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Sample records for anaplastic lymphoma cell

  1. Primary cutaneous anaplastic large-cell lymphoma.

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    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.

  2. Synchronous meningioma and anaplastic large cell lymphoma.

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    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.

  3. Pathobiology of Anaplastic Large Cell Lymphoma

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    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.

  4. [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.

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

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    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.

  6. 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.

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

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    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.

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

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

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    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.

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

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    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.

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

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    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...

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

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    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...

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

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    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.

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

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    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.

  15. 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

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

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    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....

  17. 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.

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

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    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.

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

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    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.

  20. 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.

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

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    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. Post transplant anaplastic large T-cell lymphoma

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    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.

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

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    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.

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

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    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

  5. 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

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    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

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

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    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.

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

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    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...

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

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    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.

  9. 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

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

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    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

  11. {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.

  12. 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.

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

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    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.

  14. 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

  15. 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

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

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    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.

  17. 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.

  18. 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.

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

    Science.gov (United States)

    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.

  1. 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

  2. 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.

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

    Science.gov (United States)

    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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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...

  20. 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

  1. 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.

  2. 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

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    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

  3. 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....

  4. 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

  5. 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.

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

    Science.gov (United States)

    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.

  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. 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

  9. 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

  10. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

  12. 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

  13. 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.

  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. 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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  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. 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 ...

  1. 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

  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. 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.

  4. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  4. 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.

  5. 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.

  6. 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 ...

  7. 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

  8. 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...

  9. 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.

  10. 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

  11. 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-cell

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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...

  19. 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

  20. 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)

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

    Science.gov (United States)

    2017-10-10

    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; 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; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Primary Hepatosplenic Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    M.R. Morales-Polanco

    2008-03-01

    Full Text Available Diffuse large B-cell lymphoma is the most common form of lymphoma. It usually begins in the lymph nodes; up to 40% may have an extranodal presentation. According to a definition of primary extranodal lymphoma with presentation only in extranodal sites, there are reports of large B-cell lymphomas limited to liver or spleen as separate entities, and to date there have been only three documented cases of primary hepatosplenic presentation. This paper reports a fourth case. Due to a review of the literature and the clinical course of the case reported, we conclude that primary hepatosplenic large B-cell lymphoma has been found predominantly in females older than 60 years. The patients reported had <2 months of evolution prior to diagnosis, prominent B symptoms, splenomegaly in three and hepatomegaly in two, none with lymph node involvement. All had thrombocytopenia and abnormal liver function tests; three had anemia and elevated serum lactic dehydrogenase levels, two with hemophagocytosis in bone marrow. Because of the previously mentioned data, it can be stated that primary hepatosplenic lymphoma is an uncommon and aggressive form of disease that requires immediate recognition and treatment.

  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. 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

  16. 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

  17. Osmotic homeostasis and NKLy lymphoma cells radiosensitivity

    International Nuclear Information System (INIS)

    Tishchenko, V.V.; Magda, I.N.

    1992-01-01

    In experiments with cells of ascites NKLy lymphoma differing in ploidy and position in the cell cycle, a study was made of the radiosensitivity, osmotic homeostasis peculiarities and thermoradiation changes in potassium content. It was shown that the resistance of osmotic homeostasis of NKLy cells to thermoradiation correlated with their radioresistance

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. MicroRNAs in mantle cell lymphoma

    DEFF Research Database (Denmark)

    Husby, Simon; Geisler, Christian; Grønbæk, Kirsten

    2013-01-01

    Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma. New treatment modalities, including intensive induction regimens with immunochemotherapy and autologous stem cell transplant, have improved survival. However, many patients still relapse, and there is a need...... for novel therapeutic strategies. Recent progress has been made in the understanding of the role of microRNAs (miRNAs) in MCL. Comparisons of tumor samples from patients with MCL with their normal counterparts (naive B-cells) have identified differentially expressed miRNAs with roles in cellular growth...

  3. 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- ...

  4. The mantle cells lymphoma: a proposed treatment

    International Nuclear Information System (INIS)

    Chavez Martinez, Marlene Elizabeth

    2012-01-01

    A literature review was performed on mantle cells lymphoma in the therapeutic schemes. The literature that has been used is published in journals of medicine specializing in hematology, oncology, radiation therapy, molecular biology and internal medicine. The literature review was performed to propose a scheme of treatment according to Costa Rica. Epigenetic alterations have been revealed in patients with mantle lymphoma on current researches. The mantle lymphoma pathology has been described in various forms of clinical and histological presentation, stressing the importance of detailing the different methods and diagnostic reports. Working groups have proposed and developed various chemotherapy regimens and concluded that CHOP alone is without effect in mantle cell lymphoma unlike R-hyper-CVAD, CHOP / DHAP, high-dose Ara-C. Researchers have tried to develop new treatments based vaccines, use of modified viruses, specific monoclonal antibodies. The classic treatment has been triple intrathecal therapy. The central nervous system has been one of the most momentous sites of mantle cell lymphoma infiltration because poorer patient prognosis [es

  5. Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

    Science.gov (United States)

    2018-03-12

    ALK-Positive Large B-Cell Lymphoma; Atypical Burkitt/Burkitt-Like Lymphoma; Burkitt-Like Lymphoma With 11q Aberration; Diffuse Large B-Cell Lymphoma Activated B-Cell Type; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Mucocutaneous Ulcer; High-Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Human Herpesvirus 8-Positive Neoplastic Cells Present; Intravascular Large B-Cell Lymphoma; Large B-Cell Lymphoma With IRF4 Rearrangement; Plasmablastic Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Primary Effusion 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 Lymphomatoid Granulomatosis; Recurrent Mediastinal (Thymic) Large B-Cell Cell 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 Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Small Intestinal High Grade B-Cell Lymphoma, Not Otherwise Specified; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

  6. 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

  7. Peripheral T cell lymphoma: Not otherwise specified

    Directory of Open Access Journals (Sweden)

    Anusha H Pai

    2015-01-01

    Full Text Available Peripheral T cell lymphoma (PTCL is a heterogeneous group of hematological tumors originating from mature T cells, which constitutes less than 15% of all non-Hodgkins lymphomas in adults. Primary cutaneous PTCL-not otherwise specified (NOS represent a subgroup of PTCLs with no consistent immunophenotypic, genetic or clinical features. PTCL-NOS frequently has an aggressive course with a tendency for systemic involvement, however, a well-defined therapeutic and prognostic approach has not been outlined yet. We report a case of PTCL-NOS with multiple cutaneous lesions in a young adult male with an emphasis on the treatment modality used.

  8. Angioimmunoblastic T Cell Lymphoma Mimicking Chronic Urticaria

    Directory of Open Access Journals (Sweden)

    Mohleen Kang

    2016-01-01

    Full Text Available Angioimmunoblastic T cell lymphoma (AITL is a rare but distinct type of T cell lymphoma with an aggressive course and high mortality. Most patients are diagnosed late in the disease and usually present with generalized lymphadenopathy. A minority have skin lesions at the time of diagnosis, more commonly in the form of nonspecific maculopapular rash with or without pruritus. We report a rare case of AITL presenting with chronic, recurrent angioedema and urticaria-like lesions and no palpable peripheral adenopathy. Primary Care physicians, dermatologists, and allergists must maintain a high index of suspicion for cutaneous manifestations of lymphoma, especially if the skin lesions are refractory to standard treatment. Timely diagnosis is essential to improve survival.

  9. 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.

  10. R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    2018-03-27

    CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  11. Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

    Science.gov (United States)

    2018-03-19

    Follicular T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides AJCC v7; Stage II Mycosis Fungoides AJCC v7; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides AJCC v7; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides AJCC v7

  12. 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.

  13. Sequential development of peripheral t-cell lymphoma post immunochemotherapy of diffuse large B cell lymphoma.

    Science.gov (United States)

    Wang, Jing-Wen; Chen, Jia-Yan; Lu, Chen; Tang, Xi

    2017-04-03

    Reports of sequential occurrence of two or more types of lymphoma are rare, especially when they involve different cell lineages. Herein, we report a rare case of sequential development of peripheral t-cell lymphoma following treatment of diffuse large B cell lymphoma. In a 73-year-old Chinese male patient, diffuse large B-cell lymphoma (DLBCL) was diagnosed in September 2011 based on the result of a tongue biopsy. Afterwards, he received rituximab combined with chemotherapy and local radiotherapy. Though he achieved completed remission, he had a new symptom of one enlarged left inguinal lymph node in November of 2015. A new biopsy was then performed. Immunohistochemistry and polymerase chain reaction (PCR) for gene rearrangements proved monoclonal T-cell lymphoma. We didn't detect EBV infection in either of two biopsies, nor any evidence of immune dysfunction complications. Sequential development of B-cell and T-cell malignancy in this patient maybe an example of treatment-related secondary lymphoma.

  14. [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%.

  15. Early-stage mantle cell lymphoma

    DEFF Research Database (Denmark)

    Dabaja, B S; Zelenetz, A D; Ng, A K

    2017-01-01

    Background: Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease. Patients and methods: In this 13-institution study, we examined...

  16. 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...

  17. Aberrant phenotypes in peripheral T cell lymphomas.

    Science.gov (United States)

    Hastrup, N; Ralfkiaer, E; Pallesen, G

    1989-01-01

    Seventy six peripheral T cell lymphomas were examined immunohistologically to test their reactivity with a panel of monoclonal antibodies against 11 T cell associated antigens (CD1-8, CD27, UCHL1, and the T cell antigen receptor). Sixty two (82%) lymphomas showed aberrant phenotypes, and four main categories were distinguished as follows: (i) lack of one or several pan-T cell antigens (49, 64% of the cases); (ii) loss of both the CD4 and CD8 antigens (11, 15% of the cases); (iii) coexpression of the CD4 and CD8 antigens (13, 17% of the cases); and (iv) expression of the CD1 antigen (eight, 11% of the cases). No correlation was seen between the occurrence of aberrant phenotypes and the histological subtype. It is concluded that the demonstration of an aberrant phenotype is a valuable supplement to histological assessment in the diagnosis of peripheral T cell lymphomas. It is recommended that the panel of monoclonal antibodies against T cell differentiation antigens should be fairly large, as apparently any antigen may be lost in the process of malignant transformation. Images Figure PMID:2469701

  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.

    2011-01-01

    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

  19. 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

  20. 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.

  1. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

    Directory of Open Access Journals (Sweden)

    Kayo Tokeji

    2016-01-01

    Full Text Available We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.

  2. 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 ...

  3. 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.

  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. Management of mantle cell lymphoma in the elderly patient

    NARCIS (Netherlands)

    Doorduijn, Jeanette K.; Kluin-Nelemans, Hanneke C.

    2013-01-01

    Mantle cell lymphoma is a relatively rare B-cell lymphoma with a specific genetic lesion and a typical immunophenotypic profile. The median age is 65 years. There is no curative treatment, except allogeneic stem cell transplantation for a selected group of patients. For the majority of patients,

  6. Management of mantle cell lymphoma in the elderly patient

    NARCIS (Netherlands)

    J.K. Doorduijn (Jeanette); J.C. Kluin-Nelemans (Hanneke)

    2013-01-01

    textabstractMantle cell lymphoma is a relatively rare B-cell lymphoma with a specific genetic lesion and a typical immunophenotypic profile. The median age is 65 years. There is no curative treatment, except allogeneic stem cell transplantation for a selected group of patients. For the majority of

  7. 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.

  8. Hematopoietic stem cell transplantation for indolent lymphomas

    International Nuclear Information System (INIS)

    Izutsu, Koji

    2008-01-01

    Described are the review of the transplantation in the title (SCT), and the possible impact on its application and outcome of radio-immunotherapy (RIT) by new antibody drugs like ibritumomab tiuxetan (Ibr) and tositumomab (Tos), and of chemotherapy by purine analogs. Various regimens for the combination of auto-SCT, allo-SCT, chemotherapy and total body irradiation (TBI) have been used to treat the recurrent and progressive indolent lymphoma including follicular lymphoma (FL); however, their outcomes are still controversial. Introduction of new drugs like rituximab (Rit), Ibr and Tos has made it possible to extend the options of the regimen. For instance, in auto-SCT in FL, a high dose Rit therapy is used for in vivo purging to reduce tumor cell contamination of the graft instead of the exhausting, high-cost pretreatment for the in vitro purging with cyclophosphamide (CY)/TBI hitherto. In addition, RIT by Tos at the absorbed dose of 20-27 Gy in the critical organs with CY/VP16 combination is reportedly superior to CY/VP16/TBI. In allo-SCT where recurrence frequency is known low despite high mortality due to various complications, many regimens involving fludarabine/TBI have been also reported. Thus there has been neither clear standard for SCT in the lymphoma nor yet its prognosis after the therapy with new drugs described and the accumulation of their findings hereafter is important for future SCT application. (R.T.)

  9. Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-01-26

    Adult Grade III Lymphomatoid Granulomatosis; 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; Post-transplant Lymphoproliferative Disorder; 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 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; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  10. 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

  11. Gastric and colonic mantle cell lymphoma - incidental discovery.

    Science.gov (United States)

    Pitigoi, Dan; Stoica, Victor; Stoia, Razvan; Dobrea, Camelia; Becheanu, Gabriel; Diculescu, Mircea

    2009-03-01

    A 65-year old patient, with no medical history, was admitted for lower gastrointestinal bleeding. On clinical examination the patient seemed to be in good health. However the examination was completed with a rectosigmoidoscopy revealing the presence of mucosal erosions, ulcerations, multiple papulae. The histopathological examination raised the suspicion of a colonic lymphoma. Gastric biopsies suggested a gastric MALT type lymphoma associated to the colonic lymphoma, but the immunohistochemical profile corresponded to a mantle cell lymphoma. In spite of the general poor prognosis of mantle cell lymphoma, our patient had a good clinical and endoscopic response to the standard cyclophosphamide, vincristine, prednisone (CVP) therapy. The cases of gastric and colonic mantle lymphoma are rare, the response to therapy is poor; fortunately, our patient had a complete resolution after completion of the six cycles of chemotherapy.

  12. 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...

  13. 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.

  14. 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.

  15. Primary intestinal T cell lymphomas in Indian patients - In search of enteropathic T cell lymphoma

    Directory of Open Access Journals (Sweden)

    Shet Tanuja

    2010-07-01

    Full Text Available Objective: This series of six intestinal T cell lymphomas (ITCL attempts to document enteropathy-associated T cell lymphoma (EATCL in India. Materials and Methods: A total of six ITCL were selected from 170 gastrointestinal lymphomas in last 10 years. Results: The cases studied included EATCL (4, ITCL with a CD4 positive phenotype (1 and ITCL NK/T cell type (1. Of the four EATCL, two occurred in the ileum, one in right colon and one in duodenum. In three EATCL cases, there was history of celiac disease or lactose intolerance and enteropathic changes were noted in the adjacent mucosa. These tumors had CD3+/CD8+/CD56 (+/-/CD4-/ Granzyme B+ immunophenotype. One EATCL was monomorphic small cell type (type II EATCL with a CD3+/CD8-CD56+/CD4-/ Granzyme B+ phenotype. EBER- ISH (Epstein Barr virus coded RNA′s- in situ hybridization revealed positive tumor cells in ITCL NK/T cell type and in bystander cells in three EATCL. Conclusion: ITCL are rare in Indian patients but do occur and comprise a mixture of the enteropathic and non-enteropathic subtypes.

  16. Intravascular Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Maria S. Khan MD, FACP

    2014-03-01

    Full Text Available Case Presentation . A 69-year-old Hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7, prothrombin time (PT 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (PTT 55.6 seconds, fibrin split 10 µg/L, and lactate dehydrogenase (LDH 1231 IU/L. Except for a positive DNA test for Epstein–Barr virus (EBV infection, extensive diagnostic workup for infections, malignancy, or a neurological cause was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. The patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B-cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30, and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion . Intravascular large cell B-cell lymphoma (IVLBCL is rare form of diffuse large B-cell lymphoma and tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant, and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits, and skin findings. Bone marrow, spleen, and liver are involved in a minority of patients. Nearly all patients have elevated LDH

  17. Peripheral T cell lymphoma: clinical utility of romidepsin

    Directory of Open Access Journals (Sweden)

    Sawey K

    2012-06-01

    Full Text Available Jasmine Zain, Kathryn SaweyNYU Langone Medical Center, New York, USAIntroduction: Direct therapeutic targets, such as aberrant tumor cell genes and tumor cell markers, have been the focus of cancer treatment for more than 50 years. The resulting damage to normal cells and emergence of drug-resistant tumor cells after exposure to conventional chemotherapy have led researchers to study indirect targets, like the tumor vasculature. A more recent indirect approach involves targeting the epigenetic modifiers, DNA methyltransferase and histone deacetylase. Histone deacetylase inhibitors have been shown to be active cytotoxic agents in T cell lymphoma. The current treatments approved by the US Food and Drug Administration for relapsed cutaneous T cell lymphoma are vorinostat and romidepsin. The diversity and rarity of peripheral T cell lymphomas present a challenge for effective treatment. With their poor overall survival rate, new targeted therapies need to be developed.Keywords: peripheral T cell lymphoma, treatment, romidepsin

  18. Small interfering RNA (siRNA) against Slug induces apoptosis and sensitizes human anaplastic thyroid carcinoma cells to doxorubicin.

    Science.gov (United States)

    Pan, Yinghua; Liu, Peiji; Chen, Deng; Dou, Linying

    2017-01-01

    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. SW1736 cells were transfected with Slug siRNA or/and PUMA siRNA and then exposed to DOX (0.1, 1, and 5 μ M) 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, RT-PCR 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. Targeting of Slug using siRNA inhibits growth of SW1736 cells and sensitizes SW1736 cells to DOX in vitro and vivo. Targeting of Slug 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. 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.

  19. Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2017-04-17

    B-cell Chronic Lymphocytic Leukemia; 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 Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic 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; Waldenström Macroglobulinemia

  20. Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity

    NARCIS (Netherlands)

    Bende, Richard J.; Aarts, Wilhelmina M.; Riedl, Robert G.; de Jong, Daphne; Pals, Steven T.; van Noesel, Carel J. M.

    2005-01-01

    We analyzed the structure of antigen receptors of a comprehensive panel of mature B nonHodgkin's lymphomas (B-NHLs) by comparing, at the amino acid level, their immunoglobulin (Ig)V-H-CDR3s with CDR3 sequences present in GenBank. Follicular lymphomas, diffuse large B cell lymphomas, Burkitt's

  1. miR-4295 promotes cell proliferation and invasion in anaplastic thyroid carcinoma via CDKN1A

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Mingchen; Geng, Yiwei [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Xi, Ying [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Wei, Sidong [Liver Transplantation Hepatobiliary Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Wang, Liuxing; Fan, Qingxia [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Ma, Wang, E-mail: doctormawang@126.com [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China)

    2015-09-04

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in anaplastic thyroid carcinoma (ATC), has remained elusive. Here, we identified that miR-4295 promotes ATC cell proliferation by negatively regulates its target gene CDKN1A. In ATC cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-4295, while miR-4295 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-4295 mimics significantly promoted the migration and invasion of ATC cells, whereas miR-4295 inhibitors significantly reduced cell migration and invasion. luciferase assays confirmed that miR-4295 directly bound to the 3'untranslated region of CDKN1A, and western blotting showed that miR-4295 suppressed the expression of CDKN1A at the protein levels. This study indicated that miR-4295 negatively regulates CDKN1A and promotes proliferation and invasion of ATC cell lines. Thus, miR-4295 may represent a potential therapeutic target for ATC intervention. - Highlights: • miR-4295 mimics promote the proliferation and invasion of ATC cells. • miR-4295 inhibitors inhibit the proliferation and invasion of ATC cells. • miR-4295 targets 3′UTR of CDKN1A in ATC cells. • miR-4295 negatively regulates CDKN1A in ATC cells.

  2. Prognostic Assessment in Patients with Indolent B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Luca Arcaini

    2012-01-01

    Full Text Available Follicular lymphoma (FL is an indolent lymphoma with long median survival. Many studies have been performed to build up prognostic scores potentially useful to identify patients with poorer outcome. In 2004, an international consortium coordinated by the International Follicular Lymphoma Prognostic Factor project was established and a new prognostic study was launched (FLIPI2 using progression-free survival (PFS as main endpoint and integrating all the modern parameters prospectively collected. Low-grade non-Hodgkin lymphomas were once considered as a heterogenous group of lymphomas characterized by an indolent clinical course. Each entity is characterized by unique clinicobiologic features. Some studies have been focused on prognostic factors in single lymphoma subtypes, with the development of specific-entity scores based on retrospective series, for instance splenic marginal zone lymphoma (SMZL. A widely accepted prognostic tool for clinical usage for indolent non-follicular B-cell lymphomas is largely awaited. In this paper we summarized the current evidence regarding prognostic assessment of indolent follicular and non-follicular lymphomas.

  3. Primary cutaneous peripheral T-cell lymphoma, unspecified with an indolent clinical course: a distinct peripheral T-cell lymphoma?

    LENUS (Irish Health Repository)

    Ryan, A J A

    2012-02-01

    Primary cutaneous peripheral T-cell lymphomas (PTL), unspecified, are rare lymphomas, with a poor prognosis. They grow and disseminate rapidly, leading to widespread disease. We report a case of PTL, unspecified occurring on the nose. Despite its aggressive histology, this tumour behaved indolently. It is remarkably similar, clinically and histologically, to four recently described cases that occurred on the ear.

  4. Mantle Cell Lymphoma of the Gastrointestinal Tract (Lymphomatous Polyposis

    Directory of Open Access Journals (Sweden)

    Hugh James Freeman

    1996-01-01

    Full Text Available A74-year-old male with a history of a tonsillar lymphoma developed diarrhea. Investigations led to detection of extensive intestinal lymphomatous polyposis (mantle cell lymphoma. After an aggressive clinical course with associated nodal and peripheral blood involvement, death followed within three months. Postmortem studies revealed widespread dissemination within the entire gastrointestinal tract, including the esophagus, stomach, and small and large intestines. Although this type of lymphoma is rare and accounts for only about 1% to 8% of all forms of primary B cell gastrointestinal lymphomas in North America, separation from other subtypes has become more important because of reported responses of mucosa-associated lymphoid tissue-lymphomas to antibiotics aimed at Helicobacter pylori eradication.

  5. Clinicopathological analysis of mediastinal large B-cell lymphoma and classical Hodgkin lymphoma of the mediastinum.

    Science.gov (United States)

    Yamamoto, Wataru; Nakamura, Naoya; Tomita, Naoto; Ishii, Yoshimi; Takasaki, Hirotaka; Hashimoto, Chizuko; Motomura, Shigeki; Yamazaki, Etsuko; Ohshima, Rika; Numata, Ayumi; Ishigatsubo, Yoshiaki; Sakai, Rika

    2013-05-01

    Primary mediastinal (thymic) large B-cell lymphoma (PMLBCL) and nodular sclerosing classical Hodgkin lymphoma (NSCHL) are the major histological types of lymphoma affecting the mediastinum. We reviewed 27 patients with PMLBCL and 14 patients with NSCHL. A poor performance status, high serum lactate dehydrogenase level and strong positivity for PAX5 were all significantly more common in patients with PMLBCL than in those with NSCHL. Severe fibrosis was frequent in NSCHL, but not in PMLBCL. PDL1 was expressed by 11/25 PMLBCLs (44.0%) vs. 1/9 NSCHLs (11.1%). Expression of BCL6 was significantly more frequent in PDL1-positive PMLBCL than in PDL1-negative PMLBCL, but there were no clinical differences between these two groups. Two patients with PMLBCL with a poor prognosis had CD20(-), CD79a(+), CD15(-), and CD30(-), possibly representing a subtype of mediastinal gray zone lymphoma.

  6. Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Matilde Cacciatore

    2012-01-01

    Full Text Available Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.

  7. Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-05

    Aggressive Non-Hodgkin Lymphoma; CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  8. 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

  9. 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)

  10. Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

    Science.gov (United States)

    2017-11-29

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Fanconi Anemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; 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

  11. Imaging Case: NK/T-Cell Lymphoma, Nasal Type

    Directory of Open Access Journals (Sweden)

    Srini vasan

    2015-11-01

    Full Text Available Peripheral T-cell lymphomas are a group of heterogeneous disorders and according to WHO classification, are categorized into nodal and extranodal forms. NK/T-cell lymphoma, nasal type, is a subtype of extranodal peripheral T-cell lymphoma and commonly presents as a midfacial destructive lesion. This disorder is more prevalent in Asia and South America and has a strong association with Epstein Barr Virus infection. Invasion of vessel walls by lymphoid cells, which is known as angiocentricity, is characteristic of nasal type NK/T-cell lymphoma. The tumor cells express CD2 and CD56 antigens; but not CD3. The nasal cavity is the mostly frequently affected site. Other commonly affected sites include palate and upper airways. On cross sectional imaging, the nasal involvement is seen as a diffuse sheet-like mucosal thickening along the nasal turbinates and septum or as a destructive midline mass (Figs 1,2. The latter form was previously described as a lethal midline granuloma or polymorphic reticulosis. The mass frequently extends into subcutaneous tissues of nasal ala and buccinator space (Fig.3. Regional lymphadenopathy is usually not seen. The radiological differential diagnoses for a midline nasal cavity mass include squamous cell carcinoma, minor salivary gland tumor, Wegener’s granulomatosis, and fungal infections. The imaging appearances of NK/T-cell lymphoma are often indistinguishable from the above mentioned conditions. However, predilection to involve both sides of the nasal cavity and tendency to spread as a diffuse thin sheet-like soft tissue along the walls of the nasal cavity enveloping the nasal turbinates and nasal septum favour the diagnosis of NK/T-cell lymphoma. Contiguous extension into the nasopharynx, palate, upper airways, and subcutaneous tissues can also suggest the possibility of NK/T-cell lymphoma, nasal type (Fig.4. T-cell lymphoma, compared to B-cell lymphoma, has an aggressive course and poor prognosis. The median

  12. Cutaneous lesions as presentation form of mantle cell lymphoma

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    Nayra Merino de Paz

    2011-12-01

    Full Text Available Mantle cell lymphoma is a type of no-Hodgkin lymphoma that affects extranodal areas, especially, bone narrow, digestive tract and Waldeyer ring. Here we report a case of mantle cell lymphoma IV Ann Arbor stage with cutaneous lesions on nasal dorsum and gland as the first manifestations. Skin involvement is a very rare manifestation and less than 20 cases have been reported in the literature. The importance of stablishing multidisciplinary relationships for a global approach has been shown by this clinical case.

  13. 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

  14. Mediastinal large cell lymphoma with sclerosis

    International Nuclear Information System (INIS)

    Franco, Sergio; Pulcheri, Wolmar; Spector, Nelson; Nucci, Marcio; Oliveira, Halley P. de; Morais, Jose Carlos; Romano, Sergio

    1995-01-01

    Five cases of primary mediastinal large-cell lymphoma with sclerosis diagnosed at the University Hospital Clementino Fraga Filho (Federal University of Rio de Janeiro) between 1986 and 1994 were identified. They were studied on clinical, morphological and immuno-histochemical grounds. Clinically, the disease was characterized by the young age of the patients, mediastinal involvement by bulky disease and compressive symptoms. None of the patients had evidence of extra-thoracic disease as presentation. On morphological grounds they had evidence of extra-thoracic disease at presentation. On morphological grounds they showed a mixture of immuno blasts and large follicular enter cell with sclerosis. Three of five cases proved to be of B-cell origin. Four of five patients were treated with chemotherapy. Cases 1 and with MACOP-B, and cases 3 and 4 with Pro-MACE-cytaBOM and consolidation radiation therapy. All the patients achieved a complete remission, and are alive, free of disease, with a follow-up of 1 to 8 years. (author). 28 refs., 8 figs., 2 tabs

  15. Synchronous adenocarcinoma and mantle cell lymphoma of the colon.

    Science.gov (United States)

    Padmanabhan, Vijayalakshmi; Trainer, Thomas D

    2003-02-01

    Synchronous occurrence of malignant lymphoma and carcinoma, both located in the intestinal tract, is unusual. We report a unique case of an adenocarcinoma of the cecum and a simultaneous mantle cell lymphoma of the colon, terminal ileum, and regional lymph nodes in an 85-year-old man. Grossly, the adenocarcinoma was identified as a cecal mass. Lymphomatous involvement of the gastrointestinal tract was evident only on microscopic examination. The terminal ileum and colon showed microscopic disseminated multiple mucosal nodules, with involvement of the regional lymph nodes. There was no involvement of distant organs, suggesting that the mantle cell lymphoma was early in its evolution without formation of polyps or a mass lesion. To our knowledge, this is the fourth reported case with this association and the second case that showed early involvement of the gastrointestinal tract with mantle cell lymphoma without polyp formation.

  16. JCAR014 and Durvalumab in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-02

    BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; High-Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; MYC Gene Rearrangement; 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

  17. 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.

  18. HSP90 inhibitor 17-AAG selectively eradicates lymphoma stem cells.

    Science.gov (United States)

    Newman, Bryan; Liu, Yan; Lee, Hsiu-Fang; Sun, Duxin; Wang, Yin

    2012-09-01

    Cancer stem cells (CSC; also called tumor-initiating cells) comprise tumor cell subpopulations that preserve the properties of quiescence, self-renewal, and differentiation of normal stem cells. In addition, CSCs are therapeutically important because of their key contributions toward drug resistance. The hypoxia-inducible transcription factor HIF1α is critical for CSC maintenance in mouse lymphoma. In this study, we showed that low concentrations of the HSP90 inhibitor 17-AAG eliminate lymphoma CSCs in vitro and in vivo by disrupting the transcriptional function of HIF1α, a client protein of HSP90. 17-AAG preferentially induced apoptosis and eliminated the colony formation capacity of mouse lymphoma CSCs and human acute myeloid leukemia (AML) CSCs. However, low concentrations of 17-AAG failed to eliminate highly proliferative lymphoma and AML cells (non-CSCs), in which the AKT-GSK3 signaling pathway is constitutively active. The heat shock transcription factor HSF1 is highly expressed in non-CSCs, but it was weakly expressed in lymphoma CSCs. However, siRNA-mediated attenuation of HSF1 abrogated the colony formation ability of both lymphoma and AML CSCs. This study supports the use of 17-AAG as a CSC targeting agent and, in addition, shows that HSF1 is an important target for elimination of both CSCs and non-CSCs in cancer. ©2012 AACR.

  19. Primary mediastinal large B-cell lymphoma.

    Science.gov (United States)

    Martelli, Maurizio; Ferreri, Andrés; Di Rocco, Alice; Ansuinelli, Michela; Johnson, Peter W M

    2017-05-01

    Primary mediastinal large B-cell lymphoma (PMLBCL) is a distinct clinical and biological disease from other types of DLBCL. It is more frequent in young female and constitutes 6%-10% of all DLBCL. PMLBCL is characterized by a diffuse proliferation of medium to large B-cells associated with sclerosis. Molecular analysis shows it to be a distinct entity from other DLBCL. Rituximab CHOP/MACOP-B-like regimens followed by mediastinal radiotherapy (RT) were associated with a 5-years PFS of 75%-85%. More intensive regimens, as DA-EPOCH-R without mediastinal RT, have shown very promising results, but this therapeutic advance needs to be confirmed in further prospective trials. The role of consolidative mediastinal RT should be still better assess in prospective comparative studies. PET-CT scan is a powerful tool to define the real quality of response and it is hoped that future prospective trials may allow its role in the de-escalation of mediastinal RT. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. 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

  1. Heart of Lymphoma: Primary Mediastinal Large B-Cell Lymphoma with Endomyocardial Involvement

    Directory of Open Access Journals (Sweden)

    Elisa Rogowitz

    2013-01-01

    Full Text Available Primary mediastinal B-cell lymphoma (PMBCL is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.

  2. Yttrium Y 90 Basiliximab and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Mature T-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-10

    Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma

  3. Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma

    DEFF Research Database (Denmark)

    Mansouri, Larry; Noerenberg, Daniel; Young, Emma

    2016-01-01

    lymphoma, and primary central nervous system lymphoma (3% to 4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases [22.7%]) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases [27.3%]). NFKBIE-deleted PMBL patients were more often therapy...... a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia (lymphoma, mantle cell...

  4. 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

  5. Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years with untreated mantle cell lymphoma

    DEFF Research Database (Denmark)

    Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna

    2016-01-01

    For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untr......For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years...... patients (median age 71 years) were enrolled 2009-2013. In phase I, the MTD of LEN was defined as 10 mg in cycles 2-6, and omitted in cycle 1. After six cycles, the complete remission rate (CRR) was 64% and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3 year...

  6. Diffuse Large B Cell Lymphoma of the Breast

    Directory of Open Access Journals (Sweden)

    Feryal Karaca

    2015-03-01

    Full Text Available Primary breast lymphoma is rarely encountered in Non-Hodgkin Lymphomas. However, if early diagnosis is made, and treatment is started immediately in patients with low grade and stage, patient survival is increased. 39-year old female patient applied us due to a palpable mass. She was diagnosed with the Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma after the investigations. Curative external radiotherapy was applied after 6 courses of CHOP-R chemotherapy to the patient with Stage-IIE favorable, and B symptoms. After 48-month follow up, patient follow up is being continued without any progression, or recurrence or metastasis. [Cukurova Med J 2015; 40(1.000: 151-157

  7. A B-cell lymphoma case that is unclassifiable, and intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma of lacrimal gland

    Directory of Open Access Journals (Sweden)

    Yunoki T

    2017-02-01

    Full Text Available Tatsuya Yunoki,1 Jun Murakami,2 Yukihiro Imagawa,3 Takahiko Nakajima,4 Atsushi Hayashi1 1Department of Ophthalmology, 2Department of Gastroenterology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 3Department of Ophthalmology, Osaka Kaisei Hospital, Osaka, 4Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Abstract: A 60-year-old woman presented with acute eyelid swelling and a subcutaneous hemorrhage in the right eye. Magnetic resonance imaging showed a spherical tumor of the lacrimal gland. The tumor was removed by the Kroenlein method. We diagnosed as a B-cell lymphoma that is unclassifiable, and intermediate between diffuse large B-cell lymphoma (DLBCL and Burkitt lymphoma (BL (intermediate DLBCL/BL based on its immunohistopathological examination and c-MYC/IgH rearrangement. We administered six cycles of dose-adjusted-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride, and rituximab therapy, and remission of the lymphoma was obtained. This is the first case of an intermediate DLBCL/BL of a lacrimal gland. Keywords: diffuse large B-cell lymphoma, Burkitt lymphoma, c-MYC gene, fluorescence in situ hybridization

  8. Nasosinusal Lymphoma of T Natural Killer Cells: Case Report

    Directory of Open Access Journals (Sweden)

    Castro, Victor Labres da Silva

    2011-01-01

    Full Text Available Introduction: The primary nasal lymphoma is an uncommon extranodal tumor and represents 0.44% of all Extranodal lymphomas in this region. The primary nasal lymphoma derives from the T-lineage in nearly 75% of the cases. Objective: To describe a case of nasosinusal lymphoma of T Natural Killer cells, attended in the Clinical Hospital of the Federal University of Goiás. Case Report: 48-year-old female patient with diffuse tumefaction in the left hemiface of firm-elastic consistency and painful upon digital compression. Face sinuses tomography identified a total maxillary veiling to the left and some posterior ethmoidal cells. With the diagnostic hypothesis of a tumor affection, we opted for the surgical removal via a transmaxillary approach and the material was sent for biopsy. The histopathological exam diagnosed a highly necrotic tumor of angiocentric pattern, polymorphic and atypical lymphoid population (T /NK Lymphoma; with the prognosis, the patient was submitted to chemical therapy with total regression of the facial edema. Final Comments: The otorhinolaryngologist must be attentive as regards the existence of lymphomas among the nasosinusal diseases, because the early diagnosis improves the survival as it prevents metastases, growth and local destruction.

  9. The Role of c-MYC in B-Cell Lymphomas: Diagnostic and Molecular Aspects.

    Science.gov (United States)

    Nguyen, Lynh; Papenhausen, Peter; Shao, Haipeng

    2017-04-05

    c-MYC is one of the most essential transcriptional factors, regulating a diverse array of cellular functions, including proliferation, growth, and apoptosis. Dysregulation of c-MYC is essential in the pathogenesis of a number of B-cell lymphomas, but is rarely reported in T-cell lymphomas. c-MYC dysregulation induces lymphomagenesis by loss of the tight control of c-MYC expression, leading to overexpression of intact c-MYC protein, in contrast to the somatic mutations or fusion proteins seen in many other oncogenes. Dysregulation of c-MYC in B-cell lymphomas occurs either as a primary event in Burkitt lymphoma, or secondarily in aggressive lymphomas such as diffuse large B-cell lymphoma, plasmablastic lymphoma, mantle cell lymphoma, or double-hit lymphoma. Secondary c-MYC changes include gene translocation and gene amplification, occurring against a background of complex karyotype, and most often confer aggressive clinical behavior, as evidenced in the double-hit lymphomas. In low-grade B-cell lymphomas, acquisition of c-MYC rearrangement usually results in transformation into highly aggressive lymphomas, with some exceptions. In this review, we discuss the role that c-MYC plays in the pathogenesis of B-cell lymphomas, the molecular alterations that lead to c-MYC dysregulation, and their effect on prognosis and diagnosis in specific types of B-cell lymphoma.

  10. [Current aspects of the pathology and differentiation of extranodal marginal zone B-cell lymphoma, MALT-Type, and gastrointestinal diffuse large B-cell lymphoma].

    Science.gov (United States)

    Flossbach, L; Kestler, H A; Gress, T M; Möller, P; Barth, T F

    2010-08-01

    The marginal zone B-cell lymphoma, MALT-type (MZBL, MT) is a low-grade B-cell lymphoma which is predominantly localised in the stomach with a typical morphology and cytogenetic pattern. The coexistence of a diffuse large B-cell lymphoma (DLBCL) with an MZBL, MT in the gastrointestinal tract is defined as a composite lymphoma (ComL) and represents a fascinating model of lymphoma progression. In this review we focus on current aspects regarding the molecular characterisation of MZBL, MT and gastrointestinal DLBCL and their mutual relationships. Copyright Georg Thieme Verlag KG Stuttgart New York.

  11. Chidamide Combined With R-GDP in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

    Science.gov (United States)

    2017-12-12

    Chidamide; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasm by Histology; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Cyclophosphamide; Rituximab; Gemcitabine; Cisplatin; Dexamethasone; HDAC Inhibitor

  12. Reduced number of CD1a+ cells in cutaneous B-cell lymphoma.

    Science.gov (United States)

    Schmuth, M; Sidoroff, A; Danner, B; Topar, G; Sepp, N T

    2001-07-01

    Cutaneous B-cell lymphoma is difficult to distinguish from pseudolymphoma. The histologic pattern and monoclonal restriction (immunohistochemical analysis and molecular biology) are the criteria used for differentiating these entities. CD1a+ dendritic cells have been observed in the infiltrates of T-cell lymphoma, but the presence of these CD1a+ cells has not been compared in B-cell lymphoma and pseudolymphoma. We studied the presence of CD1a+ cells on frozen sections of 23 B-cell lymphomas, 13 pseudolymphomas, and 17 T-cell lymphomas by immunohistochemical analysis. We found abundant CD1a+ dendritic cells in only 1 (4%) of 23 B-cell lymphomas, whereas in 8 (62%) of 13 pseudolymphomas and 17 (100%) of 17 T-cell lymphomas, strong CD1a staining was present. Our study demonstrates a distinct pattern of CD1a staining in the infiltrates of B-cell lymphoma and pseudolymphoma that may be of value in the differential diagnosis of these skin disorders.

  13. Gastric Marginal Zone B Cell Lymphoma of the Duodenum

    Directory of Open Access Journals (Sweden)

    A. Ndzengue

    2011-10-01

    Full Text Available Small bowel lymphomas of the extranodal type occur in the young and are characteristically associated with malabsorption syndrome. We present the case of an elderly in whom there was no malabsorption and the duodenal tumor was a gastric type marginal zone B cell lymphoma also known as gastric mucosa-associated lymphoid tissue (MALT lymphoma. A 73-year-old woman presented to the emergency room with 2 weeks of general weakness, recurrent vomiting containing food particles and abdominal distension. She had been diagnosed with diabetic gastroparesis 4 years prior. CT of the abdomen and pelvis was suggestive of gastric outlet obstruction but no evidence of pancreatic or duodenal mass. Endoscopy and biopsy of the tumor obstructing the distal first part of the duodenum confirmed a gastric marginal MALT lymphoma. The patient’s symptoms improved with radiotherapy. Gastric MALT lymphoma, an extranodal lymphoma primarily described in the stomach, can also present in the small bowel and is not associated with malabsorption.

  14. Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

    International Nuclear Information System (INIS)

    Illidge, T.M.

    1999-06-01

    Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti-CD40

  15. Discordant lymphoma consisting of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood: a case report

    Directory of Open Access Journals (Sweden)

    Caracciolo Francesco

    2011-09-01

    Full Text Available Abstract Introduction Discordant lymphomas are rare entities characterized by the simultaneous presence of two distinct types of lymphomas in different anatomic sites. We describe a very rare case of simultaneous occurrence of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood. Case presentation We report the case of a 60-year-old asymptomatic Caucasian woman in whom discordant lymphomas were discovered when a slight lymphocytosis and a conspicuous splenomegaly were observed. The different morphological, immunophenotypical and immunohistochemical features found in the different pathologic samples obtained from peripheral blood, bone marrow and spleen sections made it possible to differentiate two types of non-Hodgkin B-cell lymphomas: a mantle cell lymphoma infiltrating the spleen and a marginal zone lymphoma involving both the bone marrow and peripheral blood. Since a similar IgH gene rearrangement was found both in the bone marrow and in the spleen, the hypothesis of a common origin, followed by a different clonal selection of the neoplastic lymphocytes may be taken into consideration. Conclusion Our case emphasizes the usefulness of investigating simultaneous specimens from different anatomic sites from the same patient and the relevant diagnostic role of splenectomy.

  16. Mediastinal Gray Zone Lymphoma with Features Intermediate between Classical Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma.

    Science.gov (United States)

    Song, Haa-Na; Kim, Seok Jin; Ko, Young Hyeh; Kim, Won Seog

    2016-01-01

    Mediastinal gray zone lymphoma (MGZL) shares clinical characteristics with primary mediastinal B-cell lymphoma (PMBCL) and nodular sclerosing Hodgkin lymphoma (NSHL). However, MGZL is extremely rare, and an appropriate treatment for it has not yet been established. We retrospectively analyzed 8 patients who were treated with systemic chemotherapy for MGZL between 2007 and 2014. The patients with MGZL were predominantly young and male (median age 26 years), and 62.5% of patients had bulky disease. The overall response rate (ORR) and complete remission (CR) rate were both 75% (6/8) for all treated patients The median overall survival (OS) and progression-free survival (PFS) was 40.7 and 3.9 months, respectively. Most responders (4/6, 66.7%) were treated with R-CHOP (rituximab + cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisolone) as the frontline therapy. The CR rate of patients who received R-CHOP and those who did not was 100% (4/4) and 50% (2/4), respectively. Particularly striking was the finding that the median PFS of patients who received R-CHOP frontline chemotherapy was 11.4 months, which was superior to the median PFS of patients who did not receive R-CHOP. Of the 8 patients with MGZL who were treated with systemic chemotherapy, superior treatment responses were observed in patients who received R-CHOP as the frontline therapy. © 2016 S. Karger AG, Basel.

  17. 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

  18. File list: ALL.Bld.05.AllAg.Lymphoma,_B-Cell [Chip-atlas[Archive

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  10. Primary immunodeficiencies and B-cell lymphomas.

    Science.gov (United States)

    Martín-Mateos, María Anunciación; Piquer Gibert, Mónica

    In primary immunodeficiencies there is a failure in the anti-tumor defense. Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies characterized by an alteration in the differentiation of B lymphocytes (BL). Epstein-Barr virus (EBV) is an ubiquitous virus that selectively infects the BL. In patients with immunodeficiency, uncontrolled proliferation of infected BL and the action of viral proteins promote the development of lymphomas. At the University Hospital Sant Joan de Deu, Barcelona, 28 patients were diagnosed with CVID from 2000 to 2013. This paper describes four patients who developed non-Hodgkin's lymphoma (NHL). The lymphoma was associated with EBV in two of the cases. Patients were<18 years old, diagnosed with lymphoma between 4 and 13 years old. Two patients were treated with rituximab as monotherapy and achieved complete remission. Two patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and radiotherapy or rituximab and achieved complete remission. Early detection of EBV infections and NHL in all patients diagnosed with CVID is recommended, regardless of age at diagnosis. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  11. Primary mediastinal B-cell lymphoma and mediastinal gray zone lymphoma: do they require a unique therapeutic approach?

    Science.gov (United States)

    Dunleavy, Kieron; Wilson, Wyndham H

    2015-01-01

    Primary mediastinal B-cell lymphoma (PMBL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that is putatively derived from a thymic B cell. Accounting for up to 10% of cases of DLBCL, this subtype predominantly affects women in the third and fourth decades of life. Its clinical and molecular characteristics are distinct from other subtypes of DLBCL and, in fact, closely resemble those of nodular sclerosing Hodgkin lymphoma (NSHL). Recently, mediastinal lymphomas with features intermediate between PMBL and NSHL, called mediastinal gray-zone lymphomas, have been described. The optimal management of PMBL is controversial, and most standard approaches include a combination of immunochemotherapy and mediastinal radiation. Recently, the recognition that mediastinal radiation is associated with significant long-term toxicities has led to the development of novel approaches for PMBL that have shown excellent efficacy and challenge the need for routine mediastinal radiation.

  12. Primary Mediastinal Large B-cell Lymphoma Exhibiting Endobronchial Involvement.

    Science.gov (United States)

    Shimada, Midori; Fukuda, Minoru; Horio, Kensuke; Suyama, Takayuki; Kitazaki, Takeshi; Hashiguchi, Kohji; Fukuda, Masaaki; Shigematsu, Kazuto; Nakamura, Yoichi; Honda, Takuya; Ashizawa, Kazuto; Mukae, Hiroshi

    Primary mediastinal large B-cell lymphoma (PMLBCL) is one of the subtypes of diffuse large B-cell lymphoma. We experienced a rare case of PMLBCL that exhibited endobronchial involvement. A 33-year-old Japanese female with the chief complaints of epigastralgia, back pain, and nausea visited a primary care hospital. Computed tomography of the chest and abdomen demonstrated a bulky mass in the left anterior mediastinum, multiple pulmonary nodules, axillary lymph node swelling, and a pancreatic tumor. Fiberoptic bronchoscopy showed a white-tinged irregularly shaped endobronchial tumor accompanied by capillary vessel dilation in the left upper lobar bronchus. Taken together, these findings resulted in a diagnosis of PMLBCL.

  13. A Literature Revision in Primary Cutaneous B-cell Lymphoma.

    Science.gov (United States)

    Selva, R La; Violetti, S Alberti; Delfino, C; Grandi, V; Cicchelli, S; Tomasini, C; Fierro, M T; Berti, E; Pimpinelli, N; Quaglino, P

    2017-01-01

    The term "Primary Cutaneous B-Cell Lymphoma" (PCBCL) comprehends a variety of lymphoproliferative disorders characterized by a clonal proliferation of B-cells primarily involving the skin. The absence of evident extra-cutaneous disease must be confirmed after six-month follow-up in order to exclude a nodal non-Hodgkin's lymphoma (NHL) with secondary cutaneous involvement, which may have a completely different clinical behavior and prognosis. In this article, we have summarized the clinico-pathological features of main types of PCBCL and we outline the guidelines for management based on a review of the available literature.

  14. Discordant lymphoma consisting of mediastinal large B-cell lymphoma and nodular sclerosis Hodgkin lymphoma in the right supraclavicular lymph nodes: a case report.

    Science.gov (United States)

    Zhang, Chun; Yi, Yuanxue; Chen, Chunyan; Wang, Jianrong; Liu, Zhu

    2015-12-29

    Discordant lymphoma is defined by the simultaneous presence of two or more distinct types of lymphomas at different anatomic sites. With fewer than 20 studies reporting cases of discordant lymphoma to date, the incidence of this condition is believed to be very low. Here, we report a case of discordant lymphoma in a 34-year-old female patient that involved mediastinal large B-cell lymphoma and nodular sclerosis Hodgkin lymphoma in the right supraclavicular lymph nodes. The patient presented with a mass in the mediastinum and enlargement of the right supraclavicular lymph nodes, but no obvious signs of lymphoma. Histological examination revealed that the encapsulated mediastinal mass contained medium- or large-size tumor cells with lightly stained cytoplasm and round vesicular nuclei as well as a high percentage of mitotic cells; strongly positive immunohistochemical staining for PAX5, CD20, and CD79a also was observed. Examination of biopsied right supraclavicular lymph node tissues revealed separation by collagen fibers, extensive inflammatory cell infiltration, and large-size tumor cells, such as Reed-Sternberg cells. These tissues stained strongly positive for PAX5 and CD30, weakly positive for CD15, and negative for Epstein-Barr viral RNA. We also found monoclonal gene rearrangement in the immunoglobulin heavy chain gene in the mediastinal large B-cell lymphoma, but no monoclonal gene rearrangement in the nodular sclerosis Hodgkin lymphoma. These findings suggested that these two lymphomas were not of a common clonal origin. The patient was treated by surgical excision of the mediastinal mass followed by radio-chemotherapy, and no metastasis or recurrence occurred during a follow-up period of 32 months. A review of previously reported cases indicated that the clinical manifestations and pathological features of discordant lymphoma are diverse due to variation in the types of lymphomas involved. Physicians must have an awareness of discordant lymphoma to avoid

  15. Primary orbital precursor T-cell lymphoblastic lymphoma

    DEFF Research Database (Denmark)

    Stenman, Lisa; Persson, Marta; Enlund, Fredrik

    2016-01-01

    Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical exa...... knowledge, this is the first report of a case of T-LBL involving the extraocular muscles. Although primary T-LBL in the eye region is very rare, our findings demonstrate that lymphoma should be considered in the differential diagnosis of patients with similar symptoms.......Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical...

  16. EBV-positive B cell cerebral lymphoma 12 years after sex-mismatched kidney transplantation: post-transplant lymphoproliferative disorder or donor-derived lymphoma?

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2010-06-01

    We present a follow-up case report of possible transmission of lymphoma 12 years after deceased-donor renal transplantation from a male donor who was found at autopsy to have had an occult lymphoma. The female recipient underwent prompt transplant nephrectomy. However, 12 years later, she presented with cerebral B cell lymphoma. A donor origin for the cerebral lymphoma was supported by in situ hybridization demonstration of a Y chromosome in the lymphoma. There was a dramatic resolution of the cerebral lesions with tapering of immunosuppression and introduction of rituximab treatment. The finding of a Y chromosome in the cerebral lymphoma does not exclude a host contribution to lymphoma development.

  17. Prognostic significance of metallothionein in B-cell lymphomas

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Borregaard, Niels

    2006-01-01

    We have investigated metallothionein (MT) I and II mRNA and protein in B-cell lymphomas with particular reference to diffuse large B-cell lymphoma (DLBCL). The mRNA profiling was performed on Affymetrix arrays and showed up-regulated MT mRNA in 15 of 48 DLBCLs, including 12 of 23 activated B......-cell (ABC) and 3 of 9 type-3 lesions. In contrast, MT mRNA was low to undetectable in 16 germinal center B-cell (GCB)-type DLBCLs. Only 1 of 15 patients with up-regulated MT mRNA achieved a sustained remission, suggesting that up-regulated MT mRNA constitutes a significant risk factor for treatment failure......, in 115 DLBCLs, MT labeling of more than 20% lymphoma cells was associated with a significantly poorer 5-year survival, independent of the age, stage, or International Prognostic Index. Taken together, it is suggested that both increased MT mRNA and MT protein expression by more than 20% lymphoma cells...

  18. huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-03-26

    Adult B Acute Lymphoblastic Leukemia; BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; MYC Gene Rearrangement; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Adult Acute Lymphoblastic Leukemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  19. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma

    DEFF Research Database (Denmark)

    d'Amore, Francesco; Relander, Thomas; Lauritzsen, Grete F

    2012-01-01

    Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large...

  20. T-cell/histiocyte-rich large B-cell lymphoma of stomach.

    Science.gov (United States)

    Barut, Figen; Kandemir, Nilufer Onak; Gun, Banu Dogan; Ozdamar, Sukru Oguz

    2016-07-01

    T-cell/histiocyte-rich large B-cell lymphoma is an unusually encountered lymphoid neoplasm of stomach with aggressive course, and is an uncommon morphologic variant of diffuse large B-cell lymphoma. An ulcerated mass, 7x5x1 cm in size was observed within the gastrectomy specimen of a 76-year-old female patient. In cross sections, besides mature lymphoid cells displaying T-cell phenotype, a neoplastic formation composed of large, pleomorphic atypical lymphoid cells with, prominent nucleoli, vesicular nuclei and abundant eosinophilic cytoplasm displaying B-cell phenotype were observed. Meanwhile, histiocyte-like mononuclear cells and Reed-Sternberg-like multinuclear cells expressing CD68 and Mac387 were also observed. The diagnosis of the case was T cell/histiocyte-rich large B-cell lymphoma. This rarely encountered neoplasm should be kept in mind in the differential diagnosis of primary gastric lymphomas.

  1. Primary Breast Mucosa-Associated Lymphoid Tissue (MALT Lymphoma Transformation to Diffuse Large B-cell Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Şerife Hülya Arslan

    2012-09-01

    Full Text Available Primary non-Hodgkin’s lymphoma (NHL of the breast constitutes 0.04%-0.53% of all malignancies and 2.2% of extra nodal lymphomas. In total, 7%-8% of all B-cell lymphomas are the mucosa-associated lymphoid tissue (MALT type, of which up to 50% of primary gastric MALT lymphoma. Herein we present a patient with breast MALT lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL. A 69-year-old female presented with a mass on her left breast. Physical examination showed a 3 × 3-cm mass located 1 cm from the areola on the upper lateral quadrant of the breast at the 1 o’clock position, which was fixed and firm. Excisional biopsy was performed and pathologic examination of the specimen showed MALT lymphoma transformation to DLBCL. The patient was staged as II-EA. The rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP protocol was scheduled as treatment. Following 6 courses of R-CHOP, 2 additional courses of rituximab were administered. Positron emission tomography (PET-CT was done at the end of the treatment. PET showed that the patient was in complete remission. At the time this report was written, the patient was being followed-up at the outpatient clinic on a regular basis. Lymphoma of the breast is a rarity among malignant tumors of the breast. The most common type of lymphoma is DLBCL. Breast MALT lymphoma is extremely rare. Primary MALT lymphoma of the breast can transform from low grade to high grade and recurrence is possible; therefore, such patients should be monitored carefully for transformation.

  2. 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.

  3. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Afonso José Pereira Cortez

    2011-02-01

    Full Text Available BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not

  4. 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

  5. Orbital involvement by non-Hodgkin lymphoma NK T cells.

    Science.gov (United States)

    Hervás-Ontiveros, A; España-Gregori, E; Hernández-Martínez, P; Vera-Sempere, F J; Díaz-Llopis, M

    2014-11-01

    The case is presented of 37 year-old male with a history of nasal obstruction with right rhinorrhea, headache, hearing loss and right exophthalmos of 4 months progression. The MRI revealed that the ethmoidal and maxillary sinuses contained inflammatory tissue extending into the orbital region. The biopsy confirmed a non-Hodgkin lymphoma of natural killer (NK) T cells. Non-Hodgkin's T NK lymphoma is a rare tumor in the orbital area that requires an early detection and multi-disciplinary care to ensure appropriate monitoring and treatment. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  6. Imaging cutaneous T-Cell lymphoma with optical coherence tomography

    DEFF Research Database (Denmark)

    Ring, H.C.; Hansen Stamp, I.M.; Jemec, G.B.E.

    2012-01-01

    Aim: To investigate the presentation of a patch-stage cutaneous T-cell lymphoma (CTCL) using optical coherence tomography (OCT). Methods: A patient with a patch caused by CTCL was photographed digitally, OCT-scanned and biopsied. A normal skin area adjacent to the patch was OCT...... of cutaneous lymphoma. It may further be speculated that the differences in OCT images may reflect the biological behaviour of the infiltrate. This observation therefore suggests that OCT imaging may be a relevant tool for the in vivo investigation of mycosis fungoides and other CTCLs, but in order to verify...

  7. Large-cell lymphocytic lymphoma | Jacobs | South African Medical ...

    African Journals Online (AJOL)

    Progress in the treatment of large-cell lymphocytic lymphoma during the last decade has been such that cure has replaced palliation as the objective of treatment. In pathologically proven stage I or II disease appropriate radiotherapy is adequate. It is of major importance to recognize that even in stage III or IV disease cure is ...

  8. Treatment of Older Patients with Mantle-Cell Lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, H. C.; Hoster, E.; Hermine, O.; Walewski, J.; Trneny, M.; Geisler, C. H.; Stilgenbauer, S.; Thieblemont, C.; Vehling-Kaiser, U.; Doorduijn, J. K.; Coiffier, B.; Forstpointner, R.; Tilly, H.; Kanz, L.; Feugier, P.; Szymczyk, M.; Hallek, M.; Kremers, S.; Lepeu, G.; Sanhes, L.; Zijlstra, J. M.; Bouabdallah, R.; Lugtenburg, P. J.; Macro, M.; Pfreundschuh, M.; Prochazka, V.; Di Raimondo, F.; Ribrag, V.; Uppenkamp, M.; Andre, M.; Klapper, W.; Hiddemann, W.; Unterhalt, M.; Dreyling, M. H.

    2012-01-01

    BACKGROUND The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and

  9. Treatment of Elderly Patients With Mantle Cell Lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke C.; Doorduijn, Jeanette K.

    Treatment of elderly patients with a mantle cell lymphoma (MCL) is a challenge. High-dose cytarabine and autologous transplantation, both important components of the treatment in younger patients, are not feasible for most elderly patients. However, in fit elderly patients long progression-free

  10. Anthropometrics and prognosis in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Bendtsen, Mette Dahl; Munksgaard, Peter Svenssen; Severinsen, Marianne Tang

    2017-01-01

    Objective: The impact of body mass index (BMI) and body surface area (BSA) on survival in diffuse large B-cell lymphoma (DLBCL) is controversial. Recent studies show superior outcomes for overweight and obese patients. Patients and methods: A total of 653 R-CHOP(-like)-treated DLBCL patients were...

  11. Primary mediastinal large B-cell lymphoma, classic Hodgkin lymphoma presenting in the mediastinum, and mediastinal gray zone lymphoma: what is the oncologist to do?

    Science.gov (United States)

    Grant, Cliona; Dunleavy, Kieron; Eberle, Franziska C; Pittaluga, Stefania; Wilson, Wyndham H; Jaffe, Elaine S

    2011-09-01

    In recent years, an overlap in biologic and clinical features has been identified between classic Hodgkin lymphoma (CHL) and primary mediastinal large B-cell lymphoma (PMBL). Further strengthening this relationship is the identification of lymphomas with clinical and morphologic features transitional between the two, known as gray zone lymphomas (GZL). However, this diagnostic gray zone is not just of theoretical interest: it presents a practical problem, as the treatment approaches for CHL traditionally differ from those for aggressive B-cell lymphomas. This article reviews the treatment approach for mediastinal lymphomas, including CHL of the nodular sclerosis subtype (CHL-NS), PMBL, and mediastinal GZL. Though several trials have evaluated different regimens with or without radiation in PMBL and CHL-NS, there is a lack of prospective experience in treating GZL because of the rarity of these tumors. Historical data indicate that they have done poorly with traditional approaches developed for the treatment of either CHL or diffuse large B-cell lymphoma.

  12. Mantle cell lymphoma in the orbital and adnexal region

    DEFF Research Database (Denmark)

    Rasmussen, Peter Kristian; Sjö, L D; Prause, J U

    2009-01-01

    AIMS: To characterise clinicopathological features of mantle cell lymphoma (MCL) in the orbital and adnexal region. METHODS: Data on lymphoid lesions were retrieved searching the Danish Ocular Lymphoma Database 1980-2005. Specimens were collected from Danish pathological departments and re......-evaluated with a panel of monoclonal antibodies. For all patients with confirmed MCL the complete clinical files were collected and reviewed. RESULTS: Twenty-one patients with MCL in the orbital and adnexal region were identified comprising 9% (21/230) of all lymphoma in the ocular region. There were 18 male patients...... and three female patients with an age range from 60 to 90 years (median 75 years). Orbital and adnexal region MCL as first presenting symptom comprised 67% of the patients. Of these, 71% had bilateral involvement. The orbit (71%) and eyelids (64%) were the most commonly affected sites. All but two presented...

  13. [Primary cutaneous B-cell lymphomas: study of 22 cases].

    Science.gov (United States)

    Martín Carrasco, Pablo; Morillo Andújar, Mercedes; Pérez Ruiz, Carmen; de Zulueta Dorado, Teresa; Cabrera Pérez, Rocío; Conejo-Mir, Julián

    2016-09-02

    Primary cutaneous B-cell lymphoma (CBCL) is a very low prevalence neoplasm and constitutes 25% of all primary cutaneous lymphomas. Our objective was to discover the epidemiological, clinic and histologic characteristics of CBCL in our area. Retrospective descriptive study with patients with histologic diagnosis of CBCL followed up in our department between 2004 and 2015. Twenty-two patients with CBCL were included; 65% were men and 35% were women. Follicle centre lymphoma was the most common subtype (41%). Only 3 cases presented with node involvement and one with bone marrow invasion. Five recurrences were detected and one patient died because of the CBCL. This is one of the first CBCL series in theSpanish population. The incidence, sex, age, subtype distribution, clinical features and immunohistochemical patterns are very similar to those of the other series. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. Mantle cell lymphoma: prognostic capacity of the Follicular Lymphoma International Prognostic Index

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Christensen, Bjarne Egelund; Pedersen, Niels Tinggaard

    2006-01-01

    The International Prognostic Index (IPI) is the most commonly used prognostic model for mantle cell lymphoma (MCL). However, the prognostic value of the IPI is limited. The recently published Follicular Lymphoma International Prognostic Index (FLIPI) is built on variables, which are pertinent...... to MCL. This study was conducted to evaluate the prognostic value of FLIPI in a population-based series of 93 patients with MCL diagnosed in a 7-year period. End points of the study were response to therapy, overall survival, and disease-free survival (DFS) according to the IPI and FLIPI. Applied...... to the whole series, the FLIPI identified three risk groups with markedly different outcome with 5-year overall survival rates of 65%, 42%, and 8% respectively. Notably, the high-risk group comprised 53% of patients. In contrast, the IPI only allocated 16% of cases to the high-risk group and had a lower...

  15. 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

  16. 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.)

  17. Update in large cell lymphoma: understanding the pathology report.

    Science.gov (United States)

    Hsi, Eric D

    2015-01-01

    The diffuse aggressive large B-cell lymphomas are a heterogeneous group of B-cell malignancies. Although many are readily recognized due to characteristic clinical and pathologic features, several problematic areas still exist in diagnosis of these lymphomas due to a variety of reasons that include imprecise or difficult-to-apply diagnostic criteria, gaps in our understanding of lymphoma biology, and limitations in technologies available in the clinical laboratory compared to the research laboratory. This may result in some degree of confusion in the pathology report, particularly if the issues are not clearly explained, leading to frustration or misinterpretation on the part of the reader. In this review, I will discuss the pathologic features of a subset of the WHO 2008 classification diffuse aggressive large B-cell lymphomas, focusing on areas in which difficulties exist in diagnosis and/or biomarker marker assessment. A deeper understanding of the issues and areas of uncertainty due to limitations in our knowledge about the biology of these diseases should lead to better communication between pathologists and clinicians. © 2015 by The American Society of Hematology. All rights reserved.

  18. 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

  19. Primary Cutaneous Mantle Cell Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    L. D. Mazzuoccolo

    2013-01-01

    Full Text Available Primary cutaneous mantle cell lymphoma (MCL is a rare cutaneous proliferation of naive pregerminal CD-5 positive B cells in the skin with no extracutaneous involvement. Overexpression of cyclin D1 is pathognomonic of this condition, and surgery and radiation therapy are the most common therapeutic options. In this case, we describe the clinical, histopathological, immunohistochemical, and molecular characteristics of a new case of primary cutaneous MCL.

  20. Subcutaneous panniculitis-like T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Francis Abel

    2010-01-01

    Full Text Available This case report describes a 38 year-old lady with the clinical, histopathological, and immunohistochemical (IHC changes of subcutaneous panniculitis-like T-cell lymphoma (SPTCL. The IHC findings revealed CD8 + and CD56 - cells, which are indicative of tumors which have an indolent course. Our patient is being managed with tapering doses of corticosteroids for the last nine months with good improvement.

  1. 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

  2. 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.

  3. Two Cases of Diffuse Large B-Cell Lymphomas in the Cervical Lymph Nodes in Patients with Low-Grade Gastric Marginal Zone B-Cell Lymphoma (MALT Lymphoma).

    Science.gov (United States)

    Jung, Ji Hoon; Jung, Hwoon-Yong; Yoon, Hwan; Lee, Jae Kwang; Kang, Ji Hoon; Jeon, Sung Jin; Park, Young-Su; Kim, Jin-Ho

    2013-05-01

    It is well known that gastric mucosa-associated lymphoid tissue (MALT) lymphomas are associated with Helicobacter pylori infection and have a good prognosis. However, although rare, these low-grade lymphomas transform to the high-grade diffuse large B-cell lymphomas (DLBCLs) which are thought to be the important cause of death in patients with MALT lymphoma. We report two cases of DLBCLs in the cervical lymph nodes that occurred 10 years and 1.5 years after diagnosing low-grade gastric MALT lymphomas.

  4. 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.

  5. Update on the molecular pathogenesis and clinical treatment of mantle cell lymphoma : report of the 11th annual conference of the European Mantle Cell Lymphoma Network

    NARCIS (Netherlands)

    Dreyling, Martin; Kluin-Nelemans, Hanneke C.; Bea, Silvia; Klapper, Wolfram; Vogt, Niclas; Delfau-Larue, Marie-Helene; Hutter, Grit; Cheah, Chan; Chiappella, Annalisa; Cortelazzo, Sergio; Pott, Christiane; Hess, Georg; Visco, Carlo; Vitolo, Umberto; Klener, Pavel; Aurer, Igor; Unterhalt, Michael; Ribrag, Vincent; Hoster, Eva; Hermine, Olivier

    Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in virtually all cases. Clinically, MCL displays an aggressive course, with a

  6. Update on the molecular pathogenesis and clinical treatment of mantle cell lymphoma : report of the 10th annual conference of the European Mantle Cell Lymphoma Network

    NARCIS (Netherlands)

    Dreyling, Martin; Kluin-Nelemans, Hanneke C.; Bea, Silvia; Hartmann, Elena; Salaverria, Itziar; Hutter, Grit; Perez-Galan, Patricia; Roue, Gael; Pott, Christiane; Le Gouill, Steven; Cortelazzo, Sergio; Rule, Simon; Hess, Georg; Zaja, Francesco; Vitolo, Umberto; Szymczyk, Michal; Walewski, Jan; Ribrag, Vincent; Unterhalt, Michael; Hermine, Olivier; Hoster, Eva

    2011-01-01

    Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in virtually all cases. Clinically, MCL shows an aggressive clinical course

  7. Bortezomib in mantle cell lymphoma: comparative therapeutic outcomes

    Directory of Open Access Journals (Sweden)

    Vallumsetla N

    2015-11-01

    Full Text Available Nishanth Vallumsetla, Jonas Paludo, Prashant Kapoor Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA Abstract: Mantle cell lymphoma (MCL is an incurable, typically aggressive subtype of non-Hodgkin lymphoma, accounting for 4%–7% of newly diagnosed non-Hodgkin lymphoma cases. Chemoresistance commonly ensues in MCL, and patients with this heterogeneous disease invariably relapse, underscoring the unmet need for better therapies. Over the past few years, several novel agents with promising activity and unique mechanisms of action have been deemed effective in MCL. Bortezomib is a reversible proteasome inhibitor, approved as a single agent for patients with relapsed/refractory MCL who have received at least one prior line of therapy. Addition of bortezomib to chemoimmunotherapies has demonstrated good tolerability and superior efficacy, both in the upfront and salvage settings, and recently one such combination of bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone was approved as a frontline regimen in untreated patients with MCL. This review examines the role of bortezomib in a multitude of clinical settings and ongoing clinical trials designed to optimize its integration in the current treatment paradigms of MCL. Keywords: non-Hodgkin lymphoma, proteosome inhibitor, treatment

  8. Synchronous Pulmonary Squamous Cell Carcinoma and Mantle Cell Lymphoma of the Lymph Node

    Directory of Open Access Journals (Sweden)

    Yu Sun

    2011-01-01

    Full Text Available Synchronous occurrence of pulmonary squamous cell carcinoma and malignant lymphoma of the lymph node is not reported in the literature. We report a case of pulmonary squamous cell carcinoma coexisting with a mantle cell lymphoma involving cervical and mediastinal lymph node. It is important to recognize this synchronous occurrence histopathologically and to be aware of the existence of “in situ” MCL.

  9. 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.

  10. [Bone marrow involvement in primary mediastinal B-cell lymphoma].

    Science.gov (United States)

    Magomedova, A U; Fastova, E A; Kovrigina, A M; Obukhova, T N; Skidan, N I; Mangasarova, Ya K; Vorobyev, A I; Kravchenko, S K

    Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct type of large B-cell lymphoma. In this type of the disease, the neoplastic process is located in the anterior and superior mediastinum, frequently with compression of the superior vena cava and with tumor invasion into the adjacent organs and tissues: the pericardium, lung, pleura, etc. Despite the fact that in PMBCL progression, there may be involvement of extranodal organs, such as the kidney, adrenal glands, liver, and central nervous system, bone marrow (BM) injury is generally absent. Since BM injury in patients with diffuse large B-cell lymphoma is an independent poor prognostic indicator, there is reason to believe that BM involvement in PMBCL affects the prognosis. These cases may need intensified induction therapy followed by autologous hematopoietic stem cell transplantation; and BM injury should be monitored during the therapy. The paper gives reports of clinical cases of bone marrow involvement in 2 PMBCL patients treated at the National Research Center for Hematology, Ministry of Health of the Russian Federation.

  11. Rituximab and chemotherapy in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Sonet, Anne; Bosly, André

    2009-06-01

    Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

  12. Real world data on primary treatment for mantle cell lymphoma

    DEFF Research Database (Denmark)

    Abrahamsson, Anna; Albertsson-Lindblad, Alexandra; Brown, Peter N

    2014-01-01

    There is consensus that young patients with mantle cell lymphoma (MCL) should receive intensive immunochemotherapy regimens, but optimal treatment of elderly patients as well for as patients with limited or indolent disease is not defined. Our aim was to evaluate and compare outcome in relation...... to prognostic factors and first-line treatment in patients with MCL in a population-based data set. Data were collected from the Swedish and Danish Lymphoma Registries from the period of 2000 to 2011. A total of 1389 patients were diagnosed with MCL. During this period, age-standardized incidence MCL increased......-nine (2.4%) patients followed a watch-and-wait approach and showed a 3-year OS of 79.8%. Among patients receiving systemic treatment, rituximab (n = 766; HR = 0.66; P = .001) and autologous stem cell transplant (n = 273; HR = 0.55; P = .004) were independently associated with improved OS in multivariate...

  13. Energy and protein intake and nutritional status in non-surgically treated patients with small cell anaplastic carcinoma of the lung

    International Nuclear Information System (INIS)

    Enig, B.; Winther, E.; Hessov, I.; Aarhus Univ.

    1986-01-01

    The spontaneous food intake and nutritional status was assessed in 23 patients with small cell anaplastic carcinoma of the lung before and two times during a treatment period of 6 weeks. Radiation therapy was given for 2 weeks followed by a course of chemotherapy and another 2 weeks of radiation therapy. The energy intake decreased during the treatment from 146 to 130 per cent of basal metabolic rate (p>0.10). The protein intake remained unchanged (mean 0.9 g/kg body weight).There were insignificant and small losses of weight, body fat, free body mass and arm muscle circumference, and no changes were seen in serum albumin and serum transferrin. However, 6 patients suffered a weight loss of 5 per cent or more. No correlation existed between the nutritional parameters measured before treatment and the changes during treatment. Patients who suffered a loss of body weight could therefore not be singled out before the treatment. (orig.)

  14. 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

  15. Primary central nervous system lymphoma in Korea: comparison of B- and T-cell lymphomas.

    Science.gov (United States)

    Choi, Jong Sun; Nam, Do-Hyun; Ko, Young Hyeh; Seo, Jin Won; Choi, Yoon-La; Suh, Yeon Lim; Ree, Howe J

    2003-07-01

    The great majority of primary central nervous system lymphoma (PCNSL) is known to be of B-lineage, with T-cell PCNSL (T-PCNSL) accounting for two were negative for CD4 and CD8. Of 24 DLBCLs tested, the pattern of Bcl-6+ tumor cells was diffusely dense, similar to that of the germinal center in nine cases (37.5%), with coexpression of CD10 in three of the nine cases. T-PCNSL accounted for 16.7% of the PCNSLs; thus, in Korea it may not be as rare as previously known. The T-PCNSL presented with certain clinical and pathologic features that were distinct from B-PCNSL and displayed preponderance of CD8 expression. DLBCL of the germinal center B-cell derivation defined by bcl-6 expression comprised 37.5% of DLBCL of the brain.

  16. Characterization of the novel Sezary lymphoma cell line BKP1.

    Science.gov (United States)

    Boudjarane, John; Essaydi, Arnaud; Farnault, Laure; Popovici, Cornel; Lafage-Pochitaloff, Marina; Beaufils, Nathalie; Berda-Haddad, Yaël; Lacroix, Romaric; Nicolino-Brunet, Corinne; Le Treut, Thérèse; Zattara, Hélène; Gabert, Jean; Kahn-Perlès, Brigitte; Costello, Régis

    2015-01-01

    Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphomas primarily involving the skin. The most common types are mycosis fungoides (MF) and Sezary Syndrome (SS). We report a novel long-term fast-growing SS line termed BKP1 that was characterized by flow cytometry (FC), conventional and molecular cytogenetic [FISH/multi-FISH together with array comparative genomic hybridization (aCGH)]. FC immunophenotype of the BKP1 is CD2+CD5+CD3+CD4+CD8-CD7-CD25-CD26-CD30-CD158k+. The TCRγ characterization of BKP1 by PCR identified a clonal rearrangement. The conventional cytogenetic and Multi-FISH analysis showed complex chromosomal rearrangements. aCGH analysis highlighted the loss of genes involved in cell cycle control, in immune response (HLA, complement complex) and DNA damage repair mechanisms. The BKP1 is another lymphoma cell line thoroughly characterized that can be a valuable tool for both basic and applied research such as identification of deregulated genes and/or pathways and screening for new antilymphoma drugs. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Primary mediastinal (thymic) large B-cell lymphoma: a short review with brief discussion of mediastinal gray zone lymphoma.

    Science.gov (United States)

    Hutchinson, Charles Blake; Wang, Endi

    2011-03-01

    Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL). It commonly presents as a bulky lesion in the anterior-superior mediastinum with symptoms related to local invasion or compression. Microscopic examination typically shows infiltration of medium-large cells surrounded by collagen fibrosis. The neoplastic cells express B-cell markers, and CD30 often shows heterogeneous staining. Comparative genomic hybridization has identified gains in loci of 9p24 and 2p15 as well as Xp11.4-21 and Xq24-26. Amplification of REL and BCL11A at 2p as well as elevated expression of JAK2, PDL1, and PDL2 at 9p has been demonstrated. Nodular sclerosis classic Hodgkin lymphoma needs to be differentiated from PMBCL and cases with overlapped features have been described as mediastinal gray zone lymphoma. Primary mediastinal (thymic) large B-cell lymphoma carries a favorable prognosis in comparison to conventional DLBCL.

  18. Cerebral toxoplasmosis in a diffuse large B cell lymphoma patient

    International Nuclear Information System (INIS)

    Savsek, Lina; Opaskar, Tanja Ros

    2016-01-01

    Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8 th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance

  19. Primary mantle cell lymphoma of tonsil: Case report

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    Knežević Snežana B.

    2017-01-01

    Full Text Available Introduction: Mantle cell lymphoma is rare type of the mature B cell lymphoma. It includes 4% - 6% of all Non Hodgkin's Lymphomas. Compared to the other subtypes of lymphoma it develops more often in older men, and the median age of patients is 65 years. Primary tonsillar lymphoma accounts for less than 1% of head and neck malignancies. Method: Data obtained from medical records of the patient. Objective: Emphasize the importance of early and accurate diagnosis and early treatment of malignant diseases. Case report: Patient RP, 63 years old, presents with difficult swallowing, hoarseness, enlarged tonsils, snoring. Left tonsil almost sets into the right tonsillar vine, displaces the uvula and covers the isthmus. Respiratory sound is normal, with rhythmic action of the heart and soft abdomen. Good general condition. Echo: enlarged and actively altered lymph glands of the middle right jugular chain, the largest 148x77 mm, on the left side lymph nodes are enlarged, the largest is 143x72 mm. Echo of the abdomen inconspicuous. Lab: WBC 5.9, RBC 5.2, Hb 152, Hct 0.44, SE 10, CK 129, LDH 331, CRP 4.6, ALP 61, fibrinogen 2.4, Ca2+ 2.3, phosphate 0.8; BK, HCV, HBsAg, EB, HIV negative. X-ray of the chest inconspicuous. Admitted to the hematology department of the General Hospital. PH: Immunoproliferative disease. Immunohistochemistry, at the institute of Pathology: IHH CK AE1-AE3, PAX5 +, CD20 +, CD3, bcl2 +, bcl6-, CyklinD1 +, CD23-, CD43 +, MUM1 - / +, Ki67 + in about 20% of the tumor cells. Morphological and immunohistochemical findings: Mantle cell lymphoma. MSCD of the neck, chest and upper abdomen: Left tonsil diameter is 28x32 mm and length is 36mm, with lobular contour and heterogeneous structure, asymmetrically narrowing lumen of the airways to 7 mm. pathologically enlarged submandibular and par jugular lymph nodes (10-15 mm diameter on the left. There were no pathological findings in the lung parenchyma. Abdominal and retroperitoneal lymph nodes

  20. Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

    Science.gov (United States)

    Fernández-Guarino, M; Ortiz-Romero, P L; Fernández-Misa, R; Montalbán, C

    2014-06-01

    Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  1. A comparison between protein profiles of B cell subpopulations and mantle cell lymphoma cells

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    Lehtiö Janne

    2009-11-01

    Full Text Available Abstract Background B-cell lymphomas are thought to reflect different stages of B-cell maturation. Based on cytogenetics and molecular markers, mantle cell lymphoma (MCL is presumed to derive predominantly from naïve, pre-germinal centre (pre-GC B lymphocytes. The aim of this study was to develop a method to investigate the similarity between MCL cells and different B-cell compartments on a protein expression level. Methods Subpopulations of B cells representing the germinal centre (GC, the pre-GC mantle zone and the post-GC marginal zone were isolated from tonsils using automated magnetic cell sorting (AutoMACS of cells based on their expression of CD27 and IgD. Protein profiling of the B cell subsets, of cell lines representing different lymphomas and of primary MCL samples was performed using top-down proteomics profiling by surface-enhanced laser detection/ionization time-of-flight mass spectrometry (SELDI-TOF-MS. Results Quantitative MS data of significant protein peaks (p-value Conclusion AutoMACS sorting generates sufficient purity to enable a comparison between protein profiles of B cell subpopulations and malignant B lymphocytes applying SELDI-TOF-MS. Further validation with an increased number of patient samples and identification of differentially expressed proteins would enable a search for possible treatment targets that are expressed during the early development of MCL.

  2. Peripheral T-cell lymphoma of the eyelid

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    Makoto Ishikawa

    2009-09-01

    Full Text Available Makoto Ishikawa, Hiroshi Watabe, Masahiro Hayakawa, Takeshi YoshitomiDepartment of Ophthalmology, Akita University Faculty of Medicine, Akita, JapanPurpose: To report a case of a 25-year-old woman with previously treated peripheral T-cell lymphoma (PTCL presenting with a recurrent lower eyelid lesion.Patients and method: Case report.Results: A 25-year-old young woman with previously treated PTCL noted an induration in the skin of her left lower eyelid. Upon diagnosis of a chalazion, antibiotic eye drops and ointments as well as steroid eye drops were administered. However, the condition worsened rapidly and swelling of the lower eyelid became remarkable. An excisional biopsy revealed that the palpebral lesion was diagnosed as recurrence of PTCL. Electron irradiation was applied as a radical treatment, and the prognosis was satisfactory without recurrence at 10 months after the last irradiation.Conclusions: Although lymphoma isolated to the ocular adnexa is rare, it should always be included in the differential diagnosis of any patient presenting with progressive swelling of the eyelid or ocular region.Keywords: peripheral T-cell lymphoma, chalazion, eyelid

  3. 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...

  4. Delayed Diagnosis of Nasal Natural Killer/T-Cell Lymphoma

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    Jennifer A. Villwock

    2013-01-01

    Full Text Available Midline destructive lesions of the face have multiple possible etiologies. The majority of these cases are found to be due to an extranodal lymphoma of natural killer/T-cell-type non-Hodgkins lymphoma (NKTL. Unfortunately, diagnosis is often delayed. With variable presenting complaints, including nonspecific issues like chronic rhinosinusitis or nasal congestion, initial treatments are aimed at these presumed diagnoses. Only as the lesion progresses do overt signs of destruction occur. As with our patient, who was initially treated for presumed infection and abscess, final diagnosis often does not occur until several months, and several antibiotic courses, from initial presentation. As such, it is important for this rare entity to remain in the clinician’s differential diagnosis for nasal lesion.

  5. Lenalidomide in Diffuse Large B-Cell Lymphoma

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    Catherine Thieblemont

    2012-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is the most common form of non-Hodgkin's lymphoma (NHL in adults. Even if the natural history of DLBCL has been improved with the advent of immunochemotherapy, the survival results obtained with current treatment options clearly indicate that new agents or novel approaches are needed. Lenalidomide (Revlimid, Celgene Corporation, Summit, NJ, USA, an analogue of thalidomide, is an immunomodulatory drug with pleiotropic mechanisms of action potentially adding to immunochemotherapy. We present here the biological rational for the use of lenalidomide in DLBCL in light of recent advances in the pathophysiology of the disease and the therapeutic results of the most recent trials published in literature or reported in meetings in relapsed/refractory situations as well as in first-line treatment.

  6. Orbital mantle cell lymphoma presenting as myasthenia gravis.

    Science.gov (United States)

    Karlin, Justin; Peck, Travis; Prenshaw, Karyn; Portell, Craig A; Kirzhner, Maria

    2017-12-01

    A 69-year-old man, previously treated with pyridostigmine for myasthenia gravis (manifesting as ptosis and diplopia) was evaluated for several concomitant bilateral anterior orbital masses. Imaging revealed 3 discrete, solid masses within and around the orbits. An incisional biopsy demonstrated atypical lymphocytes positive for CD20 and Cyclin-D1, consistent with mantle cell lymphoma. The patient received induction chemotherapy with a rituximab-based regimen. He experienced resolution of his diplopia and ptosis after one cycle of chemotherapy and achieved complete remission of the orbital masses and myasthenia symptoms after 6 cycles. Myasthenia gravis is most commonly associated with thymoma, but may also be observed with other malignancies. Recognition that orbital lymphoma may coexist with myasthenia gravis will help in expediting the diagnosis of future cases and in guiding treatment decisions.

  7. Cavitary pulmonary involvement of diffuse large B-cell lymphoma transformed from extra nodal marginal zone B-cell lymphoma MALT type.

    Science.gov (United States)

    Yamane, Hiromichi; Ohsawa, Masahiro; Shiote, Yasuhiro; Umemura, Shigeki; Suwaki, Toshimitsu; Shirakawa, Atsuko; Kamei, Haruhito; Takigawa, Nagio; Kiura, Katsuyuki

    2011-12-01

    We describe a case of pulmonary diffuse large B-cell lymphoma (DLBCL), which was thought to arise from extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). A 68-year-old woman presented with a 2-month history of cough and bloody sputum. The chest X-ray and computed tomography revealed a mass with cavitation in the right lower lobe. Transbronchial biopsy specimens revealed a granulomatous infiltration without malignant cells. However, diagnosis of MALT lymphoma was established from gastric biopsy specimen. Subsequently, a right lower lobectomy was performed because of hemoptysis. Examination of the resected specimen revealed a diffuse large B-cell lymphoma, which was considered to have transformed from MALT lymphoma, because both lung and stomach lesions had the chromosomal translocation t(11;18)(q21;q21) in common. In addition, there were no nodules, masses, alveolar or interstitial infiltrates in the lung fields, which are usually observed in the case of marginal zone B-cell lymphoma of bronchial mucosa-associated lymphoid tissue. These findings indicate that involvement of DLBCL have to be considered in patients with MALT lymphoma and cavitary lesion of the lung.

  8. 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...

  9. Lenalidomide in Diffuse Large B-Cell Lymphomas

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    Annalisa Chiappella

    2012-01-01

    Full Text Available Diffuse Large B-cell Lymphomas (DLBCL are the most frequent Non-Hodgkin Lymphomas (NHL. The addition of Rituximab to the standard chemotherapy CHOP improved the outcome in this patients, but so far 40% of patients experienced relapse or progressive disease. Lenalidomide, an immunomodulatory agent, had direct tumoricidal and antiangiogenetic actions on tumor cells and was able to modulate tumor-cell microenvironment, with the restoration of impaired T-cell activity and the formation of immuno-synapsis. Based on these actions, lenalidomide represented an active drug on aggressive relapsed NHL. In this review, the most relevant clinical trials for the use of lenalidomide in DLBCL were reported. Monotherapy with lenalidomide showed an activity in term of overall response rate, with acceptable hematological and extrahematological toxicities in relapsed/refractory aggressive NHL. The role of lenalidomide as salvage therapy in both cell of origin patterns in DLBCL (germinal center B-cell/activated B-cell was reported in preliminary data. Preliminary data regarding the role of lenalidomide in addition to chemoimmunotherapy (R-CHOP in first line clinical trials were discussed; data of safety, feasibility and efficacy were promising.

  10. [Role of stem cell transplantation in treatment of primary cutaneous T‑cell lymphoma].

    Science.gov (United States)

    Stranzenbach, R; Theurich, S; Schlaak, M

    2017-09-01

    Within the heterogeneous group of cutaneous T‑cell lymphomas (CTCL) the therapeutic options for advanced and progressive forms are particularly limited. The therapeutic value of hematopoietic stem cell transplantation in CTCL was analyzed. A literature search using the keywords "hematopoietic stem cell transplantation" and "cutaneous T‑cell lymphoma" was performed in PubMed. Studies between 1990 and 2017 were taken into account. The studies identified were analyzed for relevance and being up to date. After reviewing the currently available literature no prospective randomized studies were found. Wu et al. showed a superiority of allogeneic transplantation in a comparison of autologous and allogeneic stem cell transplantation for cutaneous lymphoma. The graft-versus-lymphoma effect plays a significant role in a prolonged progression-free survival after allogeneic transplantation. By using a non-myeloablative conditioning regimen, stem cell transplantation can also be an option for elderly patients. The most extensive long-term data after allogeneic stem cell transplantation were reported by Duarte et al. in 2014. Autologous stem cell transplantation does not currently represent a therapeutic option, whereas allogeneic stem cell transplantation for advanced cutaneous T‑cell lymphoma, using a non-myeloablative conditioning scheme, does represent a therapeutic option. However, there is no consensus on the appropriate patients and the right timing. Morbidity and mortality of complications should be taken into account. Thus, this procedure is currently subject to an individual case decision.

  11. Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Inaba, Koji; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana

    2013-01-01

    There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

  12. The diagnosis and management of NK/T-cell lymphomas

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    Eric Tse

    2017-04-01

    Full Text Available Abstract Extranodal natural killer (NK/T-cell lymphoma is an aggressive malignancy of putative NK-cell origin, with a minority deriving from the T-cell lineage. Pathologically, the malignancy occurs in two forms, extranodal NK/T-cell lymphoma, nasal type; and aggressive NK-cell leukaemia. Lymphoma occur most commonly (80% in the nose and upper aerodigestive tract, less commonly (20% in non-nasal areas (skin, gastrointestinal tract, testis, salivary gland, and rarely as disseminated disease with a leukemic phase. Genetic analysis showed mutations of genes involved in the JAK/STAT pathway, RNA assembly, epigenetic regulation, and tumor suppression. In initial clinical evaluation, positron emission tomography computed tomography, and quantification of plasma EBV DNA are mandatory as they are useful for response monitoring and prognostication. In stage I/II diseases, combined chemotherapy and radiotherapy (sequentially or concurrently is the best approach. Conventional anthracycline-containing regimens are ineffective and should be replaced by non-anthracycline-containing regimens, preferably including L-asparaginase. Radiotherapy alone is associated with high systemic relapse rates and should be avoided. In stage III/IV diseases, non-anthracycline-regimens-containing L-asparaginase are the standard. In relapsed/refractory cases, blockade of the programmed death protein 1 has recently shown promising results with high response rates. In the era of effective non-anthracycline-containing regimens, autologous haematopoietic stem cell transplantation (HSCT has not been shown to be beneficial. However, allogeneic HSCT may be considered for high-risk or advanced-stage patients in remission or relapsed/refractory patients responding to salvage therapy. Prognostic models taking into account presentation, interim, and end-of-treatment parameters are useful in triaging patients to different treatment strategies.

  13. Intravascular large B-cell lymphoma : remission after rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy

    NARCIS (Netherlands)

    Horváth, Barbara; Demeter, Judit; Eros, Nóra; Hársing, Judit; Csomor, Judit; Matolcsy, András; Bottlik, Gyula; Gyori, Gabriella; Marschalkó, Márta; Kárpáti, Sarolta

    2009-01-01

    Intravascular lymphoma is an uncommon, very aggressive extranodal non-Hodgkin lymphoma that most frequently involves the skin and central nervous system. Most cases are of B-cell origin; T-cell phenotype is extremely rare. Malignant cells proliferate within the lumens of capillaries, arterioles,

  14. T-cell Lymphomas: Updates in Biology and Diagnosis.

    Science.gov (United States)

    Ondrejka, Sarah L; Hsi, Eric D

    2016-03-01

    Nodal-based peripheral T-cell lymphomas are heterogeneous malignancies with overlapping morphology and clinical features. However, the current World Health Organization classification scheme separates these tumors into prognostically relevant categories. Since its publication, efforts to uncover the gene expression profiles and molecular alterations have subdivided these categories further, and distinct subgroups are emerging with specific profiles that reflect the cell of origin for these tumors and their microenvironment. Identification of the perturbed biologic pathways may prove useful in selecting patients for specific therapies and associating biomarkers with survival and relapse. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma

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    Katherine Devitt

    2014-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

  16. Sinonasal NK/T-Cell Lymphoma with Upper Gastrointestinal Bleeding: A Case Report

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    Kuan-Jung Huang

    2003-12-01

    Full Text Available Natural killer (NK/T-cell lymphoma is the most common malignant lymphoma among sinonasal lymphomas. Diagnosis is difficult and prognosis is poor. Herein, we report the case of a 22-year-old male patient with sinonasal NK/T-cell lymphoma who first presented with nasal obstruction and left facial swelling. There was a mushroom-like mass over the hard palate, diffuse mucosal swelling in the left nasal cavity, and left orbital cellulitis. The patient underwent a Caldwell-Luc operation, functional endoscopic sinus surgery, and wide excision of the palate tumor. Pathologic examination of the maxillary sinus, nasal cavity, and palate tumor showed an NK/T-cell lymphoma. Two days after the operation, the patient suddenly had bloody stool and suffered hematemesis. A series of examinations revealed a small intestinal hemorrhage. Emergent exploratory laparotomy showed an ulcerative tumor mass with bleeding over the jejunum. Pathologic examination of the mass showed that it was the same as the sinonasal mass, an NK/T-cell lymphoma. We reviewed previous studies on nasal NK/T-cell lymphoma and found no report discussing patients with NK/T-cell lymphoma of both nasal and non-nasal origins. From this case, we learned that in patients with sinonasal NK/T-cell lymphoma, other sites may be involved.

  17. 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

  18. Follicular B Cell Lymphoma with Accompanying Ischemic Gastritis Completely Resolved by Rituximab

    OpenAIRE

    Tariq, Anam; Mehta, Neal; Peroutka, Kathryn

    2017-01-01

    Patient: Female, 89 Final Diagnosis: Follicular B-cell lymphoma with accompanying ischemic gastritis completely resolved by rituximab Symptoms: Nausea ? vomiting Medication: ? Clinical Procedure: ? Specialty: Oncology Objective: Rare disease Background: Follicular B cell lymphomas account for a significant portion of all newly diagnosed non-Hodgkin?s lymphomas. While involvement can be varied, the most common extranodal presentation is within the gastrointestinal tract beyond the stomach. In ...

  19. New targeted treatments for cutaneous T-cell Lymphomas

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    Martine Bagot

    2017-01-01

    Full Text Available Cutaneous T-cell lymphomas (CTCLs represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath is a humanized IgG1 kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections. This treatment is less efficient in mycosis fungoides (MF. Brentuximab vedotin is a chimeric anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E, a cytotoxic antitubulin agent. Brentuximab vedotin is a very interesting new treatment for advanced tumor MF, Sezary syndrome, and primary cutaneous CD30+ lymphoproliferative disorders. The main limiting adverse event is neurosensitive peripheral neuropathy. Mogamulizumab is a humanized anti-C-C chemokine receptor Type 4 monoclonal antibody with a defucosylated Fc region leading to increased antibody-dependent cellular cytotoxicity. Mogamulizumab is very efficient on aggressive peripheral T-cell lymphomas, particularly adult T-cell leukemia/lymphoma and CTCLs, especially on the blood component of tumor cells. The main limiting events are related to the concomitant depletion of regulatory T-cells. IPH4102 is a humanized monoclonal antibody that targets the immune receptor KIR3DL2/CD158k. Preclinical results with this antibody offer proofs of concept for the clinical development of IPH4102 to treat patients with advanced CTCL.

  20. Primary mediastinal large B-cell lymphoma arising from thyroid in a renal recipient with Hashimoto’s thyroiditis

    OpenAIRE

    Wu, Fang; Qu, Lu; Li, Dai-Qiang; Hu, Chun-Hong

    2015-01-01

    Primary mediastinal large B-cell lymphoma is a subtype of diffuse large B-cell lymphoma, arising in the mediastinum from putative thymic B-cell origin with distinctive clinical and genetic features. Generally, primary mediastinal large B-cell lymphoma is believed as only deriving in the mediastinum. The current study presents a rare case of primary mediastinal large B-cell lymphoma which arising from thyroid in a renal recipient with Hashimoto’s thyroiditis. Moreover, we devoted a discussion ...

  1. iNKT cells suppress the CD8+ T cell response to a murine Burkitt's-like B cell lymphoma.

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    Ryan L Bjordahl

    Full Text Available The T cell response to B cell lymphomas differs from the majority of solid tumors in that the malignant cells themselves are derived from B lymphocytes, key players in immune response. B cell lymphomas are therefore well situated to manipulate their surrounding microenvironment to enhance tumor growth and minimize anti-tumor T cell responses. We analyzed the effect of T cells on the growth of a transplantable B cell lymphoma and found that iNKT cells suppressed the anti-tumor CD8(+ T cell response. Lymphoma cells transplanted into syngeneic wild type (WT mice or Jalpha18(-/- mice that specifically lack iNKT cells grew initially at the same rate, but only the mice lacking iNKT cells were able to reject the lymphoma. This effect was due to the enhanced activity of tumor-specific CD8(+ T cells in the absence of iNKT cells, and could be partially reversed by reconstitution of iNKT cells in Jalpha 18(-/- mice. Treatment of tumor-bearing WT mice with alpha -galactosyl ceramide, an activating ligand for iNKT cells, reduced the number of tumor-specific CD8(+ T cells. In contrast, lymphoma growth in CD1d1(-/- mice that lack both iNKT and type II NKT cells was similar to that in WT mice, suggesting that type II NKT cells are required for full activation of the anti-tumor immune response. This study reveals a tumor-promoting role for iNKT cells and suggests their capacity to inhibit the CD8(+ T cell response to B cell lymphoma by opposing the effects of type II NKT cells.

  2. NK/T Cell Lymphoma: Updates in Therapy.

    Science.gov (United States)

    Suzuki, Ritsuro

    2018-02-01

    Extranodal NK/T cell lymphoma (ENKL), nasal type, is a highly aggressive lymphoma which used to show a poor clinical outcome. Expression of P-glycoprotein on lymphoma cells of ENKL is a major reason for the refractoriness to conventional chemotherapy containing anthracycline. However, recent innovative approaches have improved the outcome and prognosis of ENKL. The purpose of this review is to summarize the proceedings of treatment. Concurrent chemoradiotherapy containing platinum and several drugs including L-asparaginase, methotrexate, and alkylators shows excellent outcomes for the limited-stage ENKL. SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) or other L-asparaginase-containing therapy is promising for advanced-stage ENKL, followed by either autologous or allogeneic hematopoietic stem cell transplantation. Anti-PD-1 or other immunological checkpoint inhibitors are recently reported to be effective for relapsed/refractory ENKL thought to be due to EBV-driven upregulation of PD-L1 expression. The prognosis of ENKL is therefore improving by the introduction of these strategies. The 5-year overall survival (OS) rate of limited stage was 63.2% [95% confidence interval (CI), 55.3 to 70.0%] before 2010, but was 79.4% (95% CI, 66.9 to 87.6%) in 2010 or after. However, there still exists a room for improvement, particularly for advanced-stage patients. The 2-year OS of advanced ENKL was 30.3% (95% CI, 19.5 to 41.7%) before 2010, but was 40.5% (95% CI, 24.8 to 55.8%) in 2010 or after. Optimal treatment scheme should further be explored.

  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. Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

    OpenAIRE

    Pellicelli, Adriano M; Marignani, Massimo; Zoli, Valerio; Romano, Mario; Morrone, Aldo; Nosotti, Lorenzo; Barbaro, Giuseppe; Picardi, Antonio; Gentilucci, Umberto Vespasiani; Remotti, Daniele; D'Ambrosio, Cecilia; Furlan, Caterina; Mecenate, Fabrizio; Mazzoni, Ettore; Majolino, Ignazio

    2011-01-01

    AIM: To evaluate if indolent B cell-non Hodgkin’s lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.

  5. B-cell lymphoma in a dog with ehrlichiosis (Ehrlichia canis) and systemic histoplasmosis (Histoplasma capsulatum).

    Science.gov (United States)

    Brunker, Jill D; Hoover, John P

    2007-03-01

    A mixed breed dog treated for ehrlichiosis and systemic histoplasmosis developed a refractory thrombocytopenia. When an abdominal mass was detected, exploratory laparotomy and biopsies confirmed lymphoma, which on immunohistochemical stains was determined to be of B-cell origin. Conceivably, the B-cell lymphoma in this dog was associated with chronic inflammation from ehrlichiosis, histoplasmosis, or both.

  6. Prognostic factors in primary cutaneous large B-cell lymphomas: a European multicenter study

    NARCIS (Netherlands)

    Grange, F.; Bekkenk, M. W.; Wechsler, J.; Meijer, C. J.; Cerroni, L.; Bernengo, M.; Bosq, J.; Hedelin, G.; Fink Puches, R.; van Vloten, W. A.; Joly, P.; Bagot, M.; Willemze, R.

    2001-01-01

    Most primary cutaneous B-cell lymphomas have an excellent prognosis. However, primary cutaneous large B-cell lymphomas (PCLBCLs) of the leg have been recognized as a distinct entity with a poorer prognosis in the European Organization for Research and Treatment of Cancer (EORTC) classification. This

  7. Optimizing Outcomes in Primary Mediastinal B-cell Lymphoma.

    Science.gov (United States)

    Zinzani, Pier Luigi; Broccoli, Alessandro

    2016-12-01

    Primary mediastinal B-cell lymphoma is characterized by a high chance of cure, and cured patients have a long disease-free life-expectancy; however, prognosis is severe in the case of relapsed or refractory disease. The initial use of the most effective chemoimmunotherapy regimen is therefore crucial. Understanding who will benefit from postinduction radiotherapy is also of paramount importance; positron emission tomography may be a reliable guide for physicians in determining which patients will require consolidation. New drugs with mechanisms of action including the most relevant biologic features of the tumor may allow better disease control. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Diffuse Large B-Cell Lymphoma with Calf Muscle Localization

    Directory of Open Access Journals (Sweden)

    Laura Bourdeanu

    2011-01-01

    Full Text Available Although diffuse large B-cell lymphoma (DLBCL usually occurs in the lymph nodes, approximately 30–40% of the time it can have an extranodal site of involvement and it can arise in nearly every body site such as intestine, bone, breast, liver, skin, lung, and central nervous system. Muscle involvement of DLBCL is especially uncommon, comprising 0.5% of extranodal NHL. We report a case of a 72-year-old man with extranodal DLBCL of a unique manifestation in the calf muscle, involving predominantly the gastrocnemius muscle. The patient achieved complete response and remained free of local recurrence or metastasis following diagnosis.

  9. Diffuse large B-cell lymphoma of the oral cavity

    International Nuclear Information System (INIS)

    Carlos Bortoluzzi, Marcelo

    2010-01-01

    The authors report a case of diffuse large B-cell lymphoma (DLBL) of the oral cavity. The patient was a 73-year-old white man who first presented at the Division of Stomatology with a large nodular mass in the hard palate and a nodular lesion in the upper lip, which were diagnosed as DLBL. The patient was treated with eight cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), but the disease recurred 22 months after the end of the therapy. Both primary sites hard palate and upper lip were involved again and the patient was resubmitted to chemotherapy. (author)

  10. Primary B-cell Lymphoma of the Thyroid Featuring the Different Ultrasonographic Findings

    International Nuclear Information System (INIS)

    Kim, Ji Na; Choi, Yoon Jung; Kim, Dong Hoon

    2009-01-01

    We review here 3 cases of primary thyroid lymphoma that we experienced during the past 5 years (age range: 39-55, all of the patients were female). The clinical and various ultrasonographic characteristics together with the other imaging modalities of primary thyroid lymphomas are described. The clinical features at presentation for one patient were a goiter with rapid growth and this was accompanied by compressive symptoms. The tumors of the other 2 patients were incidentally found during screening thyroid ultrasound exams. The pathologic studies of 2 cases showed a diffuse B-cell lymphoma with associated Hashimoto's thyroiditis and one case was a B-cell lymphoma of the MALT type. An extra-thyroid extension was shown in one case. The treatments included surgery alone for two cases, and chemotherapy and radiation therapy for one case. A US exam of thyroid lymphoma can show various morphological features, and US-CNB is helpful for diagnosing thyroid lymphoma

  11. Primary B-cell Lymphoma of the Thyroid Featuring the Different Ultrasonographic Findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Na; Choi, Yoon Jung; Kim, Dong Hoon [Kangbuk Samsung Medical Center, Seoul (Korea, Republic of)

    2009-06-15

    We review here 3 cases of primary thyroid lymphoma that we experienced during the past 5 years (age range: 39-55, all of the patients were female). The clinical and various ultrasonographic characteristics together with the other imaging modalities of primary thyroid lymphomas are described. The clinical features at presentation for one patient were a goiter with rapid growth and this was accompanied by compressive symptoms. The tumors of the other 2 patients were incidentally found during screening thyroid ultrasound exams. The pathologic studies of 2 cases showed a diffuse B-cell lymphoma with associated Hashimoto's thyroiditis and one case was a B-cell lymphoma of the MALT type. An extra-thyroid extension was shown in one case. The treatments included surgery alone for two cases, and chemotherapy and radiation therapy for one case. A US exam of thyroid lymphoma can show various morphological features, and US-CNB is helpful for diagnosing thyroid lymphoma.

  12. Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma.

    Science.gov (United States)

    Yoo, Hae Yong; Kim, Pora; Kim, Won Seog; Lee, Seung Ho; Kim, Sangok; Kang, So Young; Jang, Hye Yoon; Lee, Jong-Eun; Kim, Jaesang; Kim, Seok Jin; Ko, Young Hyeh; Lee, Sanghyuk

    2016-06-01

    CTLA4 and CD28 are co-regulatory receptors with opposite roles in T-cell signaling. By RNA sequencing, we identified a fusion between the two genes from partial gene duplication in a case of angioimmunoblastic T-cell lymphoma. The fusion gene, which codes for the extracellular domain of CTLA4 and the cytoplasmic region of CD28, is likely capable of transforming inhibitory signals into stimulatory signals for T-cell activation. Ectopic expression of the fusion transcript in Jurkat and H9 cells resulted in enhanced proliferation and AKT and ERK phosphorylation, indicating activation of downstream oncogenic pathways. To estimate the frequency of this gene fusion in mature T-cell lymphomas, we examined 115 T-cell lymphoma samples of diverse subtypes using reverse transcriptase polymerase chain reaction analysis and Sanger sequencing. We identified the fusion in 26 of 45 cases of angioimmunoblastic T-cell lymphomas (58%), nine of 39 peripheral T-cell lymphomas, not otherwise specified (23%), and nine of 31 extranodal NK/T cell lymphomas (29%). We further investigated the mutation status of 70 lymphoma-associated genes using ultra-deep targeted resequencing for 74 mature T-cell lymphoma samples. The mutational landscape we obtained suggests that T-cell lymphoma results from diverse combinations of multiple gene mutations. The CTLA4-CD28 gene fusion is likely a major contributor to the pathogenesis of T-cell lymphomas and represents a potential target for anti-CTLA4 cancer immunotherapy. Copyright© Ferrata Storti Foundation.

  13. 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

  14. 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.

  15. 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...

  16. File list: InP.Bld.20.AllAg.Lymphoma,_B-Cell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.20.AllAg.Lymphoma,_B-Cell hg19 Input control Blood Lymphoma, B-Cell SRX3703...41,SRX370343,SRX370347,SRX370349,SRX370345,SRX092417,SRX370351,SRX092415 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.20.AllAg.Lymphoma,_B-Cell.bed ...

  17. File list: InP.Bld.10.AllAg.Lymphoma,_B-Cell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.10.AllAg.Lymphoma,_B-Cell hg19 Input control Blood Lymphoma, B-Cell SRX3703...41,SRX370343,SRX370347,SRX370349,SRX370351,SRX370345,SRX092417,SRX092415 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.10.AllAg.Lymphoma,_B-Cell.bed ...

  18. File list: InP.Bld.05.AllAg.Lymphoma,_B-Cell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Lymphoma,_B-Cell hg19 Input control Blood Lymphoma, B-Cell SRX3703...41,SRX370343,SRX370347,SRX370349,SRX370345,SRX370351,SRX092415,SRX092417 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.05.AllAg.Lymphoma,_B-Cell.bed ...

  19. Silicon Phthalocyanine 4 and Photodynamic Therapy in Stage IA-IIA Cutaneous T-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2015-12-03

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome

  20. TET2 mutations in B cells of patients affected by angioimmunoblastic T-cell lymphoma.

    Science.gov (United States)

    Schwartz, Friederike H; Cai, Qian; Fellmann, Eva; Hartmann, Sylvia; Mäyränpää, Mikko I; Karjalainen-Lindsberg, Marja-Liisa; Sundström, Christer; Scholtysik, René; Hansmann, Martin-Leo; Küppers, Ralf

    2017-06-01

    Angioimmunoblastic T-cell lymphomas (AITLs) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they had already been detected in haematopoietic precursor cells of AITL patients. We show by analysis of whole-tissue sections and microdissected PD1 + cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection; 92%). In two-thirds of informative AITLs (6/9), a fraction of B cells was also TET2-mutated. Investigation of four AITLs by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10% and 60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T-cell lymphoma clone. Thus, TET2-mutated haematopoietic precursor cells in AITL patients not only give rise to the T-cell lymphoma but also generate a large population of mutated mature B cells. Future studies will show whether this is a reason why AITL patients frequently also develop B-cell lymphomas. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. 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...

  2. Adult high-grade B-cell lymphoma with Burkitt lymphoma signature: genomic features and potential therapeutic targets.

    Science.gov (United States)

    Bouska, Alyssa; Bi, Chengfeng; Lone, Waseem; Zhang, Weiwei; Kedwaii, Ambreen; Heavican, Tayla; Lachel, Cynthia M; Yu, Jiayu; Ferro, Roberto; Eldorghamy, Nanees; Greiner, Timothy C; Vose, Julie; Weisenburger, Dennis D; Gascoyne, Randy D; Rosenwald, Andreas; Ott, German; Campo, Elias; Rimsza, Lisa M; Jaffe, Elaine S; Braziel, Rita M; Siebert, Reiner; Miles, Rodney R; Dave, Sandeep; Reddy, Anupama; Delabie, Jan; Staudt, Louis M; Song, Joo Y; McKeithan, Timothy W; Fu, Kai; Green, Michael; Chan, Wing C; Iqbal, Javeed

    2017-10-19

    The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes. Mutations in genes promoting the tonic B-cell receptor (BCR)→PI3K pathway ( TCF3 and ID3 ) did not differ by age, whereas effectors of chronic BCR→NF-κB signaling were associated with adult-mBL. A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation profile similar to mBL. These double-hit lymphomas may have arisen from a tumor precursor that acquired both BCL2 and MYC translocations and/or KMT2D ( MLL2 ) mutation. Gain/amplification of MIR17HG and its paralogue loci was observed in 50% of adult-mBL. In vitro studies suggested miR-17∼92 's role in constitutive activation of BCR signaling and sensitivity to ibrutinib. Overall integrative analysis identified an interrelated gene network affected by copy number and mutation, leading to disruption of the p53 pathway and the BCR→PI3K or NF-κB activation, which can be further exploited in vivo by small-molecule inhibitors for effective therapy in adult-mBL.

  3. [Mantle cell lymphoma: Towards a personalized therapeutic strategy?].

    Science.gov (United States)

    Navarro Matilla, Belén; García-Marco, José A

    2015-06-22

    Mantle cell lymphoma (MCL) is a clinically heterogeneous non-Hodgkin lymphoma with an aggressive clinical behaviour and short survival in some cases and an indolent course in others. Advances in the biology and pathogenesis of MCL have unveiled several genes involved in deregulation of cell cycle checkpoints and the finding of subclonal populations with specific recurrent mutations (p53, ATM, NOTCH2) with an impact on disease progression and refractoriness to treatment. Prognostic stratification helps to distinguish between indolent and aggressive forms of MCL. Currently, younger fit patients benefit from more intensive front line chemotherapy regimens and consolidation with autologous transplantation, while older or frail patients are treated with less intensive regimens and rituximab maintenance. For relapsing disease, the introduction of bortezomib and lenalidomide containing regimens and B-cell receptor pathway inhibitors such as ibrutinib and idelalisib in combination with immunochemotherapy have emerged as therapeutic agents with promising clinical outcomes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  4. Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Mansour Ansari

    2017-01-01

    Full Text Available Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymphoma. Immunohistochemistry (IHC results showed that the tumor was positive for CD20, CD45, and Pax-5 and negative for BCL-2, cytokeratin, and S100. He had a normal bone marrow biopsy, abdominal, pelvic and chest CT scans. He had no B symptoms. The patient received 6 cycles of R-CHOP followed by radiotherapy (36 Gy to the pelvis. Six months after treatment, the patient is well and has returned to work. We have searched PubMed for primary diffuse large cell lymphoma. Primary diffuse large cell lymphoma of the bladder is best treated according to treatment for diffuse large cell lymphoma of other sites, which includes chemotherapy and radiotherapy. As seen in our review, primary diffuse large cell lymphoma of the bladder has a similar clinical course to diffuse large cell lymphoma of other sites.

  5. Ocular and multicentric T-cell lymphoma in horse

    Directory of Open Access Journals (Sweden)

    Mariana C. Oliveira

    2016-11-01

    Full Text Available ABSTRACT. Oliveira M.C., Faleiro R.D., Santos C.C.A., Oliveira G.F., Daoualibi Y., Sonne L., Brito M.F. & Ubiali D.G. [Ocular and multicentric T-cell lymphoma in horse.] Linfoma de células T multicêntrico e ocular em equino. Revista Brasileira de Medicina Veterinária, 38(Supl.2:147-151, 2016. Setor de Anatomia Patológica, Departamento Epidemiologia e Saúde Pública, Universidade Federal Rural do Rio de Janeiro, BR 465 Km 7, Seropédica, RJ 23890-000, Brasil. E-mail: danielubiali@hotmail.com A 10-year-old gelding, mixed breed had body score condition 3 (1-10, with reluctance to move due to the loss of visual acuity in both eyes, right eye swelling and marked dyspnea. The ophthalmic examination showed no response to threat of reflection, objects test or direct reflection and consensus of both eyes. Examination with visor magnifier and Finoff transilluminator revealed buftalmia, hyphema, aqueous flare, corneal neovascularization and posterior synechiae with irregular bulging of the iris in the right eye and aqueous flare, central anterior synechiae and mature cataract in the left eye. It was found corneal integrity in both eyes with the fluorescein test. Urine sample submitted for PCR to Leptospira sp. resulted negative. Euthanasia was performed after unsuccessful treatment attempts. At necropsy there was a mass in the right eyeball, the pleural surface of the diaphragm and the mesentery. There was multifocal to coalescing whitish nodules between 1 and 4 cm in diameter in the lung, filling about 80% of the lungs’ surface, mainly in the ventral region. Morphology of masses was histopathologically compatible with lymphoma. Anti-CD3 antibody resulted positive in all samples analyzed characterizing immunophenotypic T-cell lymphoma.

  6. Neurohypophysial Receptor Gene Expression by Thymic T Cell Subsets and Thymic T Cell Lymphoma Cell Lines

    Directory of Open Access Journals (Sweden)

    I. Hansenne

    2004-01-01

    transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines, while V3R transcription is restricted to CD4+ CD8+ and CD8+ thymic cells. Neither V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data, OTR and V3R are differentially expressed during T cell ontogeny. Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment.

  7. Primary cutaneous marginal zone B-cell lymphoma: clinical and histological aspects.

    Science.gov (United States)

    Khaled, A; Sassi, S; Fazaa, B; Ben Hassouna, J; Ben Romdhane, K; Kamoun, M R

    2009-02-01

    According to the WHO-EORTC classification of cutaneous lymphomas, primary cutaneous marginal zone B-cell lymphoma are now well characterized. We report here a case of primary cutaneous marginal zone B-cell lymphoma in a 51 year-old man in which the diagnosis was made using both histology and immunopathology. The patient had no remarkable medical history, no history of either acute inflammation or insect bite, and presented with a 5 cm solitary asymptomatic erythematous firm, multinodular and infiltrated plaque on the back for 12 months. Histological examination and immunohistochemical study of a cutaneous biopsy provided a differential diagnosis between B cell lymphoma and lymphocytoma cutis. Full body work up revealed no signs of extracutaneous dissemination. The patient underwent surgical excision of the nodule. Histological examination showed a histological and immunophenotyping profile typical of primary cutaneous marginal zone B-cell lymphoma. The lesion was completely excised with clear margins and no recurrence occurred after a 12 month-follow-up period. Primary cutaneous marginal zone B-cell lymphoma are low-grade lymphomas that have an indolent course and a high tendency to recur. They should be differentiated from lymphocytoma cutis and from the other types of cutaneous B cell lymphomas that have a different course and prognosis.

  8. [Treatment of relapsed Hodgkin lymphoma after autologous stem cell transplantation].

    Science.gov (United States)

    Illés, Árpád; Simon, Zsófia; Udvardy, Miklós; Magyari, Ferenc; Jóna, Ádám; Miltényi, Zsófia

    2017-08-01

    Approximately 10-30% of Hodgkin lymphoma patients relapses or experience refractory disease after first line treatment. Nowadays, autologous stem cell transplantation can successfully salvage half of these patients, median overall survival is only 2-2.5 years. Several prognostic factors determine success of autologous stem cell transplantation. Result of transplantation can be improved considering these factors and using consolidation treatment, if necessary. Patients who relapse after autologous transplantation had worse prognosis, treatment of this patient population is unmet clinical need. Several new treatment options became available in the recent years (brentuximab vedotin and immuncheckpoint inhibitors). These new treatment options offer more chance for cure in relapsed/refractory Hodgkin patients. Outcome of allogenic stem cell transplantation can be improved by using haploidentical donors. New therapeutic options will be discussed in this review. Orv Hetil. 2017; 158(34): 1338-1345.

  9. Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice

    International Nuclear Information System (INIS)

    Muto, H; Sakata-Yanagimoto, M; Nagae, G; Shiozawa, Y; Miyake, Y; Yoshida, K; Enami, T; Kamada, Y; Kato, T; Uchida, K; Nanmoku, T; Obara, N; Suzukawa, K; Sanada, M; Nakamura, N; Aburatani, H; Ogawa, S; Chiba, S

    2014-01-01

    TET2 (Ten Eleven Translocation 2) is a dioxygenase that converts methylcytosine (mC) to hydroxymethylcytosine (hmC). TET2 loss-of-function mutations are highly frequent in subtypes of T-cell lymphoma that harbor follicular helper T (Tfh)-cell-like features, such as angioimmunoblastic T-cell lymphoma (30–83%) or peripheral T-cell lymphoma, not otherwise specified (10–49%), as well as myeloid malignancies. Here, we show that middle-aged Tet2 knockdown (Tet2 gt/gt ) mice exhibit Tfh-like cell overproduction in the spleen compared with control mice. The Tet2 knockdown mice eventually develop T-cell lymphoma with Tfh-like features after a long latency (median 67 weeks). Transcriptome analysis revealed that these lymphoma cells had Tfh-like gene expression patterns when compared with splenic CD4-positive cells of wild-type mice. The lymphoma cells showed lower hmC densities around the transcription start site (TSS) and higher mC densities at the regions of the TSS, gene body and CpG islands. These epigenetic changes, seen in Tet2 insufficiency-triggered lymphoma, possibly contributed to predated outgrowth of Tfh-like cells and subsequent lymphomagenesis. The mouse model described here suggests that TET2 mutations play a major role in the development of T-cell lymphoma with Tfh-like features in humans

  10. CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Patients With Recurrent or Refractory CD19 Positive Diffuse Large B-Cell Lymphoma or B Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-01-25

    B Acute Lymphoblastic Leukemia; CD19 Positive; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma of the Elderly; Minimal Residual Disease; Philadelphia Chromosome Positive; 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; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

  11. Peripheral T-cell Lymphoma with Cyclin D1 overexpression: a case report

    Directory of Open Access Journals (Sweden)

    Aquino Gabriella

    2012-07-01

    Full Text Available Abstract Peripheral T-cell lymphomas not otherwise specified are generally considered aggressive non-Hodgkin lymphomas, because of poor natural outcome and response to therapy. They show a complex karyotype without any specific genetic hallmark. We report a case of peripheral T-cell lymphoma not otherwise specified with heterogeneous nuclear Cyclin D1 immunohistochemical overexpression, due to gene copy gain, a phenomenon similar to that observed in Mantle Cell Lymphoma characterized by t(11;14(q13;q32. In this case report we underline the diagnostic pitfall rapresented by Cyclin D1 immunoistochemical overexpression in a T-cell lymphoma. Several pitfalls could lead to misinterpretation of diagnosis, therefore, we underlined the need to integrate the classical histology and immunohistochemistry with molecular tests as clonality or Fluorescence in situ hybridization. Virtual slide The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1117747619703769

  12. Peripheral T-cell Lymphoma with Cyclin D1 overexpression: a case report.

    Science.gov (United States)

    Aquino, Gabriella; Franco, Renato; Ronconi, Fioravante; Anniciello, Annamaria; Russo, Luigi; De Chiara, Annarosaria; Panico, Luigi

    2012-07-06

    Peripheral T-cell lymphomas not otherwise specified are generally considered aggressive non-Hodgkin lymphomas, because of poor natural outcome and response to therapy. They show a complex karyotype without any specific genetic hallmark. We report a case of peripheral T-cell lymphoma not otherwise specified with heterogeneous nuclear cyclin D1 immunohistochemical overexpression, due to gene copy gain, a phenomenon similar to that observed in mantle cell lymphoma characterized by t(11;14)(q13;q32). In this case report we underline the diagnostic pitfall represented by cyclin D1 immunohistochemical overexpression in a T-cell lymphoma. Several pitfalls could lead to misinterpretation of diagnosis, therefore, we underlined the need to integrate the classical histology and immunohistochemistry with molecular tests as clonality or fluorescence in situ hybridization. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1117747619703769.

  13. Primary intravascular large B-cell lymphoma of pituitary

    Directory of Open Access Journals (Sweden)

    K R Anila

    2012-01-01

    Full Text Available A 68-year-old retired nurse, who was a known hypertensive on medication, presented with prolonged fever of 2-month duration without any clinical evidence of infection. On examination she had altered mental status. She also had other nonspecific complaints such as sleep disturbances, loss of weight, etc. On investigation, she was found to have anemia, thrombocytopenia, raised erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and lactate dehydrogenase (LDH values. She also had electrolyte imbalance. Radiological evaluation of brain showed mass lesion in the sella turcica, suggestive of pituitary adenoma. Biochemical evaluation showed hypopituitarism. Trans-sphenoidal biopsy was done. Based on histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma (IVLBCL of pituitary was made. Our patient′s condition deteriorated rapidly and she succumbed to her illness before therapy could be initiated. We are reporting this case because of the rare subtype of large B-cell lymphoma presenting at an extremely unusual primary site.

  14. 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

  15. Extranodal marginal zone B-cell lymphoma of Mucosa-Associated Lymphoid Tissue (MALT lymphoma) in ulcerative colitis.

    Science.gov (United States)

    Terada, Tadashi

    2014-01-01

    Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) occurring in inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn's disease, has been reported, although it is extremely rare. An 18-year-old man with a two-years history of UC underwent colon endoscopy, and was found to have active total UC ranging from anus to cecum. Six biopsies were obtained. The microscopic examinations showed severe infiltrations of atypical small lymphocytes. They showed hyperchromatic nuclei and increased nucleocytoplasmic ratio and scattered immunoblastic cells. Centrocyte-like atypical lymphocytes, monocytoid cells, and plasma cells were seen in some places. Vague germinal centers were present, and apparent lymphoepithelial lesions were seen. No crypt abscesses were seen, and there were few neutrophils. No apparent other findings of UC were seen. Immunohistochemically, the atypical lymphocytes were positive for vimentin, CD45, CD20, CD79α, CD138, κ-chain, λ-chain, and p53 and Ki-67 antigen (labeling index = 63%). They were also positive for CD45RO, CD3, and CD15, but these positive cells were very scant compared with CD20 and CD79α. They were negative for CD10, CD30, CD56, cytokeratin (CK) AE1/3, CK CAM5.2, CK34BE12, CK5, CK6, CK7, CK8, CK14, CK18, CK19, CK20, EMA, chromogranin, synaptophysin, NSE, S100 protein, CEA, CA19-9, p63, and HMB45. Without clinical information, the appearances are those of MALT lymphoma. However, with clinical information, making the diagnosis of MALT lymphoma was hesitated. It is only mentioned herein that atypical lymphocytic infiltrations indistinguishable from MALT lymphoma occurred in an 18-year-old male patient with a two-year history of UC.

  16. Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

    Directory of Open Access Journals (Sweden)

    Refaeli Yosef

    2008-05-01

    Full Text Available Abstract Background We have used a mouse model based on overexpression of c-Myc in B cells genetically engineered to be self-reactive to test the hypothesis that farnesyl transferase inhibitors (FTIs can effectively treat mature B cell lymphomas. FTIs are undergoing clinical trials to treat both lymphoid and non-lymphoid malignancies and we wished to obtain evidence to support the inclusion of B cell lymphomas in future trials. Results We report that two FTIs, L-744,832 and SCH66336, blocked the growth of mature B cell lymphoma cells in vitro and in vivo. The FTI treatment affected the proliferation and survival of the transformed B cells to a greater extent than naïve B cells stimulated with antigen. In syngeneic mice transplanted with the transgenic lymphoma cells, L-744,832 treatment prevented the growth of the tumor cells and the morbidity associated with the resulting lymphoma progression. Tumors that arose from transplantation of the lymphoma cells regressed with as little as three days of treatment with L-744,832 or SCH66336. Treatment of these established lymphomas with L-744,832 for seven days led to long-term remission of the disease in approximately 25% of animals. Conclusion FTI treatment can block the proliferation and survival of self-reactive transformed B cells that overexpress Myc. In mice transplanted with mature B cell lymphomas, we found that FTI treatment led to regression of disease. FTIs warrant further consideration as therapeutic agents for mature B cell lymphomas and other lymphoid tumors.

  17. Pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymph tissue: A case report and literature review.

    Science.gov (United States)

    Wu, Y; Zhao, L; Chai, Y

    2018-03-01

    Extranodal marginal zone B-cell lymphoma of mucosa-associated lymph tissue (MALT lymphoma) is a rare subtype of marginal zone B-cell lymphoma. Most primary MALT lymphoma occurs in the stomach, while lung is an uncommon site of MALT lymphoma. We herein report a case of MALT lymphoma in a 44-year-old female who underwent a pulmonary lobectomy and received rituximab plus CHOP chemotherapy regimen. The patient had an uneventful postoperative course and a good prognosis without tumor recurrence for 3 years.

  18. Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Adv. Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With DLBCL

    Science.gov (United States)

    2018-04-12

    B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

  19. Logical analysis of diffuse large B-cell lymphomas.

    Science.gov (United States)

    Alexe, G; Alexe, S; Axelrod, D E; Hammer, P L; Weissmann, D

    2005-07-01

    The goal of this study is to re-examine the oligonucleotide microarray dataset of Shipp et al., which contains the intensity levels of 6817 genes of 58 patients with diffuse large B-cell lymphoma (DLBCL) and 19 with follicular lymphoma (FL), by means of the combinatorics, optimisation, and logic-based methodology of logical analysis of data (LAD). The motivations for this new analysis included the previously demonstrated capabilities of LAD and its expected potential (1) to identify different informative genes than those discovered by conventional statistical methods, (2) to identify combinations of gene expression levels capable of characterizing different types of lymphoma, and (3) to assemble collections of such combinations that if considered jointly are capable of accurately distinguishing different types of lymphoma. The central concept of LAD is a pattern or combinatorial biomarker, a concept that resembles a rule as used in decision tree methods. LAD is able to exhaustively generate the collection of all those patterns which satisfy certain quality constraints, through a systematic combinatorial process guided by clear optimization criteria. Then, based on a set covering approach, LAD aggregates the collection of patterns into classification models. In addition, LAD is able to use the information provided by large collections of patterns in order to extract subsets of variables, which collectively are able to distinguish between different types of disease. For the differential diagnosis of DLBCL versus FL, a model based on eight significant genes is constructed and shown to have a sensitivity of 94.7% and a specificity of 100% on the test set. For the prognosis of good versus poor outcome among the DLBCL patients, a model is constructed on another set consisting also of eight significant genes, and shown to have a sensitivity of 87.5% and a specificity of 90% on the test set. The genes selected by LAD also work well as a basis for other kinds of statistical

  20. Diffuse large B-cell lymphoma of stomach presenting with paraneoplastic cerebellar degeneration syndrome.

    Science.gov (United States)

    Nomani, Ali Zohair; Wazir, Marina; Kashmir, Saba Binte; Qureshi, Muhammad Saleem

    2014-03-01

    Paraneoplastic syndromes are most often diagnosed in the setting of a known malignancy. It is not uncommon for a paraneoplastic disorder to develop before a cancer is identified. While syndrome of cerebellar degeneration has been identified as a paraneoplastic manifestation of Hodgkin's lymphoma, thymoma, lung and breast cancer, ovarian and testicular tumors, melanoma, renal cell carcinoma, follicular lymphoma and adenocarcinoma of stomach, its association with non-Hodgkin's lymphoma and particularly diffuse large B-cell lymphoma has not been established previously. This case report describes the primary presentation with signs of paraneoplastic cerebellar degeneration as the only manifestation of an underlying diffuse large B-cell lymphoma making it the first of its kind to be formally reported. Furthermore, it also includes the identification of associated paraneoplastic antibodies for this particular syndrome.

  1. Relationships among hepatitis C virus, hepatocellular carcinoma, and diffuse large B cell lymphoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hyuk Jun; Kim, Seong Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-07-15

    Hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma (HCC). Recent studies have reported various associations between HCV and the incidence of non-Hodgkin's lymphoma. We report the radiologic findings in a rare case of simultaneous occurrence of HCC and diffuse large B cell lymphoma in a HCV carrier.

  2. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of

  3. Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Bernatsky, Sasha; Velásquez García, Héctor A; Spinelli, John; Gaffney, Patrick; Smedby, Karin E; Ramsey-Goldman, Rosalind; Wang, Sophia S.; Adami, Hans-Olov; Albanes, Demetrius; Angelucci, Emanuele; Ansell, Stephen M.; Asmann, Yan W.; Becker, Nikolaus; Benavente, Yolanda; Berndt, Sonja I.; Bertrand, Kimberly A.; Birmann, Brenda M.; Boeing, Heiner; Boffetta, Paolo; Bracci, Paige M.; Brennan, Paul; Brooks-Wilson, Angela R.; Cerhan, James R.; Chanock, Stephen J.; Clavel, Jacqueline; Conde, Lucia; Cotenbader, Karen H; Cox, David G; Cozen, Wendy; Crouch, Simon; De Roos, Anneclaire J.; De Sanjose, Silvia; Di Lollo, Simonetta; Diver, W. Ryan; Dogan, Ahmet; Foretova, Lenka; Ghesquières, Hervé; Giles, Graham G.; Glimelius, Bengt; Habermann, Thomas M.; Haioun, Corinne; Hartge, Patricia; Hjalgrim, Henrik; Holford, Theodore R.; Holly, Elizabeth A.; Jackson, Rebecca D.; Kaaks, Rudolph; Kane, Eleanor; Kelly, Rachel S.; Klein, Robert J.; Kraft, Peter; Kricker, Anne; Lan, Qing; Lawrence, Charles; Liebow, Mark; Lightfoot, Tracy; Link, Brian K.; Maynadie, Marc; McKay, James; Melbye, Mads; Molina, Thierry Jo; Monnereau, Alain; Morton, Lindsay M.; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Offit, Kenneth; Purdue, Mark P.; Rais, Marco; Riby, Jacques; Roman, Eve; Rothman, Nathaniel; Salles, Gilles; Severi, Gianluca; Severson, Richard K.; Skibola, Christine F.; Slager, Susan L.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Staines, Anthony; Teras, Lauren R.; Thompson, Carrie A.; Tilly, Hervé; Tinker, Lesley F.; Tjonneland, Anne; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C H; Vijai, Joseph; Vineis, Paolo; Virtamo, Jarmo; Wang, Zhaoming; Weinstein, Stephanie; Witzig, Thomas E.; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Yawei; Zheng, Tongzhang; Zucca, Mariagrazia; Clarke, Ann E

    2017-01-01

    Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

  4. EBV+ diffuse large B-cell lymphoma arising within atrial myxoma in Chinese immunocompetent patient.

    Science.gov (United States)

    Liu, Xiaoyan; Liu, Pu; Li, Jun

    2015-01-01

    The incidence rate of Primary cardiac lymphoma is very low. Primary cardiac lymphoma within myxoma is extremely rare disease. So far, these cases have been reported only eight in the world, which has not reported in Chinese so far. Hence, we reported the unique Chinese case of 52-year-old immunocompetent male with primary Epstein-Barr virus positive diffuse large B-cell lymphoma arising within atrial myxoma, and had no evidence of systemic lymphoma. The patient presented right sided body numbness, arm weakness no incentive and mouth twitch. A transthoracic echocardiogram revealed a large intraatrial mass, attached to the left atrial wall. The mass was removed by open thoracic surgery and subsequently diagnosed as malignant diffuse large B-cell lymphoma with myxoma by histopathology. This was the fourth case of discovered Epstein-Barr virus positive diffuse large B-cell lymphoma in a cardiac myxoma reported so far. The patient has been well by followed up for 5 months without chemotherapy. Now we discuss the importance of histodiagnosis and the proper treatment. Epstein-Barr virus positive diffuse large B-cell lymphoma arising within atrial myxoma is an extraordinary lymphoma for better prognosis, avoiding excessive treatment.

  5. Reactivation of hepatitis D virus after chemotherapy for diffuse large B cell lymphoma despite lamivudine prophylaxis

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Gerstoft, Jan; Weis, Nina Margrethe

    2010-01-01

    We describe a case of reactivation of hepatitis D virus (HDV) in a patient treated with chemotherapy for a diffuse large B cell lymphoma despite lamivudine prophylaxis. This case suggests that previously cleared HDV should be considered when administering chemotherapy to patients with lymphoma....

  6. EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT.

    Science.gov (United States)

    Ruskoné-Fourmestraux, A; Fischbach, W; Aleman, B M P; Boot, H; Du, M Q; Megraud, F; Montalban, C; Raderer, M; Savio, A; Wotherspoon, A

    2011-06-01

    This consensus report of the EGILS (European Gastro-Intestinal Lymphoma Study) group includes recommendations on the management of gastric extranodal marginal zone B-cell lymphoma of MALT. They are based on data from the literature and on intensive discussions and votings of the experts during their annual meetings.

  7. Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Kania, P W; Ino, Y

    2000-01-01

    In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data fr...

  8. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy

    DEFF Research Database (Denmark)

    Eskelund, Christian W.; Dahl, Christina; Hansen, Jakob W.

    2017-01-01

    Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM...

  9. Primary thymic extranodal marginal zone B cell lymphoma as an incidental finding in a Caucasian woman

    DEFF Research Database (Denmark)

    Krogh Petersen, Jeanette; Larsen, Thomas Stauffer; Møller, Michael Boe

    2015-01-01

    Primary thymic extranodal marginal zone B cell lymphoma (TML) is an extremely rare lymphoma strongly associated with autoimmune disease. We report an exceedingly rare case of TML found in a non-Asian population. TML was found incidentally in a 60-year-old Caucasian woman with a short history...

  10. Primary Mediastinal Large B-Cell Lymphoma during Pregnancy

    Directory of Open Access Journals (Sweden)

    Cesar A. Perez

    2012-01-01

    Full Text Available Non-Hodgkin’s Lymphoma (NHL rarely presents during pregnancy and primary mediastinal large B-cell lymphoma (PMLBCL accounts for approximately 2.5% of patients with NHL. The case of a 22-year-old woman who was diagnosed with Stage IIA PMLBCL during week 13 of her intrauterine pregnancy is described. The staging consisted in computed tomography (CT of the chest and magnetic resonance imaging (MRI of the abdomen and pelvis. She was managed with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for a total of six cycles and, because of the early presentation during the second trimester, she received the entire chemotherapy course during the pregnancy. She delivered a healthy baby at 34 weeks of pregnancy and a 18FDG-PET/CT scan demonstrated complete remission after delivery. After 20 months of follow up she remains with no evidence of disease and her 1-year-old son has shown no developmental delays or physical abnormalities. PMLBCL, although an uncommon subgroup of DLBCL, may present during pregnancy and R-CHOP should be considered as one suitable option in this complex scenario.

  11. Multifocal Extranodal Involvement of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Devrim Cabuk

    2013-01-01

    Full Text Available Endobronchial involvement of extrapulmonary malignant tumors is uncommon and mostly associated with breast, kidney, colon, and rectum carcinomas. A 68-year-old male with a prior diagnosis of colon non-Hodgkin lymphoma (NHL was admitted to the hospital with a complaint of cough, sputum, and dyspnea. The chest radiograph showed right hilar enlargement and opacity at the right middle zone suggestive of a mass lesion. Computed tomography of thorax revealed a right-sided mass lesion extending to thoracic wall with the destruction of the third and the fourth ribs and a right hilar mass lesion. Fiberoptic bronchoscopy was performed in order to evaluate endobronchial involvement and showed stenosis with mucosal tumor infiltration in right upper lobe bronchus. The pathological examination of bronchoscopic biopsy specimen reported diffuse large B-cell lymphoma and the patient was accepted as the endobronchial recurrence of sigmoid colon NHL. The patient is still under treatment of R-ICE (rituximab-ifosfamide-carboplatin-etoposide chemotherapy and partial regression of pulmonary lesions was noted after 3 courses of treatment.

  12. [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.

  13. Conjunctival mass as an initial presentation of mantle cell lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Khanlari Mahsa

    2012-12-01

    Full Text Available Abstract Background To describe a rare manifestation of mantle cell lymphoma (MCL in conjunctiva, with clinical, hisologic, immunohistologic and genetic findings together with review of the Literature. Case presentation Most ocular adnexal lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT. A few cases of ocular adnexal mantle cell lymphomas have been reported in the literature. We present a case of mantle cell lymphoma presenting as right conjunctival mass of at least three months duration in a 64-year-old man. Histopathologic examination showed a proliferation of monomorphous small-to-medium-sized lymphoid cells with cleaved nuclei in the subconjunctiva. By immunohistochemistry, the infiltrate was positive for CD20, CD5, BCL-2, cyclin D1, and the transcription factor SOX11. Fluorescent in situ hybridization demonstrated the presence of IGH-CCND1 fusion indicating t(11;14. Conclusion A rigorous approach to initial diagnosis and staging of small cell lymphomas of the ocular adnexa is needed. The recognition of ocular MCL requires appropriate immunohistochemical staining and/or genetic confirmation to differentiate this rare form of presentation of MCL from other more frequent small cell lymphomas.

  14. A Case of Successful Remission of Extensive Primary Gastric Diffuse Large B Cell Lymphoma: Radiologic, Endoscopic and Pathologic Evidence

    Directory of Open Access Journals (Sweden)

    Mike M. Bismar

    2014-04-01

    Full Text Available Though rare amongst stomach neoplasms, primary gastric diffuse large B cell lymphoma is one of the commonest extranodal non-Hodgkin lymphomas. If left untreated, it can have a devastating progression and life-threatening consequences. We present the case of a successfully treated large antral ulcer confirmed to be large B cell lymphoma as evidenced by radiologic, endoscopic and histopathologic findings. A brief discussion about the types of gastric lymphoma, their Helicobacter pylori relation and therapeutic modalities follows.

  15. The predictive significance of CD20 expression in B-cell lymphomas

    Directory of Open Access Journals (Sweden)

    Horvat Mateja

    2011-04-01

    Full Text Available Abstract Background In our recent study, we determined the cut-off value of CD20 expression at the level of 25 000 molecules of equivalent soluble fluorochrome (MESF to be the predictor of response to rituximab containing treatment in patients with B-cell lymphomas. In 17.5% of patients, who had the level of CD20 expression below the cut-off value, the response to rituximab containing treatment was significantly worse than in the rest of the patients with the level of CD20 expression above the cut-off value. The proportion of patients with low CD20 expression who might not benefit from rituximab containing treatment was not necessarily representative. Therefore the aim of this study was to quantify the CD20 expression in a larger series of patients with B-cell lymphomas which might allow us to determine more reliably the proportion of patients with the CD20 expression below the cut-off. Methods Cytological samples of 64 diffuse large B-cell lymphomas (DLBCL, 56 follicular lymphomas (FL, 31 chronic lymphocytic leukemias (CLL, 34 mantle cell lymphomas (MCL, 18 marginal zone lymphomas (MZL and 15 B-cell lymphomas unclassified were analyzed for CD20 expression by quantitative four-color flow cytometric measurements using FACSCalibur flow cytometer (BD Biosciences. Results The range of CD20 expression in different B-cell lymphomas was very broad, varying from 2 737 to 115 623 MESF in CLL and 3 549 to 679 577 MESF in DLBCL. However, when we compared the CD20 expression in the groups of patients with DLBCL, FL, MCL, MZL, CLL and B-cell lymphomas unclassified, it was found to be significantly lower (p = 0.002 only in CLL but did not significantly differ in other lymphoma types (p = NS. Fifty-three out of 218 (24.3% patients with B-cell lymphomas had the CD20 expression below the cut-off value. Conclusions The CD20 expression in CLL is significantly lower than in most histological types of mature B-cell lymphomas in which it appears to be comparable

  16. A Novel Gallium Compound Synergistically Enhances Bortezomib-induced Apoptosis in Mantle Cell Lymphoma Cells

    OpenAIRE

    Chitambar, Christopher R.; Purpi, David P.

    2010-01-01

    Combination chemotherapy forms the backbone of cancer treatment. There is a need for new drug combinations for the treatment of mantle cell lymphoma (MCL). Herein, we show that gallium maltolate, a novel gallium compound, synergizes with bortezomib, a proteasome inhibitor, to induce cell death in MCL Granta cells. Cells exposed to either agent displayed caspase-3 activation, a loss of mitochondrial membrane potential, and a decrease in chymotrypsin-like activity. These effects were increased ...

  17. 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

  18. [Central nervous system relapse in diffuse large B cell lymphoma: Risk factors].

    Science.gov (United States)

    Sancho, Juan-Manuel; Ribera, Josep-Maria

    2016-01-15

    Central nervous system (CNS) involvement by lymphoma is a complication associated, almost invariably, with a poor prognosis. The knowledge of the risk factors for CNS relapse is important to determine which patients could benefit from prophylaxis. Thus, patients with very aggressive lymphomas (such as lymphoblastic lymphoma or Burkitt's lymphoma) must systematically receive CNS prophylaxis due to a high CNS relapse rate (25-30%), while in patients with indolent lymphoma (such as follicular lymphoma or marginal lymphoma) prophylaxis is unnecessary. However, the question about CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, remains controversial. The information available is extensive, mainly based on retrospective and heterogeneous studies. There seems that immunochemotherapy based on rituximab reduces the CNS relapse rate. On the other hand, patients with increased serum lactate dehydrogenase plus more than one extranodal involvement seem to have a higher risk of CNS relapse, but a prophylaxis strategy based only on the presence of these 2 factors does not prevent all CNS relapses. Patients with involvement of testes or breast have high risk of CNS relapse and prophylaxis is mandatory. Finally, CNS prophylaxis could be considered in patients with DLBCL and renal or epidural space involvement, as well as in those cases with MYC rearrangements, although additional studies are necessary. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  19. Specific targeting of whole lymphoma cells to dendritic cells ex vivo provides a potent antitumor vaccine

    Directory of Open Access Journals (Sweden)

    Mocikat Ralph

    2007-03-01

    Full Text Available Abstract Background Dendritic cells (DC pulsed with tumor-derived antigenic material have widely been used in antitumor vaccination protocols. However, the optimal strategy of DC loading has not yet been established. Our aim was to define requirements of optimal DC vaccines in terms of in vivo protection in a murine B-cell lymphoma model. Methods We compare various loading reagents including whole parental and modified tumor cells and a single tumor-specific antigen, namely the lymphoma idiotype (Id. Bone marrow-derived DC were pulsed in vitro and used for therapy of established A20 lymphomas. Results We show that a vaccine with superior antitumor efficacy can be generated when DC are loaded with whole modified tumor cells which provide both (i antigenic polyvalency and (ii receptor-mediated antigen internalization. Uptake of cellular material was greatly enhanced when the tumor cells used for DC pulsing were engineered to express an anti-Fc receptor immunoglobulin specificity. Upon transfer of these DC, established tumor burdens were eradicated in 50% of mice. By contrast, pulsing DC with unmodified lymphoma cells or with the lymphoma Id, even when it was endowed with the anti-Fc receptor binding arm, was far less effective. A specific humoral anti-Id response could be detected, particularly following delivery of Id protein-pulsed DC, but it was not predictive of tumor protection. Instead a T-cell response was pivotal for successful tumor protection. Interaction of the transferred DC with CD8+ T lymphocytes seemed to play a role for induction of the immune response but was dispensable when DC had received an additional maturation stimulus. Conclusion Our analyses show that the advantages of specific antigen redirection and antigenic polyvalency can be combined to generate DC-based vaccines with superior antitumor efficacy. This mouse model may provide information for the standardization of DC-based vaccination protocols.

  20. Novel targets for natural killer/T-cell lymphoma immunotherapy.

    Science.gov (United States)

    Kumai, Takumi; Kobayashi, Hiroya; Harabuchi, Yasuaki

    2016-01-01

    Extranodal natural killer/T-cell lymphoma, nasal type (NKTL) is a rare but highly aggressive Epstein-Barr virus-related malignancy, which mainly occurs in nasopharyngeal and nasal/paranasal areas. In addition to its high prevalence in Asian, Central American and South American populations, its incidence rate has been gradually increasing in Western countries. The current mainstay of treatment is a combination of multiple chemotherapies and irradiation. Although chemoradiotherapy can cure NKTL, it often causes severe and fatal adverse events. Because a growing body of evidence suggests that immunotherapy is effective against hematological malignancies, this treatment could provide an alternative to chemoradiotherapy for treatment of NKTL. In this review, we focus on how recent findings could be used to develop efficient immunotherapies against NKTL.

  1. Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells.

    Science.gov (United States)

    Boice, Michael; Salloum, Darin; Mourcin, Frederic; Sanghvi, Viraj; Amin, Rada; Oricchio, Elisa; Jiang, Man; Mottok, Anja; Denis-Lagache, Nicolas; Ciriello, Giovanni; Tam, Wayne; Teruya-Feldstein, Julie; de Stanchina, Elisa; Chan, Wing C; Malek, Sami N; Ennishi, Daisuke; Brentjens, Renier J; Gascoyne, Randy D; Cogné, Michel; Tarte, Karin; Wendel, Hans-Guido

    2016-10-06

    The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous activation of B cell proliferation and drives the development of GC lymphomas in vivo. HVEM-deficient lymphoma B cells also induce a tumor-supportive microenvironment marked by exacerbated lymphoid stroma activation and increased recruitment of T follicular helper (T FH ) cells. These changes result from the disruption of inhibitory cell-cell interactions between the HVEM and BTLA (B and T lymphocyte attenuator) receptors. Accordingly, administration of the HVEM ectodomain protein (solHVEM (P37-V202) ) binds BTLA and restores tumor suppression. To deliver solHVEM to lymphomas in vivo, we engineered CD19-targeted chimeric antigen receptor (CAR) T cells that produce solHVEM locally and continuously. These modified CAR-T cells show enhanced therapeutic activity against xenografted lymphomas. Hence, the HVEM-BTLA axis opposes lymphoma development, and our study illustrates the use of CAR-T cells as "micro-pharmacies" able to deliver an anti-cancer protein. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Cyclin D3 expression in non-Hodgkin lymphoma. Correlation with other cell cycle regulators and clinical features

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Nielsen, O; Pedersen, Niels Tinggaard

    2001-01-01

    analyzed immunohistochemically for cyclin D3 expression. In 43 lymphomas (21.7%), cyclin D3 was overexpressed. T-cell lymphomas more frequently overexpressed cyclin D3 than B-cell lymphomas. Furthermore, cyclin D3-overexpressing indolent lymphomas were associated with higher proliferation rate, higher p21......Waf1 expression, lower p27Kip1 expression, and altered p53. Cyclin D3 overexpression identified a subgroup of patients with indolent B-cell lymphoma with adverse clinical features: patients were older, more frequently had "B" symptoms and extranodal involvement, and were more frequently in the high...

  3. Adult T-cell leukemia/lymphoma treatment in Bahia, Brazil

    Directory of Open Access Journals (Sweden)

    Pedro Dantas Oliveira

    Full Text Available Abstract Background: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes. Methods: Eighty-three adult T-cell leukemia/lymphoma patients (26 smoldering, 23 chronic, 16 acute, 13 lymphoma and five primary cutaneous tumoral with available data were included in this study. Results: Complete response was achieved in seven smoldering patients with symptomatic treatment, in two with chronic disease using antivirals/chemotherapy, in one with acute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide, doxorubicin, and prednisolone (VCAP; doxorubicin, ranimustine, and prednisolone (AMP; and vindesine, etoposide, carboplatin, and prednisolone (VECP]. Smoldering patients who received symptomatic treatment presented longer survival. Favorable chronic patients treated with antivirals presented longer survival compared to the unfavorable subtype. However, for the acute form, first-line chemotherapy was better, albeit without significance, than antivirals. Only one of the patients with lymphoma and primary cutaneous tumors responded. Conclusions: Watchful waiting associated with phototherapy represents the best option for smoldering adult T-cell leukemia/lymphoma with survival in Bahia being superior to that described in Japan. There was a trend of better results with zidovudine/interferon-alpha in favorable chronic disease. Excellent results were achieved in the lymphoma type treated with the LSG15 protocol. Patients are diagnosed late

  4. The relationship between HLA class II polymorphisms and somatic deletions in testicular B cell lymphomas of Dutch patients

    NARCIS (Netherlands)

    Riemersma, SA; Jordanova, ES; Haasnoot, GW; Drabbels, J; Schuuring, E; Schreuder, GMT; Kluin, PM

    2006-01-01

    Several risk factors including immune deficiencies, infections, and autoimmune diseases have been established for non-Hodgkin's lymphoma (NHL). For diffuse large B cell lymphoma (DLBCL), the most common type of lymphoma, no risk factors have been described, which may be due to the intrinsic

  5. NKT cell adjuvant-based tumor vaccine for treatment of myc oncogene-driven mouse B-cell lymphoma

    NARCIS (Netherlands)

    Mattarollo, Stephen R.; West, Alison C.; Steegh, Kim; Duret, Helene; Paget, Christophe; Martin, Ben; Matthews, Geoffrey M.; Shortt, Jake; Chesi, Marta; Bergsagel, P. Leif; Bots, Michael; Zuber, Johannes; Lowe, Scott W.; Johnstone, Ricky W.; Smyth, Mark J.

    2012-01-01

    Immunomodulators are effective in controlling hematologic malignancy by initiating or reactivating host antitumor immunity to otherwise poorly immunogenic and immune suppressive cancers. We aimed to boost antitumor immunity in B-cell lymphoma by developing a tumor cell vaccine incorporating

  6. Malignant T cells express lymphotoxin alpha and drive endothelial activation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Lauenborg, Britt; Christensen, Louise; Ralfkiaer, Ulrik

    2015-01-01

    Lymphotoxin α (LTα) plays a key role in the formation of lymphatic vasculature and secondary lymphoid structures. Cutaneous T cell lymphoma (CTCL) is the most common primary lymphoma of the skin and in advanced stages, malignant T cells spreads through the lymphatic to regional lymph nodes...... to internal organs and blood. Yet, little is known about the mechanism of the CTCL dissemination. Here, we show that CTCL cells express LTα in situ and that LTα expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTα functions as an autocrine factor by stimulating...... expression of IL-6 in the malignant cells. LTα and IL-6, together with VEGF promote angiogenesis by inducing endothelial cell sprouting and tube formation. Thus, we propose that LTα plays a role in malignant angiogenesis and disease progression in CTCL and may serve as a therapeutic target in this disease....

  7. An overview of cutaneous T cell lymphomas [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Nooshin Bagherani

    2016-07-01

    Full Text Available Cutaneous T cell lymphomas (CTCLs are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are characterized by a cutaneous infiltration of malignant monoclonal T lymphocytes. They typically afflict adults with a median age of 55 to 60 years, and the annual incidence is about 0.5 per 100,000. Mycosis fungoides, Sézary syndrome, and primary cutaneous peripheral T cell lymphomas not otherwise specified are the most important subtypes of CTCL. CTCL is a complicated concept in terms of etiopathogenesis, diagnosis, therapy, and prognosis. Herein, we summarize advances which have been achieved in these fields.

  8. Diffuse large B-cell lymphoma of the ocular adnexal region

    DEFF Research Database (Denmark)

    Rasmussen, Peter Kristian; Ralfkiaer, Elisabeth; Prause, Jan U

    2013-01-01

    III and ten patients (29%) presented with Stage IV lymphoma. The 5-year overall survival (OS) rate for the whole study group was 20%. The patients with Stage I lymphoma had a significantly better 5-year OS rate (28%) than patients in Stage II-IV (5-year OS rate, 9%). In Cox regression analysis......Purpose: To characterize the clinicopathological features of diffuse large B-cell lymphoma (DLBCL) of the ocular adnexal region. Methods: The present series of orbital and adnexal DLBCLs were found by searching the Danish Registry of Pathology between 1980 and 2009. Histological specimens were re......-seven per cent of the patients had unilateral ocular adnexal region involvement, and the orbit (76%) was the most frequently affected site. Nineteen patients (56%) presented with Stage I lymphoma. Of these, 18 were diagnosed with primary lymphoma. Four patients (12%) had Stage II, one patient (3%) had Stage...

  9. J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

    Science.gov (United States)

    Moore, Erika M; Swerdlow, Steven H; Gibson, Sarah E

    2017-10-01

    Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Imaging findings for intravascular large B-cell lymphoma of the liver

    Directory of Open Access Journals (Sweden)

    Jungmin Bae

    2015-09-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBCL is a rare subtype of extranodal diffuse large B-cell lymphoma that most commonly involves the central nervous system and skin. To our knowledge, no state-of-the art imaging findings have been reported for hepatic IVLBCL in the English literature. We report the first case of hepatic involvement of IVLBCL along with a literature review.

  11. PD-1, S-100 and CD1a expression in pseudolymphomatous folliculitis, primary cutaneous marginal zone B-cell lymphoma (MALT lymphoma) and cutaneous lymphoid hyperplasia.

    Science.gov (United States)

    Goyal, Amrita; Moore, Johanna B; Gimbel, Devon; Carter, Joi B; Kroshinsky, Daniela; Ferry, Judith A; Harris, Nancy L; Duncan, Lyn M

    2015-01-01

    Pseudolymphomatous folliculitis is a lymphoid proliferation that clinically and histopathologically mimics primary cutaneous extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In this study, we assessed the diagnostic value of three immunohistochemical markers, programmed death-1 (PD-1), CD1a and S100. We evaluated 25 cases of cutaneous lymphoid proliferations with established diagnoses, including 9 patients with pseudolymphomatous folliculitis, 11 with MALT lymphoma, and 5 with cutaneous lymphoid hyperplasia (CLH). The clinical, histopathologic and immunohistochemical characteristics were reviewed and three major characteristics assessed: (a) proportion of T cells expressing PD-1, (b) pattern of expression of CD1a by dendritic cells and (c) pattern of expression of S100 by dendritic cells. We found pseudolymphomatous folliculitis to have a significant increase in PD-1+ T cells compared with MALT lymphoma (p MALT lymphoma is significantly more likely to demonstrate a peripheral concentration of CD1a+ dendritic cells around lymphoid nodules than pseudolymphomatous folliculitis (p MALT lymphoma (p MALT lymphoma. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. High expression of LMO2 in Hodgkin, Burkitt and germinal center diffuse large B cell lymphomas

    International Nuclear Information System (INIS)

    Shams, T.M.

    2011-01-01

    The LMO 2 gene encodes a transcription factor that regulates key events in erythropoiesis, angio genesis, and embryogenesis and is highly expressed at the most immature stages of lymphopoiesis. Its implication in Hodgkin lymphoma (HL), Burkitt lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) is limited in the literature. Material and methods: An immunohistochemical study was performed on 68 lymphoma specimens showing different types including Hodgkin lymphoma (23), Burkitt lymphoma (10) and diffuse large B cell lymphoma (35). Also, seven specimens of the reactive nodal tissue were included as control. A monoclonal anti-human antibody has been used to detect LMO 2 . Results: LMO 2 was detected in all cases of HL (100%), in nine cases of BL (90%) and in all cases of DLBCL of germinal center (GC) subtype 20/35 (57.1%) but is completely negative in non-germinal center (NGC) DLBCL. In normal control of reactive nodes, LMO 2 was expressed in germinal center area but not expressed in other areas including mantle, marginal, or T cell zones. In DLBCL; there was no statistically significant relation between LMO 2 positive cases and the studied clinico pathological parameters including patient's age, sex and tumor site, stage and histological subtype. On the other hand, it was statistically significant regarding immuno phenotyping of GC versus N GC. Conclusions: LMO 2 expression is a special feature of GC DLBCL which can be used as a diagnostic marker and therapeutic target. Further studies regarding its prognostic role in patients are recommended.

  13. Two cases of uveitis masquerade syndrome caused by bilateral intraocular large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Jovanović Svetlana

    2013-01-01

    Full Text Available Introduction. Sometimes it is not easy to clinically recognize subtle differences between intraocular lymphoma and noninfectious uveitis. The most common lymphoma subtype involving the eye is B-cell lymphoma. Case report. We presented two patients aged 59 and 58 years with infiltration of the subretinal space with a large B-cell non-Hodgkin intraocular lymphoma. The patients originally had clinically masked syndrome in the form of intermediate uveitis. As it was a corticosteroid-resistant uveitis, we focused on the possible diagnosis of neoplastic causes of this syndrome. During hospitalization, the neurological symptoms emerged and multiple subretinal changes accompanied by yellowish white patches of retinal pigment epithelium with signs of vitritis, which made us suspect the intraocular lymphoma. Endocranial magnetic resonance imaging established tumorous infiltration in the region of the left hemisphere of the cerebellum. The histopathological finding confirmed the diagnosis of large B-cell non-Hodgkin lymphoma of risk moderate degree, immunoblast - centroblast cytological type. The other patient had clinical chronic uveitis accompanied by yellowish shaped white echographic changes of the retina and localized changes in the level of the subretina. The diagnosis of lymphoma was made by brain biopsy. Conclusion. Uveitis masquerade syndrome should be considered in all patients over 40 years with idiopathic steroid-resistant uveitis. Treatment begun on time can affect the course and improve the prognosis of uveitis masquerade syndrome (UMS and systemic disease.

  14. 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.

  15. 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

  16. Pharmacological inhibition of carbonic anhydrase XII interferes with cell proliferation and induces cell apoptosis in T-cell lymphomas

    NARCIS (Netherlands)

    Lounnas, Nadia; Rosilio, Célia; Nebout, Marielle; Mary, Didier; Griessinger, Emmanuel; Neffati, Zouhour; Chiche, Johanna; Spits, Hergen; Hagenbeek, Thijs J.; Asnafi, Vahid; Poulsen, Sally-Ann; Supuran, Claudiu T.; Peyron, Jean-François; Imbert, Véronique

    2013-01-01

    The membrane-bound carbonic anhydrase isoforms CAIX and CAXII, underpin a pH-regulating system that enables hypoxic tumor cell survival. Here, we observed for the first time an upregulation of CAXII in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LL) cells. First we showed that CAXII is

  17. 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...

  18. Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas.

    Science.gov (United States)

    Kokovic, Ira; Jezersek Novakovic, Barbara; Novakovic, Srdjan

    2015-03-01

    Analysis of the immunoglobulin κ light chain (IGK) gene is an alternative method for B-cell clonality assessment in the diagnosis of mature B-cell proliferations in which the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements fails. The aim of the present study was to evaluate the added value of standardized BIOMED-2 assay for the detection of clonal IGK gene rearrangements in the diagnostic setting of suspected B-cell lymphomas. With this purpose, 92 specimens from 80 patients with the final diagnosis of mature B-cell lymphoma (37 specimens), mature T-cell lymphoma (26 specimens) and reactive lymphoid proliferation (29 specimens) were analyzed for B-cell clonality. B-cell clonality analysis was performed using the BIOMED-2 IGH and IGK gene clonality assays. The determined sensitivity of the IGK assay was 67.6%, while the determined sensitivity of the IGH assay was 75.7%. The sensitivity of combined IGH+IGK assay was 81.1%. The determined specificity of the IGK assay was 96.2% in the group of T-cell lymphomas and 96.6% in the group of reactive lesions. The determined specificity of the IGH assay was 84.6% in the group of lymphomas and 86.2% in the group of reactive lesions. The comparison of GeneScan (GS) and heteroduplex pretreatment-polyacrylamide gel electrophoresis (HD-PAGE) methods for the analysis of IGK gene rearrangements showed a higher efficacy of GS analysis in a series of 27 B-cell lymphomas analyzed by both methods. In the present study, we demonstrated that by applying the combined IGH+IGK clonality assay the overall detection rate of B-cell clonality was increased by 5.4%. Thus, we confirmed the added value of the standardized BIOMED-2 IGK assay for assessment of B-cell clonality in suspected B-cell lymphomas with inconclusive clinical and cyto/histological diagnosis.

  19. 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.

  20. Prognosis of mature T cell lymphoma is poorer than that of diffuse large B cell lymphoma in IPI low-risk group, but not in intermediate- and high-risk groups.

    Science.gov (United States)

    Kihara, Rika; Watanabe, Tomoyuki; Yano, Takahiro; Uike, Naokuni; Okamura, Seiichi; Kawano, Fumio; Hanada, Shuichi; Sunami, Kazutaka; Inoue, Nobumasa; Sawamura, Morio; Yoshida, Shin-Ichiro; Shimomura, Takeshi; Kitano, Kiyoshi; Kojima, Yuki; Horibe, Keizo; Nagai, Hirokazu

    2013-01-01

    Mature T cell lymphoma has been noted for poor prognosis when compared with B cell lymphoma, even in the pre-rituximab era. To confirm this difference, a retrospective cohort study was conducted. One hundred-and nineteen patients with mature T cell lymphoma and 568 patients with diffuse large B cell lymphoma (DLBCL) who did not receive rituximab as first induction were studied. Overall survival (OS) was worse for patients with international prognostic index (IPI) scores indicating low-risk mature T cell lymphoma than for those with DLBCL (3-year OS 87 % vs. 58 %, P = 0.001), but not in other risk groups. Prognosis of mature T cell lymphoma was significantly poorer in the IPI low-risk group, as compared with DLBCL.

  1. Stem cells transplantation: clinical value of 18(F) FDG-PET/CT in lymphoma

    International Nuclear Information System (INIS)

    Peepre, Karan

    2012-01-01

    Stem cell transplantation (SCT) is a life saving procedure and advancement in medical procedure being used to treat diseases once thought incurable for a number of malignant and non-malignant life threatening diseases. Since its first successful use in 1968, SCT have been used to treat patients diagnosed with cancer. Lymphoma is classified as Hodgkin's disease (HD) (15%) or non-Hodgkin's lymphoma (NHL) (85%). Hodgkin's lymphoma is a type of lymphoma and very-very sensitive to radiotherapy and chemotherapy, first described by Thomas Hodgkin's in 1832. Hodgkin's lymphoma is characterized clinically by the orderly spread of disease from one node group to another and by the development of systemic symptoms with advanced disease. Pathologically, the disease is characterized by the presence of Reed-Sternberg cells. For HD, 10 years survival rates are 80-85% for the early stages and 40% for very advanced (stage IV) disease. Survival rates are much lower for NHL, with 60% 5 yr survival for the potentially curable tumours. Non-Hodgkin's lymphomas (NHLs) are a group of cancers that affect the immune system which is supposed to protect our body against disease. NHLs begin in the lymph nodes and are made up of malignant (cancerous) lymphocytes (either B cells or T cells). Cancer cells generally have a higher level of metabolic activity than normal tissues and use more glucose. 18 (F)-deoxy-D-glucose- positron emission tomography and computed tomography, called 18 (F) FDG-PET/CT, is widely used in clinical oncology. This tracer is a glucose analogue that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form is greatly elevated in rapidly growing malignant tumors). Evaluation of therapeutic response in Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL) patients with autologous stem cell transplantation (ASCT) is of great clinical significance in the cancer management. PET-CT has long been used to stage, restage, and evaluate the response of

  2. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.

    Science.gov (United States)

    Neelapu, Sattva S; Locke, Frederick L; Bartlett, Nancy L; Lekakis, Lazaros J; Miklos, David B; Jacobson, Caron A; Braunschweig, Ira; Oluwole, Olalekan O; Siddiqi, Tanya; Lin, Yi; Timmerman, John M; Stiff, Patrick J; Friedberg, Jonathan W; Flinn, Ian W; Goy, Andre; Hill, Brian T; Smith, Mitchell R; Deol, Abhinav; Farooq, Umar; McSweeney, Peter; Munoz, Javier; Avivi, Irit; Castro, Januario E; Westin, Jason R; Chavez, Julio C; Ghobadi, Armin; Komanduri, Krishna V; Levy, Ronald; Jacobsen, Eric D; Witzig, Thomas E; Reagan, Patrick; Bot, Adrian; Rossi, John; Navale, Lynn; Jiang, Yizhou; Aycock, Jeff; Elias, Meg; Chang, David; Wiezorek, Jeff; Go, William Y

    2017-12-28

    In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×10 6 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response. In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy

  3. Paraneoplastic Pemphigus and Bronchiolitis Obliterans in a Patient with Splenic B-cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Shiou-Han Wang

    2007-09-01

    Full Text Available Paraneoplastic pemphigus (PNP, also called paraneoplastic autoimmune multiorgan syndrome, is a rare disorder associated with underlying neoplasia. The common underlying neoplasms include non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and Castleman's disease. Though B-cell lymphoma is the most common underlying malignancy, only one case associated with splenic B-cell lymphoma has been recognized. The prognosis of PNP is very poor, and PNP-associated bronchiolitis obliterans (BO is not uncommon. Herein, we report a 44-year-old woman who initially presented with multiple oral ulcers, conjunctivitis, and numerous cutaneous blisters. Serial workup established the diagnosis of PNP and revealed an underlying splenic B-cell lymphoma. Although the mucocutaneous lesions gradually healed after splenectomy and chemotherapy, deteriorating respiratory function developed 7 months later with pathologically proven BO. She finally succumbed to respiratory failure 12 months after presentation despite intensive respiratory care.

  4. Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome

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    Vadim Gorodetskiy

    2016-01-01

    Full Text Available Sjögren’s syndrome (SS has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL. To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.

  5. 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

  6. Rapamycin Suppresses Tumor Growth and Alters the Metabolic Phenotype in T-Cell Lymphoma.

    Science.gov (United States)

    Kittipongdaja, Wasakorn; Wu, Xuesong; Garner, Justine; Liu, Xiping; Komas, Steven M; Hwang, Sam T; Schieke, Stefan M

    2015-09-01

    The mTOR pathway is a master regulator of cellular growth and metabolism. The biosynthetic and energetic demand of rapidly proliferating cells such as cancer cells is met by metabolic adaptations such as an increased glycolytic rate known as the Warburg effect. Herein, we characterize the anti-tumor effect of rapamycin in a mouse model of T-cell lymphoma and examine the metabolic effects in vitro. The murine T-cell lymphoma line, MBL2, and human cutaneous T-cell lymphoma (CTCL) lines, HH and Hut78, were used in syngeneic or standard NSG mouse models to demonstrate a marked suppression of tumor growth by rapamycin accompanied by inhibition of mTORC1/2. Analysis of the metabolic phenotype showed a substantial reduction in the glycolytic rate and glucose utilization in rapamycin-treated lymphoma cells. This was associated with reduced expression of glucose transporters and glycolytic enzymes in cultured cells and xenograft tumors. As a result of the decrease in glycolytic state, rapamycin-treated cells displayed reduced sensitivity to low-glucose conditions but continued to rely on mitochondrial oxidative phosphorylation (OXPHOS) with sensitivity to inhibition of OXPHOS. Taken together, we demonstrate that rapamycin suppresses growth of T-cell lymphoma tumors and leads to a reduction in aerobic glycolysis counteracting the Warburg effect of cancer cells.

  7. Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States

    Directory of Open Access Journals (Sweden)

    Lydia Hopp

    2015-09-01

    Full Text Available Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt’s lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12.

  8. Intestinal T-cell lymphoma with enteropathy-associated T-cell lymphoma-like features arising in the setting of adult autoimmune enteropathy.

    Science.gov (United States)

    Ciccocioppo, Rachele; Croci, Giorgio A; Biagi, Federico; Vanoli, Alessandro; Alvisi, Costanza; Cavenaghi, Giorgio; Riboni, Roberta; Arra, Mariarosa; Gobbi, Paolo G; Paulli, Marco; Corazza, Gino R

    2018-02-14

    Enteropathy-associated T-cell lymphoma is regarded as a dismal, late complication of coeliac disease, though a single case of T-cell lymphoma with such features arising in the setting of autoimmune enteropathy of the adult has been reported to date. We aim to describe the case of a 41-year-old woman complaining of severe malabsorption syndrome, who was diagnosed with autoimmune enteropathy based on the presence of flat intestinal mucosa unresponsive to any dietary restriction and positivity for enterocyte autoantibodies. Steroid therapy led to a complete recovery of both mucosal and clinical findings over 12 years, when disease relapse was accompanied by the appearance of monoclonal rearrangement of T-cell receptor-γ and peculiar T-cell phenotypic abnormalities, leading to a rapid transition to an overt T-cell lymphoma with features of the enteropathy-associated subtype. Despite intensive treatment, the patient developed cerebral metastasis and died 9 months later. Our case enhances the concept of enteropathy-associated T-cell lymphoma as a disease that may arise in the setting of enteropathies other than coeliac disease, thus representing a heterogeneous entity. Moreover, our observations support the need of a close follow-up of these patients, coupled with comprehensive characterization of mucosal biopsies. Copyright © 2018 John Wiley & Sons, Ltd.

  9. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Schmitz, Roland; Wright, George W; Huang, Da Wei; Johnson, Calvin A; Phelan, James D; Wang, James Q; Roulland, Sandrine; Kasbekar, Monica; Young, Ryan M; Shaffer, Arthur L; Hodson, Daniel J; Xiao, Wenming; Yu, Xin; Yang, Yandan; Zhao, Hong; Xu, Weihong; Liu, Xuelu; Zhou, Bin; Du, Wei; Chan, Wing C; Jaffe, Elaine S; Gascoyne, Randy D; Connors, Joseph M; Campo, Elias; Lopez-Guillermo, Armando; Rosenwald, Andreas; Ott, German; Delabie, Jan; Rimsza, Lisa M; Tay Kuang Wei, Kevin; Zelenetz, Andrew D; Leonard, John P; Bartlett, Nancy L; Tran, Bao; Shetty, Jyoti; Zhao, Yongmei; Soppet, Dan R; Pittaluga, Stefania; Wilson, Wyndham H; Staudt, Louis M

    2018-04-12

    Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88 L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).

  10. Subcutaneous 'lipoma-like' B-cell lymphoma associated with HCV infection: a new presentation of primary extranodal marginal zone B-cell lymphoma of MALT.

    Science.gov (United States)

    Paulli, M; Arcaini, L; Lucioni, M; Boveri, E; Capello, D; Passamonti, F; Merli, M; Rattotti, S; Rossi, D; Riboni, R; Berti, E; Magrini, U; Bruno, R; Gaidano, G; Lazzarino, M

    2010-06-01

    Hepatitis C virus (HCV) infection has been linked to lymphoproliferative disorders. Marginal zone B-cell lymphoma (MZL) represents one of the most frequent lymphoma subtypes associated with HCV infection. We describe an unusual subset of HCV-associated MZL characterized by subcutaneous presentation. A series of 12 HCV-positive patients presenting with subcutaneous nodules that revealed lymphoma infiltration at biopsy. Molecular analysis of immunoglobulin heavy chain (IGH) gene rearrangement and FISH investigations for t(11;18)(q21;q21) and t(14;18)(q32;q21) were carried out in nine patients. The 12 patients (median age 69.5 years), all with positive HCV serology, presented with single or multiple subcutaneous nodules resembling lipomas. Histologically the lesions showed lymphoid infiltrates, consistent with extranodal MZL of mucosa-associated lymphoid tissue (MALT). Functional IGH gene rearrangements were identified in nine tested patients, with somatic mutations in 82%, indicating a histogenesis from germinal center-experienced B cells. The t(11;18) was found in two of nine cases. Staging did not show any other lymphoma localization. In two patients, a response was achieved with antiviral treatment. Extracutaneous spread to MALT sites occurred in a case. Our observations expand the spectrum of HCV-associated lymphomas to include a subset of extranodal MZL characterized by a novel primary 'lipoma-like' subcutaneous presentation and indolent clinical course.

  11. Primary mediastinal large B-cell lymphoma arising from thyroid in a renal recipient with Hashimoto's thyroiditis.

    Science.gov (United States)

    Wu, Fang; Qu, Lu; Li, Dai-Qiang; Hu, Chun-Hong

    2015-01-01

    Primary mediastinal large B-cell lymphoma is a subtype of diffuse large B-cell lymphoma, arising in the mediastinum from putative thymic B-cell origin with distinctive clinical and genetic features. Generally, primary mediastinal large B-cell lymphoma is believed as only deriving in the mediastinum. The current study presents a rare case of primary mediastinal large B-cell lymphoma which arising from thyroid in a renal recipient with Hashimoto's thyroiditis. Moreover, we devoted a discussion to the relationship among primary mediastinal large B-cell lymphoma, immunomodulatory therapy and autoimmune diseases. The immunologic derangement induced by long-term immunomodulatory therapy and Hashimoto's thyroiditis may be the possible cause for the ectopic lymphoma.

  12. Diffuse large B-cell lymphoma of the kidney: A rare neoplasm

    Directory of Open Access Journals (Sweden)

    Ram Narayan Das

    2013-01-01

    Full Text Available Primary renal lymphoma is a rare neoplasm, but it should be kept in mind in the differential diagnosis of renal neoplasms. A middle aged man presented with symptoms of weight loss, anorexia and fullness of the abdomen after meals. On clinical and radiological examination, a renal mass was revealed and operated upon. A diagnosis of primary high grade renal lymphoma was made on histopathological examination and immunohistochemically it was further classified as diffuse large B-cell lymphoma. Unfortunately, the patient died after 5 months of diagnosis in spite of three cycles of chemotherapy following surgery. The pathological details of rare tumor are presented here.

  13. Chronic Lymphocytic Leukaemia/ Small-Cell Lymphocytic Lymphoma of the Lacrimal Sac: A Case Series.

    Science.gov (United States)

    Krishna, Yamini; Irion, Luciane D; Karim, Sozan; Dharmsena, Aruna; McCormick, Austin; Coupland, Sarah E

    2017-09-01

    Lymphomas of the lacrimal sac are rare, accounting for less than 10% of lacrimal sac malignant tumours. They may present with symptoms typical of secondary acquired nasolacrimal duct obstruction and are thus often misdiagnosed. Case series and literature review. Herein we describe 3 cases of chronic lymphocytic leukaemia (CLL)/small-cell lymphocytic lymphoma (SLL) of the lacrimal sac with immunohistochemical and in 1 case molecular confirmation. Lymphomas of the lacrimal sac should be suspected in patients with known CLL presenting with epiphora and dacryocystitis. During dacryocystorhinostomy, an incisional biopsy of the lacrimal sac is essential for confirming CLL/SLL involvement and may guide treatment.

  14. 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.

  15. Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2

    Science.gov (United States)

    2015-06-03

    Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Brain Stem Glioma; Ependymoblastoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Grade III Meningioma; Meningeal Hemangiopericytoma; Mixed Glioma; Pineal Gland Astrocytoma; Brain Tumor

  16. Primary Cutaneous Diffuse Large B-Cell Lymphoma – a Case Report

    Directory of Open Access Journals (Sweden)

    Milovanović Milena

    2017-06-01

    Full Text Available In 2005, the World Health Organization - European Organization for Research and Treatment of Cancer (WHOEORTC classified cutaneous B-cell lymphomas into 4 categories: primary cutaneous marginal zone B-cell lymphoma (PCMZL, primary cutaneous follicle center lymphoma (PCFCL, primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT, and primary cutaneous diffuse large B-cell lymphoma, other (PCDLBCL-O. The absence of evident extra-cutaneous disease is a necessary condition for the diagnosis of primary cutaneous B-cell lymphomas, because they have a completely different clinical behavior and prognosis from their nodal counterparts. PCDLBCL-O basically represents a morphological variation, lacking the typical features of PCDLBCLLT, neither confirming the definition of PCFCCL, but on the clinical ground, its behavior seems at least to partially overlap the indolent course of PCFCCL. In fact, the present WHO lymphoma classification from 2008 overcame the previous WHO-EORTC classification, including at least a part of PCDLBCL-O within the spectrum of PCFCCL. However, owing to the rarity and heterogeneity of the PCDLBCL-O, the precise clinicopathological characteristics have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Nevertheless, dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatment. We present a case of a 46-year-old Caucasian male with one large round-shaped tumor and a few scattered nodules localized on the back. The histopathological features of the lesion corresponded to PCDLBCL-O. The patient follow-up showed that he was disease-free three months after surgical excision of the lesions and adjuvant local radiotherapy. No additional therapy was introduced, including chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisolone (R-CHOP.

  17. A gene panel, including LRP12, is frequently hypermethylated in major types of B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Nicole Bethge

    Full Text Available Epigenetic modifications and DNA methylation in particular, have been recognized as important mechanisms to alter gene expression in malignant cells. Here, we identified candidate genes which were upregulated after an epigenetic treatment of B-cell lymphoma cell lines (Burkitt's lymphoma, BL; Follicular lymphoma, FL; Diffuse large B-cell lymphoma, DLBCL activated B-cell like, ABC; and germinal center like, GCB and simultaneously expressed at low levels in samples from lymphoma patients. Qualitative methylation analysis of 24 candidate genes in cell lines revealed five methylated genes (BMP7, BMPER, CDH1, DUSP4 and LRP12, which were further subjected to quantitative methylation analysis in clinical samples from 59 lymphoma patients (BL, FL, DLBCL ABC and GCB; and primary mediastinal B-cell lymphoma, PMBL. The genes LRP12 and CDH1 showed the highest methylation frequencies (94% and 92%, respectively. BMPER (58%, DUSP4 (32% and BMP7 (22%, were also frequently methylated in patient samples. Importantly, all gene promoters were unmethylated in various control samples (CD19+ peripheral blood B cells, peripheral blood mononuclear cells and tonsils as well as in follicular hyperplasia samples, underscoring a high specificity. The combination of LRP12 and CDH1 methylation could successfully discriminate between the vast majority of the lymphoma and control samples, emphasized by receiver operating characteristic analysis with a c-statistic of 0.999. These two genes represent promising epigenetic markers which may be suitable for monitoring of B-cell lymphoma.

  18. Management of cutaneous T cell lymphoma: new and emerging targets and treatment options

    Directory of Open Access Journals (Sweden)

    Li JY

    2012-03-01

    Full Text Available Janet Y Li1, Steven Horwitz2, Alison Moskowitz2, Patricia L Myskowski3, Melissa Pulitzer4, Christiane Querfeld31College of Physicians and Surgeons, Columbia University, 2Department of Medicine, Lymphoma Service, 3Department of Medicine, Dermatology Service, 4Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USAAbstract: Cutaneous T cell lymphomas (CTCL clinically and biologically represent a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the most common subtypes. Over the last decade, new immunological and molecular pathways have been identified that not only influence CTCL phenotype and growth, but also provide targets for therapies and prognostication. This review will focus on recent advances in the development of therapeutic agents, including bortezomib, the histone deacetylase inhibitors (vorinostat and romidepsin, and pralatrexate in CTCL.Keywords: novel targets, histone deacetylase inhibitors, pralatrexate, bortezomib, cutaneous T cell lymphoma

  19. Molecular Pathology of Adult T-Cell Leukemia/Lymphoma.

    Science.gov (United States)

    Ohshima, Koichi

    2015-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm of highly pleomorphic lymphoid cells. ATLL is usually widely disseminated, and it is caused by human T-cell leukemia virus type 1 (HTLV-1). It is a disease with a long latency, and affected individuals are usually exposed to the virus very early in life. The cumulative incidence of ATLL is estimated to be 2.5% among HTLV-1 carriers. ATLL cells express CD2, CD3, CD5, CD4, and CD25, as well as CCR4 and FoxP3 of the regulatory T-cell marker. HTLV-1 is causally linked to ATLL, but infection alone is not sufficient to result in neoplastic transformation. A significant finding in this connection is that the Tax viral protein leads to transcriptional activation of many genes, while the HTLV-1 basic leucine zipper factor is thought to be important for T-cell proliferation and oncogenesis. Half of ATLL cases retain the ability to express HTLV-1 Tax, which is a target of HTLV-1-specific cytotoxic T lymphocytes (CTL). An increase in HTLV-1-specific CTL responses is observed in some asymptomatic HTLV-1 carriers. Although HTLV-1-specific CTL are also present in the peripheral blood of ATLL patients, they do not expand sufficiently. We investigated the clinicopathological features and analyzed the staining of Tax-specific CTL and FoxP3. Tax-specific CTL correlated inversely with FoxP3, an increase in the ratio of CD163+ tumor-associated macrophages was associated with worse clinical prognosis, and ATLL cell lines proliferated significantly following direct co-culture with M2 macrophages. Several clinical variants of ATLL have been identified: acute, lymphomatous, chronic, and smoldering. Oligo-array comparative genomic hybridization revealed that genomic loss of 9p21.3 was a significant characteristic of acute-type, but not of chronic-type ATLL. Furthermore, we found that genomic alteration of CD58, which is implicated in immune escape, is more frequently observed in acute than in chronic ATLL. Interestingly

  20. 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

  1. Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition.

    Science.gov (United States)

    Yamazaki, Hiroki; Lai, Yu-Chang; Tateno, Morihiro; Setoguchi, Asuka; Goto-Koshino, Yuko; Endo, Yasuyuki; Nakaichi, Munekazu; Tsujimoto, Hajime; Miura, Naoki

    2017-01-01

    We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.

  2. Interleukin 21 - its potential role in the therapy of B-cell lymphomas.

    Science.gov (United States)

    Bhatt, Shruti; Sarosiek, Kristopher A; Lossos, Izidore S

    2017-01-01

    Interleukin-21 (IL-21), a member of IL-2 cytokine family, has pleotropic biological effects on lymphoid and myeloid cells. During the past 15 years, since the discovery of IL-21, great advances have been made regarding its biological activity and the mechanisms controlling IL-21-mediated cellular responses, especially in hematological malignancies. Preclinical studies have shown that IL-21R is expressed on healthy and neoplastic B-cells and exogenous IL-21 can induce direct apoptosis of IL-21R expressing B-cell non-Hodgkin lymphomas (NHL), making it a potentially attractive anti-lymphoma therapy. However, in some hematological malignancies such as multiple myeloma, Hodgkin lymphoma and Burkitt lymphoma, IL-21 can induce proliferation of neoplastic B-cells. In NHL, the underlying mechanism of cell death was found to be different between the various subtypes, including activation of different JAK/STAT signal transduction pathways or other factors. Immunomodulatory effects of IL-21 have also been reported to contribute to its anti-tumor effects as described by earlier studies in solid tumors and B-cell associated malignancies. These effects are predominantly mediated by IL-21's ability to activate cytolytic activities by NK-cells and CD4 + /CD8 + T-cells. In this review, we provide an overview of IL-21's effects in NHL, results from clinical trials utilizing IL-21, and propose how IL-21 can be therapeutically exploited for treating these lymphomas.

  3. [Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 27 cases].

    Science.gov (United States)

    Shi, Q Y; Feng, X; Chen, H; Ma, H H; Lu, Z F; Shi, Q L; Zhou, X J; Shen, Q

    2017-09-08

    Objective: To study the clinicopathologic characteristics and diagnostic criteria of primary mediastinal B-cell lymphoma (PMBL), and to distinguish PMBL from classic Hodgkin lymphoma(CHL) and systemic diffuse large B-cell lymphoma(DLBCL). Methods: The clinical features, histologic findings, results of immunohistochemical study and prgnosis in 27 PMBL cases were analyzed, with review of literature. Results: The age of patients ranged from 19 to 82 years (median age 34 years). All cases were located in the mediastinum and frequently accompanied by superior vein cava syndrome. Histologically, the tumor cells were pleomorphic and diffusely distributed. Clear cytoplasm and spindle tumor cells were seen in some cases. Varying amount of sclerosing stroma with collagen deposition was seen.Immunohistochemical study showed that the tumor cells were positive for CD20(100%, 27/27), CD30 (64.0%, 16/25), CD23 (77.3%, 17/22) and p63 (16/19). Clonal B cell gene rearrangement was seen. Conclusions: PMBL is a subtype of diffuse large B-cell lymphoma with various histomorphology. Immunohistochemistry can help to confirm the diagnosis, and the prognosis is better than diffuse large B cell lymphoma, not otherwise specified.

  4. Whole-exome and transcriptome sequencing of refractory diffuse large B-cell lymphoma

    OpenAIRE

    Park, Ha Young; Lee, Seung-Bok; Yoo, Hae-Yong; Kim, Seok-Jin; Kim, Won-Seog; Kim, Jong-Il; Ko, Young-Hyeh

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although rituximab therapy improves clinical outcome, some patients develop resistant DLBCL; however, the genetic alterations in these patients are not well documented. To identify the genetic background of refractory DLBCL, we conducted whole-exome sequencing and transcriptome sequencing for six patients with refractory and seven with responsive DLBCL. The average numbers of pathogenic somatic single nucle...

  5. Capgras syndrome associated with limbic encephalitis in a patient with diffuse large B-cell lymphoma

    OpenAIRE

    Soares Neto, Herval Ribeiro; Cavalcante, Wagner Cid Palmeira; Martins Filho, Sebastião Nunes; Smid, Jerusa; Nitrini, Ricardo

    2016-01-01

    We report the case of a patient with insidious onset and slowly progressive cognitive impairment, behavioral symptoms, temporal lobe seizures and delusional thoughts typical of delusional misidentification syndromes. Clinical presentation along with extensive diagnostic work-up revealed limbic encephalitis secondary to diffuse large B-cell lymphoma. The patient underwent immunotherapy with high-dose corticosteroid but no significant improvement was observed. No specific treatment for lymphoma...

  6. Iron Malabsorption in a Patient With Large Cell Lymphoma Involving the Duodenum

    Science.gov (United States)

    1992-01-01

    111-37. coeliac disease . Lancet 1960:1:192-4. 7. Shreeve DR. Horrocks P. Mainwaring AR. Steatorrhea and intra- 20. Green PA. Wollaeger EE. The clinical...compounded the anemia in a pa- tion in celiac disease were reversible by the institution tient with diffuse large cell lymphoma involving the of a gluten...hemoglobin. The lymphomas (5-7). The presenting symptoms mimic chest radiograph in May demonstrated an anterior me- those of celiac disease and include

  7. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

    DEFF Research Database (Denmark)

    Ralfkiaer, Ulrik; Hagedorn, Peter; Bangsgaard, Nannie

    2011-01-01

    Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL...... benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL....

  8. Meningeal marginal zone B-cell lymphoma: The meningioma trap.

    Science.gov (United States)

    Villeneuve, Alexandre; Rubin, François; Bonfils, Pierre

    2018-01-10

    To report a case of marginal zone MALT lymphoma of the temporal dura mater, initially mistaken for temporal meningioma. A 60-year-old immunocompetent woman, followed for more than 10 years for temporal meningioma causing vertigo and mixed hearing loss, presented with cervical lymphadenopathy, revealing marked progression of an intracranial lesion, leading to a diagnosis of marginal zone MALT lymphoma based on histological examination of a cervical lymph node. Treatment with 6 cycles of rituximab and bendamustine allowed complete remission of cervical lymph node and intracranial lesions, confirming the diagnosis of temporal dural mater lymphoma. Primary dural lymphoma must be part of the differential diagnosis of meningioma. Long-term follow-up allows correction of the diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells.

    Science.gov (United States)

    Katz, Samuel G; Labelle, James L; Meng, Hailong; Valeriano, Regina P; Fisher, Jill K; Sun, Heather; Rodig, Scott J; Kleinstein, Steven H; Walensky, Loren D

    2014-02-06

    Mantle cell lymphoma (MCL) is a highly aggressive B-cell lymphoma resistant to conventional chemotherapy. Although defined by the characteristic t(11;14) translocation, MCL has not been recapitulated in transgenic mouse models of cyclin D1 overexpression alone. Indeed, several genetic aberrations have been identified in MCL that may contribute to its pathogenesis and chemoresistance. Of particular interest is the frequent biallelic deletion of the proapoptotic BCL-2 family protein BIM. BIM exerts its pro-death function via its α-helical BH3 death domain that has the dual capacity to inhibit antiapoptotic proteins such as BCL-2 and MCL-1 and directly trigger proapoptotic proteins such as the mitochondrial executioner protein BAX. To evaluate a functional role for Bim deletion in the pathogenesis of MCL, we generated cyclin D1-transgenic mice harboring Bim-deficient B cells. In response to immunization, Eμ(CycD1)CD19(CRE)Bim(fl/fl) mice manifested selective expansion of their splenic mantle zone compartment. Three distinct immune stimulation regimens induced lymphomas with histopathologic and molecular features of human MCL in a subset of mice. Thus, deletion of Bim in B cells, in the context of cyclin D1 overexpression, disrupts a critical control point in lymphoid maturation and predisposes to the development of MCL. This genetic proof of concept for MCL pathogenesis suggests an opportunity to reactivate the death pathway by pharmacologic mimicry of proapoptotic BIM.

  10. 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.

  11. Mantle cell lymphoma relapsing at the lymphedematous arm.

    Directory of Open Access Journals (Sweden)

    Giuseppina Massini

    2013-02-01

    Full Text Available Lymphedema (LE is a chronic medical condition characterized by lymphatic fluid retention, resulting in tissue swelling. Cancer treatments involving lymph nodes can damage lymph drainage routes, causing accumulation of lymph fluid in the interstitial tissue of related limbs and body areas and secondary LE.  Basically, the LE has a negative impact on physical and mental quality of life. Moreover, 0.07-0.04% of long term survivors (most patients undergone mastectomy can develop the Stewart-Treves syndrome,  a rare and aggressive multifocal lymphangiosarcoma arising within the LE region. Here we describe a   45-year-old woman  with a massive LE of the left arm,  as a consequence of previous breast cancer,  who  was diagnosed after 4 years  of stage IV mantle cell lymphoma (MCL . The patient after obtaining complete remission with chemotherapy and ABMT  relapsed of MCL in lymphedema site.

  12. Central nervous system involvement in mantle cell lymphoma : clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network

    NARCIS (Netherlands)

    Cheah, C. Y.; George, A.; Gine, E.; Chiappella, A.; Kluin-Nelemans, H. C.; Jurczak, W.; Krawczyk, K.; Mocikova, H.; Klener, P.; Salek, D.; Walewski, J.; Szymczyk, M.; Smolej, L.; Auer, R. L.; Ritchie, D. S.; Arcaini, L.; Williams, M. E.; Dreyling, M.; Seymour, J. F.

    Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions.

  13. Plasmablastic transformation of low-grade B-cell lymphomas: report on 6 cases.

    Science.gov (United States)

    Martinez, Daniel; Valera, Alexandra; Perez, Nhora Silva; Sua Villegas, Luz Fernanda; Gonzalez-Farre, Blanca; Sole, Carla; Gine, Eva; Lopez-Guillermo, Armando; Roue, Gaël; Martinez, Salome; Sant, Francesc; Warzocha, Krzysztof; Robak, Tadeusz; Czader, Magdalena; Villamor, Neus; Colomo, Lluis; Campo, Elias; Martinez, Antonio

    2013-02-01

    Histologic transformation of low-grade B-cell lymphoma to diffuse large B-cell lymphoma is associated with poor prognosis. Although plasma cell differentiation is common in these lymphomas, an overt plasmablastic transformation (PBL-T) has been only rarely reported. We report 6 cases of PBL-T occurring in 3 chronic lymphocytic leukemias (CLL) and 3 follicular lymphomas. Five patients were men, and the mean age was 65 years (range, 52 to 72 y). None of them had history of immunodeficiency. In 3 cases the PBL-T occurred 34 to 85 months after the initial diagnosis, and in 3 it was detected simultaneously with the small cell component at diagnosis. All patients received chemotherapy after transformation, and 4 died 4 to 24 months after this diagnosis. In 3 cases, PBL-T occurred in an extranodal site. All PBL-Ts had immunoblastic morphology with admixed plasma cells, were CD20 and PAX5 negative, expressed λ light chain, and 5 were CD138 positive. All cases were negative for HHV8, and only 1 PBL-T was Epstein-Barr virus positive. Evidence of a clonal relationship between the small cell and PBL-T components was found in 5 cases. In 2 CLL cases, both components had 13q deletions, and in all follicular lymphoma cases both components harbored the t(14;18) translocation. MYC translocations were observed in 2 cases transformed from a CLL. In conclusion, PBL-T expands the clinicopathologic spectrum of the transformation of low-grade B-cell lymphomas. These transformed tumors are clinically, histologically, and phenotypically similar to primary plasmablastic lymphomas, but they are not associated with immunodeficiency and rarely have Epstein-Barr virus infection or MYC alterations.

  14. Perforated small intestine in a patient with T-cell lymphoma; a rare cause of peritonitis

    Directory of Open Access Journals (Sweden)

    Petrişor Banu

    2016-04-01

    Full Text Available The nontraumatic perforations of the small intestine are pathological entities with particular aspects in respect to diagnosis and treatment. These peculiarities derive from the nonspecific clinical expression of the peritonitis syndrome, and from the multitude of causes that might be the primary sources of the perforation: foreign bodies, inflammatory diseases, tumors, infectious diseases, etc. Accordingly, in most cases intestinal perforation is discovered only by laparotomy and the definitive diagnosis is available only after histopathologic examination. Small bowel malignancies are rare; among them, lymphomas rank third in frequency, being mostly B-cell non Hodgkin lymphomas. Only 10% of non-Hodgkin lymphomas are with T-cell. We report the case of a 57 years’ old woman with intestinal T-cell lymphoma, whose first clinical symptomatology was related to a complication represented by perforation of the small intestine. Laparotomy performed in emergency identified an ulcerative lesion with perforation in the jejunum, which required segmental enterectomy with anastomosis. The nonspecific clinical manifestations of intestinal lymphomas make from diagnosis a difficult procedure. Due to the fact that surgery does not have a definite place in the treatment of the small intestinal lymphomas (for cases complicated with perforation, and beyond the morbidity associated with the surgery performed in emergency conditions, prognosis of these patients is finally given by the possibility to control the systemic disease through adjuvant therapy.

  15. [Clinicopathological analysis of 23 cases of NK/T-cell lymphoma of nasal type].

    Science.gov (United States)

    Lu, Mingshen; Li, Fancai; Hou, Qiaoyan

    2009-01-01

    To improve the understanding of nasal NK/T-cell lymphoma by analyzing its phenotypic and clinicopathological features. Twenty-three cases of nasal NK/T-cell lymphoma diagnosed between 2003 and 2007 in the department of pathology of Guilin Medical College were included in the study. The expression level of TIA-1, CD56, CD3, CD20, CK and EBV markers was determined by immunohistochemistry. The results were correlated with clinicopathological features. 69.9% (16/23) of the nasal NK/T-cell lymphoma occurred in the nasal cavity. All the 23 cases displayed necrosis, ulceration and nose bleeding. 39.1% (9/23) showed angiodestructive growth pattern. 21.74% (5/23) were accompanied by squamous cell carcinoma-like epitheliomatous hyperplasia. All the cases were positive for TIA-1 and CD3. 95.7% (22/23) of the cases were positive for CD56, while 21.7% (5/23) were weakly positive for EBV. None of the cases was positive for either CD20 or CK. Nasal NK/T-cell lymphoma is characterized by multiple clinicopathological features. Attention is needed to differentiate the tumor from inflammatory lesions and low grade squamous cell carcinoma. Understanding of various morphological and phenotypic features (i.e. expression of TIA-1, CD56 and CD3, and lack of CD20 and CK) is the key for the diagnosis of nasal NK/T-cell lymphoma.

  16. Tackling mantle cell lymphoma (MCL: Potential benefit of allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Satish Shanbhag

    2010-07-01

    Full Text Available Satish Shanbhag1,2, Mitchell R Smith1, Robert VB Emmons21Department of Medical Oncology, Fox Chase Cancer Center, 2Division of Bone Marrow Transplantation, Temple University, Philadelphia, PA, USAAbstract: Mantle cell lymphoma (MCL is a type of non-Hodgkins lymphoma (NHL associated with poor progression-free and overall survival. There is a high relapse rate with conventional cytotoxic chemotherapy. Intensive combination chemotherapy including rituximab, dose intense CHOP- (cyclophosphamide-doxorubicin-vincristine-prednisone like regimens, high dose cytarabine, and/or consolidation with autologous stem cell transplant (autoSCT have shown promise in significantly prolonging remissions. Data from phase II studies show that even in patients with chemotherapy refractory MCL, allogeneic stem cell transplant (alloSCT can lead to long term disease control. Most patients with MCL are not candidates for myeloablative alloSCT due to their age, comorbidities, and performance status. The advent of less toxic reduced intensity conditioning (RIC regimens, which rely more on the graft-versus-lymphoma (GVL effect, have expanded the population of patients who would be eligible for alloSCT. RIC regimens alter the balance of toxicity and efficacy favoring its use. Treatment decisions are complicated by introduction of novel agents which are attractive options for older, frail patients. Further studies are needed to determine the role and timing of alloSCT in MCL. Currently, for selected fit patients with chemotherapy resistant MCL or those who progress after autoSCT, alloSCT may provide long term survival.Keywords: mantle cell lymphoma, allogeneic SCT, nonmyeloablative, GVL

  17. Binding of peanut lectin to germinal-centre cells: a marker for B-cell subsets of follicular lymphoma?

    OpenAIRE

    Rose, M. L.; Habeshaw, J. A.; Kennedy, R.; Sloane, J.; Wiltshaw, E.; Davies, A. J.

    1981-01-01

    The binding of horseradish-peroxidase-labelled peanut lectin (HRP-PNL) to cryostat sections of tonsil, lymphoma lymph nodes, reactive lymph nodes and miscellaneous tumours demonstrated that PNL binds selectively to lymphocytes in germinal centres. Lymph nodes from 21 patients with non-Hodgkin's lymphomas were phenotyped as cell suspensions for PNL binding, and the following surface markers: E rosetting, C3d, SIg, OK markers of T-cell subsets, Ig heavy-chain and light-chain classes. There was ...

  18. Molecular Cytogenetic Characterization Identified the Murine B-Cell Lymphoma Cell Line A-20 as a Model for Sporadic Burkitt's Lymphoma.

    Science.gov (United States)

    Guja, Karolina; Liehr, Thomas; Rincic, Martina; Kosyakova, Nadezda; Hussein Azawi, Shaymaa S

    2017-11-01

    Here, we report the first molecular cytogenetic characterization of the BALB/cAnN mouse derived B-cell non-Hodgkin lymphoma (B-cell NHL) cell lines A-20. Even though previously used as a model for testing of, for example, dexametason, up to present, no data in the genetic properties of A-20 were available. The present study closed this gap and provides evidence that A-20 is a model for B-cell NHL subgroup sporadic Burkitt's lymphoma. C-myc oncogene is involved in a translocation and copy number alterations as gain of murine 14q material could be observed. Interestingly, the cell line showed the karyotype 39,X,-X or -Y,t(2;15)(qE5;qD2),del(6)(qB3qC3),del(9)(qA3qA4),dup(14)(qE1qE4) in ~95% of the cells, being exceptionally stable for cell lines being established 38 years ago. Still, ~5% of the cells showed polyploidization followed by chromothripsis. It remains to be determined if this can be observed also in other cell lines, just has not been reported yet, and/or if it is a unique feature of A-20. Overall, finally here, the necessary genetic data to identify A-20 as a model for human sporadic Burkitt's lymphoma are provided.

  19. CD57+ T-cells are a subpopulation of T-follicular helper cells in nodular lymphocyte predominant Hodgkin lymphoma

    NARCIS (Netherlands)

    Sattarzadeh, Ahmad; Diepstra, Arjan; Rutgers, Bea; van den Berg, Anke; Visser, Lydia

    2015-01-01

    BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by lymphocyte-predominant (LP) cells in a background of CD4+ CD57+ T-cells. These cells are normally present in the germinal center of lymphoid tissues. The cells rosetting LP cells are described to be PD-1 and

  20. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy.

    Science.gov (United States)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-10-15

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Effects of oral iron chelator deferasirox on human malignant lymphoma cells.

    Science.gov (United States)

    Choi, Jong Gwon; Kim, Jung-Lim; Park, Joohee; Lee, Soonwook; Park, Seh Jong; Kim, Jun Suk; Choi, Chul Won

    2012-09-01

    Iron is essential for cell proliferation and viability. It has been reported that iron depletion by a chelator inhibits proliferation of some cancer cells. Deferasirox is a new oral iron chelator, and a few reports have described its effects on lymphoma cells. The goal of this study was to determine the anticancer effects of deferasirox in malignant lymphoma cell lines. Three human malignant lymphoma cell lines (NCI H28:N78, Ramos, and Jiyoye) were treated with deferasirox at final concentrations of 20, 50, or 100 µM. Cell proliferation was evaluated by an MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. Western blot analysis was performed to determine the relative activity of various apoptotic pathways. The role of caspase in deferasirox-induced apoptosis was investigated using a luminescent assay. The MTT assay showed that deferasirox had dose-dependent cytotoxic effects on all 3 cell lines. Cell cycle analysis showed that the sub-G1 portion increased in all 3 cell lines as the concentration of deferasirox increased. Early apoptosis was also confirmed in the treated cells by Annexin V and PI staining. Western blotting showed an increase in the cleavage of PARP, caspase 3/7, and caspase 9 in deferasirox-treated groups. We demonstrated that deferasirox, a new oral iron-chelating agent, induced early apoptosis in human malignant lymphoma cells, and this apoptotic effect is dependent on the caspase-3/caspase-9 pathway.

  2. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    International Nuclear Information System (INIS)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-01-01

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  3. Mulberry cells in the thyroid: warthin-finkeldey-like cells in hashimoto thyroiditis-associated lymphoma.

    Science.gov (United States)

    Lapadat, Razvan; Nam, Moon Woo; Mehrotra, Swati; Velankar, Milind; Pambuccian, Stefan E

    2017-03-01

    Warthin-Finkeldey type giant cells were first described in autopsies performed on young children who died during the highly lethal measles epidemic in Palermo during the winter of 1908. The cells had 8-15 nuclei without identifiable cytoplasm within the germinal centers of lymphoid organs resembling megakaryocytes. We describe a case of Hashimoto thyroiditis with an enlarging substernal throid mass. The resection specimen contained many Warthin-Finkeldey-Like Cells (WFLC) in an extranodal marginal zone lymphoma (MALT type) with focal transformation to diffuse large B-cell lymphoma. The WFLC showed nuclear features similar to those of neighboring follicular dendritic cells (FDCs), favoring the hypothesis that these cells might be the product of fusion of FDCs. This is supported by immunostaining results and the occurrence of similar cells in follicular dendritic cell sarcomas and in "dysplastic" FDCs in hyaline vascular type Castleman disease, a possible precursor of follicular dendritic cell tumors. Diagn. Cytopathol. 2017;45:212-216. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Pentoxifylline inhibits tumor necrosis factor-alpha (TNF alpha)-induced T-lymphoma cell adhesion to endothelioma cells.

    Science.gov (United States)

    Weiss, J M; Vanscheidt, W; Pilarski, K A; Weyl, A; Peschen, M; Schöpf, E; Vestweber, D; Simon, J C

    1995-05-01

    Pentoxifylline, a methylxanthine derivative, has been shown to inhibit T-cell-mediated cutaneous immune response by yet ill-understood mechanisms. Because cell adhesion to endothelial cells is a critical step in the initiation of such immune responses, we analyzed whether pentoxifylline would affect this process. To address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2), either untreated or stimulated with tumor necrosis factor-alpha (TNF alpha), was studied. Pentoxifylline reduced the ability of endothelioma cells stimulated with different concentrations of TNF alpha, but not of untreated endothelioma cells, to bind T-lymphoma cells in dose-dependent (10(-5)-10(-3) M) fashion. Selective incubation of either endothelioma cells or T-lymphoma cells revealed that pentoxifylline acted exclusively on the endothelioma cells, even when added after TNF alpha stimulation. We questioned whether pentoxifylline suppressed T-lymphoma cell/endothelioma cell interactions by interfering with adhesion molecules expressed by either cell. However, as determined by flow cytometry, pentoxifylline did not alter TNF alpha-induced upregulation of intercellular adhesion molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or alpha 4-integrin expression on T-lymphoma cells, suggesting that rather than affecting quantitative expression of these adhesion molecules, pentoxifylline might modulate their avidity. We conclude that pentoxifylline in therapeutically achievable concentrations is a potent inhibitor of TNF alpha-induced T-lymphoma cell adhesion to endothelioma cells. This finding may account, at least in part, for the recently discovered anti-inflammatory action of pentoxifylline.

  5. A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma).

    Science.gov (United States)

    Kiesewetter, Barbara; Troch, Marlene; Dolak, Werner; Müllauer, Leonhard; Lukas, Julius; Zielinski, Christoph C; Raderer, Markus

    2013-03-01

    Mucosa associated lymphoid tissue lymphoma shares certain features with multiple myeloma. In view of this and the activity of lenalidomide in various B-cell lymphomas, we have initiated a phase II study of lenalidomide in patients with mucosa associated lymphoid tissue lymphoma. Patients with histologically verified advanced stages of this lymphoma were included in the study. Treatment consisted of oral lenalidomide 25 mg Days 1-21, with a 7-day break after each cycle. A total of 18 patients were included in the trial: 5 had gastric and 13 had extragastric mucosa associated lymphoid tissue lymphoma, but 2 discontinued therapy during the first course of therapy. In the intent to treat analysis, an overall response rate of 61% was seen (11 of 18; 6 complete and 5 partial remissions). Three patients had stable disease while 2 progressed. Side effects were manageable and included neutropenia (grade III in 3 patients) as the leading hematotoxicity. After a median follow up of 20.3 months, one patient has died from lymphoma while the remaining patients are alive and relapse-free. These data suggest activity of lenalidomide monotherapy in mucosa associated lymphoid tissue lymphoma. The study protocol had been approved by the Ethical Board of the Medical University Vienna (EK-No.: 146/09), and before opening the trial, it had been registered at www.clinicaltrials.gov. (identifier: NCT00923663).

  6. Targeting B-cell non Hodgkin lymphoma: New and old tricks.

    Science.gov (United States)

    Solimando, Antonio Giovanni; Ribatti, Domenico; Vacca, Angelo; Einsele, Hermann

    2016-03-01

    The management of B-cell malignancies continues to pose a clinical challenge. In the past years, rituximab (anti-CD20) emerged as the standard of care in the induction treatment of follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL), as well as in other subsets. Since the benefits of immuno-chemotherapy have been clearly demonstrated in a whole range of lymphomas, several innovative approaches are being explored to achieve significant responses, particularly in refractory B-cell non-Hodgkin lymphoma (NHL) cases. Studies of the comparative effectiveness and structure/function relationship of therapeutic monoclonal antibodies, together with an increased understanding of the molecular features of NHLs, have led to the development of a range of novel therapies, many of which target the tumor in a tailored fashion. Although several molecules can help clinicians to dissect the pathological mechanisms acting in the natural history of the disease, the main purpose of this review emphasize the recent developments in targeting the B-cell NHLs surface. These novel approaches are illustrated, and the new intriguing opportunities offered by bispecific antibodies and antibody-associated immune modulation are addressed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Cytotoxicity of arctigenin and matairesinol against the T-cell lymphoma cell line CCRF-CEM.

    Science.gov (United States)

    Su, Shan; Cheng, Xinlai; Wink, Michael

    2015-09-01

    Arctigenin and matairesinol possess a diversity of bioactivities. Here we investigated the cytotoxicity of arctigenin and matairesinol against a T-cell lymphoma cell line CCRF-CEM and the underlying mechanisms that have not been explored before. The cytotoxic activity was investigated using MTT assay. The cell cycle arrest and reactive oxygen species (ROS) accumulation were determined by flow cytometric analysis. The apoptosis induction was assessed using Annexin V/Propidium Iodide assay. The gene quantification analysis was measured through real-time polymerase chain reaction. Arctigenin and matairesinol exhibited significant antiproliferative activity against CCRF-CEM cells after 72 h treatment with IC50 values of 1.21 ± 0.15 μm and 4.27 ± 0.41 μm, respectively. In addition, both lignans arrest CCRF-CEM cells in the S phase. Furthermore, they could induce apoptosis in CCRF-CEM cells in a concentration- and time-dependent manner. Interestingly, the lignans differentially regulated the expression of several key genes involved in apoptosis pathways, including Bax, Bad and caspase-9. Moreover, both lignans could increase ROS levels in CCRF-CEM cells. Our study provides an insight into the potential of arctigenin and matairesinol as good candidates for the development of novel agents against T-cell lymphoma. © 2015 Royal Pharmaceutical Society.

  8. 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

  9. Case of Small Bowel Perforation due to Enteropathy-Type T-Cell Lymphoma

    Science.gov (United States)

    Kim, Yong Seok; Park, Jun Seok; Kim, Beom Gyu; Cha, Seong Jae; Chi, Kyong Choun; Park, Sung Jun; Chang, In Taik; Park, Sung Il

    2009-01-01

    Enteropathy-type T-cell lymphoma (ETTL) is a rare disease with a poor prognosis. According to the World Health Organization (WHO) classification, it is a subtype of the peripheral T-cell lymphomas. This disease is associated with gluten-sensitive enteropathy, has a high risk of intestinal perforation and obstruction, and is refractory to chemotherapeutic treatment. We report the case of a 73-year-old woman who was diagnosed with enteropathy-type T-cell lymphoma of the small intestine, which was positive for the markers of cytotoxic T cells, CD3, CD8, and CD56, on immunohistochemical staining after resection of the perforated terminal ileum. PMID:20046432

  10. A rare case of signet ring cell lymphoma: Diagnosis aided by immunofluorescent staining

    Directory of Open Access Journals (Sweden)

    Charusheela R Gore

    2017-01-01

    Full Text Available Signet ring cell lymphomas are the proliferations of malignant lymphoid cells containing cytoplasmic vacuoles or globules which displace the nuclei, imparting it a signet ring appearance. This rare tumor is a variant of non-Hodgkin lymphoma. Signet ring appearance is due to cytoplasmic accumulation of immunoglobulin or vacuoles derived from multivesicular bodies. These cells, particularly with cytoplasmic vacuoles, may be mistaken for adenocarcinoma cells. We are presenting one such case where immunofluorescence helped us to demonstrate the immunoglobulins on fine needle aspiration smears. This is an innovative technique and has not been reported earlier. Our aim of presenting this case is to review the awareness of this rare lymphoma among pathologists to give due consideration for avoiding inappropriate investigations and treatment.

  11. Brazilian experience using high dose sequential chemotherapy followed by autologous hematopoietic stem cell transplantation for malignant lymphomas

    Directory of Open Access Journals (Sweden)

    Bruno Kosa Lino Duarte

    2011-12-01

    Full Text Available OBJECTIVE: To evaluate the use of high-dose sequential chemotherapy in a Brazilian population. METHODS: High-dose cyclophosphamide followed by autologous hematopoietic stem cell transplantation is an effective and feasible therapy for refractory/relapsed lymphomas; this regimen has never before been evaluated in a Brazilian population. All patients (106 with high-grade non-Hodgkin lymphoma and 77 with Hodgkin's lymphoma submitted to this treatment between 1998 and 2006 were analyzed. Chemotherapy consisted of the sequential administration of high-dose cyclophosphamide (4 or 7 g/m² and granulocyte-colony stimulating factor (300 µg/day, followed by peripheral blood progenitor cell harvesting, administration of etoposide (2g/m² and methotrexate (8 g/m² only for Hodgkin's lymphoma and autologous hematopoietic stem cell transplantation. RESULTS: At diagnosis, non-Hodgkin lymphoma patients had a median age of 45 (range: 8-65 years old, 78% had diffuse large B-cell lymphoma and 83% had stage III/IV disease. The Hodgkin's lymphoma patients had a median age of 23 (range: 7-68 years old, 64.9% had the nodular sclerosis subtype and 65% had stage III/IV disease. Nine Hodgkin's lymphoma patients (13% and 10 (9% non-Hodgkin lymphoma patients had some kind of cardiac toxicity. The overall survival, disease-free survival and progression-free survival in Hodgkin's lymphoma were 29%, 59% and 26%, respectively. In non-Hodgkin lymphoma, these values were 40%, 49% and 31%, respectively. High-dose cyclophosphamide-related mortality was 10% for Hodgkin's lymphoma and 5% for non-Hodgkin lymphoma patients. High-dose cyclophosphamide dosing had no impact on toxicity or survival for both groups. CONCLUSIONS: Despite a greater prevalence of poor prognostic factors, our results are comparable to the literature. The incidence of secondary neoplasias is noteworthy. Our study suggests that this approach is efficient and feasible, regardless of toxicity-related mortality.

  12. Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice

    International Nuclear Information System (INIS)

    Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

    1980-01-01

    The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable

  13. Hepatosplenic Gamma/DeltaT-Cell Lymphoma Masquerading as Alcoholic Hepatitis and Methadone Withdrawal

    Directory of Open Access Journals (Sweden)

    H.A. Lopez Morra

    2007-09-01

    Full Text Available Hepatosplenic gamma/delta T-cell lymphoma is a rare neoplasm of mature gamma/delta T-cells with sinusoidal infiltration of spleen, liver, and bone marrow. Patients are predominantly adolescent and young adult males and usually present with marked hepatosplenomegaly. Pancytopenia is another common finding. Despite an initial response to treatment, patients have a median survival of one to two years. In this report, we document a case of alcoholic hepatitis and methadone withdrawal masquerading unsuspected, hepatosplenic gamma/delta T-cell lymphoma with unusual CD20 positivity.

  14. Subcutaneous panniculitis-like T-cell lymphoma: MRI features and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Levine, Benjamin D.; Seeger, Leanne L.; Motamedi, Kambiz [UCLA-Santa Monica Medical Center and Orthopedic Hospital, Department of Radiological Sciences, Santa Monica, CA (United States); James, Aaron W. [UCLA-Santa Monica Medical Center and Orthopedic Hospital, Department of Pathology and Laboratory Medicine, Santa Monica, CA (United States)

    2014-09-15

    Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) represents a rare subclassification of peripheral T-cell lymphoma (PTCL). We present a case of a 21-year-old female who presented with a 1-month history of pain in the left buttock and hip, tender left inguinal lymph nodes, fevers, and night sweats. Percutaneous core needle biopsy was diagnostic for SPTCL with CD8+ cells positive for cytotoxic granules. Magnetic resonance imaging (MRI) features of SPTCL with a review of the literature are discussed. (orig.)

  15. Primary B cell lymphoma of the tongue base: a case report.

    Science.gov (United States)

    Bechir, Achour; Asma, Achour; Haifa, Regaieg; Nesrine, Abdessayed; Yosra, Ben Youssef; Badreddine, Sriha; Abderrahim, Khelif

    2016-01-01

    Primary non-Hodgkin's lymphoma's of the tongue is very rare and accounts for 1% of all malignant tumor of the oral cavity. Clinical features are non-specific ulcerative lesions that do not heal. In the literature, the majority of cases are diffuse large B cell type however, T cell phenotype also may occur. We describe a 77 years old man, who presented with an ulcerative mass in the left margin of the tongue the diagnosis diffuse large B cell lymphoma was confirmed. The patient is actually on treatment R-mini CEOP and has favorable evolution.

  16. Mantle cell lymphoma: 2012 update on diagnosis, risk-stratification, and clinical management.

    Science.gov (United States)

    Vose, Julie M

    2012-06-01

    Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood, and bone marrow with a short remission duration to standard therapies and a median overall survival of 4-5 years. Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t(11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98% of cases. The absence of SOX-11 or a low Ki-67 may correlate with a more indolent form of MCL. The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma. The mantle cell lymphoma international prognostic index (MIPI) is the prognostic model most often used and incorporates ECOG performance status, age, leukocyte count, and lactic dehydrogenase. A modification of the MIPI also adds the Ki-67 proliferative index if available. The median overall survival (OS) for the low-risk group was not reached (5-year OS of 60%). The median OS for the intermediate risk group was 51 and 29 months for the high-risk group. For selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a cytarabine containing regimen ± autologous stem cell transplantation should be considered. For older MCL patients with intermediate or high risk MIPI, combination chemotherapy with R-CHOP, R-Bendamustine, or a clinical trial should be considered. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor), BTK inhibitors or CAL-101 (B-cell receptor inhibitors) or lenalidamide (antiangiogenesis) have clinical activity in MCL patients. Autologous or allogeneic stem cell transplantation can also be considered in young patients. Copyright © 2012

  17. Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

    2010-01-01

    -cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

  18. 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

  19. The outcome of primary mediastinal large B-cell lymphoma

    International Nuclear Information System (INIS)

    Fang Hui; Li Yexiong; Qi Shunan; Liu Qingfeng; Wang Shulian; Jin Jing; Wang Weihu; Song Yongwen; Liu Xinfan; Yu Zihao

    2008-01-01

    Objective: To investigate the treatment outcome and failure in patients with primary mediastinal large B-cell lymphoma(PMBL). Methods: Between Jan. 1992 and Oct. 2006, a total of 46 patients with pathologically confirmed PMBL were reviewed, including 14 with Ann Arbor Stage I disease, 23 with Stage II disease, 3 with Stage III disease and 6 with Stage IV disease. Stage I + II disease was present in 80% of the patients. All patients were treated with chemotherapy, and 29 also received radiotherapy. Twenty-seven patients (59%) were treated with first generation regimen (CHOP), 9 (20%) with third generation regimens (MACOP-B, ProMACE/CytaBOM, m-BACOD, or ProMACE-MOPP), and 10 (22%) with high-dose chemotherapy (HDCT/APBSCT). Rituximab was administered to 16 patients (35%). For most patients who received radiotherapy, an involved field was used with a median dose of 45 Gy in 23 fractions. Results: The rate of complete remission, partial remission and progression disease was 41%, 30% and 24%, respectively. The 5-year overall survival rate (OS) for all patients was 35%. The 2- and 5-year OS was 79% and 63% for stage I + II and 51% and 0 for stage III + IV, respectively (χ 2 =4.35,P=0.037). The 2-year progression free survival rate was 63% and 11%, respectively(χ 2 =17.77, P=0.000). The 5- year OS was 80% for the patients with CR, 50% for those with PR, and 0 for those with progression disease (χ 2 =19.58, P=0.003). With a median follow-up of 22 months, progression disease and relapse occurred in 19 patients. Conclusions: Survival of patients with advanced stage PMBL is poor. Further studies are needed to confirm the optimal treatment. Radiotherapy often plays a pivotal role in local control. (authors)

  20. Breast Cancer Mimic: Cutaneous B-Cell Lymphoma Presenting as an Isolated Breast Mass

    Directory of Open Access Journals (Sweden)

    Margaret Taghavi

    2014-10-01

    Full Text Available Background: Primary cutaneous B-cell lymphoma typically localizes to the skin, and dissemination to internal organs is rare. Lymphomatous involvement of the breasts is also rare. We describe the clinical and radiological findings of an unusual case of primary cutaneous B-cell lymphoma presenting as an isolated breast mass without associated skin changes. Case Presentation: The patient was a 55-year-old Caucasian female who initially presented with cutaneous B-cell lymphoma around her eyes and forehead with recurrence involving the skin between her breasts. Three years after terminating treatment due to a lack of symptoms, she presented for an annual screening mammogram that found a new mass in her upper inner right breast without imaging signs of cutaneous extension. On physical examination, there were no corresponding skin findings. Due to the suspicious imaging features of the mass that caused concern for primary breast malignancy, she underwent a core biopsy which revealed cutaneous B-cell lymphoma. Conclusion: When evaluating patients with a systemic disease who present with findings atypical for that process, it is important to still consider the systemic disease as a potential etiology, particularly with lymphoma given its reputation as a great mimicker.

  1. B-cell lymphoma of the heart: A rare diagnosis.

    Science.gov (United States)

    Matos, António P; Palas, João; Doulaptsis, Constantinos; Ramalho, Miguel; Duarte, Sérgio; Bogaert, Jan

    2014-12-01

    We present a case of a primary cardiac lymphoma in a 60-year-old woman. The clinical presentation was non-specific and the diagnosis was suggested by its appearance on multidetector computed tomography. The final diagnosis was achieved by histopathological study and was corroborated by a decrease in tumor volume after targeted chemotherapy. A brief review of the appearance of primary cardiac lymphomas in imaging studies is presented. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  2. Cutaneous T-cell lymphoma in a patient infected with human immunodeficiency virus type 1. Use of radiation therapy

    International Nuclear Information System (INIS)

    Goldstein, J.; Becker, N.; DelRowe, J.; Davis, L.

    1990-01-01

    A patient with cutaneous T-cell lymphoma (CTCL) and acquired immune deficiency syndrome (AIDS) is presented. The patient had a localized lesion on his scalp. Evaluation for systemic lymphoma was negative. A biopsy specimen showed superficial and deep dermal infiltrates of pleomorphic lymphocytes. Immunohistochemistry was consistent with T-cell lymphoma. The patient was treated successfully with local irradiation. He remained free of further systemic and cutaneous recurrences of the lymphoma until he died 8 months after treatment of pneumonia. This case is the first to our knowledge to describe a localized CTCL in a patient infected with human immunodeficiency virus type 1 (HIV-1)

  3. Diffuse aggressive B-cell lymphomas of the gastrointestinal tract. An immunophenotypic and gene rearrangement analysis of 22 cases

    NARCIS (Netherlands)

    van Krieken, J. H.; Medeiros, L. J.; Pals, S. T.; Raffeld, M.; Kluin, P. M.

    1992-01-01

    Twenty-two diffuse aggressive B-cell lymphomas of the gastrointestinal tract were studied using light microscopic examination, immunohistochemical methods, and Southern blot analysis. The results suggest that diffuse aggressive B-cell gastrointestinal tract lymphomas may be divided into two groups:

  4. Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON)

    DEFF Research Database (Denmark)

    Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin

    2018-01-01

    on either regimen alone. METHODS: In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group......BACKGROUND: Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data....... The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials.gov, number NCT02460276. FINDINGS: Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark...

  5. Spontaneous regression of primary diffuse large B-cell lymphoma, leg type.

    Science.gov (United States)

    Alcántara-González, J; González-García, C; Fernández-Guarino, M; Jaén-Olasolo, P

    2014-01-01

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT) accounts for approximately 20% of all primary cutaneous B-cell lymphomas and tends to present as infiltrated nodules, tumors, and plaques on the legs in the elderly. Unlike other primary cutaneous large B-cell lymphomas, it has a poor prognosis and tends to require treatment with systemic chemotherapy. We present the case of an 82-year-old patient with a 1-year history of nodules and plaques on her right leg. Biopsy led to a diagnosis of PCLBCL LT and the lesions resolved without treatment within 1 month of the first visit. This is an atypical course of PCLBCL LT and we believe that it is the first such case to be reported in the literature. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  6. Advances in the role of cytogenetic analysis in the molecular diagnosis of B-cell lymphomas.

    Science.gov (United States)

    Grange, Béatrice; Callet-Bauchu, Evelyne; Salles, Gilles; Sujobert, Pierre

    2017-06-01

    Cytogenetic abnormalities represent essential determinants of diagnosis and prognosis in B-cell lymphomas. Their theranostic value is increasingly significant with the development of targeted therapies, in order to adapt the treatment at diagnosis as well as when relapse occurs. Areas covered: As the significance of these biomarkers is influenced by the technology used to detect them, an overview describing the strength and weakness of conventional and emerging technologies is provided. This review also updates the diverse cytogenetic abnormalities found in B-cell lymphomas, emphasizing their value in treatment decision. Expert commentary: Cytogenetics remains an essential analysis for the diagnostic work-up of lymphomas. As whole genome sequencing becomes more and more affordable routinely, the next challenge will be to recover all the information conveyed by conventional karyotype, including the analysis of the clonal architecture at the single cell level, in whole genome data.

  7. [Primary cutaneous T-cell lymphoma of the penis complicated by Fournier gangrene: a case report].

    Science.gov (United States)

    Zhou, Zun-lin; Wang, Chuan-yun; Xu, Zhi-shun; Zheng, Bao-zhong

    2008-06-01

    To explore the clinical presentation, pathologic characteristics, diagnosis and treatment of cutaneous T-cell lymphoma of the penis. A 49-year-old man presented with painful swelling and inflammation of the foreskin, failed to respond to antibiotic treatment and dorsal incision, and was instead complicated by Fournier gangrene. Then he underwent debridement and pathological examination. Pathological results indicated cutaneous T-cell lymphoma of the penis. Immunohistochemistry showed CD3 and CD45 RO to be positive, but CD30, CD79a, CD20 and HMB negative. The patient was treated by interferon alpha and ultraviolet B for 2 weeks, followed by total removal of the external genitalia because of necrosis of the corpus spongiosum, which involved the scrotum and right testis on pathological examination. Cutaneous T-cell lymphoma of the penis is a rare condition and easily mis diagnosed in the early phase. Definitive diagnosis depends on pathological study.

  8. Implementation and importance of fluorescence in situ hybridization (fish) in paraffin tissues for categorization of B-cell lymphoma unclassifiable, with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Carvajal Cuenca, Alejandra

    2011-01-01

    The diagnostic criteria have been defined based on the tools that the country has acquired and international guidelines for pure entities: the LB, LDCGB, and the new entity of B lymphoma unclassifiable with features intermediate LDCGB and LB. The fluorescence in situ hybridization for the translocation (8;14) has been implemented in paraffin tissues for proper categorization. A total of 21 cases have been studied: the characteristics of patients, morphology, immunohistochemistry and the presence or absence of the translocation (8;14). Twelve of the cases have been classified as B-cell lymphoma unclassifiable with features intermediate between LDCGB and LB. Furthermore, nine of the cases were classified in LB. Fluorescence in situ hybridization (FISH) has been negative in 5 of the 21 cases. The diagnosis of lymphoma with features bordering between the LB and the LDCGB has been imperative for the survival of the patient and the corresponding treatment [es

  9. EBV-positive diffuse large B-cell lymphoma of the elderly

    NARCIS (Netherlands)

    C.Y. Ok (Chi Young); T.G. Papathomas (Thomas); L.J. Medeiros (L. Jeffrey); K.H. Young (Ken)

    2013-01-01

    textabstractEpstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly, initially described in 2003, is a provisional entity in the 2008World Health Organization classification system and is defined as an EBV-positive monoclonal large B-cell proliferation that occurs in

  10. Clinical and pathological features of testicular diffuse large B-cell lymphoma : a heterogeneous disease

    NARCIS (Netherlands)

    Kuper-Hommel, Marion J. J.; Janssen-Heijnen, Maryska L. G.; Vreugdenhil, Gerard; Krol, Augustinus D. G.; Kluin-Nelemans, Hanneke C.; Coebergh, Jan-Willem W.; van Krieken, J. Han J. M.

    Most testicular lymphomas are of diffuse large B-cell (DLBCL) type with an outcome inferior to nodal DLBCL. Within an apparently homogeneous group of testicular DLBCLs, small cell components, plasmacytoid differentiation and lymphoepithelial lesions (LELs), features of extranodal marginal zone

  11. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2)

    DEFF Research Database (Denmark)

    Eskelund, Christian W.; Kolstad, Arne; Jerkeman, Mats

    2016-01-01

    In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen...

  12. Ubiquitin-specific protease 2 decreases p53-dependent apoptosis in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Wei, Tianling; Biskup, Edyta; Gjerdrum, Lise Mette Rahbek

    2016-01-01

    Treatment of advanced cutaneous T-cell lymphomas (CTCL) is challenging because they are resistant to conventional chemotherapy. USP2 has been shown to promote resistance to chemotherapeutic agents in several cancer models.We show here USP2 is expressed in quiescent and activated T-cells and its e...

  13. DNA double-strand break rejoining in human follicular lymphoma and glioblastoma tumor cells

    NARCIS (Netherlands)

    Macann, AMJ; Britten, RA; Poppema, S; Pearcey, R; Rosenberg, E; Allalunis-Turner, MJ; Murray, D

    2000-01-01

    Follicle center cell lymphoma is among the most radioresponsive of human cancers. To assess whether this radioresponsiveness might be a result of a compromised ability of the tumor cells to accomplish the biologically-effective repair of DNA double-strand breaks (DSBs), we have measured i) the

  14. Differential effect of baicalein on ionizing radiation induced cell death in normal lymphocytes and lymphoma cells

    International Nuclear Information System (INIS)

    Patwardhan, R.S.; Sharma, Deepak; Checker, Rahul; Santosh Kumar, S.

    2013-01-01

    Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a naturally occurring flavone, present in Indian and Chinese medicinal plants has been reported to possess potent antioxidant activity. Previous reports from our laboratory have elucidated the radical scavenging and radioprotective potential of this compound in cell free system. To investigate potential of baicalein as a radioprotector, we have studied its effect on normal lymphocytes and lymphoma cells (EL-4 cells) in presence of radiation. Baicalein protected murine splenic lymphocytes against radiation (4Gy) induced apoptosis as assessed by propidium iodide staining. It inhibited background cell death in lymphocytes whereas, baicalein induced concentration dependent cell death in EL-4 cells and did not protect against radiation induced apoptosis. Interestingly, baicalein scavenged radiation derived ROS (reactive oxygen species) in both the cell types suggesting that, it is not exhibiting differential antioxidant action. Despite scavenging radiation derived ROS, which are principal mediators of radiation induced cell death, baicalein induced cell death in EL-4 cells. To investigate the reason for this differential behavior, we investigated the effect of baicalein on pro-survival molecules viz. ERK and NF-kB. Baicalein induced phosphorylation of ERK in normal lymphocytes in a time dependent manner, but, it did not alter pERK levels in EL-4 cells. Baicalein treatment per se induced degradation of IkBα and increased nuclear accumulation of NF-kB in normal lymphocytes. Whereas, baicalein pre-treatment reduced basal NF-kB levels in EL-4 cells and it also suppressed TNF-α induced nuclear accumulation of NF-kB. This study suggests that, differential regulation of pro-survival transcription factor NF-kB may be playing a role in differential effect of baicalein in normal lymphocytes and lymphoma cells. (author)

  15. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma.

    Science.gov (United States)

    Khouri, Issa F; Lee, Ming-S; Saliba, Rima M; Jun, Gu; Fayad, Luis; Younes, Anas; Pro, Barbara; Acholonu, Sandra; McLaughlin, Peter; Katz, Ruth L; Champlin, Richard E

    2003-12-01

    Patients with relapsed mantle-cell lymphoma have poor prognosis and short survival. Our aim was to determine the efficacy of nonablative allogeneic stem-cell transplantation in patients with relapsed mantle-cell lymphoma. Eighteen patients were treated in one of two consecutive trials. Thirteen patients underwent a conditioning regimen of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days), and high-dose rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m2 daily for 4 days), fludarabine (30 mg/m2 daily for 2 days), and cytarabine (1,000 mg/m2 daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. The median age was 56.5 years. Patients underwent a median of three prior chemotherapy regimens. Prior autologous transplantation failed in five (28%) patients and 16 (89%) had chemosensitive disease. Donor cell engraftment occurred in all patients. Eight patients (44%) required no platelet or RBC transfusion, and acute graft-versus-host disease of greater than grade 2 did not develop in any patient. The day-100 mortality was 0%. Complete remission (CR) occurred in 17 patients. Three patients progressed, and one was reinduced into continuous CR with donor lymphocyte infusion. With a median follow-up period of 26 months, the actuarial probability of current-event-free-survival at 3 years was 82% (95% CI, 65% to 99%). Our data suggest that nonablative allogeneic transplantation is a safe and potentially effective strategy for patients with relapsed and chemosensitive mantle-cell lymphoma.

  16. B-cell Lymphoma in retrieved femoral heads: a long term follow up

    Directory of Open Access Journals (Sweden)

    van Kemenade Folkert J

    2009-05-01

    Full Text Available Abstract Background A relatively high incidence of pathological conditions in retrieved femoral heads, including a group of patients having low grade B-cell lymphoma, has been described before. At short term follow up none of these patients with low-grade B-cell lymphoma showed evidence of systemic disease. However, the long term follow up of these patients is not known. Methods From November 1994 up to and including December 2005 we screened all femoral heads removed at the time of primary total hip replacement histopathologically and included them in the bone banking protocol according to the guidelines of the American Associations of Tissue Banks (AATB and the European Association of Musculo-Skeletal Transplantation (EAMST. We determined the percentage of B-cell lymphoma in all femoral heads and in the group that fulfilled all criteria of the bone banking protocol and report on the long-term follow-up. Results Of 852 femoral heads fourteen (1.6% were highly suspicious for low-grade B-cell lymphoma. Of these 852 femoral heads, 504 were eligible for bone transplantation according to the guidelines of the AATB and the EAMST. Six femoral heads of this group of 504 were highly suspicious for low-grade B-cell lymphoma (1.2%. At long term follow up two (0.2% of all patients developed systemic malignant disease and one of them needed medical treatment for her condition. Conclusion In routine histopathological screening we found variable numbers of low-grade B-cell lymphoma throughout the years, even in a group of femoral heads that were eligible for bone transplantation. Allogenic transmission of malignancy has not yet been reported on, but surviving viruses are proven to be transmissible. Therefore, we recommend the routine histopathological evaluation of all femoral heads removed at primary total hip arthroplasty as a tool for quality control, whether the femoral head is used for bone banking or not.

  17. Efficacy and prognosis of antiviral therapy on hepatitis C following treatment of lymphoma in HCV-positive diffuse large-cell lymphoma.

    Science.gov (United States)

    Tsutsumi, Yutaka; Nakayama, Chie; Kamada, Koki; Kikuchi, Ryo; Kudo, Daiki; Ito, Shinichi; Matsuoka, Satomi; Shiratori, Souichi; Yamamoto, Yoshiya; Naruse, Hirohito; Teshima, Takanori

    2017-12-01

    The purpose of this study is to study the usefulness of post-remission antiviral therapy in cases of HCV-RNA-positive diffuse large-cell lymphoma. Antiviral therapy against HCV was performed after remission using CHOP or CHOP-like chemotherapy in combination with rituximab in five successive cases of HCV-RNA-positive diffuse large-cell lymphoma. The control groups consisted of a group of HCV-RNA-positive diffuse large-cell lymphoma cases prior to this trial (control 1), and a group of cases that tested negative for HIV, HCV, and HBV (control 2). All the cases were in remission at the time of initial treatment. There were no significant differences between the three groups in terms of age, sex, treatment, stage, or International Prognosis Index (IPI). When HCV antiviral therapy was performed after treatment for diffuse large-cell lymphoma, we observed no recurrence or deaths, and the 2-year overall survival and progression-free survival rates were significantly greater than those in the control 1 group (P = 0.0246). It is possible that a better prognosis can be achieved by performing HCV antiviral therapy after achieving remission in cases of HCV-RNA-positive diffuse large-cell lymphoma through the use of R-CHOP or similar treatments.

  18. Structural genomic alterations in primary mediastinal large B-cell lymphoma.

    Science.gov (United States)

    Twa, David D W; Steidl, Christian

    2015-01-01

    Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive non-Hodgkin lymphoma that displays phenotypic and genotypic similarity to Hodgkin lymphoma and diffuse large B-cell lymphoma. Studies using genome-wide discovery tools have revealed specific, recurrent structural aberrations as critical somatic events in the pathogenesis of PMBCL. These structural alterations prominently include transcript and protein altering rearrangements and copy number variations of the programmed death ligands 1 (CD274) and 2 (PDCD1LG2), CIITA, JAK2 and REL. Importantly, evidence is emerging that these acquired structural genomic changes, in synergy with other somatic alterations, contribute to PMBCL pathogenesis by influencing tumor microenvironment interactions that favor malignant B-cell growth. The means by which these rearrangements arise are not well understood. However, analysis of breakpoint junctions at base-pair resolution provides preliminary insight into putative rearrangement mechanisms. As the field also anticipates predictive value and therapeutic targeting of structural changes involving programmed death ligands and JAK2, a review of therapies that will likely shape future lymphoma treatment is needed.

  19. Follicular B Cell Lymphoma with Accompanying Ischemic Gastritis Completely Resolved by Rituximab.

    Science.gov (United States)

    Tariq, Anam; Mehta, Neal; Peroutka, Kathryn

    2017-06-02

    BACKGROUND Follicular B cell lymphomas account for a significant portion of all newly diagnosed non-Hodgkin's lymphomas. While involvement can be varied, the most common extranodal presentation is within the gastrointestinal tract beyond the stomach. In addition, the stomach has a diffuse multivessel vascular supply, which decreases the likelihood of developing ischemic gastritis. CASE REPORT An 89-year-old woman with history of diabetes, deep venous thromboembolism, and hypertension was referred due to a newly diagnosed retroperitoneal mass. Biopsy of a left para-aortic node was consistent with low-grade follicular B cell lymphoma. Following mainstream treatment guidelines, rituximab was administered. Approximately 12 hours later, the patient presented to the Emergency Department with intractable vomiting and nausea. After admission, an esophagogastroduodenoscopy (EGD) revealed extensive ischemic gastritis. Due to recurrent ascites requiring frequent paracenteses, and the clinical aggressiveness of the patient's underlying lymphoma, a second dose of rituximab was administered with concurrent initiation of total parenteral nutrition. Approximately 1 week later, the patient underwent a repeat EGD for quality of life planning while in hospice. The repeat EGD revealed resolved ischemic gastritis. Her diet was advanced and she was subsequently discharged home. CONCLUSIONS Rituximab alone shows promise in treating extensive follicular B cell lymphoma complicated by ischemic gastritis, which has not been previously reported in the literature.

  20. A defect of the INK4-Cdk4 checkpoint and Myc collaborate in blastoid mantle cell lymphoma-like lymphoma formation in mice.

    Science.gov (United States)

    Vincent-Fabert, Christelle; Fiancette, Rémi; Rouaud, Pauline; Baudet, Christel; Truffinet, Véronique; Magnone, Virginie; Guillaudeau, Angélique; Cogné, Michel; Dubus, Pierre; Denizot, Yves

    2012-04-01

    Mantle cell lymphoma (MCL) is a B-cell malignancy characterized by a monoclonal proliferation of lymphocytes with the co-expression of CD5 and CD43, but not of CD23. Typical MCL is associated with overexpression of cyclin D1, and blastoid MCL variants are associated with Myc (alias c-myc) translocations. In this study, we developed a murine model of MCL-like lymphoma by crossing Cdk4(R24C) mice with Myc-3'RR transgenic mice. The Cdk4(R24C) mouse is a knockin strain that expresses a Cdk4 protein that is resistant to inhibition by p16(INK4a) as well as other INK4 family members. Ablation of INK4 control on Cdk4 does not affect lymphomagenesis, B-cell maturation, and functions in Cdk4(R24C) mice. Additionally, B cells were normal in numbers, cell cycle activity, mitogen responsiveness, and Ig synthesis in response to activation. By contrast, breeding Cdk4(R24C) mice with Myc-3'RR transgenic mice prone to develop aggressive Burkitt lymphoma-like lymphoma (CD19(+)IgM(+)IgD(+) cells) leads to the development of clonal blastoid MCL-like lymphoma (CD19(+)IgM(+)CD5(+)CD43(+)CD23(-) cells) in Myc/Cdk4(R24C) mice. Western blot analysis revealed high amounts of Cdk4/cyclin D1 complexes as the main hallmark of these lymphomas. These results indicate that although silent in nonmalignant B cells, a defect in the INK4-Cdk4 checkpoint can participate in lymphomagenesis in conjunction with additional alterations of cell cycle control, a situation that might be reminiscent of the development of human blastoid MCL. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Nasal Extranodal Natural Killer/T Cell Lymphoma in a 69-Year Old Female: A Case Report

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    Duygu Mert, Mehmet Sinan Dal, Fazilet Duygu

    2016-09-01

    Full Text Available Mature natural killer /T-cell (NK/T-cell lymphomas are a rarely occurring subgroup of Non Hodgkin Lymphomas (NHL. A large majority of NK/T cell lymphomas are extranodal. Nasal type is the most common one. As clinical symptoms are usually nasal obstruction associated with mass lesion and epistaxis in extranodal NK/T cell lymphomas. Their diagnosis is usually delayed when the disease is advanced, it may have serious consequences. The aim of the present article was to present the clinical, radiological and histopathological findings of a 69-year old female patient who had refractory ulcerated wound on left side of nose and followed for soft tissue infection. It was diagnosed with extranodal NK/T cell lymphoma after deep biopsy was obtained from the lesion and to discuss this rare disease in view of literature data. J Microbiol Infect Dis 2016;6(3: 140-144

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

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    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.

  3. Impact of Growth Factor Independence 1 in Human T-Cell Lymphomas

    DEFF Research Database (Denmark)

    Dabrowska, Magdalena Julia; Dybkær, Karen; Johansen, Preben

    2009-01-01

    Impact of Growth Factor Independence 1 in Human T-Cell Lymphomas; Pathogenic Potential Identified by Insertional Mutagenesis in a Murine T-Cell Lymphoma Model. Magdalena Julia Dabrowska *,1, Karen Dybkaer *,1, Preben Johansen *,2, Hans Erik Johnsen1 and Finn Skou Pedersen *,3 1 Department...... of Hematology, Aalborg Hospital, Aalborg, Denmark, 2 Department of Pathology, Aalborg Hospital, Aalborg, Denmark, 3 Department of Molecular Biology, Aarhus University, Aarhus, Denmark   Abstract 5047 Introduction: The transcriptional repressor and oncogene Growth factor independence 1 (Gfi1) has a major...

  4. SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma – a Nordic Lymphoma Group study

    DEFF Research Database (Denmark)

    Nordström, Lena; Sernbo, Sandra; Eden, Patrik

    2014-01-01

    Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI......-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating...

  5. [Advances of treatment for extranodal NK/T-cell lymphoma --- review].

    Science.gov (United States)

    Zhang, Song-Song; Wei, Min; Yu, Li

    2011-08-01

    Extranodal NK/T-cell lymphoma is a rare pathological type, incidence of which is 2% - 10% of the primary NHL cases, showing a broad morphologic spectrum with frequent necrosis. Extranodal NK/T-cell lymphoma occurs more frequently in Asian population, especially in Southern China and Southeast Asian population. It is reported that the incidence of ENKL among lymphomas (1314 cases) in Asian countries was 4 times as much as the Western countries (22% vs. 5%) by the International Peripheral T-cell Lymphoma Project. Nasal NK/T-cell lymphoma most commonly occurred in the nasal cavity or other parts of the upper aerodigestive tract, and is highly associated with EBV (Epstein-Barr virus) infection, which is highly aggressive and its prognosis generally is poor. The mean survival time is about 12-38 months. It is important to accurately assess the patients prognosis for an optimal treatment. Localized disease (stage I and II) often has a relatively good prognosis through local radiation or combined therapy. There is a paucity of data to guide therapy in advanced disease. Generally, combining therapy is the most commonly selected approach for advanced disease. The conditions of the patients with advanced, relapsed or refractory diseases have been improved by high-intensity chemotherapy combined with radiation, and a regimen containing L-asparaginase L-Asp. Recently some studies have demonstrated promising outcomes in the selected cases by high-dose chemotherapy supplemented with auto-or allo-HSCT. Targeting therapy is also developing quickly. This current review mainly focuses on the advance of treatment for extranodal NK/T-cell lymphoma.

  6. Hemophagocytic lymphohistiocytosis associated with hepatosplenic T-cell lymphoma: case report

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    Vitor Ribeiro Paes

    2014-12-01

    Full Text Available Hepatosplenic T-cell lymphoma (HSTCL is a rare non-Hodgkin lymphoma, marked by liver, spleen, and bone marrow sinusoidal infiltration, with an aggressive clinical course, which represents a difficult diagnostic task for clinicians and pathologists. Another equally severe and challenging condition is the hemophagocytic lymphohistiocytosis (also called hemophagocytic syndrome [HS], which is often associated with hematologic malignancies and infectious diseases. The authors report the case of a 56-year-old woman diagnosed with HSTCL based on bone marrow aspirate flow cytometry and skin biopsy. The patient underwent a cycle of chemotherapy but the outcome was unfavorable with multiple organ failure. The laboratory analysis was consistent with HS. The autopsy confirmed both the remaining lymphoma in the pulmonary vessels and the hemophagocytic cells in the spleen and bone marrow.

  7. Proton beam therapy in a patient with cutaneous T cell lymphoma of the penis

    International Nuclear Information System (INIS)

    Iijima, Shigeruko; Fujisawa, Yuji; Horiuchi, Sanae; Takahashi, Hideharu; Ueno, Kenichi; Kitagawa, Toshio; Mori, Naoyoshi.

    1987-01-01

    A 68-year-old man had multiple tumors as the relapse sign of cutaneous T cell lymphoma. The patient received proton beam therapy with a total dose of 21 Gy for local recurrent lymphoma on the ventral side of the penis. The tumor began to decrease, with concomitant erosion, by delivering 8 Gy. It completely disappeared at 4 days after the completion of irradiation schedule. The erosion was the severest at one month after that. Hematuria and difficulty in urination were not observed. Postmortem histology showed no evidence of viable cancer cells. The use of conventional radiation may induce radiation injuries to the surrounding critical organ, although lymphoma has been recognized as radiosensitive. In view of no evidence of urethral damage, as observed in this patient, proton beams are considered suitable in radiation treatment for the penis. (Namekawa, K.)

  8. Imaging findings of childhood B-cell lymphoblastic lymphoma in the mental region: a case report.

    Science.gov (United States)

    Lam, Phong D; Kuribayashi, Ami; Sakamoto, Junichiro; Nakamura, Shin; Harada, Hiroyuki; Kurabayashi, Tohru

    2017-03-01

    Lymphoblastic lymphoma (LBL) is an uncommon neoplasm that accounts for about 5% of all non-Hodgkin's lymphomas. Approximately 90% of LBLs are of immature T-cell lineage, with B-cell lymphoblastic lymphoma (B-LBL) accounting for only about 10%. Owing to infrequency, the clinicopathological features and the imaging findings of B-LBL are not well defined. LBLs frequently affect extranodal sites. The most common site is the skin, followed by the bone, and the head and neck region is rarely involved. We report herein a case of childhood B-LBL occurring in the mental region, with emphasis on the findings of several imaging studies, including contrast-enhanced CT, MRI and fluorodeoxyglucose-positron emission tomography/CT.

  9. Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network

    DEFF Research Database (Denmark)

    Hoster, Eva; Klapper, Wolfram; Hermine, Olivier

    2014-01-01

    PURPOSE: Mantle-cell lymphoma (MCL) is a distinct B-cell lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned...... to be performed on the cohort of the two recently completed randomized trials of the European MCL Network. PATIENTS AND METHODS: Data of 958 patients with MCL (median age, 65 years; range, 32 to 87 years) treated upfront in the trials MCL Younger or MCL Elderly were pooled to assess the prognostic value of MIPI.......9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline characteristics constituting the MIPI, age, performance status, lactate dehydrogenase level, and WBC count, were confirmed as independent prognostic factors for OS and TTF. The validity of MIPI...

  10. Malignant conjunctival T cell lymphoma diagnosed by punch biopsy as a primary manifestation of systemic cancer

    Directory of Open Access Journals (Sweden)

    Isola V

    2012-05-01

    Full Text Available Vincenzo Isola,1 Danilo Mazzacane,1 Noemi Defelice,1 Antonio D’Amico,1 Laura Dezza,2 Antonio Marti,3 Alfredo Pece,1,41Department of Ophthalmology, Melegnano Hospital, 2Oncology Service, 3Department of Radiology, 4Fondazione Retina 3000, Milan, ItalyAbstract: This report documents a case of T cell lymphoma manifesting only with a conjunctival mass. A 67-year-old man underwent a diagnostic punch biopsy, histopathological examination, and immunohistochemical study for a pink-yellow colored mass infiltrating the bulbar conjunctiva in the lower fornix of the eyelid. A biopsy specimen of the conjunctival mass was found histopathologically to be a malignant T cell lymphoma. Systemic involvement was diagnosed within four weeks after the initial diagnosis by computed tomography, showing evidence of extension at the level of the ethmoidal cells, optic nerve, periorbital tissue, and pancreas. T cell lymphoma of the conjunctiva as a primary manifestation of systemic cancer is an uncommon entity. Punch biopsy may be the first diagnostic pathway useful to initiate a search for systemic involvement of a malignant lymphoid tumor of T cell lineage.Keywords: conjunctiva, cancer, T cell lymphoma, biopsy

  11. Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells

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    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.

  12. Small cell lung cancer: CT evaluation and comparison with nonhodgkin's lymphoma

    International Nuclear Information System (INIS)

    Whang, Sun Hee; Lee, Kyung Soo; Lee, Byoung Ho

    1991-01-01

    We analyzed plain radiographic and computed tomographic (CT) features of 26 biopsy proven small cell lung cancer (SCLC). Eleven cases of non Hodgkin's lymphoma involving the thorax were also reviewed and compared with the small cell lung cancer for differential diagnostic clues. Centrally manifesting lymphadenopathy was the main findings of SCLC in both plain radiographs and CT. The most frequently involved lymph nodes were subcarinal, right lower paratracheal, left lower paratracheal, and right tracheobronchial node. The most difficult site to identify the lymphadenopathy with simple radiograph was subcarinal, paraesophageal, pulmonary ligamental, anterior mediastinal (group 6), and left upper paratracheal nodes CT scan revealed lymphadenopathy clearly in all of these Groups. Right lower paratracheal and subcarinal nodes were involved frequently in both SCLC's and lymphomas. Bilateral tracheobronchial and bilateral intrapulmonary nodes were involved more frequently in SCLC's while anterior mediastinal, upper paratracheal, and aorticopulmonary (AP) window nodes were involved predominantly in lymphomas. Cystic low attenuation, presumed necrosis lymphadenopathy, was noted in two cases of lymphomas but not found in SCLC's at all. In conclusion, the CT could detect involved lymphadenopathy in SCLC more accurately than plain radiograph and the sites of involved lymphadenopathy may give a differential diagnostic clue between SCLC and lymphoma

  13. T Cell/Histiocyte-Rich Large B Cell Lymphoma of the Thymus: A Diagnostic Pitfall

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    Jie Xu

    2016-01-01

    Full Text Available T cell/histiocyte-rich large B cell lymphoma (THRLBCL is predominantly a nodal disease, with extranodal involvement, such as bone marrow, spleen, and liver. However, primary THRLBCL has never been reported in the thymus in the English literature. Here we report a case of THRLBCL presenting as mediastinal mass and lymphadenopathy. Based on the frozen section diagnosis of “thymoma,” a 12 cm mass was excised. A year later she developed multiple enlarged lymph nodes and pulmonary nodules. Consultant review of the excised mediastinal mass showed scattered large atypical cells that were CD20+ and PAX-5+ and negative for pan-cytokeratin, AE1, and AE3, compatible with THRLBCL and excluding thymoma. The excised lymph nodes were replaced by diffuse infiltrate of small CD3+ lymphocytes and histiocytes with intermingled large CD20+ B lymphoma cells scattered throughout the section. A diagnosis of THRLBCL was made in lymph node, similar to previous thymic lesion. A clonal rearrangement of immunoglobulin heavy chain (IGH gene was detected, further supporting the diagnosis. This is the first reported case of THRLBCL in thymus. Correct recognition of this entity is critical, because of the difference in therapeutic impact on these patients.

  14. Emperipolesis in a Case of Adult T Cell Lymphoblastic Lymphoma (Mediastinal type-Detected at FNAC and Imprint Cytology

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    Amita K

    2011-11-01

    Full Text Available Emperipolesis is a condition in which viable hematopoetic cells are seen intact in the cytoplasm of host cell without damage. This phenomenon is seen in many physiologic and pathologic conditions, its presence in Rosai Dorfman disease (RDD is characteristic of the disease. However emperipolesis is an uncommon finding in malignant lymphoma both Hodgkins and non-Hodgkin’s lymphoma, wherein it has been described in bone marrow aspirate and tissue culture. In contrast there are only two case reports of emperipolesis phenomenon described in non-Hodgkin’s lymphoma in tissue sections. We report a case of an adult T cell lymphoblastic lymphoma (mediastinal type with features of emperipolesis demonstrated at fine needle aspiration cytology (FNAC and imprint cytology of cervical lymph nodes. To our knowledge, this is the first case report of emperipolesis in a case of adult T cell lymphoblastic lymphoma (mediastinal type-detected at FNAC and imprint cytology.

  15. Radiation-induced interphase death observed in human T-cell lymphoma cells established as a nude mouse tumor line

    International Nuclear Information System (INIS)

    Igarashi, T.; Yoshida, S.; Miyamoto, T.

    1990-01-01

    Interphase death of cells occurs physiologically in healthy animal tissues as well as in tissues pathologically injured by radiation or drugs. An active self-destruction process has been found to play a major role in the interphase death of highly radiosensitive cells. However, the mechanism of this radiation-induced interphase death in human lymphoma has not yet been studied in detail. In the present study, we examined a lymphoma derived from a child lymphoblastic lymphoma bearing CD1, CD4, and CD8 antigens and established in nude mice. Low-dose x-irradiation of this lymphoma induced interphase cell death with characteristic morphological and biological changes of an active self-destruction process, i.e., changes in cell surface appearance seen using scanning electron microscopy and nuclear fragmentation accompanied with an increase in free DNA. The process was proved to require protein synthesis. It was concluded that the radiosensitivity of this T-cell lymphoma of common thymic type is mainly due to the occurrence of the active self-destruction process

  16. Primary thyroid marginal zone B-cell lymphoma MALT-type in a patient with rheumatoid arthritis.

    Science.gov (United States)

    Serefhanoglu, Songul; Tapan, Umit; Ertenli, Ihsan; Kalyoncu, Umut; Uner, Aysegul

    2010-09-01

    Autoimmune diseases are defined as specific, adapted immune reactions against self antigens. Immune mechanism deficiency is a causal factor for B-cell lymphoma in primary Sjögren's syndrome and autoimmune thyroid disease. Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a 67-fold and parotid lymphoma is a 44-fold increased risk in Sjögren's syndrome and thyroiditis. MALT lymphoma was not reported in rheumatoid arthritis. We herein report the case of a 56-year-old woman with maltoma of thyroid in rheumatoid arthritis patient.

  17. Gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma: characteristics, outcomes, and prognostication among a large multicenter cohort.

    Science.gov (United States)

    Evens, Andrew M; Kanakry, Jennifer A; Sehn, Laurie H; Kritharis, Athena; Feldman, Tatyana; Kroll, Aimee; Gascoyne, Randy D; Abramson, Jeremy S; Petrich, Adam M; Hernandez-Ilizaliturri, Francisco J; Al-Mansour, Zeina; Adeimy, Camille; Hemminger, Jessica; Bartlett, Nancy L; Mato, Anthony; Caimi, Paolo F; Advani, Ranjana H; Klein, Andreas K; Nabhan, Chadi; Smith, Sonali M; Fabregas, Jesus C; Lossos, Izidore S; Press, Oliver W; Fenske, Timothy S; Friedberg, Jonathan W; Vose, Julie M; Blum, Kristie A

    2015-09-01

    Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty-three percent of patients presented with MGZL, whereas 57% had non-MGZL (NMGZL). NMGZL patients were older (50 versus 37 years, P = 0.0001); more often had bone marrow involvement (19% versus 0%, P = 0.001); >1 extranodal site (27% versus 8%, P = 0.014); and advanced stage disease (81% versus 13%, P = 0.0001); but they had less bulk (8% versus 44%, P = 0.0001), compared with MGZL patients. Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone +/- rituximab (CHOP+/-R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine +/- rituximab (ABVD+/-R) 30%, and dose-adjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, outcomes in MGZL patients seemed similar compared with that of NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival for all patients. Additionally, patients treated with ABVD+/-R had markedly inferior 2-year PFS (22% versus 52%, P = 0.03) compared with DLBCL-directed therapy (CHOP+/-R and DA-EPOCH-R), which persisted on Cox regression (hazard ratio, 1.88; 95% confidence interval, 1.03-3.83; P = 0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (hazard ratio, 0.35; 95% confidence interval, 0.18-0.69; P = 0.002). Collectively, GZL is a heterogeneous

  18. Blastoid Variant Mantle Cell Lymphoma with Complex Karyotype Including 11q Duplication

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    Özge Özer

    2014-09-01

    Full Text Available We describe a case of blastoid mantle cell lymphoma with a complex karyotype. The blastoid variant is a rare type of non-Hodgkin lymphoma exhibiting an aggressive clinical course. Mantle cell lymphoma is a distinct entity of mature B-cell neoplasms genetically characterized by the presence of t(11;14. In the present case, conventional analysis revealed structural abnormalities of chromosomes 2, 4, 6, 10, 13, and 19, along with 3 additional marker chromosomes. The derivative 1 chromosome determined in the case was a result of t(1p;11q. Our interesting finding was the presence of a different translocation between 11q and chromosome 1 in addition to t(11;14. Thus, the resulting 11q duplication was believed to additionally increase the enhanced expression of cyclin D1 gene, which is responsible in the pathogenesis of the disease. Fluorescence in situ hybridization method by the t(11;14 probe revealed clonal numerical abnormalities of chromosomes 11 and 14 in some cells. The detection of multiple abnormalities explains the bad prognosis in the present case. On the basis of our findings, we can easily conclude that results of cytogenetic analyses of similar mantle cell lymphoma patients would provide clues about new responsible gene regions and disease prognosis. In conclusion, it has been suggested that the presence of multiple chromosomal aberrations in addition to the specific t(11;14 may have a negative impact on clinical course and survival rate.

  19. Primary duodenal NK/T-cell lymphoma with massive bleeding: A case report

    Science.gov (United States)

    Li, Jian-Zhong; Tao, Jin; Ruan, Dan-Yun; Yang, Yi-Dong; Zhan, Ya-Shi; Wang, Xing; Chen, Yu; Kuang, Si-Chi; Shao, Chun-Kui; Wu, Bin

    2012-01-01

    Primary natural killer/T-cell (NK/T-cell) lymphoma of the gastrointestinal tract is a very rare disease with a poor prognosis, and the duodenum is quite extraordinary as a primary lesion site. Here, we describe a unique case of a primary duodenal NK/T-cell lymphoma in a 26-year-old man who presented with abdominal pain and weight loss. Abdominal computed tomography scan demonstrated a hypodense tumor in the duodenum. Because of massive upper gastrointestinal tract bleeding during hospitalization, the patient was examined by emergency upper gastrointestinal endoscopy. Under endoscopy, an irregular ulcer with mucosal edema, destruction, necrosis, a hyperplastic nodule and active bleeding was observed on the duodenal posterior wall. Following endoscopic hemostasis, a biopsy was obtained for pathological evaluation. The lesion was subsequently confirmed to be a duodenal NK/T-cell lymphoma. The presenting symptoms of primary duodenal NK-/T-cell lymphoma in this patient were abdominal pain and gastrointestinal bleeding, and endoscopy was important for diagnosis. Despite aggressive treatments, the prognosis was very poor. PMID:22724088

  20. CASE REPORT: Esophageal and Gastric T-Cell Lymphoma: A Rare Entity

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    Raja Shekhar R.Sappati Biyyani

    2012-01-01

    Full Text Available Background: Primary gastrointestinal T-cell lymphomas are extremely rare entity and are much less common than B-Cell lymphomas. Case History: A primary T-cell lymphoma was diagnosed in an octogenarian African American male with a history of diabetes mellitus type-II, remote history of prostate cancer, hypertension, obesity and hyperlipidemia. He had symptoms of dysphagia, early satiety, lossof appetite and loss of weight. He was Helicobacter pylori IgG antibody positive and on treatment. Result of first biopsy duringendoscopy showed only heavy lymphoid infiltrate. But, due to high suspicion of malignancy, a second upper gastrointestinal endoscopy and biopsy was performed .This biopsy from the large deep 3cm friable ulcer with nodular base was taken which showed atypical lymphoid cells positive for CD3 and CD7 and negative for CD5, CD4 , CD8 and CD56 . The combination of the histological, immunohistological stain results and the gene rearrangement results confirmed T cell lymphoma. The patient died after 5 months after5 cycles of chemotherapeutic agents of severe dehydration and complications from sepsis.