means of multi drug resistance efflux complex and improved physicochemical features that allowed the greater passive cellular membrane permeation. The enhanced activity of PTX-LAA prodrugs, in terms of potency and onset of the effect, as well as the interesting intracellular accumulation data suggest that these compounds can be further tested as possible alternatives to PTX for the treatment of resistant cancer cells.

  17. Effectiveness of interferon-beta and temozolomide combination therapy against temozolomide-refractory recurrent anaplastic astrocytoma

    Directory of Open Access Journals (Sweden)

    Arai Hajime

    2007-08-01

    Full Text Available Abstract Background Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ, has demonstrated promising activity against recurrent glioma, the effects last only a few months and drug resistance develops thereafter in most cases. Induction of O6-methylguanine-DNA methyltransferase (MGMT in tumors is considered to be responsible for resistance to TMZ. Interferon-beta has been reported to suppress MGMT in an experimental glioma model. Here we report a patient with TMZ-refractory anaplastic astrocytoma (AA who was treated successfully with a combination of interferon-beta and TMZ. Case presentation A patient with recurrent AA after radiation-chemotherapy and stereotactic radiotherapy was treated with TMZ. After 6 cycles, the tumor became refractory to TMZ, and the patient was treated with interferon-beta at 3 × 106 international units/body, followed by 5 consecutive days of 200 mg/m2 TMZ in cycles of 28 days. After the second cycle the tumor decreased in size by 50% (PR. The tumor showed further shrinkage after 8 months and the patient's KPS improved from 70% to 100%. The immunohistochemical study of the initial tumor specimen confirmed positive MGMT protein expression. Conclusion It is considered that interferon-beta pre-administration increased the TMZ sensitivity of the glioma, which had been refractory to TMZ monotherapy.

  18. Anaplastic carcinoma of the pancreas: is there a role for palliative surgical procedure?

    Science.gov (United States)

    Vaithianathan, Rajan; Panneerselvam, Senthil; Santhanam, Ramachandran

    2014-01-01

    Anaplastic carcinoma (AC) or undifferentiated carcinoma of the pancreas is a rare variant among the malignant pancreatic neoplasms. These tumors have a poor prognosis with survival measured in months. The role of surgical palliation to improve the quality of life is not well defined in these patients. We report a case of AC of pancreas in a 65-year-old male patient. Patient had upper abdominal pain with frequent bilious vomiting. Computed tomography scan of the abdomen showed a mass in the body of pancreas with possible infiltration of duodenojejunal flexure (DJF). Laparotomy revealed an inoperable mass with posterior fixity and involvement of the DJF. Patient underwent a palliative duodenojejunostomy. Tissue biopsy from the tumor showed pleomorphic type AC with giant cells. Patient had good symptomatic relief from profuse vomiting and progressed well at follow up. AC of pancreas is a rare and aggressive malignancy with dismal outlook. If obstructive symptoms are present due to duodenal involvement, a palliative bypass may be a worthwhile surgical option in selected cases.

  19. Multidisciplinaly total-cell-kill treatment of bronchogenic small cell anaplastic carcinoma

    International Nuclear Information System (INIS)

    Ota, Kazuo; Nishimura, Minoru; Urata, Atsuo; Murakami, Minoru; Goto, Tatsuhiko

    1981-01-01

    Survival time of the patients with bronchogenic small cell anaplastic cancer was studied. Combined treatment with six-drug combination chemotherapy ''METVFC'' (mitomycin C + cyclophosphamide + toyomycin + vincristine + 5-FU + cytosine arabinoside) and radiotherapy (5,000 rads in total) was given to 14 cases of limited disease of small cell carcinoma. Median survival was 8 months, one year and two year survival rates were 47% and 27%, respectively. Combined treatment with METVFC and small dose radiotherapy of 100 or 200 rads irradiation 4 hours before chemotherapy, followed by remission consolidation of 3,000 -- 4,000 rads radiotherapy, thereafter second line chemotherapy of ''COAM'' (cyclophosphamide + vincristine + ACNU + methotrexate) was given to 4 cases of limited disease of small cell carcinoma. All cases survived more than 1.5 years and two of them have retained complete remission more than 1.5 years. There are 6 cases with small cell carcinoma survived more than 3 years out of total 128 cases. They are all those of limited disease. They received combined treatment of chemotherapy and radiotherapy simultaneously or alternatively, followed by remission maintenance chemotherapy. One case of them died from cancer. Two cases died from another disease without lung cancer. Three cases survived healthy more than 3 to 8 years. In the limited disease, small cell carcinoma of the lung might be curable if the complete remission could continue more than three years. (author)

  20. Computational diagnosis of canine lymphoma

    Science.gov (United States)

    Mirkes, E. M.; Alexandrakis, I.; Slater, K.; Tuli, R.; Gorban, A. N.

    2014-03-01

    One out of four dogs will develop cancer in their lifetime and 20% of those will be lymphoma cases. PetScreen developed a lymphoma blood test using serum samples collected from several veterinary practices. The samples were fractionated and analysed by mass spectrometry. Two protein peaks, with the highest diagnostic power, were selected and further identified as acute phase proteins, C-Reactive Protein and Haptoglobin. Data mining methods were then applied to the collected data for the development of an online computer-assisted veterinary diagnostic tool. The generated software can be used as a diagnostic, monitoring and screening tool. Initially, the diagnosis of lymphoma was formulated as a classification problem and then later refined as a lymphoma risk estimation. Three methods, decision trees, kNN and probability density evaluation, were used for classification and risk estimation and several preprocessing approaches were implemented to create the diagnostic system. For the differential diagnosis the best solution gave a sensitivity and specificity of 83.5% and 77%, respectively (using three input features, CRP, Haptoglobin and standard clinical symptom). For the screening task, the decision tree method provided the best result, with sensitivity and specificity of 81.4% and >99%, respectively (using the same input features). Furthermore, the development and application of new techniques for the generation of risk maps allowed their user-friendly visualization.

  1. INTRAOCULAR NON-HODGKINS-LYMPHOMA

    NARCIS (Netherlands)

    HOOYMANS, JMM; TIMMERMAN, Z

    1990-01-01

    Usually eye symptoms precede the infiltration of non-Hodgkin's lymphoma in the central nervous system or in other organs. Early treatment of the tumor by irradiation, to which it is highly sensitive, can preserve the vision and prolong the life of the patient. Such therapy however is often delayed

  2. Computational diagnosis of canine lymphoma

    International Nuclear Information System (INIS)

    Mirkes, E M; Gorban, A N; Alexandrakis, I; Tuli, R; Slater, K

    2014-01-01

    One out of four dogs will develop cancer in their lifetime and 20% of those will be lymphoma cases. PetScreen developed a lymphoma blood test using serum samples collected from several veterinary practices. The samples were fractionated and analysed by mass spectrometry. Two protein peaks, with the highest diagnostic power, were selected and further identified as acute phase proteins, C-Reactive Protein and Haptoglobin. Data mining methods were then applied to the collected data for the development of an online computer-assisted veterinary diagnostic tool. The generated software can be used as a diagnostic, monitoring and screening tool. Initially, the diagnosis of lymphoma was formulated as a classification problem and then later refined as a lymphoma risk estimation. Three methods, decision trees, kNN and probability density evaluation, were used for classification and risk estimation and several preprocessing approaches were implemented to create the diagnostic system. For the differential diagnosis the best solution gave a sensitivity and specificity of 83.5% and 77%, respectively (using three input features, CRP, Haptoglobin and standard clinical symptom). For the screening task, the decision tree method provided the best result, with sensitivity and specificity of 81.4% and >99%, respectively (using the same input features). Furthermore, the development and application of new techniques for the generation of risk maps allowed their user-friendly visualization

  3. Drugs Approved for Hodgkin Lymphoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Hodgkin lymphoma. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  4. EAMJ May Lymphomas.indd

    African Journals Online (AJOL)

    2009-05-05

    May 5, 2009 ... NHL were categorised as low or high grade according to the criteria from the Kiel classification. ..... J. Cancer. 1993; 54: 26-36. 9. Walter, P.R., Klotz, F., Alfy-Gattas, T., et al. Malignant lymphomas in Gabon (equatorial Africa): a morphologic study of 72 cases. Hum. Pathol. 1991;. 22:1040-1043. 10. Cool, C.D. ...

  5. Lymphoma of the cervix uteri

    Science.gov (United States)

    Amna, Fatima Abu; Howell, Rosemary; Raj, Shinod

    2009-01-01

    A 46-year-old woman of Asian origin presented with heavy intermenstrual and postcoital bleeding caused by the rare entity of primary non-Hodgkin’s lymphoma of the cervix uteri, with no evidence of disease elsewhere. Prompt diagnosis by biopsy avoided unnecessary surgery, and instead appropriate treatment with chemoradiotherapy was administered. PMID:21909338

  6. Primary Vitreoretinal Lymphoma -- A Review.

    Science.gov (United States)

    Araujo, Iguaracyra; Coupland, Sarah E

    2017-01-01

    Primary vitreoretinal lymphoma (PVRL) is the most common intraocular lymphoma occurring in the eye. It is a high-grade typically B-cell malignancy, arising in the retina, and is often associated with central nervous system (CNS) disease and thereby a poor prognosis. It needs to be distinguished from choroidal low-grade B-cell lymphomas, which do not disseminate to the brain and have a good prognosis. Because of the rarity of PVRL, information is lacking regarding its true incidence, its geographical or ethnic variation, and underlying risk factors apart from immunosuppression associated with human immunodeficiency virus (HIV) and Epstein Barr virus. PVRL often presents masquerading as other intraocular diseases and is therefore often associated with diagnostic delays. This is compounded by the fragility of the neoplastic B cells, which hampers vitrectomy yields and pathological work-up. The latter includes cytomorphology and immunoprofiling, with adjunctive tests such as cytokine analysis, polymerase chain reaction for clonality, MYD88 mutational testing, and possibly bespoke next generation sequencing. Recent examinations of PVRL and CNS lymphoma (CNSL) using whole genome sequencing confirm that these tumors arise from activated postgerminal center cells, reflecting their aggressive course in most cases. The treatment of PVRL varies between centers and is dependent on presence or absence of concomitant CNS disease. The prognosis remains poor, and yet progress is steadily being made through international collaborative clinical trials. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  7. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Lymphoma or Leukemia

    Science.gov (United States)

    2013-01-31

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  8. A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma

    Science.gov (United States)

    AbouYabis, Abeer N.; Shenoy, Pareen J.; Sinha, Rajni; Flowers, Christopher R.; Lechowicz, Mary Jo

    2011-01-01

    Anthracycline-based chemotherapy remains standard treatment for peripheral T-cell lymphoma (PTCL) although its benefits have been questioned. We performed systematic literature review and meta-analyses examining the complete response (CR) and overall survival (OS) rates for patients with PTCL. The CR rate for PTCL patients ranged from 35.9% (95% CI 23.4–50.7%) for enteropathy-type T-cell lymphoma (ETTL) to 65.8% (95% CI 54.0–75.9%) for anaplastic large cell lymphoma (ALCL). The 5-year OS was 38.5% (95% CI 35.5–41.6%) for all PTCL patients and ranged from 20.3% (95% CI 12.5–31.2%) for ETTL to 56.5% (95% CI 42.8–69.2%) for ALCL. These data suggest that there is marked heterogeneity across PTCL subtypes in the benefits of anthracycline-based chemotherapy. While anthracyclines produce CR in half of PTCL patients, this yields reasonable 5-year OS for patients with ALCL but not for those with PTCL-NOS or ETTL. Novel agents and regimens are needed to improve outcomes for these patients. PMID:22084700

  9. Medicinal therapy of malignant lymphomas

    International Nuclear Information System (INIS)

    Aul, C.; Schroeder, M.; Giagounidis, A.

    2002-01-01

    Chemotherapy represents the most important therapeutic option in malignant lymphomas. Low to intermediate risk Hodgkin's disease is treated by a combination of chemotherapy and radiation. The new chemotherapy protocol BEACOPP has improved the outcome of advanced stages in comparison with the internationally accepted standard protocol COPP/ABVD. Dependent on the initial staging, cure rates between 50 and 95% can be achieved. Indolent non-Hodgkin's lymphomas usually present in advanced stages of disease. Chemotherapy in these cases has palliative character and aims at improving patients'quality of life and at avoiding complications due to the disease. In aggressive and very aggressive non-Hodgkin's lymphoma chemotherapy is curative and must be initiated immediately irrespective of the staging results. The efficacy of the standard protocol CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone), that was established in the 1970s, has recently been improved by shortening of the therapy interval (CHOP-14 vs.CHOP-21),addition of etoposide (CHOEP) and combination with the monoclonal antibody rituximab (R-CHOP). The value of high dose chemotherapy with stem cell transplantation has been shown unequivocally only for aggressive non-Hodgkin lymphoma and relapsed Hodgkin's disease responsive to chemotherapy. The therapeutic strategy of malignant lymphomas is likely to be improved within the next years due to the introduction of novel cytostatic agents, the broadening application of monoclonal antibodies,upcoming new transplantation procedures and the development of substances with molecular targets.To rapidly increase our current knowledge on the topic it is mandatory to include patients into the large national and international multicenter studies. (orig.) [de

  10. Tandem autologous-allo-SCT is feasible in patients with high-risk relapsed non-Hodgkin's lymphoma.

    Science.gov (United States)

    Crocchiolo, R; Castagna, L; Fürst, S; El-Cheikh, J; Faucher, C; Oudin, C; Granata, A; Bouabdallah, R; Coso, D; Chabannon, C; Balzarotti, M; Santoro, A; Blaise, D

    2013-02-01

    Allo-SCT is used to exploit GVL effect in high-risk relapsed non-Hodgkin's lymphoma (NHL). Here, we retrospectively analyzed 34 high-risk NHL patients who underwent auto-SCT followed closely by reduced-intensity allo-SCT ('tandem auto-allo') from January 2002 to November 2010. The search for an allogeneic donor was started at the beginning of salvage regimen. Median patients' age was 47 (27-68) years; histotypes were: diffuse large B-cell n=5, follicular n=14, transformed follicular n=4, mantle-cell n=5, plasmocytoid lymphoma n=1, anaplastic large T-cell n=2, peripheral T-cell n=3. Donors were HLA-identical siblings (n=29) or 10/10-matched unrelated individuals (n=5). Median interval between auto-SCT and allo-SCT was 77 days (36-197). At a median follow-up of 46 (8-108) months since allo-SCT, 5-year OS is 77% (61-93) and PFS is 68% (51-85). Disease relapse or progression occurred in six patients, 100-day TRM was 0%, 2-year TRM incidence was 6%. In conclusion, tandem transplantation is feasible in high-risk NHL patients having a HLA-identical donor. This approach could represent a suitable therapeutic option for those patients with high-risk NHL potentially benefitting from further therapy after auto-SCT. Donor searches should be started promptly whenever such an approach is chosen.

  11. [Primary mediastinal lymphoma; a clinicopathologic case series].

    Science.gov (United States)

    Sugimoto, Seiichiro; Soh, Junichi; Maki, Yuho; Kurosaki, Takeshi; Yamane, Masaomi; Toyooka, Shinichi; Oto, Takahiro; Miyoshi, Shinichiro

    2012-07-01

    Treatment for primary mediastinal lymphoma generally involves chemotherapy and radiotherapy, and treatment regimens depend on histologic subtypes of lymphoma. The histologic subtype of lymphoma is mostly determined by computed tomography (CT)-guided core-needle biopsy or surgical procedures, including thoracotomy, thoracoscopy and mediastinoscopy. We describe the clinicopathologic features and diagnostic procedures of 8 cases of primary mediastinal lymphoma. The male-to-female ratio was 1:1, and median age at diagnosis was 27 years. The median size of the primary mediastinal tumor on CT was 8.5 cm. Five patients were diagnosed by CT-guided core-needle biopsy, 1 by open biopsy and 2 by surgery. Three patients were diagnosed with nodular sclerosis Hodgkin lymphoma, 3 with mediastinal diffuse large B-cell lymphoma, 1 with precursor T-lymphoblastic leukemia/lymphoma and 1 with thymic extranodal marginal zone B-cell lymphoma. According to their histological subtypes, 5 patients were treated with chemoradiotherapy, 2 patients with chemotherapy and 1 patient of thymic extranodal marginal zone B-cell lymphoma with surgery alone. All patients survived in the median follow-up of 34.5 months. Appropriate biopsy procedure should be performed in patients with suspected mediastinal lymphoma.

  12. Radiotherapy of adult nodal non Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Gamen, G.; Thirion, P.

    1999-01-01

    The role of radiotherapy in the treatment of nodal non-Hodgkin's lymphoma has been modified by the introduction of efficient chemotherapy and the development of different pathological classifications. The recommended treatment of early-stage aggressive lymphomas is primarily a combination chemotherapy. The interest of adjuvant radiotherapy remains unclear and has to be established through large prospective trials. If radiation therapy has to be delivered, the historical results of exclusive radiation therapy showed that involved-fields and a dose of 35-40 Gy (daily fraction of 1.8 Gy, 5 days a week) are the optimal schedule. The interest of radiotherapy in the treatment of advanced-stage aggressive lymphoma is yet to be proven. Further studies had to stratify localized stages according to the factors of the International Prognostic Index. For easy-stage low-grade lymphoma, radiotherapy remains the standard treatment. However, the appropriate technique to use is controversial. Involved-field irradiation at a dose of 35 Gy seems to be the optimal schedule, providing a 10 year disease-free survival rate of 50 % and no major toxicity. There is no standard indication of radiotherapy in the treatment advanced-stage low-grade lymphoma. For 'new' nodal lymphoma's types, the indication of radiotherapy cannot be established (mantle-zone lymphoma, marginal zone B-cell lymphoma) or must take into account the natural history (Burkitt's lymphoma, peripheral T-cell lymphoma) and the sensibility to others therapeutic methods. (authors)

  13. Carfilzomib and Hyper-CVAD in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoma

    Science.gov (United States)

    2018-03-01

    Contiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia

  14. Comorbidity as an independent prognostic factor in elderly patients with peripheral T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Zhao H

    2016-03-01

    Full Text Available Haifeng Zhao,1,* Tengteng Wang,1,* Yafei Wang,1 Yong Yu,1 Xiaofan Wang,1 Zhigang Zhao,1 Hongliang Yang,1 Bei Yan,2 Xiaoxiong Wu,2 Wanming Da,3 Yizhuo Zhang1,* 1Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 2Department of Hematology, First Affiliated Hospital of Chinese People’s Liberation Army General Hospital, 3Department of Hematology, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of the present study was to investigate the role of comorbidities in the outcomes of patients with peripheral T-cell lymphoma (PTCL in a Chinese population. Fifty-six newly diagnosed PTCL patients aged >60 years were enrolled in our institution between April 2008 and August 2014. Medical record details including clinical parameters, pathological status, and treatment were reviewed. Prognostic factors were assessed using univariate and multivariate analyses. Forty-one (73.2% patients with PTCL, not otherwise specified (PTCL-NOS, nine (16.1% with angioimmunoblastic T-cell lymphoma, and six (10.7% with anaplastic large cell lymphoma were recruited in this study. Twenty-eight (50% had at least one comorbidity. Univariate analysis showed that an Eastern Cooperative Oncology Group score of 2–4, the presence of B symptoms, an International Prognostic Index (IPI score of 3–5, and a Charlson Comorbidity Index (CCI score ≥2 were significantly associated with shortened overall survival (OS, whereas the presence of B symptoms, an IPI of 3–5, and a CCI ≥2 were associated with worsened progression-free survival (PFS. Multivariate analysis indicated that a high CCI (≥2 and a high IPI (3–5 were poor independent prognostic factors for OS and PFS in the elderly patients with PTCL. Comorbidity was identified as a new

  15. Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma

    Science.gov (United States)

    2018-02-05

    Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma

  16. Targeting of slug sensitizes anaplastic thyroid carcinoma SW1736 cells to doxorubicin via PUMA upregulation.

    Science.gov (United States)

    Dong, Anbing; Jiao, Xuelong; Chen, Dong; Hao, Fengyun; Zhang, Kejun

    2016-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers and often shows resistance to multimodal therapeutic approaches. It has been shown that the transcriptional repressor Slug inhibits the chemotherapeutic agent-induced apoptosis of cancer cells. We evaluated whether targeting of Slug could augment doxorubicin (DOX)-induced apoptosis of ATC cells. We also determined changes in PUMA (p53-upregulated modulator of apoptosis) expression levels to identify possible mechanisms of their combined actions. Methods SW1736 cells were transfected with Slug siRNA or/and PUMA siRNA and then exposed to DOX (0.1, 1, and 5 mM) for selected times. Scrambled siRNA was used as a control. The effects on cell viability were determined via MTT assay. Apoptosis was assessed using TUNEL assays and annexin V staining, and was confirmed by flow cytometry analyses. Slug and PUMA levels were determined using western blotting and immunofluorescence analyses. We used a subcutaneous implanted tumor model of SW1736 cells in nude mice to assess the effects of Slug silencing in combination with DOX on tumor development. Apoptosis was assessed via TUNEL assay. Results Targeting of Slug using siRNA combined with DOX led to lower cell viability than treatment with DOX alone in SW1736 cells. TUNEL and flow cytometry analyses showed that targeting of Slug enhanced DOX-induced apoptosis of SW1736 cells. In addition, targeting of Slug increased PUMA expression, and targeting of PUMA restored the chemoresistance of SW1736/Slug siRNA cells to DOX. Conclusions Knockdown of Slug enhanced the antitumor activity of DOX in SW1736 cells via induction of PUMA upregulation. Our results suggest that targeting of Slug has good potential for the development of new therapeutic strategies for ATC.

  17. A spindle cell anaplastic pancreatic carcinoma with rhabdoid features following curative resection.

    Science.gov (United States)

    Abe, Tomoyuki; Amano, Hironobu; Hanada, Keiji; Okazaki, Akihisa; Yonehara, Shuji; Kuranishi, Fumito; Nakahara, Masahiro; Kuroda, Yoshinori; Noriyuki, Toshio

    2016-08-01

    Anaplastic pancreatic carcinoma (ANPC) accounts for ~5% of all pancreatic ductal adenocarcinoma cases. Due to its rarity, its clinical features and surgical outcomes remain to be clearly understood. A 74-year-old woman was admitted to Onomichi General Hospital (Onomichi, Japan) in April 2015 without any significant past medical history. Contrast-enhanced computed tomography (CT) revealed a 9.5×8.0 cm tumor in the body and tail of the pancreas. The patient developed acute abdominal pain 3 weeks later and the CT revealed massive abdominal bleeding caused by tumor rupture. The tumor increased in size and reached 12.0×10.0 cm in maximal diameter. The tumor doubling time was estimated to be 13 days. 18 F-fluorodeoxyglucose (FDG) positron emission tomography/CT confirmed the absence of distant metastasis since FDG accumulation was detected only in the tumor lesion. Emergency distal pancreatectomy and splenectomy were performed. Histologically, the tumor was classified as a spindle cell ANPC with rhabdoid features. The patient succumbed to mortality 8 months following the surgery while undergoing systemic adjuvant chemotherapy for multiple liver metastases. ANPC is difficult to detect in the early stages due to its progressive nature and atypical radiological findings. Long-term survival can be achieved only by curative resection; therefore, surgical resection must be performed whenever possible, even if the chance of long-term survival following surgery is considered dismal. As the present case suggested, spindle cell ANPC with rhabdoid features is highly aggressive and curative-intent resection must not be delayed.

  18. Treatment and prognosis of anaplastic thyroid carcinoma: experience from a single institution in China.

    Directory of Open Access Journals (Sweden)

    Chuanzheng Sun

    Full Text Available BACKGROUND: Anaplastic thyroid carcinoma (ATC, a highly aggressive malignancy, has a poor prognosis, and the consensus on the most effective treatment is needed. METHODS: Clinical data from all ATC patients treated in our institution over a 30-year period (between May 1980 and May 2010 were analyzed retrospectively with regard to mortality and survival rates (Kaplan-Meier. Multivariate analysis was performed using a Cox proportional hazards model. RESULTS: Sixty cases were analyzed. The overall 1- and 3-year survival rates were 35.0% and 22.9%, respectively. Univariate analysis showed that the best prognosis was seen in patients younger than 55 years, those without distant metastases, those with white blood cell (WBC counts < 10.0 × 10(9/L or blood platelet (PLT counts < 300.0 × 10(9/L at presentation, those who did not receive chemotherapy, and those who received radiotherapy doses ≥ 40 Gy or underwent surgery plus postoperative radiotherapy. According to multivariate analysis, the WBC count at first presentation and the type of therapeutic regimen independently influenced survival. CONCLUSIONS: We found that the elevated peripheral PLT count may be an adverse prognostic factor of ATC patients. The prognosis for ATC is especially poor for patients with distant metastasis, a WBC count ≥ 10.0×10(9/L, a PLT count ≥ 300.0 × 10(9/L, or age ≥ 55 years. WBC count at presentation and surgery with or without postoperative radiotherapy independently influenced the prognosis. Intensive treatment combining surgery with postoperative radiotherapy is recommended for ATC patients with stage IVA/B disease.

  19. Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma.

    Science.gov (United States)

    Gómez Sáez, José Manuel; Jiménez-Fonseca, Paula; Santamaría Sandi, Javier; Capdevila Castillón, Jaume; Navarro González, Elena; Zafón Llopis, Carles; Ramón Y Cajal Asensio, Teresa; Riesco Eizaguirre, Garcilaso; Grande Pulido, Enrique; Galofré Ferrater, Juan Carlos

    2015-03-01

    Anaplastic thyroid cancer (ATC) is the most aggressive solid tumour known and is a rare but highly lethal form of thyroid cancer that requires a multidisciplinary team approach. No Spanish consensus exists for management of patients with ATC. The Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) of the Spanish Society of Oncology, in agreement with the Boards of these Societies, commissioned an independent task force to develop a wide consensus on ATC. The relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The consensus includes the characteristics, diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active treatment), approaches to advanced/metastatic disease, palliative care options, monitoring, and long-term follow-up of ATC. For operable disease, a combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin, cisplatin and paclitaxel, is the best treatment strategy. Cytotoxic drugs are poorly effective for advanced/metastatic ATC. On the other hand, targeted agents may represent a viable therapeutic option. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for clinical trials or for hospice/palliative care depending on their preference. This is the first Spanish consensus for ATC, and provides recommendations for management of this extremely aggressive malignancy. Novel systemic therapies are being tested, and more effective combinations are needed to improve patient outcomes. Although more aggressive radiotherapy has reduced locoregional recurrence, mean

  20. Modern radiation therapy for primary cutaneous lymphomas

    DEFF Research Database (Denmark)

    Specht, Lena; Dabaja, Bouthaina; Illidge, Tim

    2015-01-01

    , either as the sole treatment or as part of a multimodality approach. Radiation therapy of primary cutaneous lymphomas requires the use of special techniques that form the focus of these guidelines. The International Lymphoma Radiation Oncology Group has developed these guidelines after multinational...... meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the International Lymphoma Radiation Oncology Group steering committee on the use of radiation therapy in primary cutaneous lymphomas in the modern era.......Primary cutaneous lymphomas are a heterogeneous group of diseases. They often remain localized, and they generally have a more indolent course and a better prognosis than lymphomas in other locations. They are highly radiosensitive, and radiation therapy is an important part of the treatment...

  1. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  2. Protease activity of the API2-MALT1 fusion oncoprotein in MALT lymphoma development and treatment.

    Science.gov (United States)

    Rosebeck, Shaun; Lucas, Peter C; McAllister-Lucas, Linda M

    2011-05-01

    Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a prototypical cancer that occurs in the setting of chronic inflammation and an important model for understanding how deregulated NF-κB transcriptional activity contributes to malignancy. Most gastric MALT lymphomas require ongoing antigenic stimulation for continued tumor growth, and Stage I disease is usually cured by eradicating the causative microorganism, Helicobacter pylori, with antibiotics. However, in a subset of MALT lymphomas, chromosomal translocations are acquired that render the lymphoma antigen-independent. The recurrent translocation t(11;18)(q21;q21) is associated with failure to respond to antibiotic therapy and increased rate of dissemination. This translocation creates the API2-MALT1 fusion oncoprotein, which comprises the amino terminus of inhibitor of apoptosis 2 (API2 or cIAP2) fused to the carboxy terminus of MALT1. A common characteristic of chromosomal translocations in MALT lymphoma, including t(11;18), is that genes involved in the regulation of the NF-κB transcription factor are targeted by the translocations, and these genetic perturbations thereby result in deregulated, constitutive NF-κB stimulation. In the last decade, great insights into the roles of API2 and MALT1 in NF-κB signaling have been made. For example, recent pivotal studies have uncovered the long sought-after proteolytic activity of MALT1 and have demonstrated its critical involvement in the survival of certain lymphomas. Here, we review the current understanding of the role of MALT1 in normal lymphocyte function and lymphomagenesis. We then highlight our recent work that has revealed an intriguing link between the proteolytic activity of the API2-MALT1 fusion and its ability to influence lymphomagenesis by cleaving a key NF-κB regulatory protein, NF-κB-inducing kinase.

  3. Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-09

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma

  4. Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma line

    DEFF Research Database (Denmark)

    Holland, J; Owens, T

    1997-01-01

    Intercellular adhesion molecule 1 (ICAM-1) (CD54) is an adhesion molecule of the immunoglobulin superfamily. The interaction between ICAM-1 on B lymphocytes and leukocyte function-associated antigen 1 on T cells plays a major role in several aspects of the immune response, including T-dependent B...... cell activation. While it was originally believed that ICAM-1 played a purely adhesive role, recent evidence suggests that it can itself transduce biochemical signals. We demonstrate that cross-linking of ICAM-1 results in the up-regulation of class II major histocompatibility complex, and we...... investigate the biochemical mechanism for the signaling role of ICAM-1. We show that cross-linking of ICAM-1 on the B lymphoma line A20 induces an increase in tyrosine phosphorylation of several cellular proteins, including the Src family kinase p53/p56(lyn). In vitro kinase assays showed that Lyn kinase...

  5. Primary bony Hodgkin’s lymphoma

    OpenAIRE

    Binesh, Fariba; Mirjalili, Mohammad Reza; Akhavan, Ali; Navabii, Hossein

    2012-01-01

    Hodgkin’s lymphoma most commonly presents with progressive painless enlargement of peripheral lymph nodes, especially around the cervical region. At the time of diagnosis osseous involvement is uncommon and even in the late stages only 9–35% of cases have any bony involvement. Rarely Hodgkin’s lymphoma presents as an osseous lesion without involvement of lymph nodes, therefore the histological diagnosis of osseous Hodgkin’s lymphoma can be problematic. Here, the authors present a rare case of...

  6. Abdominal manifestations of extranodal lymphoma: pictorial essay

    Energy Technology Data Exchange (ETDEWEB)

    Fajardo, Lais; Cardia, Patricia Prando; Prando, Adilson, E-mail: laisfajardo@gmail.com [Centro Radiologico Campinas/Hospital Vera Cruz, Campinas, SP (Brazil); Ramin, Guilherme de Araujo; Penachim, Thiago Jose; Martins, Daniel Lahan [Pontificia Universidade Catolica de Campinas (PUC- Campinas), SP (Brazil)

    2016-11-15

    In the appropriate clinical setting, certain aspects of extranodal abdominal lymphoma, as revealed by current cross-sectional imaging techniques, should be considered potentially diagnostic and can hasten the diagnosis. In addition, diagnostic imaging in the context of biopsy-proven lymphoma can accurately stage the disease for its appropriate treatment. The purpose of this article was to illustrate the various imaging aspects of extranodal lymphoma in the abdomen. (author)

  7. Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy

    NARCIS (Netherlands)

    Hoeve, M A; Gisbertz, I A; Schouten, H C; Schuuring, E; Bot, F J; Hermans, J; Hopman, A; Kluin, P M; Arends, J E; van Krieken, J H

    1999-01-01

    Gastric MALT lymphoma is a distinct entity related to Helicobacter pylori gastritis. Some studies suggest a role for trisomy 3 in the genesis of these lymphomas, but they mainly focused on low-grade MALT lymphoma. Gastric MALT lymphoma, however, comprises a spectrum from low- to high-grade cases.

  8. Severe pneumonia associated with ibrutinib monotherapy for CLL and lymphoma.

    Science.gov (United States)

    Kreiniz, Natalia; Bejar, Jacob; Polliack, Aaron; Tadmor, Tamar

    2018-02-01

    In recent years, there have been major advances in the treatment of chronic lymphocytic leukemia (CLL) particularly since the development of novel therapeutic agents, mostly "biological drugs." One of the obvious advantages of these agents is the decreased rate of infectious complications occurring during the course of therapy, compared to the use of standard immuno-chemotherapy regimens. Here, we describe 3 patients with CLL and 1 with mantle cell lymphoma who developed severe life-threatening pneumonias, during monotherapy with ibrutinib. The first case was a 70-year-old woman with relapsed CLL who developed bilateral pneumonia with hypoxia 1 week after starting ibrutinib. She did not respond to broad-spectrum antibiotics and was treated empirically with trimethoprim-sulphamethoxazole and improved. In the second case, we describe a 76-year-old woman with relapsed CLL who developed recurrent pneumonia after 3 years of treatment with ibrutinib. Presuming that ibrutinib was the cause of pneumonitis with secondary infection, it was stopped with subsequent improvement. The third patient a 67 year-old man died because of severe bilateral necrotizing pneumonia due to invasive aspergillosis and mucormycosis with pulmonary hemorrhage. The fourth patient with relapsed mantle cell lymphoma died because of severe bilateral pneumonia, caused by pseudomonas and candida, despite receiving appropriate antibiotics. From this experience, we hypothesize that the etiology of severe pneumonia associated with ibrutinib treatment is probably multifactorial, involving factors like preexisting immune-suppression, drug induced pneumonitis and infections. We suggest that patients with CLL or other lymphoproliferative disorders with suspected pneumonia during monotherapy with ibrutinib should be very carefully evaluated and need to undergo complete diagnostic workup to establish an exact diagnosis. Understanding which patients with CLL or lymphoma treated with kinase inhibitors are at a

  9. AIDS-related non-Hodgkin-lymphoma

    International Nuclear Information System (INIS)

    Deweese, T.L.; Hazuka, M.B.; Hommel, D.J.; Kinzie, J.J.; Daniel, W.E.

    1989-01-01

    Patients with acquired immunodeficiency syndrome (AIDS) have shown an increased propensity for developing non-Hodgkins lymphoma (NHL). In order to assess the response to and overall treatment benefit of radiation therapy in AIDS-related lymphoma, the authors have reviewed the records of 15 patients with AIDS and NHL treated with radiation therapy. Of those patients with central nervous system (CNS) involvement, 54% showed disease progression or no improvement during treatment. Conversely, AIDS patients with lymphoma outside the CNS were more likely to respond to radiation therapy and have longer survival. The authors conclude that the efficacy of radiation therapy in AIDS patients with lymphoma might depend on CNS involvement

  10. Imaging of primary pediatric lymphoma of bone

    International Nuclear Information System (INIS)

    Milks, Kathryn S.; McLean, Thomas W.; Anthony, Evelyn Y.

    2016-01-01

    Primary pediatric bone lymphoma is a rare form of non-Hodgkin lymphoma. Unlike nodal forms of lymphoma, imaging abnormalities in lymphoma of bone do not resolve rapidly in conjunction with treatment and radiologic findings can remain abnormal for years, making it difficult to evaluate treatment response. To evaluate the utility of imaging in assessment of patients with primary pediatric bone lymphoma. At our institution between 2004 and 2013, six cases of pathology-proven primary pediatric bone lymphoma were diagnosed. Retrospective chart review was performed to assess imaging utilization. Our data were qualitatively compared with existing literature to construct an algorithm for imaging patients with primary lymphoma of bone. Imaging evaluation of patients with primary pediatric bone lymphoma was highly variable at our institution. Conventional imaging was routinely used to evaluate response to treatment, despite lack of appreciable osseous change. Imaging in the absence of symptoms did not alter clinical management. Only positron emission tomography CT (PET/CT) proved capable of demonstrating imaging changes from the pretreatment to the post-treatment scans that were consistent with the clinical response to treatment. Surveillance imaging is likely unnecessary in patients with a known diagnosis of pediatric lymphoma of bone. Pretreatment and post-treatment PET/CT is likely sufficient to assess response. There is little data to support the use of interim and surveillance PET/CT. (orig.)

  11. Ongoing trials in low-grade lymphoma

    Directory of Open Access Journals (Sweden)

    Alexander Burchardt

    2011-10-01

    Full Text Available There are many therapies available for the management of low-grade lymphoma. With follicular lymphoma, for example, combination of chemotherapy and rituximab (immuno-chemo - therapy and consecutive maintenance therapy for 2 years is the current standard of care. To date, the most widely used regimen seems to be rituximab combined with cyclo phosphamide, doxorubicin, vincristine, and prednisone (RCHOP. Substitution of liposomal doxorubicin in place of conventional doxorubicin may improve outcomes in this indication, although evidence for its use in low-grade lymphoma is not as relevant as in aggressive lymphoma. Bendamustine, in combination with rituximab, has shown very good efficacy and tolerability in several lymphoma types, particularly follicular lymphoma and other low-grade lymphomas. Other combinations, such as those including bortezomib and lenalidomide, are under investigation in low-grade lymphoma, and the duration of rituximab maintenance therapy following bendamustine−rituximab-containing induction is being researched by the German Study Group for Indolent Lymphoma (StiL.

  12. Follicular lymphoma of the ocular adnexal region

    DEFF Research Database (Denmark)

    Rasmussen, Peter Kristian; Ralfkiaer, E.; Prause, J.U.

    2015-01-01

    Purpose To characterize the clinicopathological features of follicular lymphoma of the ocular adnexal region. Methods Retrospective nation-based study of Danish patients with ocular adnexal follicular lymphoma from January 1st 1980 through December 31st 2009. Results Twenty-four patients with ocu......Purpose To characterize the clinicopathological features of follicular lymphoma of the ocular adnexal region. Methods Retrospective nation-based study of Danish patients with ocular adnexal follicular lymphoma from January 1st 1980 through December 31st 2009. Results Twenty-four patients...

  13. Plasmablastic lymphoma mimicking orbital cellulitis

    Science.gov (United States)

    Merkx, Matthias A. W.; Weijs, Willem L. J.; Gerlach, Niek L.; Bergé, Stefaan J.

    2008-01-01

    Introduction Orbital cellulitis is an uncommon, potentially devastating condition that, when not promptly and adequately treated, can lead to serious sequelae. The presenting clinical signs are proptosis, swelling, ophthalmoplegia, pain and redness of the peri-orbital tissues. A number of cases have been reported in which these symptoms have been mistakenly interpreted as being secondary to an orbital infection whilst, in fact, other pathology was present. Discussion We add another case in which, on clinical grounds and after radiological assessment and laboratory tests, a working diagnosis of orbital cellulitis of the left eye was made. It was only after histopathological analysis of a soft tissue specimen from the maxillary sinus that a diagnosis of an AIDS-related plasmablastic lymphoma was made. The patient was referred to the department of haematology where chemotherapeutic treatment for the lymphoma and the HIV infection was started. This case report adds another differential diagnosis of orbital cellulitis to the existing literature. PMID:18597126

  14. T- Lymphoblastic lymphoma in adults

    OpenAIRE

    Santini,Gino; Porcellini,Adolfo; Zupo,Simona; Truini,Mauro

    2008-01-01

    Adult T-lymphoblastic lymphoma is rare and has a poor prognosis. In the 80s, following the introduction of sequential, intensified chemotherapy, complete remissions in the order of 75%-95% of treated patients, were achieved. However, several patients, namely those with advanced disease, continued to relapse either in remission or during maintenance therapy. Moreover, all these early studies were not able to detect any valuable prognostic index to predict the outcome. In an attempt to reduce t...

  15. Cellular backpackers deliver lymphoma drugs.

    Science.gov (United States)

    2015-08-01

    Researchers have attached capsules containing the drug SN-38, a relative of irinotecan, to T cells. When infused into mice with a cancer similar to Burkitt lymphoma, the T cells entered the spleen, lymph nodes, and bone marrow where B-cell tumors occurred, increasing the amount of drug reaching the tumors compared with other methods, and prolonging survival. ©2015 American Association for Cancer Research.

  16. [Weiss' nasal lymphoma (histiocytic, malignant)].

    Science.gov (United States)

    Pons, S; Ortiz Medina, A

    1984-01-01

    We presented a patient with a deforming and necrotizing syndrome of the nasal pyramid. The histopathology demonstrated a lymphoma. The original works of Weiss are related. The diseases is characterized by: ecotaxis of the nasal pyramid, localized persistency during a long time, malaise in advanced studies and sensibility to radiations. We proposed the name linfoma histiocitico maligno nasal de Weiss and consider it as a autonomous entity.

  17. Methylation profiling of mediastinal gray zone lymphoma reveals a distinctive signature with elements shared by classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma

    Science.gov (United States)

    Eberle, Franziska C.; Rodriguez-Canales, Jaime; Wei, Lai; Hanson, Jeffrey C.; Killian, J. Keith; Sun, Hong-Wei; Adams, Lisa G.; Hewitt, Stephen M.; Wilson, Wyndham H.; Pittaluga, Stefania; Meltzer, Paul S.; Staudt, Louis M.; Emmert-Buck, Michael R.; Jaffe, Elaine S.

    2011-01-01

    Background Mediastinal gray zone lymphoma is a newly recognized entity with transitional morphological and immunophenotypic features between the nodular sclerosis subtype of Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma. Diagnostic criteria for mediastinal gray zone lymphoma are still challenging, and the optimal therapy is as yet undetermined. Epigenetic changes have been implicated in the loss of the B-cell program in classical Hodgkin’s lymphoma, and might provide a basis for the immunophenotypic alterations seen in mediastinal gray zone lymphoma. Design and Methods We performed a large-scale DNA methylation analysis of microdissected tumor cells to investigate the biological underpinnings of mediastinal gray zone lymphoma and its association with the related entities classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma, making comparisons with the presumptively less related diffuse large B-cell lymphoma. Results Principal component analysis demonstrated that mediastinal gray zone lymphoma has a distinct epigenetic profile intermediate between classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma but remarkably different from that of diffuse large B-cell lymphoma. Analysis of common hypo- and hypermethylated CpG targets in mediastinal gray zone lymphoma, classical Hodgkin’s lymphoma, primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma was performed and confirmed the findings of the principal component analysis. Based on the epigenetic profiles we were able to establish class prediction models utilizing genes such as HOXA5, MMP9, EPHA7 and DAPK1 which could distinguish between mediastinal gray zone lymphoma, classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma with a final combined prediction of 100%. Conclusions Our data confirm a close relationship between mediastinal gray zone lymphoma and both classical Hodgkin’s lymphoma and primary

  18. Methylation profiling of mediastinal gray zone lymphoma reveals a distinctive signature with elements shared by classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma.

    Science.gov (United States)

    Eberle, Franziska C; Rodriguez-Canales, Jaime; Wei, Lai; Hanson, Jeffrey C; Killian, J Keith; Sun, Hong-Wei; Adams, Lisa G; Hewitt, Stephen M; Wilson, Wyndham H; Pittaluga, Stefania; Meltzer, Paul S; Staudt, Louis M; Emmert-Buck, Michael R; Jaffe, Elaine S

    2011-04-01

    Mediastinal gray zone lymphoma is a newly recognized entity with transitional morphological and immunophenotypic features between the nodular sclerosis subtype of Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma. Diagnostic criteria for mediastinal gray zone lymphoma are still challenging, and the optimal therapy is as yet undetermined. Epigenetic changes have been implicated in the loss of the B-cell program in classical Hodgkin's lymphoma, and might provide a basis for the immunophenotypic alterations seen in mediastinal gray zone lymphoma. We performed a large-scale DNA methylation analysis of microdissected tumor cells to investigate the biological underpinnings of mediastinal gray zone lymphoma and its association with the related entities classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma, making comparisons with the presumptively less related diffuse large B-cell lymphoma. Principal component analysis demonstrated that mediastinal gray zone lymphoma has a distinct epigenetic profile intermediate between classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma but remarkably different from that of diffuse large B-cell lymphoma. Analysis of common hypo- and hypermethylated CpG targets in mediastinal gray zone lymphoma, classical Hodgkin's lymphoma, primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma was performed and confirmed the findings of the principal component analysis. Based on the epigenetic profiles we were able to establish class prediction models utilizing genes such as HOXA5, MMP9, EPHA7 and DAPK1 which could distinguish between mediastinal gray zone lymphoma, classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma with a final combined prediction of 100%. Our data confirm a close relationship between mediastinal gray zone lymphoma and both classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma. However, important differences

  19. Vaccine Therapy With or Without Cryosurgery in Treating Patients With Residual, Relapsed, or Refractory B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-03-21

    Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Adult Diffuse Mixed Cell Lymphoma; Adult Diffuse Small Cleaved Cell Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Adult Immunoblastic Large Cell Lymphoma; Adult Lymphoblastic Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia With Nodal Disease

  20. [Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma)].

    Science.gov (United States)

    Takahashi, Tsutomu; Suzumiya, Junji

    2014-03-01

    Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) is a B-cell tumor thought to originate from B-lymphocytes that are normally present in the marginal zone of lymphoid follicles of the lymphoid tissue. About 50% of MALT lymphoma occurs in gastrointestinal tract. The majority of patients present with localized disease and indolent clinical progression. In localized gastric MALT lymphoma with Helicobacter pylori (HP) infection, HP eradication is recommended as first line therapy. In those without HP infection and localized non-gastric MALT lymphoma, involved field radiation therapy(IFRT) is recommended as first line therapy. Patients in advanced stage and salvage setting are managed according to the recommendations for advanced follicular lymphoma. The long-term survival rate of MALT lymphoma patients is 80-90%.

  1. Precision Medicine Approach to Anaplastic Thyroid Cancer: Advances in Targeted Drug Therapy Based on Specific Signaling Pathways.

    Science.gov (United States)

    Samimi, Hilda; Fallah, Parviz; Naderi Sohi, Alireza; Tavakoli, Rezvan; Naderi, Mahmood; Soleimani, Masoud; Larijani, Bagher; Haghpanah, Vahid

    2017-03-01

    Personalized medicine is a set of diagnostic, prognostic and therapeutic approaches in which medical interventions are carried out based on individual patient characteristics. As life expectancy increases in developed and developing countries, the incidence of diseases such as cancer goes up among people in the community. Cancer is a disease that the response to treatment varies from one person to another and also it is costly for individuals, families, and society. Among thyroid cancers, anaplastic thyroid carcinoma (ATC) is the most aggressive, lethal and unresponsive form of the disease. Unfortunately, current drugs are not targetable, and therefore they have restricted role in ATC treatment. Consequently, mortality of this cancer, despite advances in the field of diagnosis and treatment, is one of the most important challenges in medicine. Cellular, molecular and genetic evidences play an important role in finding more effective diagnostic and therapeutic approaches. Review of these evidences confirms the application of personalized medicine in cancer treatment including ATC. A growing body of evidence has elucidated that cellular and molecular mechanisms of cancer would pave the way for defining new biomarkers for targeted therapy, taking into account individual differences. It should be noted that this approach requires further progress in the fields of basic sciences, pharmacogenetics and drug design. An overview of the most important aspects in individualized anaplastic thyroid cancer treatment will be discussed in this review.

  2. Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas

    Science.gov (United States)

    2017-09-28

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Chronic Lymphocytic

  3. Rituximab and Interleukin-12 in Treating Patients With B-Cell Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2013-08-23

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  4. Primary effusion lymphoma associated with Human Herpes Virus-8 and Epstein Barr virus in an HIV-infected woman from Kampala, Uganda: a case report

    Directory of Open Access Journals (Sweden)

    Osuwat Lawrence O

    2011-02-01

    Full Text Available Abstract Introduction Primary effusion lymphoma is a recently recognized entity of AIDS related non-Hodgkin lymphomas. Despite Africa being greatly affected by the HIV/AIDS pandemic, an extensive MEDLINE/PubMed search failed to find any report of primary effusion lymphoma in sub-Saharan Africa. To our knowledge this is the first report of primary effusion lymphoma in sub-Saharan Africa. We report the clinical, cytomorphologic and immunohistochemical findings of a patient with primary effusion lymphoma. Case presentation A 70-year-old newly diagnosed HIV-positive Ugandan African woman presented with a three-month history of cough, fever, weight loss and drenching night sweats. Three weeks prior to admission she developed right sided chest pain and difficulty in breathing. On examination she had bilateral pleural effusions. Haematoxylin and eosin stained cytologic sections of the formalin-fixed paraffin-embedded cell block made from the pleural fluid were processed in the Department of Pathology, Makerere University, College of Health Sciences, Kampala, Uganda. Immunohistochemistry was done at the Institute of Haematology and Oncology "L and A Seragnoli", Bologna University School of Medicine, Bologna, Italy, using alkaline phosphatase anti-alkaline phosphatase method. In situ hybridization was used for detection of Epstein-Barr virus. The tumor cells were CD45+, CD30+, CD38+, HHV-8 LANA-1+; but were negative for CD3-, CD20-, CD19-, and CD79a- and EBV RNA+ on in situ hybridization. CD138 and Ki-67 were not evaluable. Our patient tested HIV positive and her CD4 cell count was 127/μL. Conclusions A definitive diagnosis of primary effusion lymphoma rests on finding a proliferation of large immunoblastic, plasmacytoid and anaplastic cells; HHV-8 in the tumor cells, an immunophenotype that is CD45+, pan B-cell marker negative and lymphocyte activated marker positive. It is essential for clinicians and pathologists to have a high index of suspicion of

  5. Pyruvate kinase blood test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003357.htm Pyruvate kinase blood test To use the sharing features on this page, ... energy when oxygen levels are low. How the Test is Performed A blood sample is needed. In the laboratory, white blood ...

  6. Parotid lymphomas - clinical and computed tomogrphic imaging ...

    African Journals Online (AJOL)

    Objective. To review the clinical presentation and computed tomography (CT) imaging characteristics of all parotid lymphomas diagnosed at the study institution over a 7-year period. Design. Retrospective chart review of parotid lymphomas diagnosed between 1997 and 2004. Subjects. A total of 121 patients with parotid ...

  7. Misdiagnosis of tuberculosis in patients with lymphoma ...

    African Journals Online (AJOL)

    Abstract. Background. Since 1970, the incidence of lymphoma, a potentially curable disease, has risen by 80% in the general population and in HIVpositive patients. Given its clinical similarities to tuberculosis (TB), lymphoma may be misdiagnosed and patients treated unnecessarily with potentially harmful TB medication.

  8. Review Of Lymphoma Classification | Mayun | Highland Medical ...

    African Journals Online (AJOL)

    Lymphomas are malignant neoplasms characterized by the proliferation of cells native to the lympoid tissue i.e lymphocytes, histiocytes and their precursors and derivatives. These heterogenous neoplasms are of the monoclonal origin. Lymphoma have been broadly classified into two main categories; Hodkin disease (HD) ...

  9. Report : Workshop on mediastinal grey zone lymphoma

    NARCIS (Netherlands)

    Poppema, Sibrand; Kluiver, Joost; Atayar, Cigdem; van den Berg, Anke; Rosenwald, A.; Hummel, M.; Lenze, D.; Lammert, H.; Stein, H.; Joos, S.; Barth, T.; Dyer, M.; Lichter, P.; Klein, U.; Cattoretti, G.; Gloghini, A.; Tu, Y.H.; Stolovitzky, G.A.; Califano, A.; Carbone, A.; Dalla-Favera, R.; Melzner, I.; Bucur, A.J.; Bruderlein, S.; Dorsch, K.; Hasel, C.; Barth, T.F.E.; Leithauser, F.; Moller, P.

    There are several indications that classical Hodgkin lymphoma (cHL) and at least a proportion of cases of Primary Mediastinal B cell Lymphoma (PMBL) are derived from B cells at similar stages of differentiation and share common pathogenic mechanisms. The first indication was the existence of

  10. Atypical intrathoracic manifestations of Burkitt's lymphoma

    International Nuclear Information System (INIS)

    Nzeh, D.A.

    1988-01-01

    Analysis of the plain chest radiographs of 11 children with Burkitt's lymphoma showed that mediastinal adenopathy was the commonest abnormality present. One child showed a pulmonary infiltrative pattern which had previously been undescribed in this disease. Nigerian children with this lymphoma present more commonly with mediastinal glandular enlargement whereas pleural effusion is more frequently encountered in Caucasians. (orig.)

  11. Immunohistochemical prognostic indicators of lymphoma tumors ...

    African Journals Online (AJOL)

    and Cyclin D1). Lymphoma tissues were obtained from 50 patients (Royal Medical Services 1990 - 1996), which were diagnosed as Hodgkin's and NonHodgkin's lymphoma. Specimens were reassessed by examining new sections; these sections were analyzed for p53 and Cyclin D1 levels by using immunohisochemisty ...

  12. Parotid lymphomas - clinical and computed tomogrphic imaging ...

    African Journals Online (AJOL)

    Results. Ten patients with histologically proven lymphoma of the parotid gland were identified from among 121 patients with parotid neoplasms, an incidence in this series of 8.3%. All lymphomas were of non- Hodgkin's type. All patients presented with a painless unilateral parotid swelling. Most patients had a short history of ...

  13. Characteristics of Hodgkin's lymphoma after infectious mononucleosis

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Askling, Johan; Rostgaard, Klaus

    2003-01-01

    BACKGROUND: Infectious mononucleosis-related Epstein-Barr virus (EBV) infection has been associated with an increased risk of Hodgkin's lymphoma in young adults. Whether the association is causal remains unclear. METHODS: We compared the incidence rates of Hodgkin's lymphoma in two population-bas...

  14. Radiotherapy of primary gastric malignant lymphoma

    International Nuclear Information System (INIS)

    Monzen, Yoshio; Mutsukura, Masahide; Moriuchi, Yukiyoshi

    2017-01-01

    Fifteen patients with primary gastric malignant lymphoma who underwent radiotherapy were examined. Median age was 68 years, and male to female ratio was 1:2. All the cases were stage I including 7 cases of diffuse large B-cell lymphoma (DLBCL), 7 cases of MALT lymphoma, and 1 case of follicular lymphoma. Therapy methods were as follows. For DLBCL, 30 Gy of radiotherapy was performed after chemotherapy. For six cases of MALT lymphomas, 30 Gy of radiotherapy was performed. For one patient diagnosed as high-grade gastric MALT lymphoma was treated in the same way as DLBCL. For one patient with follicular lymphoma, 30 Gy of radiotherapy was performed. The radiotherapy was applied with 3-dimensional fixed multi-portal irradiation, with the reduced irradiation of the liver and kidney. There was no recurrence of disease in all cases, and all patients have been alive, and no-recurrence living periods are 20 to 120 months. There was no harmful adverse event, and the tumor had disappeared with 30 Gy of radiation therapy in all cases. Considering the occurrence of secondary cancer, it was considered that a dosage of more than 30 Gy was not necessary for primary gastric malignant lymphoma. (J.P.N.)

  15. T cell immunosurveillance controls B lymphoma development

    OpenAIRE

    Kallies, Axel

    2014-01-01

    We recently showed a critical role for T cells in the immunosurveillance of nascent B cell lymphomas arising from mutations impacting plasma cell differentiation. Our data suggest that CD8+ T cells continuously eliminate mutated B cells that fail to downregulate their co-stimulatory machinery and the Fas death receptor, thus constraining B lymphoma pathogenesis.

  16. Brain accumulation of the EML4-ALK inhibitor ceritinib is restricted by P-glycoprotein (P-GP/ABCB1) and breast cancer resistance protein (BCRP/ABCG2)

    NARCIS (Netherlands)

    Kort, Anita; Sparidans, Rolf|info:eu-repo/dai/nl/075047144; Wagenaar, Els; Beijnen, Jacob|info:eu-repo/dai/nl/071919570; Schinkel, Alfred H.

    2015-01-01

    We aimed to clarify the roles of the multidrug transporters ABCB1 and ABCG2 in oral availability and brain accumulation of ceritinib, an oral anaplastic lymphoma kinase (ALK) inhibitor used to treat metastatic non-small cell lung cancer (NSCLC) after progression on crizotinib. Importantly, NSCLC is

  17. Nasogastric tube-administered alectinib achieved long-term survival in a crizotinib-refractory nonsmall cell lung cancer patient with a poor performance status.

    Science.gov (United States)

    Kanai, Osamu; Kim, Young Hak; Nakatani, Koichi; Fujita, Kohei; Mio, Tadashi

    2017-06-01

    Alectinib shows remarkable efficacy against anaplastic lymphoma kinase (ALK)-positive nonsmall cell lung cancer (NSCLC), with minimal adverse effects. Therefore, alectinib may provide a survival benefit to ALK-positive NSCLC patients with a poor performance status. If the medication cannot be taken by mouth, the patient may be given alectinib through a nasogastric tube.

  18. Identification of CARS-ALK fusion in primary and metastatic lesions of an inflammatory myofibroblastic tumor

    NARCIS (Netherlands)

    Debelenko, LV; Arthur, DC; Pack, SD; Helman, LJ; Schrump, DS; Tsokos, M

    Inflammatory myofibroblastic tumor (IMT) is a rare childhood neoplasm. The natural history of this disease is poorly understood. Recently chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene have been implicated in this tumor. We have studied a case of ALK-positive soft

  19. Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma : An expert consensus

    NARCIS (Netherlands)

    Cappuzzo, Federico; Moro-Sibilot, Denis; Gautschi, Oliver; Boleti, Ekaterini; Felip, Enriqueta; Groen, Harry J. M.; Germonpre, Paul; Meldgaard, Peter; Arriola, Edurne; Steele, Nicola; Fox, Jesme; Schnell, Patrick; Engelsberg, Arne; Wolf, Juergen

    Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC. This was due to the striking response data observed with crizotinib

  20. FDG-PET/CT in lymphoma

    Directory of Open Access Journals (Sweden)

    Maria M D′souza

    2013-01-01

    Full Text Available Lymphomas are a heterogeneous group of diseases that arise from the constituent cells of the immune system or from their precursors. 18F-fludeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT is now the cornerstone of staging procedures in the state-of-the-art management of Hodgkin′s disease and aggressive non-Hodgkin′s lymphoma. It plays an important role in staging, restaging, prognostication, planning appropriate treatment strategies, monitoring therapy, and detecting recurrence. However, its role in indolent lymphomas is still unclear and calls for further investigational trials. The protean PET/CT manifestations of lymphoma necessitate a familiarity with the spectrum of imaging findings to enable accurate diagnosis. A meticulous evaluation of PET/CT findings, an understanding of its role in the management of lymphomas, and knowledge of its limitations are mandatory for the optimal utilization of this technique.

  1. FDG-PET/CT in lymphoma

    International Nuclear Information System (INIS)

    D'souza, Maria M; Jaimini, Abhinav; Bansal, Abhishek; Tripathi, Madhavi; Sharma, Rajnish; Mondal, Anupam; Tripathi, Rajendra Prashad

    2013-01-01

    Lymphomas are a heterogeneous group of diseases that arise from the constituent cells of the immune system or from their precursors. 18F-fludeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) is now the cornerstone of staging procedures in the state-of-the-art management of Hodgkin's disease and aggressive non-Hodgkin's lymphoma. It plays an important role in staging, restaging, prognostication, planning appropriate treatment strategies, monitoring therapy, and detecting recurrence. However, its role in indolent lymphomas is still unclear and calls for further investigational trials. The protean PET/CT manifestations of lymphoma necessitate a familiarity with the spectrum of imaging findings to enable accurate diagnosis. A meticulous evaluation of PET/CT findings, an understanding of its role in the management of lymphomas, and knowledge of its limitations are mandatory for the optimal utilization of this technique

  2. A Case of Primary Ileocecal Lymphoma

    Directory of Open Access Journals (Sweden)

    Wulyo Rajabto

    2016-12-01

    Full Text Available Primary lymphoma in gastrointestinal tract is not very common. Ileocecal region is the commonest site for primary lymphoma and diffuse large B cell lymphoma (DLBCL is the most prevalent subtype. The clinical presentation in this condition is pain in right lower quadrant region and this can very confusing since many diseases can also cause this problem like infection and inflammatory disease. In this paper, we report a case of primary lymphoma subtype DLBCL in ileocecal region that come to emergency department with ileus obstruction. Abdominal computerized tomography (CT scan and colonoscopy revealed tumour in ileocecal region ascendens colon. Hemicolectomy was performed and the specimen was sent to pathology which revealed Non-Hodgkin Lymphoma with subtype DLBCL CD20 (+. The patient had undergone of Rituximab, Cyclophosphamide, Doxorubicine, Vincristin, and Prednison (RCHOP chemotherapy regimen and had complete remission.

  3. Evaluation of bone lesions of lymphomas

    International Nuclear Information System (INIS)

    Marugg, S.; Berchtold, C.; Elke, M.

    1985-01-01

    Skeletal involvement of non-Hodgkin's lymphoma is found in 11-16%, in Hodgkin's disease in 7.6-34%. Primary lymphoma of bone has an incidence of 1-50% among all non-Hodgkin's lymphoma. The occurrence of skeletal lesions is higher in infants and children than in adults. Skeletal lesions caused by Hodgkin's and non-Hodgkin's lymphoma are mostly seen in the axial skeleton including the skull, whereas the primary lymphoma of bone seems to prefer a more peripheral site. The aggressiveness of the tumor growth can be measured by the method of Lodwick, by judging the edge characteristic, the penetration of the cortex, the periostal and scleotic reaction. 3 examples illustrate this method. Conventional radiographs need only be performed when there is reason to believe a lesion is located in an area of structural importance, such as the neck of the femur, and in cases of skeletal pain of unknown origin. (orig.) [de

  4. Radiological characteristics of AIDS- related lymphoma

    International Nuclear Information System (INIS)

    Ramos, Gloria Maria Martins G.; Marchiori, Edson

    1996-01-01

    The epidemic of acquired immunodeficiency syndrome (AIDS) increased the incidence of lymphoma, particularly the non-Hodgkin's lymphoma. The lymphoma in immune deficient patients is usually high-grade, very aggressive and with poor prognostic. We report the radiologic characteristics of AIDS-related lymphoma in 19 patients and correlate with the literature. The disease was predominant in homosexual male patients, with mean age of 38 years. The radiological characteristics are nonspecific to differential diagnosis, but we must suspect of lymphoma. We found ring-enhanced lesions in the radiologic studies of central nervous system. Hylar and mediastinal lymphadenopath, nodules and alveolar infiltration were detected on thoracic examinations. Abdominal examinations showed hepatosplenomegaly, lymphadenopathy, hepatic focal lesions and thickneded with distorted mucosa in the alimentary tract. Bone involvement presented as focal and disseminated destructive lesions. (author)

  5. Primary thoracic epidural lymphoma: A rare cause of spinal cord ...

    African Journals Online (AJOL)

    Spinal epidural lymphoma is a rare entity that is not often considered in the differential diagnosis of an epidural mass in a previously healthy individual. Pfatients with Primary Spinal Epidural Lymphomas (PSELs) have negative diagnostic work up for systemic lymphoma and unlike disseminated lymphoma, they achieve ...

  6. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO

    NARCIS (Netherlands)

    Reuss, D.E.; Mamatjan, Y.; Schrimpf, D.; Capper, D.; Hovestadt, V.; Kratz, A.; Sahm, F.; Koelsche, C.; Korshunov, A.; Olar, A.; Hartmann, C.; Reijneveld, J.C.; Wesseling, P.; Unterberg, A.; Platten, M.; Wick, W.; Herold-Mende, C.; Aldape, K.; Deimling, A. von

    2015-01-01

    The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A IIWHO2007) and anaplastic astrocytoma WHO grade III (AA III WHO2007). Patients with A II WHO2007 are significantly younger and survive significantly longer than those with AA III WHO2007. So

  7. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival : a grading problem for WHO

    NARCIS (Netherlands)

    Reuss, David E.; Mamatjan, Yasin; Schrimpf, Daniel; Capper, David; Hovestadt, Volker; Kratz, Annekathrin; Sahm, Felix; Koelsche, Christian; Korshunov, Andrey; Olar, Adriana; Hartmann, Christian; Reijneveld, Jaap C.; Wesseling, Pieter|info:eu-repo/dai/nl/157872866; Unterberg, Andreas; Platten, Michael; Wick, Wolfgang; Herold-Mende, Christel; Aldape, Kenneth; von Deimling, Andreas

    2015-01-01

    The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A IIWHO2007) and anaplastic astrocytoma WHO grade III (AA IIIWHO2007). Patients with A IIWHO2007 are significantly younger and survive significantly longer than those with AA IIIWHO2007. So far,

  8. Copanlisib and Nivolumab in Treating Participants With Recurrent or Refractory Diffuse Large B-cell Lymphoma or Primary Mediastinal Large B-cell Lymphoma

    Science.gov (United States)

    2018-03-29

    Diffuse Large B-Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  9. Individualized management of follicular lymphoma.

    Science.gov (United States)

    Bai, Bing; Huang, Hui-Qiang

    2015-03-01

    Follicular lymphoma (FL) is the most common indolent non-hodgkin lymphoma. Most patients with FL are diagnosed with advanced disease and are considered incurable. The classical prognostic index in FL is the FL international prognostic index (FLIPI). The management of FL is mainly determined by histologic grading, clinical stage, and tumor burden. For patients with stage I and II disease, an involved-site radiation therapy (ISRT) is recommended and may be potentially curative approach with 60% to 80% of 10-year overall survival (OS) rates, while patients with stage III and IV should be treated with systemic therapy. The watchful waiting is still an option for patients without symptoms or/and low tumor burden. Induction of immuno-chemotherapy combined with consolidation of rituximab maintenance (MR) is standard care for patients with symptomatic disease or with high tumor burden when treatment indicated. The major indication for systemic therapy is including candidate for clinical trials, threatened end organ function, cytopenia secondary to lymphoma bulky disease and steady progress etc. at present time. Routine baseline and regular hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing is strongly recommended for all patients before the initiation of immuno-chemotherapy in order to minimize the risk of hepatitis B virus (HBV) reactivation which has been observed approximately 20% to 50% of patients with positive HBsAg and 3% to 45% of patients with positive HBcAb. Prophylactic antiviral treatment in patients who are HBsAg-positive or HBcAb-positive is indicated before immuno-chemotherapy. The management for elderly patients should be carefully selected to avoid overtreatment and severe toxicities. Individualized dose adjustment for chemotherapy and an adequate supportive treatment are essential for this special population. Novel agents such as lenalidomide, ibrutinib and idelalisib are promising. In conclusion, individualized management

  10. Mucosa-associated lymphoid tissue lymphoma arising from the kidney

    Science.gov (United States)

    Niwa, Naoya; Tanaka, Nobuyuki; Horinaga, Minoru; Hongo, Hiroshi; Ito, Yujiro; Watanabe, Takuro; Masuda, Takeshi

    2014-01-01

    Primary renal lymphoma is rare, and most are intermediate- and high-grade lymphomas of B-cell lineage, such as diffuse large B-cell or Burkitt lymphoma. We report a case of low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) arising from the kidney. Only a few cases of primary renal MALT lymphoma have been published. PMID:24554980

  11. Cholecalciferol in Improving Survival in Patients With Newly Diagnosed Cancer With Vitamin D Insufficiency

    Science.gov (United States)

    2017-07-06

    Aggressive Non-Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Hepatosplenic T-Cell Lymphoma; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Nasal Type Extranodal NK/T-Cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Primary Cutaneous Anaplastic Large Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Small Lymphocytic Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma

  12. Genetics of Follicular Lymphoma Transformation

    Directory of Open Access Journals (Sweden)

    Laura Pasqualucci

    2014-01-01

    Full Text Available Follicular lymphoma (FL is an indolent disease, but 30%–40% of cases undergo histologic transformation to an aggressive malignancy, typically represented by diffuse large B cell lymphoma (DLBCL. The pathogenesis of this process remains largely unknown. Using whole-exome sequencing and copy-number analysis, we show here that the dominant clone of FL and transformed FL (tFL arise by divergent evolution from a common mutated precursor through the acquisition of distinct genetic events. Mutations in epigenetic modifiers and antiapoptotic genes are introduced early in the common precursor, whereas tFL is specifically associated with alterations deregulating cell-cycle progression and DNA damage responses (CDKN2A/B, MYC, and TP53 as well as aberrant somatic hypermutation. The genomic profile of tFL shares similarities with that of germinal center B cell-type de novo DLBCL but also displays unique combinations of altered genes with diagnostic and therapeutic implications.

  13. Radiotherapy in primary cerebral lymphoma

    International Nuclear Information System (INIS)

    Legros, L.; Benezery, K.; Lagrange, J.L.

    1999-01-01

    Primary cerebral lymphoma is a rare disease with an unfavorable prognosis. Whole brain radiotherapy has been the standard treatment, but neither the optimal radiation fields nor optimal dose level of the regimen are as yet firmly establisheD. From this review of the literature, it seems that the whole brain must be treated, and a boost to the area of the primary site must be discussed. With regard to dose, the radiation dose-response relationship is not clearly proven. Yet, a minimum dose of 40 Gy is necessary, and the maximum dose is set at 50 Gy because of late neurological sequelae. Because of the poor prognosis of this disease and the risk of late sequelae, other avenues have been explored. Chemotherapy has been studied, seem to have a survival advantage and combinations of radiotherapy and chemotherapy, especially with high-dose methotrexate. Because primary cerebral lymphoma is an uncommon disease, randomized clinical trials that compare radiotherapy alone to chemotherapy plus radiotherapy may not be feasible. Finally, even if chemotherapy seems to have a survival advantage, the regimen of chemotherapy is still a matter of debate. (authors)

  14. 17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression.

    Science.gov (United States)

    Xiao, Y; Guan, J

    2015-01-01

    Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti-tumor activity in hematologic malignancies. However, Flavopiridol-induced protective autophagy may lead to drug resistance. Here we found that Hsp90 inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol by suppressing flavopiridol-triggered protective autophagy. The suppressing effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and growth suppression in MCL cells. Our study may provide some insights into CDKI -targeted chemotherapies.

  15. Severe vincristine-induced polyneuropathy in a teenager with anaplastic medulloblastoma and undiagnosed Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Aghajan, Yasmin; Yoon, Janet M; Crawford, John Ross

    2017-04-24

    Severe neuropathy is a known adverse effect of vincristine in patients with Charcot-Marie-Tooth disease (CMT). We present the case of a 16-year-old girl with anaplastic medulloblastoma treated with gross total resection and high-dose craniospinal radiation with adjuvant vincristine chemotherapy who developed acute-onset severe quadriplegia and vocal cord paralysis. Vincristine and radiation therapy were discontinued. Although her neuropathy slowly improved over several weeks, she developed metastatic extraneural medulloblastoma and died 5 months after diagnosis. Subsequent genetic testing revealed previously asymptomatic and undiagnosed CMT1A. Our case highlights the importance of early recognition of acute vincristine neurotoxicity that should raise suspicion of an underlying hereditary neuropathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Anaplastic Thyroid Carcinoma: Current Treatments and Potential New Therapeutic Options with Emphasis on TfR1/CD71

    Directory of Open Access Journals (Sweden)

    Rosalba Parenti

    2014-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most aggressive human cancers. Actually, ATC is refractory to conventional therapies, including surgery, chemotherapy, radiotherapy, and radioiodine (131I therapy. Accordingly, genetic and molecular characterizations of ATC have been frequently and periodically reviewed in order to identify potential biological markers exploitable for target therapy. This review briefly focuses on main molecular events that characterize ATC and provides an update about preclinical studies. In addition, the overexpression of transferrin receptor 1 (TfR1/CD71 by neoplastic cells of ATC is emphasized in that it could represent a potential therapeutic target. In this regard, new therapeutic approaches based on the use of monoclonal or recombinant antibodies, or transferrin-gallium-TfR1/CD71 molecular complexes, or lastly small interfering RNAs (siRNAs are proposed.

  17. An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma.

    Science.gov (United States)

    Stival, Alessia; Lucchesi, Maurizio; Farina, Silvia; Buccoliero, Anna Maria; Castiglione, Francesca; Genitori, Lorenzo; de Martino, Maurizio; Sardi, Iacopo

    2015-09-04

    Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

  18. Large cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal differentiation: A case report of a rare tumor

    Directory of Open Access Journals (Sweden)

    Amany A. Fathaddin

    2014-01-01

    Full Text Available Medulloblastoma is an embryonal neuroepithelial tumor of the cerebellum and is the most common malignant central nervous system tumor in children. Different histological variants and patterns have been described. The classic variant represents the majority of cases. This report describes a rare case of large cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal differentiation arising in the cerebellum of a 3-year-old boy who presented with headache and vomiting. Magnetic resonance imaging demonstrated a heterogeneously enhanced lesion in the fourth ventricle. Surgical resection of the tumor was accomplished, but a residual tumor was left behind because of the involvement of the brainstem. Postoperatively, the patient received chemotherapy and radiotherapy. Currently, 20 months after treatment, the patient has survived without further progression. Pathological examination revealed a high grade primitive neuronal tumor with foci of myogenic features, melanin containing epithelial elements and ganglion-like cells, which were confirmed by immunohistochemistry.

  19. Primary lymphocytic lymphoma of lacrimal gland.

    Science.gov (United States)

    Romero-Caballero, M D; Lozano-García, I; Gómez-Molina, C; Gil-Liñán, A I; Arcas, I

    2017-02-01

    We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Clinical presentation and staging of Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Gallamini, Andrea; Hutchings, Martin; Ramadan, Safaa

    2016-01-01

    In the present chapter the authors present a brief overview of the diagnostic methods proposed over time for Hodgkin lymphoma (HL) spread detection, moving from surgical procedures, through standard radiological and functional imaging techniques to the present state of the art for HL staging....... The main body of the review will be dedicated to the recently published guidelines for lymphoma staging (including HL) agreed by the experts during the 12th International Congress for Malignant Lymphoma in Lugano. The recommendations of the panel on how to integrate flurodeoxyglucose positron emission...

  1. Primary multifocal osseous lymphoma in a child

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Takashi S.P. [University of Iowa, Carver College of Medicine, Iowa City, IA (United States); Ferguson, Polly J. [University of Iowa, Department of Pediatrics, Iowa City, IA (United States); Khanna, Geetika [Washington University, Mallinckrodt Institute of Radiology, St Louis, MO (United States)

    2008-12-15

    We report a case of primary multifocal osseous lymphoma in a 6-year-old girl presenting with multifocal osteolytic lesions without systemic symptoms or identifiable non-osseous primary tumor. The differential diagnoses for such a presentation include histiocytosis X, chronic recurrent multifocal osteomyelitis, acute lymphoblastic leukemia, metastatic disease, and primary bone lymphoma. Although non-Hodgkin lymphoma is common in the pediatric population, its presentation as a primary bone tumor, especially with multifocal disease, is extremely rare and is frequently misdiagnosed. We hope that awareness of this entity will help radiologists achieve timely diagnosis and intervention. (orig.)

  2. Primary multifocal osseous lymphoma in a child

    International Nuclear Information System (INIS)

    Sato, Takashi S.P.; Ferguson, Polly J.; Khanna, Geetika

    2008-01-01

    We report a case of primary multifocal osseous lymphoma in a 6-year-old girl presenting with multifocal osteolytic lesions without systemic symptoms or identifiable non-osseous primary tumor. The differential diagnoses for such a presentation include histiocytosis X, chronic recurrent multifocal osteomyelitis, acute lymphoblastic leukemia, metastatic disease, and primary bone lymphoma. Although non-Hodgkin lymphoma is common in the pediatric population, its presentation as a primary bone tumor, especially with multifocal disease, is extremely rare and is frequently misdiagnosed. We hope that awareness of this entity will help radiologists achieve timely diagnosis and intervention. (orig.)

  3. CNS Intravascular Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Amer Awad

    2011-01-01

    Full Text Available Intravascular lymphoma is a rare but well-described entity. The clinical manifestations are heterogeneous. We report a case of a 59-year-old woman who presented initially with syncope followed by subacute cognitive decline that progressed to minimally conscious state. Shortly after the transfer to our tertiary center the patient died. Brain autopsy disclosed the diagnosis of B-cell intravascular lymphoma. We speculate that syncope could be the first manifestation of central nervous system intravascular lymphoma and should be considered in the differential diagnosis of unexplained syncope. In addition, we stress the importance of early brain biopsy in unexplained white matter disease.

  4. Radiation Pneumonitis after Radiotherapy of Neck Lymphoma

    Directory of Open Access Journals (Sweden)

    Min Wei

    2014-01-01

    Full Text Available Radiotherapy is still one of the effective means for treatment of malignant tumors up to now. Particularly, it is an indispensable effective measure for treatment of some lymphoma patients. In routine work, radiation pneumonitis (RP is the most significant complication of acute treatment-related toxicities in lung cancer; however, serious radioactive pneumonia is rare for the radiotherapy of neck lymphoma because the volume of the lungs affected by radiation dose was very small. We report a lymphoma case, where the patient had undergone radiotherapy for the bilateral neck and bilateral supraclavicular/infraclavicular area. Following completion of radiotherapy, the patient developed severe radiation pneumonitis.

  5. Radiation pneumonitis after radiotherapy of neck lymphoma.

    Science.gov (United States)

    Wei, Min; Cai, Jun; Tong, Tao; Yu, Shihua; Yang, Yonghua; Zhang, Weijia; Yang, Jiyuan

    2014-01-01

    Radiotherapy is still one of the effective means for treatment of malignant tumors up to now. Particularly, it is an indispensable effective measure for treatment of some lymphoma patients. In routine work, radiation pneumonitis (RP) is the most significant complication of acute treatment-related toxicities in lung cancer; however, serious radioactive pneumonia is rare for the radiotherapy of neck lymphoma because the volume of the lungs affected by radiation dose was very small. We report a lymphoma case, where the patient had undergone radiotherapy for the bilateral neck and bilateral supraclavicular/infraclavicular area. Following completion of radiotherapy, the patient developed severe radiation pneumonitis.

  6. Lymphoma type MALT of the parotid gland

    International Nuclear Information System (INIS)

    Frometa Neirai, Carlos; Gonzalez Gomez, Juan Manuel; Arredondo Lopez, Miguel

    2010-01-01

    The lymphomas type MALT or the mucosa-associated lymphoid tissue, are the most recent variety of non-Hodgkin lymphomas present mainly in the gastric mucosa associated with Helycobacter pylori infection and in the thyroid gland in relation to Hashimoto's thyroiditis. Frequently the origin of this lesion can't be determined only by cytology study, thus it is necessary the histopathology analysis for a definitive diagnosis in most cases. Present paper includes the case of male patient with bilateral volume increase of both parotid glands and a diagnosis cytopathological of a benign lymphoepithelial process and the development of a type MALT lymphoma in relation to the right parotid gland. (author)

  7. Conjunctival marginal zone B-cell lymphoma (MALT lymphoma) with amyloid and relapse in the stomach.

    Science.gov (United States)

    Topalkara, A; Ben-Arie-Weintrob, Y; Ferry, J A; Foster, C S

    2007-01-01

    The authors report a localized (primary) conjunctival marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue (MALT)-type), with amyloid deposition with relapse in the stomach, 14 months after the initial diagnosis. Ocular adnexal marginal zone B-cell MALT lymphoma is often localized at diagnosis; some relapse in typical MALT sites. There are few reports of localized conjunctival lymphoma with a relapse in the stomach. The authors suggest that all patients with localized ocular adnexal lymphoma be followed for an extended period.

  8. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

    OpenAIRE

    Chettiankandy, Tabita Joy; Tupkari, Jagdish Vishnu; Kumar, Keshav; Ahire, Manisha Sandeep

    2016-01-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Burkitt's lymphoma (BL), is a diagnostic provisional category in the World Health Organization 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typica...

  9. Lymphoplasmacytic lymphoma-Waldenstrom's macroglobulinemia.

    Science.gov (United States)

    Vitolo, Umberto; Ferreri, Andrés J M; Montoto, Silvia

    2008-08-01

    The presence of IgM paraproteinemia in low-grade lymphomas is usually considered a clinical syndrome known as Waldenstrom's macroglobulinemia (WM). In the WHO classification, WM is associated to lymphoplasmacytic lymphoma (LPL); it is a clinicopathologic entity characterized by a monoclonal expansion of predominantly small B-lymphocytes with variable plasmacytoid differentiation. LPL constitutes less than 5% of all NHL and it is associated with hepatitis C virus infection in 26% of cases. Cells of LPL/WM are B cells positive for monocytic Ig light chains, IgM, pan-B-cell markers, and negative for CD3 and CD103. The t(9;14)(p13;q32) is present in 50% of LPL, and determines PAX-5 over-expression. 6q21 deletion is observed in 42% of cases. LPL occurs in older adults. Clinical presentation usually consists of disseminated disease, but extranodal involvement and leukemic phase are rare. Most WM patients have symptoms attributable to tumour infiltration and/or monoclonal protein. In fact, a monoclonal serum paraprotein of IgM type and hyperviscosity symptoms may occur in more than 20% of cases (WM). Hyperviscosity syndrome is usually manifested by bleeding, blurring or loss of vision, dizziness, headache, and neurologic symptoms. Malignant infiltration of the CNS (Bing-Neel syndrome) is uncommon. LPL/WM is an indolent malignancy that is not usually curable with conventional treatments. The median survival of patients with LPL or WM is 50-60 months, transformation to large cell lymphoma may occur. Stage definition is irrelevant in WM considering that initiation of therapy is decided on the bases of prognostic factors and the development of disease-related symptoms and signs. The main adverse prognostic factors are older age, B symptoms, anemia, low albumin serum levels, raised SGOT, and high beta 2-microglobulin values. Several therapeutic alternatives for newly diagnosed or relapsed LPL/WM are available; however, the best location for every strategy is a matter of

  10. Lymphoma – histopathology in changing clinical perspective ...

    African Journals Online (AJOL)

    Background. Lymphoma management has traditionally been dominated by nodal histopathology. Unfortunately, many different classifications coexisted and frequent revisions have often obscured clinical·correlations. Some improvement in understanding histogenesis followed the introduction of immunophenotyping, while ...

  11. Stages of Adult Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... with gastric MALT lymphoma may also have Helicobacter gastritis or an autoimmune disease , such as Hashimoto thyroiditis ... diagnosed, tests are done to find out if cancer cells have spread within the lymph system or ...

  12. Treatment Options for Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... with gastric MALT lymphoma may also have Helicobacter gastritis or an autoimmune disease , such as Hashimoto thyroiditis ... diagnosed, tests are done to find out if cancer cells have spread within the lymph system or ...

  13. Emerging diagnostic tests for vitreoretinal lymphoma.

    Science.gov (United States)

    Dawson, Abby C; Williams, Keryn A; Appukuttan, Binoy; Smith, Justine R

    2018-04-19

    Vitreoretinal lymphoma, which most commonly is diffuse large B cell non-Hodgkin in type, is a rare cancer with high morbidity and high mortality. Making a tissue diagnosis of vitreoretinal lymphoma is a major challenge for clinicians due to biological and technical factors. Yet, the delay in start of treatment may have vision- and life- threatening consequences, and there is considerable interest in the application of molecular assays to improve the accuracy of the diagnostic process: detection of a clonal immunoglobulin heavy chain rearrangements in lymphoma cells by polymerase chain reaction; measurement of vitreous or aqueous interleukin-10 protein levels in ocular fluids; and identification of mutations in the myeloid differentiation primary response gene 88 in tumour cells. In this article, we review the historical development and current application of each of these molecular methods. We also discuss future opportunities for the molecular diagnosis of vitreoretinal lymphoma through next generation sequencing technologies. This article is protected by copyright. All rights reserved.

  14. Hashimoto's thyroiditis, Sjogren's syndrome and orbital lymphoma.

    OpenAIRE

    Ko, G. T.; Chow, C. C.; Yeung, V. T.; Chan, H.; Cockram, C. S.

    1994-01-01

    A 69 year old Chinese housewife presented with periorbital puffiness, and dry eyes and mouth. Subsequent investigations confirmed the presence of Hashimoto's thyroiditis, Sjogren's syndrome and orbital lymphoma. This unusual combination is discussed with reference to previous publications.

  15. Primary conjunctival follicular lymphoma mimicking chronic conjunctivitis.

    Science.gov (United States)

    Labrador Velandia, S; García Lagarto, E; Saornil, M A; García Álvarez, C; Cuello, R; Diezhandino, P

    2016-02-01

    The case is presented of a 43 year-old male patient with chronic follicular conjunctivitis, negative bacterial serology, and refractory to local treatment. The incisional biopsy performed showed to be consistent with reactive lymphoid hyperplasia. A year later, a new incisional biopsy showed follicular lymphoma, with no systemic involvement, and he was treated with local radiotherapy. When a chronic follicular conjunctivitis is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis that can range from chronic inflammation, reactive lymphoid hyperplasia to lymphoma. Follicular lymphoma is rare among conjunctival lymphomas, and the staging is indispensable for the correct therapeutic approach. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Malignant lymphomas of the head and neck

    International Nuclear Information System (INIS)

    Motoori, Tadashi; Mihashi, Katsuhiko; Sueyoshi, Fumio; Mihashi, Shigenobu; Hirano, Minoru

    1982-01-01

    A retrospective review of 75 patients of malignant lymphoma treated at the Department of Otolaryngology, Kurume University Hospital, during the 10 years from 1971 to 1980 was carried out. In this study, the determinate cases consist of previously untreated 61 patients with histological diagnosis of malignant lymphomas. The results were seen as follows; (1) A patient of Hodgkin's disease, mixed cellularity (MC) in CS III, nodal lesion, was a 26-year-old male. He is currently alive 45 months after the initial treatment with no evidence of relapsing lesion. (2) In 60 patients with non Hodgkin's lymphomas, 1-, 2-, and 5-year cumulative survival rates calculated by the actuarial method were 65.5%, 54.8%, and 44.8%, respectively. (3) In patients with non-Hodgkin's lymphomas in early stages or of the Waldeyer's ring, prognosis was better. (4) Patients in advanced stages presented lower survival rate. (5) Diffuse lymphoma, plemorphic type showed the worst survival rate. (6) Among 31 deaths, 21(68%) were death from tumor dissemination, 5(16%) from complication, 2(6%) from unknown cause, 3(10%) from intercurrent disease. (7) Pulmonary complications, particularly, pneumonitis was the most serious complication in non-Hodgkin's lymphomas. (8) Relapse rate was 44% in early stages. Relapse occurred most frequently within 1 year, but there were some late relapses. (9) Two patients with non-Hodgkin's lymphomas of the Waldeyer's ring had a gastrointestinal involvement at relapse. (10) Lastly, we propose diagnostic and therapeutic protocols for the patients with malignant lymphomas. (author)

  17. Primary pulmonary Hodgkin’s lymphoma

    OpenAIRE

    Lluch-Garcia, R; Briones-Gomez, A; Castellano, E Monzó; Sanchez-Toril, F; Lopez, A; Brotons, B

    2010-01-01

    A 21-year-old man presented to hospital with a two-month history of productive cough with no other symptoms. Radiology revealed a cavitating lesion in the left upper lobe for which a variety of diagnoses were considered. A biopsy revealed primary pulmonary Hodgkin’s lymphoma. Primary pulmonary Hodgkin’s lymphoma is an uncommon initial presentation; lung lesions usually occur later in the course of the disease. Following diagnosis, the patient began chemotherapy and full remission was achieved...

  18. Radiation Pneumonitis after Radiotherapy of Neck Lymphoma

    OpenAIRE

    Wei, Min; Cai, Jun; Tong, Tao; Yu, Shihua; Yang, Yonghua; Zhang, Weijia; Yang, Jiyuan

    2014-01-01

    Radiotherapy is still one of the effective means for treatment of malignant tumors up to now. Particularly, it is an indispensable effective measure for treatment of some lymphoma patients. In routine work, radiation pneumonitis (RP) is the most significant complication of acute treatment-related toxicities in lung cancer; however, serious radioactive pneumonia is rare for the radiotherapy of neck lymphoma because the volume of the lungs affected by radiation dose was very small. We report a ...

  19. NKT Cell Responses to B Cell Lymphoma.

    Science.gov (United States)

    Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B; Page, Carly; Younger, Kenisha M; Tiper, Irina V; Frieman, Matthew; Kimball, Amy S; Webb, Tonya J

    2014-06-01

    Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

  20. 68. Unusual presentation of mediastinal lymphoma and role of cardiac MRI

    Directory of Open Access Journals (Sweden)

    N. Mahmood

    2016-07-01

    node and was reported as Diffuse Large B-Cell lymphoma of non-germinal center subtype with anaplastic features. Bone marrow biopsy was also performed as well PET oncology to complete staging process. The case was discussed in the multi-disciplinary oncology board and planned for chemotherapy with CHOP with no need for any cardiac intervention at this moment. The care of the patient was transferred to the hematology team with close follow-up by cardiology team. He received the chemotherapy for 4 cycles and had a repeat cardiac MRI which showed the complete resolution of the intra-cardiac mass. Patients with DLBCL typically present with a rapidly enlarging symptomatic mass, most usually nodal enlargement in the neck or abdomen, or, in the case of primary mediastinal large B cell lymphoma, the mediastinum, but may present as a mass lesion anywhere in the body. The prognosis is good as the rate of remission with chemotherapy is good. The cardiac MRI can assist in diagnosis.