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Sample records for cell lymphoma mimicking

  1. B Cell Lymphoma mimicking Rheumatoid Arthritis.

    PubMed

    Cosatti, M A; Pisoni, C N; Altuve, J L; Lorente, C

    2016-01-01

    Non Hodking´s lymphoma (NHL) may involve bones but synovial involvement is uncommon. We describe a patient who presented with polyarthritis, sicca symptoms and rash suggestive of rheumatoid arthritis. An atypical skin rash prompted skin and synovial biopsies. A diagnosis of synovial and skin malignant large B-cell lymphoma anaplastic subtype was performed. Chemotherapy with dexamethasone, vincristine and rituximab was started. Following treatment the patient had complete resolution of cutaneous and articular lymphoma manifestations. PMID:27419896

  2. Diffuse Large B Cell Lymphoma Mimicking Granulomatosis with Polyangiitis

    PubMed Central

    Horowitz, Netanel; Ben-Itzhak, Ofer; Braun-Moscovici, Yolanda

    2016-01-01

    In a patient with systemic multiorgan disease with overlapping features, the differential diagnosis included infectious diseases, malignancies, and systemic autoimmune or inflammatory diseases. We present an unusual case of a young male with B cell lymphoma who presented with symptoms mimicking systemic vasculitis and review the existing literature. PMID:27293945

  3. Angiotrophic large cell lymphoma mimicking multiple sclerosis associated transverse myelitis.

    PubMed

    Ormsby; Prayson; Heard

    1999-09-01

    Angiotrophic large cell lymphoma (ALCL) is a rare disease characterized by a proliferation of malignant lymphoid cells, usually of B-cell origin, within the lumina of small vessels and frequently involving the central nervous system (CNS). ALCL generally follows a rapidly fatal course and is rarely diagnosed prior to autopsy. Tumour cells are rarely present on examination of peripheral blood, cerebrospinal fluid (CSF) or bone marrow, therefore, an early diagnosis is heavily dependent on recognition of neurological manifestations which are present in over 80% of cases. A pre-mortem diagnosis of ALCL can be made in cases where brain biopsy has been performed. We report a case of a 45-year-old woman demonstrating clinical and laboratory features suggestive of multiple sclerosis associated transverse myelitis (MSA-TM) in whom ALCL was unexpectedly discovered at autopsy. Microscopic examination revealed diffuse CNS vascular involvement by neoplastic cells and prominent myelopathy of the upper thoracic spinal cord associated with ascending and descending tract degeneration of the spinal motor and sensory tracts. Neoplastic cells were immunoreactive for B-cell lymphoid markers. The present case is the first to demonstrate neoplastic B-cell clonality in ALCL using polymerase chain reaction (PCR) to detect abnormal V-D-J immunoglobulin gene rearrangements. ALCL should be considered in the differential diagnosis whenever a transverse myelitis is present in association with global encephalopathy and elevated serum lactate dehydrogenase. The neurological manifestations of ALCL with particular reference to its presentation as MSA-TM is discussed. Copyright 1999 Harcourt Publishers Ltd. PMID:10844781

  4. Intestinal Intravascular Large B-cell Lymphoma Mimicking Ulcerative Colitis with Secondary Membranoproliferative Glomerulonephritis.

    PubMed

    Kaneyuki, Daisuke; Komeno, Yukiko; Yoshimoto, Hiroshi; Yoshimura, Naoki; Iihara, Kuniko; Ryu, Tomiko

    2016-01-01

    A 47-year-old woman with ulcerative colitis (UC) was admitted to our hospital for renal dysfunction and progressive anemia. Colonoscopy revealed intestinal lesions and pathological findings showed intravascular large B-cell lymphoma (IVLBCL). According to the polymerase chain reaction analysis of sequential rectal specimens, we concluded that she suffered from intestinal BCL, not UC. After chemotherapy, her renal function progressed to nephrotic syndrome. The pathological findings of renal biopsy specimens indicated membranoproliferative glomerulonephritis (MPGN). Chemotherapy was continued and led to the remission of BCL and MPGN. We herein describe the first case of intestinal IVLBCL mimicking UC with secondary MPGN. PMID:27580553

  5. Human immunodeficiency virus-positive secondary syphilis mimicking cutaneous T-cell lymphoma.

    PubMed

    Yamashita, Michiko; Fujii, Yoshiyuki; Ozaki, Keiji; Urano, Yoshio; Iwasa, Masami; Nakamura, Shingen; Fujii, Shiro; Abe, Masahiro; Sato, Yasuharu; Yoshino, Tadashi

    2015-01-01

    Malignant syphilis or lues maligna is a severe form of secondary syphilis that was commonly reported in the pre-antibiotic era, and has now reemerged with the advent of the human immunodeficiency virus (HIV) epidemic. However, the characteristic histopathological findings of malignant syphilis remain controversial. The aim of this case report was to clarify the clinical and histopathological findings of HIV-positive malignant secondary syphilis. A Japanese man in his forties complained of fever, skin lesions, headache, and myalgia without lymphadenopathy during the previous 4 weeks. The skin lesions manifested as erythematous, nonhealing, ulcerated papules scattered on his trunk, extremities, palm, and face. Although the skin lesions were suspected to be cutaneous T-cell lymphomas on histological analyses, they lacked T-cell receptor Jγ rearrangement; moreover, immunohistochemical analyses confirmed the presence of spirochetes. The patient was administered antibiotics and anti-retroviral therapy, which dramatically improved the symptoms. On the basis of these observations of the skin lesions, we finally diagnosed the patient with HIV-associated secondary syphilis that mimicked cutaneous T-cell lymphoma. The patient's systemic CD4+ lymphocyte count was very low, and the infiltrate was almost exclusively composed of CD8+ atypical lymphocytes; therefore, the condition was easily misdiagnosed as cutaneous lymphoma. Although the abundance of plasma cells is a good indicator of malignant syphilis on skin histological analyses, in some cases, the plasma cell count may be very low. Therefore, a diagnosis of malignant secondary syphilis should be considered before making a diagnosis of primary cutaneous peripheral T-cell lymphoma or lymphoma associated with HIV infection. PMID:26449225

  6. Human immunodeficiency virus-positive secondary syphilis mimicking cutaneous T-cell lymphoma.

    PubMed

    Yamashita, Michiko; Fujii, Yoshiyuki; Ozaki, Keiji; Urano, Yoshio; Iwasa, Masami; Nakamura, Shingen; Fujii, Shiro; Abe, Masahiro; Sato, Yasuharu; Yoshino, Tadashi

    2015-10-08

    Malignant syphilis or lues maligna is a severe form of secondary syphilis that was commonly reported in the pre-antibiotic era, and has now reemerged with the advent of the human immunodeficiency virus (HIV) epidemic. However, the characteristic histopathological findings of malignant syphilis remain controversial. The aim of this case report was to clarify the clinical and histopathological findings of HIV-positive malignant secondary syphilis. A Japanese man in his forties complained of fever, skin lesions, headache, and myalgia without lymphadenopathy during the previous 4 weeks. The skin lesions manifested as erythematous, nonhealing, ulcerated papules scattered on his trunk, extremities, palm, and face. Although the skin lesions were suspected to be cutaneous T-cell lymphomas on histological analyses, they lacked T-cell receptor Jγ rearrangement; moreover, immunohistochemical analyses confirmed the presence of spirochetes. The patient was administered antibiotics and anti-retroviral therapy, which dramatically improved the symptoms. On the basis of these observations of the skin lesions, we finally diagnosed the patient with HIV-associated secondary syphilis that mimicked cutaneous T-cell lymphoma. The patient's systemic CD4+ lymphocyte count was very low, and the infiltrate was almost exclusively composed of CD8+ atypical lymphocytes; therefore, the condition was easily misdiagnosed as cutaneous lymphoma. Although the abundance of plasma cells is a good indicator of malignant syphilis on skin histological analyses, in some cases, the plasma cell count may be very low. Therefore, a diagnosis of malignant secondary syphilis should be considered before making a diagnosis of primary cutaneous peripheral T-cell lymphoma or lymphoma associated with HIV infection.

  7. Disseminated Mycobacterium marinum Infection With a Destructive Nasal Lesion Mimicking Extranodal NK/T Cell Lymphoma

    PubMed Central

    Asakura, Takanori; Ishii, Makoto; Kikuchi, Taku; Kameyama, Kaori; Namkoong, Ho; Nakata, Noboru; Sugita, Kayoko; Tasaka, Sadatomo; Shimizu, Takayuki; Hoshino, Yoshihiko; Okamoto, Shinichiro; Betsuyaku, Tomoko; Hasegawa, Naoki

    2016-01-01

    Abstract Mycobacterium marinum is a ubiquitous waterborne organism that mainly causes skin infection in immunocompetent patients, and its disseminated infection is rare. Extranodal NK/T cell lymphoma, nasal type (ENKL) usually localizes at the nasal and/or paranasal area, but occasionally disseminates into the skin/soft tissue and gastrointestinal tract. Compromised immunity is a risk factor for developing nontuberculous mycobacterial (NTM) infection and malignant lymphoma, and the 2 diseases may share similar clinical presentation; however, only a few reports have described NTM infection mimicking malignant lymphoma. A 43-year-old Japanese man presented to our hospital complaining of multiple progressive skin nodules and purulent nasal discharge for 3 weeks. He was diagnosed with Crohn disease with refractory enteropathic arthritis and has been treated with anti-tumor necrosis factor alpha agents for 25 years. Fiberoptic nasal examination revealed septal perforation with hemorrhagic mucus and purulent rhinorrhea. Histological examination of the nasal septum revealed the infiltration of atypical medium-to-large-sized cells with erosion. The cells were positive for cytoplasmic CD3, granzyme B, and Epstein–Barr virus-encoded small RNA. Histological examination of the skin nodules and auricle also showed infiltration of atypical lymphocytes. The patient was tentatively diagnosed with ENKL, and chemotherapy was considered. However, the skin lesions decreased in size after discontinuation of immunosuppressive agents and minocycline administration. Two weeks later, nasal septum and lavage fluid and left leg skin cultures were positive for M marinum, and minocycline was discontinued. The skin and the nasal lesions improved after 2 months. To the best of our knowledge, this is the first case of disseminated M marinum infection with a destructive nasal lesion mimicking ENKL. The differentiation between M marinum infection and ENKL is clinically important because

  8. Disseminated intravascular large-cell lymphoma with initial presentation mimicking Guillain-Barré syndrome.

    PubMed

    Jiang, Qin Li; Pytel, Peter; Rowin, Julie

    2010-07-01

    We report a patient with intravascular large B-cell lymphoma who initially presented with acute ascending weakness and sensory changes. Electrodiagnostic testing and cerebral spinal fluid (CSF) studies were initially suggestive of a demyelinating polyneuropathy. Further clinical evaluation and testing were consistent with mononeuropathy multiplex. Autopsy revealed disseminated intravascular large-cell lymphoma. Intravascular large-cell lymphoma should be considered in the differential diagnosis of a rapidly evolving neuropathy associated with other organ involvement.

  9. Diffuse Large B-Cell Lymphoma Mimicking Schwannoma of Lumbar Spine

    PubMed Central

    Kim, Seung-Kook; Lee, Sun-Ho; Kim, Eun-Sang

    2016-01-01

    A rare case of solitary diffuse large B-cell lymphoma arising from the lumbar spinal nerve root is reported. A 37-year-old man presented with a 3-month history of progressive numbness and paraparesis in both legs. The initial diagnosis was benign primary intradural extramedullary tumor including schwannoma and meningioma. Histopathological examination revealed diffuse large B-cell lymphoma. While a well-defined T1 isointense mass is common in primary spinal schwannoma, the present case was atypical and had a yellowish neural component. The pathogenesis and radiological findings of spinal diffuse large B-cell lymphoma are discussed and related literature is reviewed. PMID:27437017

  10. Lymph node involvement by mycosis fungoides and Sézary syndrome mimicking angioimmunoblastic T-cell lymphoma.

    PubMed

    LeBlanc, Robert E; Lefterova, Martina I; Suarez, Carlos J; Tavallaee, Mahkam; Kim, Youn H; Schrijver, Iris; Kim, Jinah; Gratzinger, Dita

    2015-09-01

    Clinical management of cutaneous T-cell lymphoma (CTCL) and angioimmunoblastic T-cell lymphoma (AITL) differs markedly. Diagnostic distinction is critical. Herein, we describe a series of 4 patients with clinically, molecularly, and histopathologically annotated mycosis fungoides or Sézary syndrome whose nodal disease mimicked AITL. The patients otherwise exhibited classic clinical manifestations of mycosis fungoides/Sézary syndrome preceding the onset of lymphadenopathy by 1 to 5 years. Skin biopsies revealed epidermotropic infiltrates characteristic of CTCL. Lymph node biopsies revealed dense CD4+ T-cell infiltrates that coexpressed follicular helper T-cell markers and were accompanied by proliferations of high endothelial venules and arborizing CD21+ follicular dendritic cell networks. Two patients had T-cell receptor gene rearrangement studies performed on their skin, lymph node, and peripheral blood demonstrating identical polymerase chain reaction clones in all 3 tissues. A small secondary clonal B-cell population was present in 1 patient that mimicked the B-cell proliferations known to accompany AITL and persisted on successive nodal biopsies over several years. This latter phenomenon has not previously been described in CTCL. The potential for patients to be misdiagnosed with AITL for lack of consideration of advanced-stage CTCL with nodal involvement underscores the necessity of information sharing among the various pathologists and clinicians involved in the care of each patient.

  11. Subcutaneous Panniculitis-Like T Cell Lymphoma Mimicking Early-Onset Nodular Panniculitis

    PubMed Central

    Shen, Guifen; Dong, Lingli; Zhang, Shengtao

    2016-01-01

    Patient: Male, 24 Final Diagnosis: Subcutaneous panniculitis-like T-cell lymphoma Symptoms: Fever • skin nodules Medication: — Clinical Procedure: Skin biopsy • PET-CT Specialty: Hematology Objective: Rare disease Background: Subcutaneous panniculitis-like T cell lymphoma is a very uncommon subtype of cutaneous T cell lymphoma. The manifestations of this rare disease are atypical at onset, and may mimic some rheumatic or dermatologic diseases, which causes the delay of diagnosis and treatment. Case Report: We report a 24-year-old man suffering from intermittent fever and skin nodules on the left anterior chest wall, who was initially misdiagnosed with nodular panniculitis and finally diagnosed with subcutaneous panniculitis-like T cell lymphoma through repeat examination of biopsy of the skin nodule. Positron emission tomography revealed extracutaneous adipose tissue involvement. Subsequently, hemophagocytic syndrome occurred while under a conventional dose of glucocorticoid, but remission was induced by treatment with cyclosporine A and high doses of dexamethasone. Conclusions: In order to avoid the delay diagnosis and inappropriate treatment of subcutaneous panniculitis-like T cell lymphoma, in addition to a thorough physical examination, PET-CT and disease-specific pathologic, immunophenotypic, and T cell receptor tests of the skin biopsy should be performed. Extracutaneous involvement, especially hemophagocytic syndrome, indicated worse prognosis. Even so, cyclosporine A plus high-dose corticosteroid could be an option of treatment. PMID:27342380

  12. Cutaneous T cell lymphoma mimicking cutaneous histiocytosis: differentiation by flow cytometry.

    PubMed

    Baines, S J; McCormick, D; McInnes, E; Dunn, J K; Dobson, J M; McConnell, I

    2000-07-01

    A two-year-old, neutered female cross-bred labrador had multiple cutaneous nodules, biopsies of which revealed pathological changes consistent with cutaneous histiocytosis. During a period of one month the dog developed multicentric lymphadenopathy, a retrobulbar mass and masses within the quadriceps and cervical muscles. Fine needle aspiration cytology of the cutaneous nodules and lymph nodes and histological examination of the cutaneous nodules and muscle masses suggested the presence of lymphoblastic lymphoma. A definitive diagnosis of CD8+ T cell lymphoma was achieved by immunophenotyping the tumour cells by flow cytometry.

  13. Langerhans Cell Histiocytosis in an Infant Mimicking a Lymphoma at Presentation

    PubMed Central

    Madasu, Anjan; Noor Rana, Asim; Banat, Saleh; Humad, Hani; Mustafa, Rashid; AlJassmi, Abdulrahman Mohd

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare disorder characterized by proliferation and accumulation of clonal dendritic cells with varied clinical presentation and an unpredictable course. We report a 5-month-old infant with LCH who presented with severe respiratory distress, a large mediastinal mass, significant generalized lymphadenopathy, and hepatosplenomegaly. Lymphoma, especially T cell lymphoblastic lymphoma, can present with superior mediastinal syndrome needing urgent empirical therapy without biopsy. However, lack of response prompted a biopsy which confirmed it to be a case of LCH and that leads to appropriate therapy and survival. There have been reports of LCH presenting with isolated mediastinal mass or with generalized lymphadenopathy, but the combined presentation of generalized lymphadenopathy with large mediastinal mass, hepatosplenomegaly, and fever in an infant has rarely been reported. Conclusion. LCH should also be considered in the differential diagnosis of an infant presenting with generalized lymphadenopathy, mediastinal mass, hepatosplenomegaly, and fever. PMID:26587301

  14. Lymphomatoidgastropathy mimicking extranodal NK/T cell lymphoma, nasal type: A case report

    PubMed Central

    Terai, Tomohiro; Sugimoto, Mitsushige; Uozaki, Hiroki; Kitagawa, Tetsushi; Kinoshita, Mana; Baba, Satoshi; Yamada, Takanori; Osawa, Satoshi; Sugimoto, Ken

    2012-01-01

    Extranodal natural killer (NK)/T-cell lymphoma, nasal type, exhibits aggressive tumor behavior and carries a poor prognosis. Recently, lymphomatoid gastropathy with NK/T cell infiltration into gastric mucosa has been recognized as a pseudo-malignant disease which regresses without treatment. Because the conventional immunohistochemical criteria of lymphomatoid gastropathy is similar to that of extranodal NK/T-cell lymphoma nasal type, it is difficult to distinguish between the two conditions by histopathological evaluation only. Here, we report a rare case of lymphomatoid gastropathy in a 57-year-old female. Gastroendoscopy on routine check-up revealed elevated reddish lesions < 1 cm in diameter in the gastric fornix and body. Although repeat endoscopies at 1 and 6 mo later revealed no gastric lesions at any locations without any treatments, at 12 mo later gastric lymphomatoid lesions recurred at gastric fornix and body. Histological examination of endoscopic biopsy specimens at 12 mo showed atypical NK cell infiltration with CD3+, CD4-, CD5-, CD7+, CD8-, CD20-, CD30-, CD56+, CD79a- and T-cell-restricted intracellular antigen-1+ into gastric mucosa. After treatment for Helicobacter pylori (H. pylori) eradication, the lesions disappeared in all locations of the gastric fornix and body over the subsequent 12 mo. Here, we report a case of H. pylori-positive lymphomatoid gastropathy with massive NK-cell proliferation, and also review the literature concerning newly identified lymphomatoid gastropathy based on comparison of extra nodal NK/T-cell lymphoma nasal type. In any case, these lesions are evaluated with biopsy specimens, the possibility of this benign entity should be considered, and excessive treatment should be carefully avoided. Close follow-up for this case of lymphomatoid gastropathy is necessary to exclude any underlying malignancy. PMID:22563204

  15. NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series.

    PubMed

    Mansoor, Adnan; Pittaluga, Stefania; Beck, Paul L; Wilson, Wyndham H; Ferry, Judith A; Jaffe, Elaine S

    2011-02-01

    Intestinal T-cell and natural killer (NK)-cell lymphomas are clinically aggressive and can be challenging to diagnose in small endoscopic biopsies. We describe 8 patients in whom atypical NK-cell lymphoproliferative lesions mimicked NK- or T-cell lymphoma. The patients (2 men; 6 women; ages 27-68 years) presented with vague gastrointestinal symptoms with lesions involving stomach, duodenum, small intestine, and colon. At endoscopy, the lesions exhibited superficial ulceration, edema, and hemorrhage. Biopsies revealed a mucosal infiltrate of atypical cells with an NK-cell phenotype (CD56(+)/TIA-1(+)/Granzyme B(+)/cCD3(+)), which displaced but did not invade the glandular epithelium. Epstein-Barr virus-encoded RNA in situ hybridization was negative, and T-cell receptor-γ gene rearrangement showed no evidence of a clonal process. Based on an original diagnosis of lymphoma, 3 patients received aggressive chemotherapy followed by autologous bone marrow transplantation in 2. Five patients were followed without treatment. However, no patient developed progressive disease or died of lymphoma (median follow-up, 30 months). Repeat endoscopies in 6 of 8 patients showed persistence or recurrence of superficial gastrointestinal lesions. This unique entity mimics intestinal and NK-/T-cell lymphomas on endoscopic biopsies and can result in erroneous diagnosis, leading to aggressive chemotherapy. We propose the term "NK-cell enteropathy" for this syndrome of as yet unknown etiology.

  16. Primary cardiac lymphoma mimicking infiltrative cardiomyopathy.

    PubMed

    Lee, Ga Yeon; Kim, Won Seog; Ko, Young-Hyeh; Choi, Jin-Oh; Jeon, Eun-Seok

    2013-05-01

    Primary cardiac lymphoma is a rare malignancy which has been described as thickened myocardium due to the infiltration of atypical lymphocytes and accompanying intracardiac masses. Here, we report a case of a primary cardiac lymphoma without demonstrable intracardiac masses, mimicking infiltrative cardiomyopathy. A 40-year-old male presented with exertional dyspnoea and was diagnosed as having restrictive cardiomyopathy with severely decreased LV systolic function. Endomyocardial biopsy was performed and the diagnosis of primary cardiac lymphoma was confirmed. After appropriate chemotherapy, he recovered his systolic function fully. PMID:23248217

  17. Primary pulmonary T-cell lymphoma mimicking pneumonia: A case report and literature review

    PubMed Central

    YANG, LINGYI; FENG, WEI; CHEN, CHENG; ZHANG, XIUQIN; ZHU, YEHAN; LEI, WEI; HUANG, JIAN-AN

    2016-01-01

    Primary pulmonary T-cell lymphoma is an extremely rare neoplasm. The present study describes the case of an elderly male patient who was admitted to hospital with initial symptoms including a fever, coughing and dyspnea. A chest computed tomography scan detected pneumonia-like features, including multiple variable nodules, ground-glass opacities, patchy infiltration and subpleural consolidation, which progressed rapidly. No mediastinal or hilar adenopathy was noted. The patient was initially diagnosed with severe pneumonia; however, the patient developed severe respiratory failure and extensive progression in radiographic manifestation despite receiving a combination treatment of broad-spectrum antibiotics and antifungal agents. Negative results were obtained for anti-nuclear antibodies and anti-neutrophil cytoplasmic antibody assays, which eliminated the possibility that the patient was affected by a connective tissue disease. A bronchoscopy with transbronchial lung biopsy was not performed on account of intolerance. A histological examination, which was performed using specimens obtained via video-assisted thoracoscopic surgery, allowed the final diagnosis of T-cell lymphoma to be confirmed. Unfortunately, the patient succumbed to respiratory failure and a probable thoracic hemorrhage prior to the initiation of chemotherapy. PMID:27347063

  18. Primary Renal Lymphoma Mimicking a Subcapsular Hematoma: A Case Report

    PubMed Central

    Dedekam, Erik; Graham, Jess; Strenge, Karen; Mosier, Andrew D.

    2013-01-01

    Primary renal lymphoma (PRL) is a rare entity with a history of controversy regarding its existence. Lymphomatous involvement of the kidney is more commonly seen secondarily to spread from an adjacent lymphomatous mass, rather than arising primarily from the kidney. PRL can mimic other renal lesions such as renal cell carcinoma, renal abscess, and metastasis; therefore, an early diagnosis is crucial to guide treatment and properly assess prognosis. We present a rare case of a 77 year-old male who presented with hematuria and PRL mimicking a subcapsular hematoma. PMID:24421949

  19. Primary renal lymphoma mimicking a subcapsular hematoma: a case report.

    PubMed

    Dedekam, Erik; Graham, Jess; Strenge, Karen; Mosier, Andrew D

    2013-08-01

    Primary renal lymphoma (PRL) is a rare entity with a history of controversy regarding its existence. Lymphomatous involvement of the kidney is more commonly seen secondarily to spread from an adjacent lymphomatous mass, rather than arising primarily from the kidney. PRL can mimic other renal lesions such as renal cell carcinoma, renal abscess, and metastasis; therefore, an early diagnosis is crucial to guide treatment and properly assess prognosis. We present a rare case of a 77 year-old male who presented with hematuria and PRL mimicking a subcapsular hematoma. PMID:24421949

  20. Primary mediastinal large B-cell lymphoma and its mimickers: a rare case report with literature review.

    PubMed

    Win, T T; Kamaludin, Z; Husin, A

    2016-08-01

    Primary mediastinal large B-cell lymphoma (PMLBL) is an uncommon non-Hodgkin lymphoma with a distinct clinicopathological entity in the WHO classification of lymphoid malignancies. It is known to originate from B-cells of the thymus. It mimics thymic neoplasms and other lymphomas clinically and histopathologically. We reported a 33-year-old obese man who presented with shortness of breath off and on for 4 years. Radiologically, there was a huge anterior mediastinal mass. Tru-cut biopsy was initially diagnosed as type-A thymoma. Histopathological examination of the excised specimen revealed PMLBL with stromal fibrosis and sclerosis which created a diagnostic difficulty. The neoplastic cells varied from medium-sized to large pleomorphic cells, including mononuclear cells with centroblastic and immunoblastic features as well as bi-lobed Reed Sternberg (RS)-like cells and horse-shoe like hallmark cells. Some interlacing spindle cells and epithelioid cells were also present. Immunohistochemically, tumour cells expressed diffuse positivity for LCA, CD20, CD79a, CD23, Bcl2, MUM-1 and heterogenous positivity for CD30 and EMA, and were negative for CD10, CD15 and ALK. Ki67 scoring was very high. Tumour cells infiltrated into peri-thymic fat and pericardium. No malignant cells were detected in the pleural fluid and there was no bone marrow infiltration. The patient showed partial response to 6 cycles of RICE chemotherapy, and was planned for second line chemotherapy using hyper-CVAD regimen followed by autologous stem cell transplantation. This case illustrates the importance of thorough sampling and immunohistochemistry in differentiating PMLBL from its differential diagnoses. PMID:27568673

  1. Cutaneous lymphoid hyperplasia mimicking cutaneous lymphoma in a hyperthyroid cat.

    PubMed

    Snead, Elisabeth; Kerr, Moira; Macdonald, Valerie

    2013-10-01

    A 12-year-old neutered male domestic shorthair cat presented for chronic, localized, swelling and crusting of the left upper lip, weight loss, sporadic vomiting, and focal alopecia between the scapulae was diagnosed with hyperthyroidism and regional eosinophilic lymphadenitis. Treatment with methimazole exacerbated an underlying hypersensitivity disorder leading to marked generalized lymphadenopathy that histologically mimicked lymphoma.

  2. Cutaneous lymphoid hyperplasia mimicking cutaneous lymphoma in a hyperthyroid cat

    PubMed Central

    Snead, Elisabeth; Kerr, Moira; MacDonald, Valerie

    2013-01-01

    A 12-year-old neutered male domestic shorthair cat presented for chronic, localized, swelling and crusting of the left upper lip, weight loss, sporadic vomiting, and focal alopecia between the scapulae was diagnosed with hyperthyroidism and regional eosinophilic lymphadenitis. Treatment with methimazole exacerbated an underlying hypersensitivity disorder leading to marked generalized lymphadenopathy that histologically mimicked lymphoma. PMID:24155419

  3. Unusual Presentation of Anaplastic Large Cell Lymphoma with Clinical Course Mimicking Fever of Unknown Origin and Sepsis: Autopsy Study of Five Cases

    PubMed Central

    Mosunjac, Marina B.; Sundstrom, J. Bruce; Mosunjac, Mario I.

    2008-01-01

    Aim To describe a subset of cases with the unusual clinical and histomorphological presentation of anaplastic large cell lymphoma (ALCL) mimicking fever of unknown origin (FUO) and sepsis. Methods A pathology database was searched using full term Systematized Nomenclature of Medicine codes for ALCL to identify 23ALCL cases from the period 1999-2006. Of those, five cases that did not have a correct premortem diagnosis were further analyzed to elucidate the reasons for delayed and incorrect pre-mortem diagnosis. The analyzed data included clinical presentation, duration of symptoms, duration of hospital stay, premortem presumed cause of death, white blood cell count, platelet count, anion gap and blood pH, liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase), lactate, coagulation tests (prothrombin time, partial thromboplastin time, fibrinogen, D-dimers), microbiology cultures, and radiology and surgical pathology reports. Autopsy reports were reviewed for description of major gross findings, initial clinical diagnosis, and cause of death. Results Five fatal and pre-mortem unrecognized ALCL cases were characterized by rapid decline, with histologic findings showing predominantly extranodal involvement, intravascular lymphomatosis, and hemophagocytosis. The cases were also characterized by unusual clinical manifestations including a FUO, sepsis, and disseminated intravascular coagulation-like picture, lactic acidosis, hepatosplenomegaly, and absence of significant peripheral adenopathy. Conclusions There is a distinct group of ALCLs with unique and specific clinical, gross autopsy, and histopathologic findings. Recognition of this clinical variant may facilitate early detection and potentially timely diagnosis and therapy. PMID:18925700

  4. Xanthogranulomatous Appendicitis Mimicking Residual Burkitt's Lymphoma After Chemotherapy

    PubMed Central

    Nam, Soomin; Choi, Sung-Eun; Kim, Yu Ri; Baik, Seung Hyuk; Sohn, Seung-Kook

    2016-01-01

    The case of a 23-year-old female treated with aggressive high-dose therapy for Burkitt's lymphoma is reported. A positron emission tomography and computed tomography scan after completion of chemotherapy revealed a residual hypermetabolic lesion in the right pelvic cavity. A pelvic magnetic resonance imaging scan showed circumferential wall thickening at the tip of the appendix. A laparoscopic exploration and appendectomy were performed, and a pathologic examination of the resected appendix revealed xanthogranulomatous appendicitis. This is a rare case of a xanthogranulomatous appendicitis mimicking remnant Burkitt's lymphoma after completion of chemotherapy. PMID:27218100

  5. T-Cell Lymphoma

    MedlinePlus

    ... are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing). Lymphomas are ... also be involved. This group of PTCLs is aggressive and requires combination chemotherapy upon diagnosis. For more ...

  6. Poorly differentiated medullary carcinoma of the colon with an unusual phenotypic profile mimicking high grade large cell lymphoma – a unique case report and review of the literature

    PubMed Central

    Nguyen, Johnny; Coppola, Domenico; Shan, Yuan; Zhang, Ling

    2014-01-01

    Medullary carcinoma (MC) of the colon and rectum is a rare entity, accounting for less than 0.1% of colonic adenocarcinoma that poses a diagnostic challenge for the practicing pathologist. Poorly differentiated or undifferentiated MC with an unusual histological appearance and immunoprofile in addition to heavy lymphoid infiltrate could make it problematic when differentiating it from a high grade lymphoma, in particular anaplastic large B- or T-cell lymphoma, plasmablastic lymphoma, and other undifferentiated neoplasms. Here we reported a unique case of an 81 y/o woman presenting with a 7.0 cm colon mass detected by computed tomography (CT) scan. A partial transverse and ileum resection with appendectomy were performed. Microscopic examination revealed sheets of large, pleomorphic, mitotically-active cells with abundant eosinophilic cytoplasm and multiple prominent nucleoli, growing with a pushing border and poor glandular formation in a background of intratumoral lymphocytes. The neoplastic cells were only focally positive for keratins (<10%); diffusely and strongly positive for vimentin and CD10 with high proliferative index (Ki-67, 90%). The tumor cells were also aberrantly positive for CD30, CD79a and CD43 (diffusely or focally), resulting in a diagnostic dilemma between colonic MC and high grade lymphoma. Careful examination and additional immunohistochemical stains performed proved there was no evidence of T or B-cell lymphoma, melanoma, or other types of primary colon or metastatic carcinomas. This case highlights the difficulty in distinguishing a high grade lymphoma and poorly differentiated colonic MC, and, also the aberrant expression of CD10 and a significant loss of pancytokeratin could result in a diagnostic pitfall. PMID:24551312

  7. A rare case of the upper extremity diffuse large B-cell lymphoma mimicking soft tissue sarcoma in an elderly patient.

    PubMed

    Mamorska-Dyga, Aleksandra; Ronny, Faisal M H; Puccio, Carmelo; Islam, Humayun; Liu, Delong

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with about 30% of new cases presenting with extranodal disease. Lesions originating from soft tissues of the upper extremities are extremely rare and may mimic other malignancies like sarcoma. We present a case of an elderly patient with right upper extremity (RUE) mass which was proven to be DLBCL instead of sarcoma. We emphasize the increasing need for investigating new therapeutic options for patients of extreme age and/or with underlying heart disease. PMID:27486587

  8. A case of extranodal NK/T-cell lymphoma, nasal type mimicking typical manifestations of adult-onset Still's disease (AOSD) with hemophagocytic syndrome: diagnostic consideration between malignant lymphoma without lymphadenopathy and AOSD.

    PubMed

    Kato, Takashi; Tanabe, Juichi; Kanemoto, Motoko; Kobayashi, Chiharu; Morita, Sho; Karahashi, Taro

    2009-01-01

    A 25-year-old Japanese man was suffering from high fever, sore throat, arthralgia, and macular salmon-pink eruption. The superficial lymph node was not palpable, and computed tomographic scans from the neck to pelvis demonstrated hepatosplenomegaly without apparent lymphadenopathy. Therefore, the possibility of malignant lymphoma was considered to be extremely low. Serology for Epstein Barr virus (EBV) and cytomegalovirus showed a postinfectious state, and blood culture was negative. Serum rheumatoid factor and antinuclear antibody were negative. Leukocytopenia (2.4 x 10(3)/mul) was observed, and thus a diagnosis of adult-onset Still's disease (AOSD) with hemophagocytic syndrome (HPS) was made. Fifty-five milligrams of prednisolone daily improved his symptoms and leukocytopenia promptly, but high fever with severe and progressive thrombocytopenia occurred 12 days later. Bone marrow aspiration revealed the presence of lymphoma cells and hemophagocytosis, and the CD45 gating analysis showed expanding population of CD2(+), CD3(-), and CD56(+) cells. Further, mucosal ulceration in the nasal cavity was detected. Therefore, a diagnosis of extranodal natural killer (NK)/T-cell lymphoma, nasal type, concomitant with HPS was made, and treatment with dexamethasone, etoposide, ifosfamide, carboplatin (DeVIC) regimen ameliorated his symptoms and platelet transfusion dependency. Later, a high titer of serum EBV-DNA was detected, which supported the diagnosis. Diagnosing AOSD, extranodal presentation of malignant lymphoma such as extranodal NK/T-cell lymphoma, nasal type, should be carefully considered. PMID:19609486

  9. AT13387 in Treating Patients With Relapsed or Refractory Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma, or Diffuse Large B-cell Lymphoma

    ClinicalTrials.gov

    2016-10-06

    Anaplastic Large Cell Lymphoma, ALK-Positive; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma

  10. Primary dural non-hodgkin's lymphoma mimicking meningioma: A case report and review of literature.

    PubMed

    Kudrimoti, Jyoti K; Gaikwad, Manish J; Puranik, Shaila C; Chugh, Ashish P

    2015-01-01

    A 42-year-old immunocompetent female presented with headache, vomiting and diminished unilateral vision. Computed tomography and magnetic resonance imaging were suggestive of high-grade meningioma. Neurological examination and routine hematological parameters were within normal limits. Craniotomy was performed; the tumor was arising from the dura mater, which was completely resected. Hematoxylin and eosin showed lesion comprising a tumor mass with monomorphic population of tumor cells arranged in sheets and small follicles. The tumor cells were immunoreactive for leukocyte common antigen and CD20 and immunonegative for glial fibrillary acid protein, epithelial membrane antigen, cytokeratin, CD3 and CD30. Rest of the body scan was normal. A diagnosis of primary dural non-Hodgkin's lymphoma was made. We report this exceedingly rare case of primary dural non-Hodgkin's lymphoma, which mimicked clinically and radiologically as meningioma. PMID:26458614

  11. The effect of combined IL10 siRNA and CpG ODN as pathogen-mimicking microparticles on Th1/Th2 cytokine balance in dendritic cells and protective immunity against B cell lymphoma

    PubMed Central

    Pradhan, Pallab; Qin, Hong; Leleux, Jardin; Gwak, Dongho; Sakamaki, Ippei; Kwak, Larry W.; Roy, Krishnendu

    2014-01-01

    Success of an immunotherapy for cancer often depends on the critical balance of T helper 1 (Th1) and T helper 2 (Th2) responses driven by antigen presenting cells, specifically dendritic cells (DCs). Th1-driven cytotoxic T cell (CTL) responses are key to eliminating tumor cells. It is well established that CpG oligonucleotides (ODN), a widely studied Toll-like receptor 9 (TLR9) agonist, used to enhance Th1 response, also induces high levels of the anti-inflammatory, Th2-promoting cytokine IL10, which could dampen the resulting Th1 response. Biomaterials-based immunomodulatory strategies that can reduce IL10 production while maintaining IL12 levels during CpG delivery could further enhance the Th1/Th2 cytokine balance and improve anti-tumor immune response. Here we report that dual-delivery of IL10-silencing siRNA along with CpG ODN to the same DCs using pathogen-mimicking microparticles (PMPs), significantly enhances their Th1/Th2 cytokine ratio through concurrent inhibition of CpG-induced IL10 production. Co-delivery of poly(I:C), a TLR3 agonist had only minor effects on IL10 levels. Further, simultaneous immunotherapy with CpG ODN and IL10 siRNA enhanced immune protection of an idiotype DNA vaccine in a prophylactic murine model of B cell lymphoma whereas co-delivery of poly(I:C) and CpG did not enhance protection. These results suggest that PMPs can be used to precisely modulate TLR ligand-mediated immune-stimulation in DCs, through co-delivery of cytokine-silencing siRNAs and thereby boost antitumor immunity. PMID:24720881

  12. Late-onset Anticonvulsant Hypersensitivity Syndrome Mimicking Lymphoma.

    PubMed

    Geduk, Ayfer; Birtas Atesoglu, Elif; Mehtap, Ozgur; Terzi Demirsoy, Esra; Can, Burak; Tarkun, Pinar; Hacihanefioglu, Abdullah

    2015-01-01

    Anticonvulsant hypersensitivity syndrome is a fatal, idiosyncratic drug reaction that is caused by aromatic antiepileptic drugs. This cutaneous drug reaction is also called pseudolymphoma because of its clinical and histological similarities with malignant lymphoma. The primary clinical findings are fever, skin rashes, enlarged lymph nodes, single or multiple internal organ involvement and hematological abnormalities. Typically, anticonvulsant hypersensitivity syndrome occurs 1-8 weeks after drug administration. We herein present the case of a patient who had been on anticonvulsant therapy for five years and died from late-onset anticonvulsant hypersensitivity syndrome. PMID:26666613

  13. Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2016-04-26

    B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma,; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

  14. Mantle Cell Lymphoma.

    PubMed

    Cheah, Chan Yoon; Seymour, John F; Wang, Michael L

    2016-04-10

    Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma previously considered to have a poor prognosis. Large gains were made in the first decade of the new century when clinical trials established the importance of high-dose therapy and autologous stem-cell rescue and high-dose cytarabine in younger patients and the benefits of maintenance rituximab and bendamustine in older patients. In particular, greater depth of understanding of the molecular pathophysiology of MCL has resulted in an explosion of specifically targeted new efficacious agents. In particular, agents recently approved by the Food and Drug Administration include the proteasome inhibitor bortezomib, immunomodulator lenalidomide, and Bruton's tyrosine kinase inhibitor ibrutinib. We review recent advances in the understanding of MCL biology and outline our recommended approach to therapy, including choice of chemoimmunotherapy, the role of stem-cell transplantation, and mechanism-based targeted therapies, on the basis of a synthesis of the data from published clinical trials. PMID:26755518

  15. Anaplastic Large Cell Lymphoma

    MedlinePlus

    ... called primary cutaneous ALCL and follows a less aggressive course. In almost all cases of primary cutaneous ... kinase (ALK). While both lymphomas are treated as aggressive lymphomas, the prognosis for ALCL depends on whether ...

  16. 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

    ClinicalTrials.gov

    2014-09-02

    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

  17. Stromal Cell Contribution to Human Follicular Lymphoma Pathogenesis

    PubMed Central

    Mourcin, Frédéric; Pangault, Céline; Amin-Ali, Rada; Amé-Thomas, Patricia; Tarte, Karin

    2012-01-01

    Follicular lymphoma (FL) is the prototypical model of indolent B cell lymphoma displaying a strong dependence on a specialized cell microenvironment mimicking normal germinal center. Within malignant cell niches in invaded lymph nodes and bone marrow, external stimuli provided by infiltrating stromal cells make a pivotal contribution to disease development, progression, and drug resistance. The crosstalk between FL B cells and stromal cells is bidirectional, causing activation of both partners. In agreement, FL stromal cells exhibit specific phenotypic, transcriptomic, and functional properties. This review highlights the critical pathways involved in the direct tumor-promoting activity of stromal cells but also their role in the organization of FL cell niche through the recruitment of accessory immune cells and their polarization to a B cell supportive phenotype. Finally, deciphering the interplay between stromal cells and FL cells provides potential new therapeutic targets with the aim to mobilize malignant cells outside their protective microenvironment and increase their sensitivity to conventional treatment. PMID:22973275

  18. Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma

    ClinicalTrials.gov

    2016-04-25

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  19. [Molecular pathogenesis of peripheral T-cell lymphoma (1): angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified and anaplastic large cell lymphoma].

    PubMed

    Couronné, Lucile; Bastard, Christian; Gaulard, Philippe; Hermine, Olivier; Bernard, Olivier

    2015-10-01

    Peripheral T-cell lymphomas (PTCL) belong to the group of non-Hodgkin lymphoma and particularly that of mature T/NK cells lymphoproliferative neoplasms. The 2008 WHO classification describes different PTCL entities with varying prevalence. With the exception of the histological subtype "ALK positive anaplastic large cell lymphoma", PTCL are characterized by a poor prognosis. The mechanisms underlying the pathogenesis of these lymphomas are not yet fully understood, but development of genomic high-throughput analysis techniques now allows to extensively identify the molecular abnormalities present in tumor cells. This review aims to summarize the current knowledge and recent advances about the molecular events occurring at the origin or during the natural history of main entities of PTCL. It will be published in two parts : the first is focused on the three more frequent entities, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, and anaplastic large cell lymphoma. The second (which will appear in the november issue) will describe other subtypes less frequent and of poor prognosis : extranodal NK/T-cell lymphoma, nasal type, adult T-cell leukemia/lymphoma, and enteropathy-associated T-cell lymphoma. T or NK cell lymphoproliferative disorders with leukemic presentation, primary cutaneous T-cell lymphoma and very rare subtypes of PTCL whose prevalence is less than 5% (hepatosplenic T-cell lymphoma and subcutaneous panniculitis-like T cell lymphoma) will not be discussed herein. PMID:26481023

  20. Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

    ClinicalTrials.gov

    2016-10-25

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

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

    ClinicalTrials.gov

    2016-10-25

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; 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; Recurrent Adult Acute Lymphoblastic Leukemia; 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 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 and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  2. Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation

    ClinicalTrials.gov

    2016-06-09

    Contiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Stage I Mantle Cell Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Mantle Cell Lymphoma

  3. Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-09-12

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

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

    ClinicalTrials.gov

    2016-06-08

    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

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

    ClinicalTrials.gov

    2016-06-01

    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

  6. Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-06-10

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

  7. [Molecular pathogenesis of peripheral T cell lymphoma (2): extranodal NK/T cell lymphoma, nasal type, adult T cell leukemia/lymphoma and enteropathy associated T cell lymphoma].

    PubMed

    Couronné, Lucile; Bastard, Christian; Gaulard, Philippe; Hermine, Olivier; Bernard, Olivier

    2015-11-01

    Peripheral T-cell lymphomas (PTCL) belong to the group of non-Hodgkin lymphoma and particularly that of mature T /NK cells lymphoproliferative neoplasms. The 2008 WHO classification describes different PTCL entities with varying prevalence. With the exception of histologic subtype "ALK positive anaplastic large cell lymphoma", PTCL are characterized by a poor prognosis. The mechanisms underlying the pathogenesis of these lymphomas are not yet fully understood, but development of genomic high-throughput analysis techniques now allows to extensively identify the molecular abnormalities present in tumor cells. This review aims to summarize the current knowledge and recent advances about the molecular events occurring at the origin or during the natural history of main entities of PTCL. The first part published in the October issue was focused on the three more frequent entities, i.e. angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, and anaplastic large cell lymphoma. The second part presented herein will describe other subtypes less frequent and of poor prognosis : extranodal NK/T-cell lymphoma, nasal type, adult T-cell leukemia/lymphoma, and enteropathy-associated T-cell lymphoma. PMID:26576610

  8. Monoclonal Antibody Therapy and Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-08

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved 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; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved 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; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved 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; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; 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 III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell 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 Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2

  9. Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-10

    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

  10. Genetically Engineered Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Indolent B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2014-08-04

    B-cell Chronic Lymphocytic Leukemia; 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 Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  11. Hepatosplenic alphabeta T cell lymphoma.

    PubMed

    Nagai, Yuya; Ikegame, Kazuhiro; Mori, Minako; Inoue, Daichi; Kimura, Takaharu; Shimoji, Sonoko; Togami, Katsuhiro; Tabata, Sumie; Kurata, Masayuki; Imai, Yukihiro; Matsushita, Akiko; Nagai, Kenichi; Ogawa, Hiroyasu; Takahashi, Takayuki

    2010-04-01

    A 32-year-old male with chronic hepatitis B was admitted to a hospital with cellulitis in the right leg in September 2006. Pancytopenia, hepatosplenomegaly, and systemic superficial lymph node swelling were noted, and he was referred to our hospital. He developed fever and liver dysfunction in June 2007 and underwent a splenectomy. His pancytopenia subsequently improved. A pathologic diagnosis of hepatosplenic alphabeta T cell lymphoma was made by examining spleen tissue and biopsy specimens of the liver and mesenteric lymph node. He had stage IVB disease because neoplastic T cells were noted in the bone marrow. The response of the lymphoma to conventional chemotherapy including the CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone) and DeVIC (dexamethasone, etoposide, ifoshamide, carboplatin) regimens was poor and transient. A partial remission was obtained with an ESHAP (etoposide, cisplatin, cytarabine, methylprednisolone) regimen. Therefore, we planned a bone marrow transplantation (BMT) from an HLA-haploidentical sibling donor. He was moved to the Department of Hematology, Hyogo Medical College, to receive this BMT as part of a clinical trial. During the conditioning procedure for the transplantation, however, he died of septicemia. Since hepatosplenic alphabeta T cell lymphoma is very rare with only 23 reported cases to date, herein we report this case and discuss the therapeutic strategy. PMID:20217452

  12. Sporadic Burkitt Lymphoma Mimicking Osteomyelitis of the Mandible Revealing Clinically Unsuspected HIV Infection.

    PubMed

    Sivolella, Stefano; Rizzo, Giovanni; Valente, Marialuisa; Lumachi, Franco

    2015-09-01

    Adult sporadic Burkitt lymphoma is a rare and highly aggressive malignancy, accounting for approximately 1-2% of adult lymphomas in Western countries, and exclusively intra-oral localization is very uncommon. We describe a rare case of a moderately painful sporadic Burkitt lymphoma localized in the posterior third of the left mandibular bone, initially misdiagnosed as osteomyelitis-like lesion, in a patient Epstein-Barr virus infection-negative with unknown human immunodeficiency virus (HIV) positivity and acquired immunodeficiency syndrome. A 52-year-old man was referred to our Department complaining of persistent moderate pain localized in the left mandibular arch. According to clinical and radiological features, a diagnosis of post-extraction osteomyelitis was made and a surgical revision, including soft and hard tissue biopsy, was performed. Histopathology revealed the presence of a diffuse proliferation of lymphoid cells, exhibiting the typical 'starry-sky' appearance that was consistent with the diagnosis of B-type non-Hodgkin lymphoma. Unexpectedly, HIV seropositivity was also found, but the patient was unaware of this, and the history did not reveal any particular risk factor for HIV infection. Positron-emission tomography showed a highly (18)F-fluorodeoxyglucose-avid mass in the left maxillofacial region and extensive disease in bone marrow and mediastinum. Thus, the patient was referred to our onco-hematological team for final assessment and care. In conclusion, sporadic Burkitt lymphoma is an aggressive malignancy, which rarely affects adults with initial intra-oral manifestations. In the presence of abnormal gingival or alveolar lesions, a non-odontogenic disease should be suspected and the appropriate diagnostic test should be performed.

  13. Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2016-09-29

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  14. Primary cutaneous B-cell lymphoma.

    PubMed

    Bogle, Melissa A; Riddle, Christy C; Triana, Emily M; Jones, Dan; Duvic, Madeleine

    2005-09-01

    Primary cutaneous B-cell lymphomas include extranodal marginal zone B-cell lymphoma, follicular lymphoma, large B-cell lymphoma, and, rarely, mantle cell lymphoma. Our purpose in conducting this review was to determine the clinical and behavioral characteristics of primary cutaneous B-cell lymphomas, their relationship to infectious triggers, and therapeutic response. We conducted a retrospective chart review of 23 adult patients presenting to the dermatology clinic at M. D. Anderson Cancer Center with primary cutaneous B-cell lymphoma between January 1999 and May 2003. Primary cutaneous B-cell lymphomas generally present on the head and neck, with the trunk and extremities afflicted to a lesser extent. Patients were found to have serologic evidence of prior infection with Borrelia burgdorferi (n = 10), Helicobacter pylori (n = 5), and Epstein-Barr virus (n = 6). Overall, treatment of primary cutaneous B-cell lymphoma should involve multiple modalities; however, specific treatment aimed at concurrent or suspected infection, particularly B burgdorferi, is a helpful adjunct and may achieve complete remission in a small subset of patients.

  15. Gray zone lymphoma: better treated like hodgkin lymphoma or mediastinal large B-cell lymphoma?

    PubMed

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

    2012-09-01

    Although primary mediastinal large B-cell lymphoma (PMBL) and classic Hodgkin lymphoma of the nodular sclerosis type (CHL-NS) are distinct diseases, they share several clinical characteristics and biologic features. Given that, it is not surprising that there exist mediastinal lymphomas that do not fit well into either category but have clinical and morphologic features overlapping and transitional between PMBL and CHL-NS. The term mediastinal gray zone lymphoma (MGZL) has been used for these tumors, which are included in the World Health Organization classification as "B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma." Although several studies have evaluated different therapeutic strategies in PMBL and CHL-NS, there is a paucity of prospective experience treating MGZL, given its rarity and relatively recent recognition. Historically, diseases that today would be categorized as MGZL were probably called "anaplastic large-cell lymphoma Hodgkin-like," and their outcome with standard approaches was poor, with short overall survivals. In this review-following a discussion of the biology and clinical features of MGZL, and how they compare to PMBL and CHL-NS-we outline how the treatment of PMBL and CHL-NS has evolved in recent years, and how we believe MGZL should be approached therapeutically. PMID:22833351

  16. Peripheral T-cell lymphoma.

    PubMed

    Foss, Francine M; Zinzani, Pier Luigi; Vose, Julie M; Gascoyne, Randy D; Rosen, Steven T; Tobinai, Kensei

    2011-06-23

    Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive diseases associated with poor outcome. Studies that focus specifically on PTCL are emerging, with the ultimate goal of improved understanding of disease biology and the development of more effective therapies. However, one of the difficulties in classifying and studying treatment options in clinical trials is the rarity of these subtypes. Various groups have developed lymphoma classifications over the years, including the World Health Organization, which updated its classification in 2008. This article briefly reviews the major lymphoma classification schema, highlights contributions made by the collaborative International PTCL Project, discusses prognostic issues and gene expression profiling, and outlines therapeutic approaches to PTCL. These include the standard chemotherapeutic regimens and other modalities incorporating antifolates, conjugates, histone deacetylase inhibitors, monoclonal antibodies, nucleoside analogs, proteasome inhibitors, and signaling inhibitors. As this review emphasizes, the problem has now evolved into an abundance of drugs and too few patients available to test them. Collaborative groups will aid in future efforts to find the best treatment strategies to improve the outcome for patients with PTCL.

  17. Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)

    ClinicalTrials.gov

    2016-07-04

    Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom Macroglobulinemia

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

    ClinicalTrials.gov

    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

  19. [A Case of Intravascular Lymphoma Mimicking Acute Sinusitis in Which the Outcome was Unfortunate].

    PubMed

    Kambara, Rumi; Horii, Arata; Osak, Yasuhiro; Inohara, Hidenori

    2015-06-01

    Intravascular large B-cell lymphomas (IVLBCL) are a rare and aggressive non-Hodgkin Lymphoma characterized by proliferation of malignant lymphoid cells into the small blood vessels of the whole body. Making a diagnosis is very difficult due to the lack of mass formation and lymph node enlargement, resulting in a poor prognosis. We report herein on a case of IVLBCL which was proved by a biopsy of the nasal mucosa during endoscopic sinus surgery. A 77-year-old woman was admitted with complaints of headache, rhinorrhea, and fever. Computed tomography showed a shadow in the ethmoid sinus on both sides but without polyps. We suspected acute sinusitis and started therapy, however, high fever persisted with worsening of the patient's general condition. Pathological analysis of biopsy specimens from the nasal cavity and sinuses revealed proliferation of malignant lymphoid cells into the small blood vessels and the final diagnosis was IVLBCL. Chemotherapy was initially effective for her general condition but she died 13 months after the first visit. It is important to suspect IVLBCL, if there is any deterioration of the patient's general condition and persistence of the disease against treatment. The nasal cavity is recommended as a site of random biopsy because of its rich population of small blood vessels.

  20. Alvocidib, Fludarabine Phosphate, and Rituximab in Treating Patients With Lymphoproliferative Disorders or Mantle Cell Lymphoma

    ClinicalTrials.gov

    2013-06-03

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Mantle Cell 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 Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Splenic Marginal Zone Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

  1. Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-02-09

    Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Hepatosplenic T-Cell Lymphoma; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma

  2. Study of BKM120 & Rituximab in Patients With Relapsed or Refractory Indolent B-Cell Lymphoma

    ClinicalTrials.gov

    2016-10-18

    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 Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  3. Alisertib With and Without Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-15

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt 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; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  4. 18F-FDG PET/CT Findings in Acute Epstein-Barr Virus Infection Mimicking Malignant Lymphoma

    PubMed Central

    Ørbæk, Mathilde; Graff, Jesper; Markova, Elena; Kronborg, Gitte; Lebech, Anne-Mette

    2016-01-01

    We present a case demonstrating the diagnostic work-up and follow-up of a patient with acute Epstein-Barr virus (EBV) infection in which the clinical picture and imaging on 18F-FDG PET/CT mimicked malignant lymphoma. Follow-up 18F-FDG PET/CT scan in the patient performed 7 weeks after the abnormal scan revealed complete resolution of the metabolically active disease in the neck, axillas, lung hili, and spleen. This case highlights inflammation as one of the most well established false positives when interpreting 18F-FDG PET/CT scans. PMID:27187482

  5. (18)F-FDG PET/CT Findings in Acute Epstein-Barr Virus Infection Mimicking Malignant Lymphoma.

    PubMed

    Ørbæk, Mathilde; Graff, Jesper; Markova, Elena; Kronborg, Gitte; Lebech, Anne-Mette

    2016-01-01

    We present a case demonstrating the diagnostic work-up and follow-up of a patient with acute Epstein-Barr virus (EBV) infection in which the clinical picture and imaging on (18)F-FDG PET/CT mimicked malignant lymphoma. Follow-up (18)F-FDG PET/CT scan in the patient performed 7 weeks after the abnormal scan revealed complete resolution of the metabolically active disease in the neck, axillas, lung hili, and spleen. This case highlights inflammation as one of the most well established false positives when interpreting (18)F-FDG PET/CT scans. PMID:27187482

  6. Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

    ClinicalTrials.gov

    2016-02-23

    Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  7. Primary Cutaneous CD8-Positive Epidermotropic Cytotoxic T Cell Lymphomas

    PubMed Central

    Berti, Emilio; Tomasini, Dario; Vermeer, Maarten H; Meijer, Chris JLM; Alessi, Elvio; Willemze, Rein

    1999-01-01

    Cutaneous T cell lymphomas (CTCL) generally have the phenotype of CD3+, CD4+, CD45RO+ memory T cells. CTCL expressing a CD8+ T cell phenotype are extremely rare and ill-defined. To elucidate whether these CD8+ CTCL represent a distinct disease entity, the clinical, histological, and immunophenotypical features of 17 CD8+ CTCL were reviewed. None of the 17 cases expressed markers characteristic of natural killer cells or γ/δ T cells. Nine of 17 cases showed the characteristic clinical and histological features as well as clinical behavior of well defined types of CTCL, such as mycosis fungoides (2 cases), pagetoid reticulosis (2 cases), lymphomatoid papulosis (2 cases), and CD30+ large T cell lymphoma (2 cases), all of which usually express a CD4+ T cell phenotype, and 1 case of subcutaneous panniculitis-like T cell lymphoma. The other 8 cases formed a homogeneous group showing a distinctive set of clinicopathological and immunophenotypical features, not consistent with that of other well defined types of CTCL. Clinical characteristics included presentation with generalized patches, plaques, papulonodules, and tumors mimicking disseminated pagetoid reticulosis; metastatic spread to unusual sites, such as the lung, testis, central nervous system, and oral cavity, but not to the lymph nodes; and an aggressive course (median survival, 32 months). Histologically, these lymphomas were characterized by band-like infiltrates consisting of pleomorphic T cells or immunoblasts, showing a diffuse infiltration of an acanthotic epidermis with variable degrees of spongiosis, intraepidermal blistering, and necrosis. The neoplastic cells showed a high Ki-67 proliferation index and expression of CD3, CD8, CD7, CD45RA, βF1, and TIA-1 markers, whereas CD2 and CD5 were frequently lost. Expression of TIA-1 pointed out that these lymphomas are derived from a cytotoxic T cell subset. The results of this and other studies reviewed herein suggest that these strongly epidermotropic

  8. Study of Bortezomib and Panobinostat in Treating Patients With Relapsed/Refractory Peripheral T-cell Lymphoma or NK/T-cell Lymphoma

    ClinicalTrials.gov

    2014-06-26

    Peripheral T-cell Lymphoma (Not Otherwise Specified); Angioimmunoblastic T-cell Lymphoma; Extranodal NK/T-cell Lymphoma Nasal Type; Enteropathy- Type T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Anaplastic Large Cell Lymphoma (ALCL) (ALK-1 Negative); Relapsed ALCL (ALK-1 Positive) Post Autologous Transplant

  9. Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma.

    PubMed

    Gualco, Gabriela; Weiss, Lawrence M; Bacchi, Carlos E

    2008-10-01

    Immunohistochemical determination of p63 protein is frequently used in the pathologic diagnosis of nonhematological solid tumors. In malignant hematological disease, p63 expression has been reported in 22% of follicular lymphoma, about 35% of diffuse large B-cell lymphoma, 23% of chronic lymphocytic leukemia, and in some cases of blast crisis of chronic myelogenous leukemia. Anaplastic large cell lymphoma is a rare disease that accounts for less than 5% of all cases of non-Hodgkin's lymphoma. There is little information concerning p63 expression in this specific type of lymphoma. In some cases, the morphological and phenotypic features between anaplastic large cell lymphoma and classical Hodgkin's lymphoma are similar, making this differential diagnosis challenging. We studied p63 expression using a tissue microarray approach in 154 cases of anaplastic large cell lymphoma, including 38% anaplastic large cell kinase positive and 62% anaplastic large cell kinase negative, and 58 Hodgkin's lymphoma cases. Sixty-eight cases of anaplastic large cell lymphoma (44%) showed p63 nuclear positivity (41% of anaplastic large cell kinase positive and 47% of anaplastic large cell kinase negative). Of 130 cases of systemic-anaplastic large cell lymphoma, 42% showed p63 positivity. The neoplastic cells expressed p63 in 38% of the cases of CD45-negative/anaplastic large cell kinase-negative null cell-type anaplastic large cell lymphoma, a subgroup that offers the most difficulties in the differential diagnosis with classical Hodgkin's lymphoma. In contrast, none of the cases of classical Hodgkin's lymphoma demonstrated any p63 expression. These results demonstrate that p63 protein expression is frequently expressed in a subset of anaplastic large cell lymphoma cases and may be used as a potential tool in the differential diagnosis between anaplastic large cell lymphoma and classical Hodgkin's lymphoma.

  10. Aggressive Lymphoma "Sarcoma Mimicker" Originating in the Gluteus and Adductor Muscles: A Case Report and Literature Review.

    PubMed

    Elkourashy, Sarah A; Nashwan, Abdulqadir J; Alam, Syed I; Ammar, Adham A; El Sayed, Ahmed M; Omri, Halima El; Yassin, Mohamed A

    2016-01-01

    Extranodal lymphoma (ENL) occurs in approximately 30%-40% of all patients with non-Hodgkin lymphoma and has been described in almost all organs and tissues. However, diffuse large B-cell lymphoma is the most common histological subtype of non-Hodgkin lymphoma, primarily arising in the retroperitoneal region. In this article, we report a rare case of an adult male diagnosed with primary diffuse large B-cell lymphoma of the gluteal and adductor muscles with aggressive bone involvement. All appropriate radiological and histopathological studies were done for diagnosis and staging. After discussion with the lymphoma multidisciplinary team, it was agreed to start on R-CHOP protocol (rituximab, cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin®), and prednisone) as the standard of care, which was later changed to R-CODOX-M/R-IVAC protocol (rituximab, cyclophosphamide, vincristine (Oncovin®), doxorubicin, and high-dose methotrexate alternating with rituximab, ifosfamide, etoposide, and high-dose cytarabine) due to inadequate response. Due to the refractory aggressive nature of the disease, subsequent decision of the multidisciplinary team was salvage chemotherapy and autologous stem cell transplant. The aim of this case report was to describe and evaluate the clinical presentation and important radiological features of extranodal lymphoma affecting the musculoskeletal system. PMID:27398038

  11. CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-26

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia

  12. Romidepsin for cutaneous T-cell lymphoma.

    PubMed

    Prince, H Miles; Dickinson, Michael; Khot, Amit

    2013-12-01

    Cutaneous T-cell lymphomas are relatively rare lymphomas and the most common form is mycosis fungoides. Its rare leukemic variant is Sezary syndrome. Advanced-stage disease is typically treated with bexarotene (a retinoid), IFN-α or conventional chemotherapeutic agents, but relapses are inevitable. Histone deacetylase inhibitors that modify the epigenome are an attractive addition to the armamentarium. Based on two large Phase II studies, the US FDA approved intravenous romidepsin for patients with relapsed/refractory cutaneous T-cell lymphomas. Romidepsin provides a subset of patients with an opportunity for prolonged clinical responses with a tolerable side-effect profile.

  13. An overview of cutaneous T cell lymphomas

    PubMed Central

    Bagherani, Nooshin; Smoller, Bruce R.

    2016-01-01

    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. PMID:27540476

  14. Clinical Management Updates in Mantle Cell Lymphoma.

    PubMed

    Chen, Robert; Sanchez, James; Rosen, Steven T

    2016-04-01

    Mantle cell lymphoma is an aggressive B-cell non-Hodgkin lymphoma that is often considered incurable. Different clinical and biological biomarkers can be utilized to categorize this lymphoma into various risk levels. Several randomized trials reported in 2015 shed light on the optimal induction therapy. Recent advances include: (1) identification of new pathways to target, (2) novel therapeutics to treat patients with relapsed/refractory disease, and (3) monitoring of minimal residual disease and adoption of a maintenance therapy approach to prevent relapses post induction or post stem cell transplantation. Due to the efforts of translational/clinical research, the overall survival of patients with mantle cell lymphoma has increased and should continue to improve. PMID:27083466

  15. Rituximab, Rasburicase, and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Advanced B-Cell Leukemia or Lymphoma

    ClinicalTrials.gov

    2014-09-10

    Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Small Noncleaved Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Untreated Childhood Acute Lymphoblastic Leukemia

  16. Treatment of T cell lymphoma in dogs.

    PubMed

    Moore, Antony S

    2016-09-17

    Overall, canine lymphoma remains one of the most chemotherapy-responsive cancers in the dog. In addition to the stage and the substage of disease, T cell phenotype is the most consistently important prognostic factor. T cell lymphoma (TCL) in dogs is a heterogeneous disease; dogs with a separate entity of indolent TCL can have a considerably better prognosis than dogs with other forms of lymphoma, and indolent TCL may not always require immediate treatment. In contrast, high-grade TCL is an aggressive disease, and when treated with CHOP-based protocols, dogs with this high-grade TCL have a complete remission rate as low as 40 per cent, relapse earlier and have shorter survival time than dogs with a comparable stage, high-grade B cell lymphoma. This review describes the different disease entities that comprise canine TCL, discusses prognosis for each and treatment options that appear to give the best outcomes. PMID:27634860

  17. Large cell lymphoma stage IA/IAE.

    PubMed

    Nussbaum, H; Koo, C; Kagan, A R; Rao, A; Ryoo, M C

    1991-06-01

    Fifty-two patients with large cell lymphoma stage IA/IAE were retrospectively reviewed for the purpose of evaluation of treatment methods. All pathology slides were reviewed by one pathologist with a special interest in lymphoma. There were 24 patients at stage IA and 28 at stage IAE. Twenty-six patients were treated with radiation alone (10 IA, 16 IAE) and 26 patients were treated with radiation therapy and chemotherapy (13 IA, 13 IAE). Patients treated with radiation therapy alone and those with combined modality therapy (CMT) have similar survival curves with p values greater than 0.05. Recurrence patterns are similar for either method of treatment. While the majority of the literature recommends CMT for large cell lymphoma, our study of 52 patients reveals no difference in survival or recurrence patterns for these patients by either method of treatment. We recommend radiation therapy alone for stage IA/IAE large cell lymphoma, with chemotherapy held in reserve for failure.

  18. Treatment of T cell lymphoma in dogs.

    PubMed

    Moore, Antony S

    2016-09-17

    Overall, canine lymphoma remains one of the most chemotherapy-responsive cancers in the dog. In addition to the stage and the substage of disease, T cell phenotype is the most consistently important prognostic factor. T cell lymphoma (TCL) in dogs is a heterogeneous disease; dogs with a separate entity of indolent TCL can have a considerably better prognosis than dogs with other forms of lymphoma, and indolent TCL may not always require immediate treatment. In contrast, high-grade TCL is an aggressive disease, and when treated with CHOP-based protocols, dogs with this high-grade TCL have a complete remission rate as low as 40 per cent, relapse earlier and have shorter survival time than dogs with a comparable stage, high-grade B cell lymphoma. This review describes the different disease entities that comprise canine TCL, discusses prognosis for each and treatment options that appear to give the best outcomes.

  19. CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma

    ClinicalTrials.gov

    2016-07-11

    Acute Myeloid Leukemia; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T-cell Prolymphocytic Leukemia; T-cell Large Granular Lymphocytic Leukemia; Peripheral T-cell Lymphoma, NOS; Angioimmunoblastic T-cell Lymphoma; Extranodal NK/T-cell Lymphoma, Nasal Type; Enteropathy-type Intestinal T-cell Lymphoma; Hepatosplenic T-cell Lymphoma

  20. Lenalidomide Therapy for Patients With Relapsed and/or Refractory, Peripheral T-Cell Lymphomas

    ClinicalTrials.gov

    2012-04-18

    Peripheral T-cell Lymphomas; Adult T-cell Leukemia; Adult T-cell Lymphoma; Peripheral T-cell Lymphoma Unspecified; Angioimmunoblastic T-cell Lymphoma; Anaplastic Large Cell Lymphoma; T/Null Cell Systemic Type; Cutaneous t-Cell Lymphoma With Nodal/Visceral Disease

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

    ClinicalTrials.gov

    2015-06-03

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

  2. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    ClinicalTrials.gov

    2016-07-08

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  3. Radiolabeled Monoclonal Antibody With or Without Peripheral Stem Cell Transplantation in Treating Children With Recurrent or Refractory Lymphoma

    ClinicalTrials.gov

    2013-01-16

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma

  4. Rituximab and Interleukin-12 in Treating Patients With B-Cell Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    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

  5. Bortezomib and Azacitidine in Treating Patients With Relapsed or Refractory T-Cell Lymphoma

    ClinicalTrials.gov

    2013-12-02

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Small Intestine Lymphoma; T-cell Large Granular Lymphocyte Leukemia

  6. Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas

    ClinicalTrials.gov

    2016-08-24

    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

  7. Synchronous Occurrence of Primary Cutaneous Anaplastic Large Cell Lymphoma and Squamous Cell Carcinoma

    PubMed Central

    Park, Ji-Hye; Lee, Jae Ho; Lim, Youngkyoung; Lee, You Jin

    2016-01-01

    CD30+ lymphoproliferative disorders (LPD) represent a spectrum of T-cell lymphoma including lymphomatoid papulosis and anaplastic large cell lymphoma (ALCL). Epidermis overlying cutaneous CD30+ LPD often shows epidermal hyperplasia, hyperkeratosis, crusting, and ulceration and it is difficult to distinguish from carcinoma such as keratoacanthoma (KA) or squamous cell carcinoma (SCC). Several cases of pseudocarcinomatous hyperplasia mimicking KA or SCC in CD30+ LPD have been reported. The relationship between CD30+ LPD and epithelial proliferations has not yet well understood. It was reported that a variety of mediators, including epidermal growth factor (EGF), transforming growth factor-α and EGFR from CD30+ LPD could attribute to epidermal hyperplasia. However, separate and distinct SCC occurring in CD30+ LPD has rarely been reported. Herein, we present a rare case of coexistence of SCC and cutaneous ALCL located on the same region. PMID:27489433

  8. Nivolumab in Treating Patients With HTLV-Associated T-Cell Leukemia/Lymphoma

    ClinicalTrials.gov

    2016-10-17

    Acute Adult T-Cell Leukemia/Lymphoma; Adult T-Cell Leukemia/Lymphoma; Chronic Adult T-Cell Leukemia/Lymphoma; HTLV-1 Infection; Lymphomatous Adult T-Cell Leukemia/Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Smoldering Adult T-Cell Leukemia/Lymphoma

  9. Vaccine Therapy With or Without Cryosurgery in Treating Patients With Residual, Relapsed, or Refractory B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-04-19

    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

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

    ClinicalTrials.gov

    2016-09-08

    Follicular Variant Peripheral T-Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

  11. Stem Cell Transplant Can Help HIV Patients Battling Lymphoma

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159395.html Stem Cell Transplant Can Help HIV Patients Battling Lymphoma: Study ... for lymphoma, and a new study concludes that stem cell transplant should be standard treatment in these cases. ...

  12. A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)

    ClinicalTrials.gov

    2016-06-24

    T-cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepato-splenic T-cell Lymphoma; Adult T-cell Leukemia/Lymphoma; Enteropathy Associated T-cell Lymphoma; NK T-cell Lymphoma; Transformed Mycosis Fungoides

  13. CTOP/ITE/MTX Compared With CHOP as the First-line Therapy for Newly Diagnosed Young Patients With T Cell Lymphoma

    ClinicalTrials.gov

    2013-11-24

    ALK-negative Anaplastic Large Cell Lymphoma; Peripherial T Cell Lymphoma,Not Otherwise Specified; Angioimmunoblastic T Cell Lymphoma; Enteropathy Associated T Cell Lymphoma; Hepatosplenic T Cell Lymphoma; Subcutaneous Panniculitis Like T Cell Lymphoma

  14. Genomic landscape of cutaneous T cell lymphoma

    PubMed Central

    Choi, Jaehyuk; Goh, Gerald; Walradt, Trent; Hong, Bok S.; Bunick, Christopher G.; Chen, Kan; Bjornson, Robert D.; Maman, Yaakov; Wang, Tiffany; Tordoff, Jesse; Carlson, Kacie; Overton, John D.; Liu, Kristina J.; Lewis, Julia M.; Devine, Lesley; Barbarotta, Lisa; Foss, Francine M.; Subtil, Antonio; Vonderheid, Eric C.; Edelson, Richard L.; Schatz, David G.; Boggon, Titus J.; Girardi, Michael; Lifton, Richard P.

    2015-01-01

    Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes. We performed exome and whole genome DNA sequence and RNA sequencing on purified CTCL and matched normal cells. The results implicate mutations in 17 genes in CTCL pathogenesis, including genes involved in T cell activation and apoptosis, NFκB signaling, chromatin remodeling, and DNA damage response. CTCL is distinctive in that somatic copy number variants (SCNVs) comprise 92% of all driver mutations (mean of 11.8 pathogenic SCNVs vs. 1.0 somatic single nucleotide variants per CTCL). These findings have implications for novel therapeutics. PMID:26192916

  15. Composite lymphoma: EBV-positive classic Hodgkin lymphoma and peripheral T-cell lymphoma: a case report.

    PubMed

    Gualco, Gabriela; Chioato, Lucimara; Van Den Berg, Anke; Weiss, Lawrence M; Bacchi, Carlos E

    2009-01-01

    Composite lymphomas are rare and defined as hematopoietic neoplasms with more than 1 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 T-cell non-Hodgkin lymphoma and classic Hodgkin lymphoma. We report a case of a 55-year-old woman with cervical and mediastinal lymphadenopathy, fever, weight loss, and night sweats. A cervical lymph node biopsy revealed a composite lymphoma with classic Hodgkin lymphoma and peripheral T-cell lymphoma components. The bone marrow was not involved. The patient refused treatment and died of disease progression 2 months after diagnosis. The biopsied lymph node showed 2 distinct populations, one composed of large cells including typical Reed-Sternberg cells and their variants, with expression of CD30, CD15, PAX5, and LMP-1. The other component was more abundant and comprised polymorphic medium-sized cells with convoluted nuclei; CD3, CD5, CD2, and CD4 expression; and negativity for CD30, cytotoxic granules, and B-cell markers. Epstein-Barr virus DNA of subtype A was identified only in the Hodgkin cells. Clonal T-cell receptor gamma and beta gene rearrangements were detected in the T-cell component, whereas monoclonal immunoglobulin H gene rearrangement was found in the Hodgkin cells.

  16. Epigenetics and B-cell Lymphoma

    PubMed Central

    Shaknovich, Rita; Melnick, Ari

    2011-01-01

    STRUCTURED ABSTRACT Purpose of review It has only recently become apparent that mutations in epigenetic mechanisms and perturbation of epigenomic patterning are frequent events in B-cell lymphomas. The purpose of this review is to highlight these new findings and provide a conceptual framework for understanding how epigenetic modifications might contribute to lymphomagenesis. Recent findings Somatic mutations affecting histone methyltransferases such as EZH2 and MLL2, histone demethylases including UTX and JMJD2C and histone acetyltransferases including CBP and p300 are recurrent and common in lymphomas. These mutations result in disruption of chromatin structure and functions of other proteins, ultimately causing aberrant transcriptional programming affecting multiple gene networks. Widespread perturbation of cytosine methylation patterning now appears to be a hallmark of B-cell lymphomas and occurs in specific patterns that can distinguish disease subtypes. Therapeutic targeting strategies can overcome abnormal epigenetic mechanisms and potently kill lymphoma cells. Summary Newly discovered epigenetic lesions may provide critical insights into the genesis of B-cell lymphomas but further studies are required to understand how they affect biological mechanism. Epigenetic lesions offer tremendous opportunities for the development of improved biomarkers and treatments. PMID:21577103

  17. Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

    ClinicalTrials.gov

    2015-11-23

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic 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; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; 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 Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved 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; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  18. Romidepsin for peripheral T-cell lymphoma.

    PubMed

    Khot, Amit; Dickinson, Michael; Prince, H Miles

    2013-08-01

    Peripheral T-cell lymphoma (PTCL) is comprised of a rare heterogeneous group of diseases with diverse clinical presentations; however outcomes associated with conventional chemotherapy are generally poor in the majority of patients. Newer approaches, which include dose-intensification and agents with novel mechanisms of action, are needed to improve outcomes in this group of patients. In this review we examine the results of two recent large Phase II trials with romidepsin, a histone deacetylase inhibitor which shows considerable activity and good tolerability in patients with T-cell lymphoma. These initial results observed with single-agent romidepsin provide a foundation for exploring combination strategies and demonstrates proof-of-principle that other such drugs with similar mechanisms of action may be effective in T-cell lymphoma.

  19. Gamma-delta t-cell lymphomas.

    PubMed

    Foppoli, Marco; Ferreri, Andrés J M

    2015-03-01

    Gamma-delta T-cell lymphomas are aggressive and rare diseases originating from gamma-delta lymphocytes. These cells, which naturally play a role in the innate, non-specific immune response, develop from thymic precursor in the bone marrow, lack the major histocompatibility complex restrictions and can be divided into two subpopulations: Vdelta1, mostly represented in the intestine, and Vdelta2, prevalently located in the skin, tonsils and lymph nodes. Chronic immunosuppression such as in solid organ transplanted subjects and prolonged antigenic exposure are probably the strongest risk factors for the triggering of lymphomagenesis. Two entities are recognised by the 2008 WHO Classification: hepatosplenic gamma-delta T-cell lymphoma (HSGDTL) and primary cutaneous gamma-delta T-cell lymphoma (PCGDTL). The former is more common among young males, presenting with B symptoms, splenomegaly and thrombocytopenia, usually with the absence of nodal involvement. Natural behaviour of HSGDTL is characterised by low response rates, poor treatment tolerability, common early progression of disease and disappointing survival figures. PCGDTL accounts for <1% of all primary cutaneous lymphomas, occurring in adults with relevant comorbidities. Cutaneous lesions may vary, but its clinical behaviour is usually aggressive and long-term survival is anecdotal. Available literature on gamma-delta T-cell lymphomas is fractioned, mostly consisting of case reports or small cumulative series. Therefore, clinical suspicion and diagnosis are usually delayed, and therapeutic management remains to be established. This review critically analyses available evidence on diagnosis, staging and behaviour of gamma-delta T-cell lymphomas, provides recommendations for therapeutic management in routine practice and discusses relevant unmet clinical needs for future studies.

  20. Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant

    ClinicalTrials.gov

    2015-08-12

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/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; 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; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult

  1. Primary Uterine Peripheral T-cell Lymphoma

    PubMed Central

    Gong, Jing; Dong, Aisheng; Wang, Yang; Zhang, Xuefeng; Yang, Panpan; Wang, Li; Jing, Wei

    2016-01-01

    Abstract Primary uterine non-Hodgkin's lymphoma is extremely rare accounting for <1% of all extranodal non-Hodgkin's lymphomas. Imaging findings of primary uterine lymphoma have rarely been reported before. We present magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT findings in a patient with primary uterine peripheral T-cell lymphoma. A 27-year-old female presented with intermittent fever with neutropenia for 7 months. MRI showed an ill-defined mass involved both the uterine corpus and cervix, resulting in diffuse enlargement of the uterus. This mass showed inhomogeneous hypointensity on unenhanced T1-weighted images, hyperintensity on diffusion-weighted imaging, relative hypointensity compared to the surrounding myometrium on T2-weighted images and lower enhancement than the surrounding myometrium on enhanced T1-weighted images. FDG PET/CT showed intense FDG uptake in the thickened wall of the uterine corpus and cervix with SUVmax of 26.9. There were multiple hypermetabolic lymph nodes in the pelvis and retroperitoneum. Uterine curettage and CT-guided biopsy of the uterine mass revealed peripheral T-cell lymphoma. Bone marrow biopsy revealed no evidence of lymphomatous involvement. The imaging and pathologic findings were consistent with primary uterine lymphoma. After 3 circles of chemotherapy, follow-up enhanced MRI showed decreased thickness of the uterine wall. Despite its rarity, primary uterine non-Hodgkin's lymphoma should be taken into consideration when a uterine tumor shows large size, relative hypointesity on both T2-weighted images and enhanced T1-weighted images compared to the surrounding myometrium, and intense FDG uptake on PET/CT. MRI may be helpful for describing the relationship between the tumor and adjacent structures. FDG PET/CT may be useful for tumor detection and staging. PMID:27124063

  2. Natural killer cell lymphoma of the parotid gland.

    PubMed

    Furukawa, Masayuki; Suzuki, Hideaki; Tohmiya, Yasuo; Matsuura, Kazuto; Takahashi, Etsu; Ichinohasama, Ryo; Kobayashi, Toshimitsu

    2003-01-01

    The majority of all parotid lymphomas are of the non-Hodgkin type and of B-cell origin. Primary natural killer cell lymphomas of the parotid gland are extremely rare. We present a case of natural killer cell lymphoma in a 34-year-old woman. The disease was refractory to chemotherapy, and the patient eventually succumbed due to lymphoma-associated hemophagocytic syndrome. PMID:14564097

  3. Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

    ClinicalTrials.gov

    2016-10-27

    Activated B-Cell-Like Diffuse Large B-Cell Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  4. NHL - Extranodal T-cell lymphoma

    PubMed Central

    Devi, Seema; Sinha, Richi; Singh, Rakesh Kumar; Mehta, Gagan

    2015-01-01

    Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a rare lymphoid neoplasm that in the past has been grouped with a variety of granulomatous diseases. ENKL occurs in all age groups. However, it seems to occur more often in people in their 50s and affects more men than women. It is strongly linked to the Epstein-Barr virus (EBV), especially in people of Asian countries. Because this type of lymphoma occurs in organs or tissues other than lymph nodes, it is called ENKL. This is a case report of a 25-year-old female patient who presented with a nonhealing ulcer at the right nasal ala involving the upper lip and cheek for the last 2 months, which had been treated with antitubercular treatment without success. After biopsy and immunohistochemical (IHC) analysis, the patient had been diagnosed a case of extranodal T-cell lymphoma. PMID:26668464

  5. Necrobiotic cutaneous T-cell lymphoma.

    PubMed

    Woollons, A; Darvay, A; Khorshid, S M; Whittaker, S; Jones, R R

    1999-11-01

    We report 3 patients with granulomatous cutaneous T-cell lymphoma (CTCL) who showed necrobiosis histologically with palisading granulomas. Although granulomatous change may be present in up to 4% of cases of CTCL, necrobiosis is rare. Misdiagnosis may occur if epidermotropism is minimal or if atypical cells are masked by the granulomatous infiltrate. T-cell receptor gene analysis confirmed the presence of clonal T-cell populations in lesional skin from all 3 cases.

  6. CCI-779 in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2014-05-07

    B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Malignant Neoplasm; 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 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; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  7. Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma

    ClinicalTrials.gov

    2016-03-08

    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; 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 Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  8. Primary Mediastinal B-Cell Lymphoma

    PubMed Central

    Pileri, Stefano A.; Gaidano, Gianluca; Zinzani, Pier Luigi; Falini, Brunangelo; Gaulard, Philippe; Zucca, Emanuele; Pieri, Federica; Berra, Eva; Sabattini, Elena; Ascani, Stefano; Piccioli, Milena; Johnson, Peter W. M.; Giardini, Roberto; Pescarmona, Edoardo; Novero, Domenico; Piccaluga, Pier Paolo; Marafioti, Teresa; Alonso, Miguel A.; Cavalli, Franco

    2003-01-01

    Although primary mediastinal (thymic) large B-cell lymphoma has been primarily studied, its precise phenotype, molecular characteristics, and histogenesis are still a matter of debate. The International Extranodal Lymphoma Study Group collected 137 such cases for extensive pathological review. Histologically, the lymphomatous growth was predominantly diffuse with fibrosis that induced compartmentalized cell aggregation. It consisted of large cells with varying degrees of nuclear polymorphism and clear to basophilic cytoplasm. On immunohistochemistry, the following phenotype was observed: CD45+, CD20+, CD79a+, PAX5/BSAP+, BOB.1+, Oct-2+, PU.1+, Bcl-2+, CD30+, HLA-DR+, MAL protein+/−, Bcl-6+/−, MUM1/IRF4+/−, CD10−/+, CD21−, CD15−, CD138−, CD68−, and CD3−. Immunoglobulins were negative both at immunohistochemistry and in situ hybridization. Molecular analysis, performed in 45 cases, showed novel findings. More than half of the cases displayed BCL-6 gene mutations, which usually occurred along with functioning somatic IgVH gene mutations and Bcl-6 and/or MUM1/IRF4 expression. The present study supports the concept that a sizable fraction of cases of this lymphoma are from activated germinal center or postgerminal center cells. However, it differs from other aggressive B-cell lymphomas in that it shows defective immunoglobulin production despite the expression of OCT-2, BOB.1, and PU.1 transcription factors and the lack of IgVH gene crippling mutations. PMID:12507907

  9. Patients With Celiac Disease and B-Cell Lymphoma Have a Better Prognosis Than Those With T-Cell Lymphoma

    PubMed Central

    Halfdanarson, Thorvardur R.; Rubio–Tapia, Alberto; Ristow, Kay M.; Habermann, Thomas M.; Murray, Joseph A.; Inwards, David J.

    2013-01-01

    Background & Aims Celiac disease (CD) is associated with an increased risk of lymphoma. However, relatively few studies have assessed the outcome of patients diagnosed with both CD and lymphoma. We evaluated the temporal association between lymphoma and CD, along with clinical presentation, response to therapy, and prognosis. Methods Patients diagnosed with both CD and lymphoma were identified retrospectively in a tertiary referral center. Clinical characteristics and survival were analyzed. Results Sixty-three patients (36 men) were identified who had been diagnosed with lymphoma and CD. Thirty-six (57%) were diagnosed with CD before they were diagnosed with lymphoma. The most common histologic entity was diffuse, large, B-cell lymphoma, which affected 18 (29%) patients. Complete information for staging was available in 59 patients; 24 (38%) had stage IV disease. Only chemotherapy or only radiation therapy was used for 43 (68%) and 11 (17%) patients, respectively. The 5- and 10-year cumulative survival rates for the entire cohort were 58% and 39%, respectively. Survival of patients with T-cell lymphoma was shorter than for all other lymphomas (119.4 vs 22.8 mo; P = .02). Conclusions CD is associated with B- and T-cell lymphomas. Patients with B-cell lymphomas had a better prognosis than those with T-cell lymphoma. Therapy is unsatisfactory for enteropathy-type T-cell lymphoma. PMID:20851210

  10. Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS

    ClinicalTrials.gov

    2016-09-21

    Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic; Lymphoma; Lymphoma, Mantle-cell; Lymphoma, Non-Hodgkin; Hodgkin Disease

  11. Granuloma inguinale mimicking as squamous cell carcinoma of penis.

    PubMed

    Pilani, Abhishek; Vora, Rita; Anjaneyan, Gopikrishnan

    2014-01-01

    Granuloma inguinale (GI) is an acquired chronic, slowly progressive, mildly contagious disease of venereal origin, characterized by granulomatous ulceration of the genitalia and neighboring sites, with little or no tendency to spontaneous healing caused by Klebsiella (Calymmatobacterium) granulomatis. A 55-year-old male presented with fissured, foul smelling, fungating growth over prepuce with phimosis mimicking squamous cell carcinoma (SCC) without lymphadenopathy. It started with painless papulonodular showed pseudoepitheliomatous hyperplasia, infiltration in dermis, acanthosis and vacuolated macrophages suggestive of GI and not showing any histopathological features of SCC. Patient was successfully treated by giving cotrimoxazole twice a day for 21 days. Here, we presented a case of GI mimicking SCC of penis, which was diagnosed on basis of histopathology and treated with excision followed by medical therapy with cotrimoxazole. PMID:24958990

  12. CPI-613, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-12

    B-cell Adult Acute Lymphoblastic Leukemia; 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 Acute Lymphoblastic Leukemia; 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 Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  13. Therapeutic options in peripheral T cell lymphoma.

    PubMed

    Zhang, Yaping; Xu, Wei; Liu, Hong; Li, Jianyong

    2016-01-01

    Peripheral T cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphomas with a very poor prognosis. The standard first-line treatments have resulted in unsatisfactory patient outcomes. With the exception of low-risk anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), the majority of patients relapse rapidly; the current 5-year overall survival rates are only 10-30%. Novel targeted therapies and combination chemotherapies are required for the treatment of patients with PTCL. In recent years, some retrospective and prospective studies have been performed concerning PTCL. Consequently, a number of novel agents and their relevant combination therapies have been identified, including histone deacetylase inhibitors, immunoconjugates, antifolates, monoclonal antibodies, immunomodulatory agents, nucleoside analogs, proteasome inhibitors, kinase inhibitors, bendamustine, L-asparaginase, and other targeted agents. It is hoped that these innovative approaches will finally improve outcomes in patients with PTCL. This review summarizes the currently available approaches for the treatment of PTCL with an emphasis on potential new agents, including the role of stem cell transplantation. PMID:27071634

  14. T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Presenting as a Primary Central Nervous System Lymphoma.

    PubMed

    Advani, Pooja; Starr, Jason; Swaika, Abhisek; Jiang, Liuyan; Qiu, Yushi; Li, Zhimin; Tun, Han W

    2015-12-29

    Primary central nervous system (PCNSL) lymphoma is an aggressive extranodal non-Hodgkin lymphoma, and most cases are classified as diffuse large B-cell lymphoma (DLBCL) by histology. T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) represents a distinct subtype of diffuse large B-cell lymphoma and is characterized by the presence of scattered large neoplastic B-cells in a background of abundant T-cells and histiocytes. This is in contrast to the dense perivascular cuffing of neoplastic B-cells in classic DLBCL. T-cell/histiocyte-rich large B-cell lymphoma should be considered in PCNSL cases in which neoplastic B-cells are sparse and scattered. Immunohistochemistry will help identify the B-cells and surrounding infiltrate rich in Tlymphocytes and histiocytes. Future studies exploring the biology of TCRLBCL and the crosstalk between the neoplastic cells and the surrounding inflammatory infiltrate may provide exciting prospects for future therapies for TCRLBCL. PMID:26788280

  15. Lenalidomide And Rituximab as Maintenance Therapy in Treating Patients With B-Cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-11-25

    Adult Non-Hodgkin Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; 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; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; 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; 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

  16. Infection-mimicking materials to program dendritic cells in situ

    NASA Astrophysics Data System (ADS)

    Ali, Omar A.; Huebsch, Nathaniel; Cao, Lan; Dranoff, Glenn; Mooney, David J.

    2009-02-01

    Cancer vaccines typically depend on cumbersome and expensive manipulation of cells in the laboratory, and subsequent cell transplantation leads to poor lymph-node homing and limited efficacy. We propose that materials mimicking key aspects of bacterial infection may instead be used to directly control immune-cell trafficking and activation in the body. It is demonstrated that polymers can be designed to first release a cytokine to recruit and house host dendritic cells, and subsequently present cancer antigens and danger signals to activate the resident dendritic cells and markedly enhance their homing to lymph nodes. Specific and protective anti-tumour immunity was generated with these materials, as 90% survival was achieved in animals that otherwise die from cancer within 25days. These materials show promise as cancer vaccines, and more broadly suggest that polymers may be designed to program and control the trafficking of a variety of cell types in the body.

  17. Novel Therapies for Aggressive B-Cell Lymphoma

    PubMed Central

    Foon, Kenneth A.; Takeshita, Kenichi; Zinzani, Pier L.

    2012-01-01

    Aggressive B-cell lymphoma (BCL) comprises a heterogeneous group of malignancies, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and mantle cell lymphoma (MCL). DLBCL, with its 3 subtypes, is the most common type of lymphoma. Advances in chemoimmunotherapy have substantially improved disease control. However, depending on the subtype, patients with DLBCL still exhibit substantially different survival rates. In MCL, a mature B-cell lymphoma, the addition of rituximab to conventional chemotherapy regimens has increased response rates, but not survival. Burkitt lymphoma, the most aggressive BCL, is characterized by a high proliferative index and requires more intensive chemotherapy regimens than DLBCL. Hence, there is a need for more effective therapies for all three diseases. Increased understanding of the molecular features of aggressive BCL has led to the development of a range of novel therapies, many of which target the tumor in a tailored manner and are summarized in this paper. PMID:22536253

  18. [Primary mediastinal B-cell lymphoma].

    PubMed

    Coso, D; Rey, J; Bouabdallah, R

    2010-02-01

    Primary mediastinal B-cell lymphoma (PMBL) is a clinicopathological entity among the world health organization classification of lymphoid neoplasms. PMBL often concerns young adults, and the disease remains a localized disease in the majority of cases. The outcome of patients with PMBL is variable and unlike diffuse large cell lymphomas, the international prognostic index seems to be less applicable to such disease. The combination of rituximab and chemotherapy is the gold standard treatment of patients with good prognosis features and allows high cure rates. However, high-dose chemotherapy supported by peripheral blood stem cell support is often warranted in poor-prognosis patients. The use of positrons emission tomography examination is more and more used in such situations to select the best therapeutic strategy. PMID:20207294

  19. Are T cells at the origin of B cell lymphomas?

    PubMed

    Meyer-Hermann, Michael E

    2007-02-21

    Lymphoma pathogenesis is at least in some cases related to transformed B cells (BCs) arising from germinal centre reactions (GCRs). In this article possible deregulations of GCRs are investigated using in silico simulations. It is found that the final differentiation of BCs as regulated by helper T cells (TCs) is the best candidate mechanism for such a deregulation. This shifts the paradigm of BC lymphoma pathogenesis from BC transformations to an emphasized role of TC-BC interactions. PMID:17070849

  20. Bryostatin 1 Plus Vincristine in Treating Patients With Progressive or Relapsed Non-Hodgkin's Lymphoma After Bone Marrow or Stem Cell Transplantation

    ClinicalTrials.gov

    2013-01-09

    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 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

  1. Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.

    PubMed

    Aukema, Sietse M; Kreuz, Markus; Kohler, Christian W; Rosolowski, Maciej; Hasenclever, Dirk; Hummel, Michael; Küppers, Ralf; Lenze, Dido; Ott, German; Pott, Christiane; Richter, Julia; Rosenwald, Andreas; Szczepanowski, Monika; Schwaenen, Carsten; Stein, Harald; Trautmann, Heiko; Wessendorf, Swen; Trümper, Lorenz; Loeffler, Markus; Spang, Rainer; Kluin, Philip M; Klapper, Wolfram; Siebert, Reiner

    2014-04-01

    Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.

  2. Histone Deacetylase Inhibitors for Cutaneous T-Cell Lymphoma.

    PubMed

    Duvic, Madeleine

    2015-10-01

    Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin's T-cell lymphomas that present as skin lesions. Mycosis fungoides with large cell transformation has a 5-year overall survival of 32% with involved skin and 7% with extracutaneous involvement. Failure to cure advanced MF with large cell transformation and peripheral T-cell lymphoma has resulted in a search for novel targeted agents including antibodies and gene modulators. Histone deacetylase inhibitors are small molecules that seem to be particularly active for T-cell lymphoma. PMID:26433847

  3. Iodine I 131 Tositumomab, Etoposide and Cyclophosphamide Followed by Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2014-08-04

    Anaplastic Large 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; 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 Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  4. The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases.

    PubMed

    Gualco, Gabriela; Natkunam, Yasodha; Bacchi, Carlos E

    2012-05-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, is a diagnostic provisional category in the World Health Organization (WHO) 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. Typically, these cases share features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this study, we present 10 cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and have organized the criteria described by the WHO into four patterns along with detailed clinical, morphological and immunophenotypic characterization and outcome data. Our findings show a male preponderance, median age of 37 years and a mediastinal presentation in 80% of cases. All cases expressed at least two markers associated with B-cell lineage and good response to combination chemotherapy currently employed for non-Hodgkin lymphomas.

  5. Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection

    ClinicalTrials.gov

    2015-08-18

    Adult B Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; HIV Infection; Intraocular Lymphoma; Multicentric Angiofollicular Lymphoid Hyperplasia; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; 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 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 Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Plasma Cell Myeloma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

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

    PubMed

    Tokeji, Kayo; Sakaguchi, Sachi; Kurimoto, Tomoko; Fujimura, Junya; Shimizu, Toshiaki

    2016-01-01

    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. PMID:27668103

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

    PubMed Central

    Kurimoto, Tomoko; Fujimura, Junya; Shimizu, Toshiaki

    2016-01-01

    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. PMID:27668103

  8. Cell of origin of transformed follicular lymphoma.

    PubMed

    Kridel, Robert; Mottok, Anja; Farinha, Pedro; Ben-Neriah, Susana; Ennishi, Daisuke; Zheng, Yvonne; Chavez, Elizabeth A; Shulha, Hennady P; Tan, King; Chan, Fong Chun; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Sehn, Laurie H; Marra, Marco A; Shah, Sohrab P; Steidl, Christian; Connors, Joseph M; Scott, David W; Gascoyne, Randy D

    2015-10-29

    Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. PMID:26307535

  9. Cell of origin of transformed follicular lymphoma.

    PubMed

    Kridel, Robert; Mottok, Anja; Farinha, Pedro; Ben-Neriah, Susana; Ennishi, Daisuke; Zheng, Yvonne; Chavez, Elizabeth A; Shulha, Hennady P; Tan, King; Chan, Fong Chun; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Sehn, Laurie H; Marra, Marco A; Shah, Sohrab P; Steidl, Christian; Connors, Joseph M; Scott, David W; Gascoyne, Randy D

    2015-10-29

    Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL.

  10. Microsatellite instability in follicle centre cell lymphoma.

    PubMed

    Randerson, J; Cawkwell, L; Jack, A; Child, J A; Lewis, F; Hall, N; Johnson, P; Evans, P; Barrans, S; Morgan, G J

    1996-04-01

    Fluorescent polymerase chain reaction (PCR) was used to assay 12 microsatellite markers (APC x 2, DCC, P53 x 2, RB1, NM23, WT1, D6S260, D6S262, D6S281 and TNFa) to look for evidence of microsatellite instability in 40 cases of follicle centre cell lymphoma (FCC). Evidence of novel alleles seen in the tumour tissue but not the normal uninvolved tissue was seen in seven cases (17%). In only two of these cases (5%) was more than one locus involved but in these cases multiple affected loci were seen (4/12 and 7/12 respectively). The detection of microsatellite instability indicates a DNA repair defect such as that which would be predicted to occur in cells with mutated mismatch repair genes, a novel finding in FCC lymphoma. PMID:8611453

  11. Rituximab, Romidepsin, and Lenalidomide in Treating Patients With Recurrent or Refractory B-cell Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-09

    B-cell Adult Acute Lymphoblastic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; 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

  12. Basal cell adenoma of maxillary sinus mimicking ameloblastoma.

    PubMed

    Bhagde, Priya Anil; Barpande, Suresh Ramchandra; Bhavthankar, Jyoti Dilip; Humbe, Jayanti G

    2016-01-01

    Basal cell adenoma (BCA) is a rare basaloid tumor, with only 20% of cases occurring in minor salivary glands. Histologically, BCA is characterized by the presence of basaloid cells and may frequently be mistaken with canalicular adenoma, basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma. Immunohistochemistry may aid in arriving at a final diagnosis as in the present case. Reported here is a case of locally aggressive BCA. Histologically, the lesion mimicked ameloblastoma and other entities which posed a diagnostic challenge. There are no reports of BCA presenting as an aggressive lesion available in English literature so far; moreover, merely a single case of BCA of maxillary sinus has been previously reported to the best of our cognition. This case report highlights the rarity of this tumor with regards to its site of origin, clinical behavior and histopathological mimics. PMID:27194878

  13. Engineered nanoparticles mimicking cell membranes for toxin neutralization.

    PubMed

    Fang, Ronnie H; Luk, Brian T; Hu, Che-Ming J; Zhang, Liangfang

    2015-08-01

    Protein toxins secreted from pathogenic bacteria and venomous animals rely on multiple mechanisms to overcome the cell membrane barrier to inflict their virulence effect. A promising therapeutic concept toward developing a broadly applicable anti-toxin platform is to administer cell membrane mimics as decoys to sequester these virulence factors. As such, lipid membrane-based nanoparticulates are an ideal candidate given their structural similarity to cellular membranes. This article reviews the virulence mechanisms employed by toxins at the cell membrane interface and highlights the application of cell-membrane mimicking nanoparticles as toxin decoys for systemic detoxification. In addition, the implication of particle/toxin nanocomplexes in the development of toxoid vaccines is discussed.

  14. Vorinostat and Combination Chemotherapy With Rituximab in Treating Patients With HIV-Related Diffuse Large B-Cell Non-Hodgkin Lymphoma or Other Aggressive B-Cell Lymphomas

    ClinicalTrials.gov

    2016-10-25

    AIDS-Related Diffuse Large Cell Lymphoma; AIDS-Related Plasmablastic Lymphoma; AIDS-Related Primary Effusion Lymphoma; Grade 3b Follicular Lymphoma; HIV Infection; Plasmablastic Lymphoma; Primary Effusion Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  15. Primary B-cell lymphoblastic lymphoma of the testis.

    PubMed

    Tombolini, Flavia; Lacetera, Vito; Gini, Guido; Capelli, Debora; Leoni, Pietro; Montironi, Rodolfo; Galosi, Andrea Benedetto; Muzzonigro, Giovanni

    2014-12-01

    We present a rare case of primary lymphoblastic B-cell lymphoma of the testis focusing on ultrasonographic and pathological features and clinical implications. Pathological examination revealed primary testicular lymphoblastic B-cell lymphoma which was treated with adjuvant chemotherapy, including rachicentesis with administration of chemotherapy and with radiotherapy of contralateral testis. Primary testicular lymphoblastic B cell lymphoma is an aggressive disease and it is necessary a multimodal therapy (surgery, chemotherapy and radiotherapy) to prevent metastasis. PMID:25641484

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

    ClinicalTrials.gov

    2016-10-13

    Diffuse 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; Transformed Recurrent Non-Hodgkin Lymphoma

  17. Cell of origin of transformed follicular lymphoma

    PubMed Central

    Kridel, Robert; Mottok, Anja; Farinha, Pedro; Ben-Neriah, Susana; Ennishi, Daisuke; Zheng, Yvonne; Chavez, Elizabeth A.; Shulha, Hennady P.; Tan, King; Chan, Fong Chun; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Sehn, Laurie H.; Marra, Marco A.; Shah, Sohrab P.; Steidl, Christian; Connors, Joseph M.; Scott, David W.

    2015-01-01

    Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell–like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell–like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. PMID:26307535

  18. Bortezomib and Filgrastim in Promoting Stem Cell Mobilization in Patients With Non-Hodgkin Lymphoma or Multiple Myeloma Undergoing Stem Cell Transplant

    ClinicalTrials.gov

    2016-04-19

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; 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; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; 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; Progressive Hairy Cell Leukemia, Initial Treatment; 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

  19. Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2012-10-11

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  20. Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated High- or High-Intermediate-Risk Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2016-03-01

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  1. Romidepsin for cutaneous T-cell lymphoma.

    PubMed

    Prince, H Miles; Dickinson, Michael

    2012-07-01

    Cutaneous T-cell lymphomas (CTCL) are relatively rare lymphomas with an annual incidence of approximately 0.2 to 0.8/100,000 and comprise a variety of clinical entities; mycosis fungoides or its leukemic variant Sezary syndrome account for the majority of cases. Advanced-stage disease is typically treated with bexarotene (a retinoid), interferon, or conventional chemotherapeutic agents, but relapses are inevitable. Histone deacetylase inhibitors, which modify the epigenome, are an attractive addition to the armamentarium. On the basis of 2 large phase II studies, the U.S. Food and Drug Administration approved intravenous romidepsin for patients with relapsed and/or refractory CTCL. Romidepsin provides a subset of patients with an opportunity for prolonged clinical responses with a tolerable side effect profile.

  2. Lymphoma

    MedlinePlus

    Lymphoma is a cancer of a part of the immune system called the lymph system. There are many types of lymphoma. One type is Hodgkin disease. The rest are called non-Hodgkin lymphomas. Non-Hodgkin lymphomas begin when a type of ...

  3. Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-09-15

    Adult Acute Lymphoblastic Leukemia in Remission; 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; Hepatosplenic T-cell 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 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 Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  4. Plasmablastic lymphoma exclusively involving bones mimicking osteosarcoma in an immunocompetent patient

    PubMed Central

    Sarker, Azmal Kabir; Im, Hyung-Jun; Paeng, Jin Chul; Cheon, Gi Jeong; Kang, Keon Wook; Chung, June-Key; Lee, Dong Soo

    2016-01-01

    Abstract Background: It has been known that plasmablastic lymphoma (PBL) is a neoplasm of immunocompromised patients occurring in soft tissue of oral cavity or in the vicinity whereas bone is an unlikely site to harbor PBL. However, its occurrence is increasingly being reported in immunocompetent individuals in either osseous or extra-oral sites. To our best knowledge, F-18 FDG PET/CT findings of PBL involving bones in an immunocompetent patient have not been reported, yet . Case summary: We report a case of PBL involving multiple bones in an immunocompetent patient. Features of different imaging modalities including F-18 Fluoro-deoxy glucose (FDG) positron emission tomography/computed tomography (PET/CT) were correlated well as findings of osteosarcoma in mandible with metastatic lesions. However, the histopathology and immunohistochemistry (IHC) of bone tissues from 2 separate biopsy sites revealed features of PBL. Conclusion: awareness to F-18 FDG PET/CT findings of PBL involving bones in an immunocompetent patient may prevent misdiagnosis. PMID:27428232

  5. Carfilzomib, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

    ClinicalTrials.gov

    2016-08-01

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

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

    ClinicalTrials.gov

    2016-07-29

    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

  7. Combination Chemotherapy and Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2016-10-30

    Anaplastic Large Cell Lymphoma, ALK-Negative; Anaplastic Large Cell Lymphoma, ALK-Positive; Hepatosplenic T-Cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Stage II Angioimmunoblastic T-cell Lymphoma; Stage II Enteropathy-Associated T-Cell Lymphoma; Stage III Angioimmunoblastic T-cell Lymphoma; Stage III Enteropathy-Associated T-Cell Lymphoma; Stage IV Angioimmunoblastic T-cell Lymphoma; Stage IV Enteropathy-Associated T-Cell Lymphoma

  8. Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia

    ClinicalTrials.gov

    2016-07-29

    Post-transplant Lymphoproliferative Disorder; B-Cell Prolymphocytic Leukemia; Recurrent Adult Burkitt 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; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Recurrent Lymphoplasmacytic Lymphoma

  9. Extranodal Marginal Zone Lymphoma (MALT) – Like Presentations of Angioimmunoblastic T-cell lymphoma: A T-cell lymphoma masquerading as a B-cell lymphoproliferative disorder

    PubMed Central

    Kaffenberger, Ben; Haverkos, Brad; Tyler, Kelly; Wong, Henry; Porcu, Pierluigi; Gru, Alejandro Ariel

    2014-01-01

    Angioimmunoblastic T-cell lymphoma (AITL) is the second most common type of peripheral T-cell lymphoma (PTCL) worldwide, and in some countries the most common form. Clinically, AITL usually presents with systemic symptoms, diffuse lymphadenopathy, hepatosplenomegaly and common laboratory abnormalities such as hypergammaglobulinemia. Skin rashes are seen in 50–80% of patients. AITL derives follicular T-helper cells (TFH), that express germinal center markes and produces hyperactivation of B-cell seen in AITL. Although the histologic features of AITL in the skin could be similar to pathologic findings present in lymph node biopsies, we present herein 2 cases of AITL with histologic and immunophenotypic features that were somewhat suggestive of extranodal marginal zone lymphoma (MALT).Caution is urged to exclude the possibility of a systemic T-cell lymphoma such as AITL in cutaneous and lymph node B-cell proliferations. PMID:25839892

  10. Diffuse large B-cell lymphoma in patient after treatment of angioimmunoblastic T-cell lymphoma.

    PubMed

    Skugor, Nives Dzeko; Perić, Zinaida; Vrhovac, Radovan; Radić-Kristo, Delfa; Kardum-Skelin, Ika; Jaksić, Branimir

    2010-03-01

    Relatively few cases of Epstein-Barr (EBV)-positive B-cell lymphomas arising in patients with angioimmunoblastic T-cell lymphoma (AITL) have been reported. We report a case of AITL in which diffuse large B-cell lymphoma arose 13 months after the initial diagnosis of AITL. In a 36-year-old female patient, evaluated for moderate leukocytosis, peripheral and abdominal lymphadenopathy AITL was diagnosed in March 2008, based on results of fine-needle aspiration cytology (FNAC) of the enlarged cervical and supraclavicular lymph nodes. The diagnosis was also confirmed by immunophenotyping and histopathology of the cervical lymph nodes. The patient initially recieved FED chemotherapy (fludarabine, cyclophosphamide, dexamethasone) followed by elective autologous hematopoietic stem cell transplantation. In April 2009 the patient was hospitalized because of fever, pancytopenia, hyperbilirubinemia and peripheral lymphadenopathy. The FNAC of the enlarged cervical lymph nodes was performed again, but this time the smears were composed of polymorphous population of lymphocytes with the predomination of large cells, CD20+ on immunocytochemical stains. The immunophenotyping confirmed a predomination of monoclonal mature B-cells. Patient had high number of EBV DNA copies in plasma and serologic testing revealed increased titers of EBV VCA IgG and EBV EBNA IgG. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) was then administered, resulting in good partial response of the disease. Reduced intensity allogeneic stem cell transplantation performed thereafter, resulted in complete remission of the disease. AITL is a rare lymphoproliferative disorder in which the neoplastic T-cells represent the minority of the lymph node cell population and almost all cases harbor EBV-infected B-cells. Various authors postulated that immunodeficiency in AITL patients together with immunosuppressive effects of cytotoxic drugs, may be responsible for EBV

  11. Adult T-cell leukemia-lymphoma.

    PubMed

    Tsukasaki, Kunihiro

    2012-04-01

    Adult T-cell leukemia-lymphoma (ATL) was first described in 1977 as a distinct clinico-pathological entity with a suspected viral etiology. Subsequently, a novel RNA retrovirus, human T-cell leukemia/lymphotropic virus type 1 (HTLV-1) was isolated from a cell line established from the leukemic cells of an ATL patient, and the finding of a clear association with ATL led to its inclusion among human carcinogenic pathogens. The three major routes of HTLV-1 transmission are mother-to-child infections via breast milk, sexual intercourse, and blood transfusions. HTLV-1 infection early in life, presumably from breast feeding, is crucial in the development of ATL. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into four categories, acute, lymphoma, chronic, and smoldering types defined by organ involvement, and LDH and calcium values. In cases of acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL), intensive chemotherapy such as VCAP-AMP-VECP is usually recommended. In cases of favorable chronic or smoldering ATL (indolent ATL), watchful waiting until disease progression has been recommended although the long term prognosis was inferior to those of, for instance, chronic lymphoid leukemia. Retrospective analysis suggested that the combination of interferon alpha and zidovudine was apparently promising for the treatment of ATL, especially for types with leukemic manifestation. Allogeneic hematopoietic stem cell transplantation is also promising for the treatment of aggressive ATL possibly reflecting graft vs. ATL effect. Several new agent-trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody. Two steps should be considered for the prevention of HTLV-1-associated ATL. The first is the prevention of HTLV-1 infections and the second is the prevention of ATL among HTLV-1 carriers. So far, no agent has been found to be

  12. Verrucous tumor mimicking squamous cell carcinoma in immunocompetent patient.

    PubMed

    Ruiz-Villaverde, Ricardo; Sanchez-Cano, Daniel; Martinez-Peinado, Carmen M; Galan-Gutierrez, Manuel

    2016-01-01

    Mycobacteria cause a range of diseases in both immunocompetent and immunosuppressed individuals. An increase in non-tuberculous mycobacterial (NTM) infections targeting skin has been described. Many hypotheses have been developed in order to explain it: the increasing burden of immunocompromised individuals, immigration from endemic countries, improved laboratory identification techniques, and changes inhuman behavior that expose individuals to this NTM. Mycobacterium mucogenicum group comprises M. mucogenicum, Mycobacterium aubagnense, and Mycobacterium phocaicum. This group of organisms was first named Mycobacterium chelonae-like organism in 1982. Most clinically significant cases of those organisms involved catheter-related infections. Nevertheless, we report an interesting patient with a cutaneous infection produced by M. mucogenicum mimicking a squamous cell carcinoma; an excellent response to combined therapy with rifampicin and clarythromicin was observed. PMID:27267196

  13. Extranodal NK/T Cell Lymphoma Causing Cardiorespiratory Failure

    PubMed Central

    2016-01-01

    Extranodal NK/T cell lymphoma is an uncommon malignancy usually involving the sinonasal area. We report an unusual case of extranodal NK/T cell lymphoma diagnosed in a 62-year-old Caucasian male who died of progressive cardiorespiratory failure but had no clinically detectable upper respiratory system lesions. The initial diagnosis was made cytologically on a sample of pericardial fluid that contained neoplastic lymphoid cells. These cells were positive for CD2, cytoplasmic CD3, and Epstein-Barr virus and negative for CD56. The diagnosis was confirmed at the autopsy, which disclosed lymphoma infiltrates in the myocardium, lungs, stomach, and pancreas. The death was caused by heart and lung failure due to uncontrollable arrhythmia and respiratory insufficiency due to the lymphoma infiltrates. To the best of our knowledge, this is the first case of extranodal NK/T cell lymphoma presenting with cardiopulmonary failure. PMID:27493813

  14. Hematopoietic stem cell transplantation for non-Hodgkin lymphoma.

    PubMed

    Bhatt, Vijaya Raj; Vose, Julie M

    2014-12-01

    Up-front rituximab-based chemotherapy has improved outcomes in non-Hodgkin lymphoma (NHL); refractory or relapsed NHL still accounts for approximately 18,000 deaths in the United States. Autologous hematopoietic stem cell transplantation (SCT) can improve survival in primary refractory or relapsed aggressive NHL and mantle cell lymphoma and in relapsed follicular or peripheral T-cell lymphoma. Autologous SCT as a consolidation therapy after first complete or partial remission in high-risk aggressive NHL, mantle cell lymphoma, and peripheral T-cell lymphoma may improve progression-free survival. Allogeneic SCT offers a lower relapse rate but a higher nonrelapse mortality resulting in overall survival similar to autologous SCT. PMID:25459180

  15. Extranodal NK/T Cell Lymphoma Causing Cardiorespiratory Failure.

    PubMed

    Li, Yiting; Damjanov, Ivan

    2016-01-01

    Extranodal NK/T cell lymphoma is an uncommon malignancy usually involving the sinonasal area. We report an unusual case of extranodal NK/T cell lymphoma diagnosed in a 62-year-old Caucasian male who died of progressive cardiorespiratory failure but had no clinically detectable upper respiratory system lesions. The initial diagnosis was made cytologically on a sample of pericardial fluid that contained neoplastic lymphoid cells. These cells were positive for CD2, cytoplasmic CD3, and Epstein-Barr virus and negative for CD56. The diagnosis was confirmed at the autopsy, which disclosed lymphoma infiltrates in the myocardium, lungs, stomach, and pancreas. The death was caused by heart and lung failure due to uncontrollable arrhythmia and respiratory insufficiency due to the lymphoma infiltrates. To the best of our knowledge, this is the first case of extranodal NK/T cell lymphoma presenting with cardiopulmonary failure. PMID:27493813

  16. Clinical implications of immunologic phenotyping in cutaneous T cell lymphoma.

    PubMed

    Vonderheid, E C; Tan, E; Sobel, E L; Schwab, E; Micaily, B; Jegasothy, B V

    1987-07-01

    The composition of cutaneous lesions from 158 patients with confirmed cutaneous T cell lymphoma, 91 patients with suspected cutaneous T cell lymphoma, and 145 patients with lymphoid disorders other than cutaneous T cell lymphoma was quantitated in situ with the use of commercially available murine monoclonal antibodies that identify the Pan T, T-helper/inducer (Th), T cytotoxic/suppressor (Ts), and Pan B lymphocyte subsets. On average, cutaneous infiltrates of confirmed cutaneous T cell lymphoma were found to contain significantly more Th and less Ts or Pan B cells compared to benign lymphoid disorders. Moreover, when analyzed in terms of the type of lesion examined by biopsy, the absolute amount of Th cells progressively expands with increasing magnitudes of infiltrate in the dermis while the amount of Ts and Pan B cells remains relatively constant among lesions. A useful diagnostic criterion (anti-Leu 1/4 greater than or equal to 70% and anti-Leu 3a/anti-Leu 2a ratio greater than or equal to 6) correctly discriminated between cutaneous T cell lymphoma and non-cutaneous T cell lymphoma in 87.5% of cases. A positive immunodiagnostic result also may be useful for the prediction of subsequent histopathologic confirmation of cutaneous T cell lymphoma in patients who have suspect lymphoid infiltrates, such as alopecia mucinosis or idiopathic generalized erythroderma, when first seen. With the use of multivariate analysis, stage and possibly the percentage of Th cells within the T cell component in cutaneous infiltrates were covariates with significant relationships to survival in patients with confirmed cutaneous T cell lymphoma. In addition, Ts cells in infiltrates did not correlate significantly with observed responses to topical treatment and subsequent course in pretumorous mycosis fungoides. These results indicate that Ts cells play little biologic role in modifying the natural history of cutaneous T cell lymphoma.

  17. Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)

    ClinicalTrials.gov

    2016-08-31

    B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

  18. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

    PubMed Central

    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. Typically, these cases share features intermediate between DLBCL and classical BL or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this article, we present a “classical unclassifiable lymphoma with features intermediate between DLBCL and BL” in a young male patient and review of literature. PMID:27601842

  19. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

    PubMed Central

    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. Typically, these cases share features intermediate between DLBCL and classical BL or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this article, we present a “classical unclassifiable lymphoma with features intermediate between DLBCL and BL” in a young male patient and review of literature.

  20. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review.

    PubMed

    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. Typically, these cases share features intermediate between DLBCL and classical BL or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this article, we present a "classical unclassifiable lymphoma with features intermediate between DLBCL and BL" in a young male patient and review of literature. PMID:27601842

  1. Cutaneous primary B-cell lymphomas: from diagnosis to treatment*

    PubMed Central

    Lima, Margarida

    2015-01-01

    Primary cutaneous B-cell lymphomas are a heterogeneous group of mature B-cells neoplasms with tropism for the skin, whose biology and clinical course differ significantly from the equivalent nodal lymphomas. The most indolent forms comprise the primary cutaneous marginal zone and follicle center B-cell lymphomas that despite the excellent prognosis have cutaneous recurrences very commonly. The most aggressive forms include the primary cutaneous large B-cell lymphomas, consisting in two major groups: the leg type, with poor prognosis, and others, the latter representing a heterogeneous group of lymphomas from which specific entities are supposed to be individualized over time, such as intravascular large B-cell lymphomas. Treatment may include surgical excision, radiotherapy, antibiotics, corticosteroids, interferon, monoclonal antibodies and chemotherapy, depending on the type of lymphoma and on the type and location of the skin lesions. In subtypes with good prognosis is contraindicated overtreatment and in those associated with a worse prognosis the recommended therapy relies on CHOP-like regimens associated with rituximab, assisted or not with local radiotherapy. We review the primary cutaneous B-cell lymphomas, remembering the diagnostic criteria, differential diagnosis, classification, and prognostic factors and presenting the available therapies. PMID:26560215

  2. Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant

    ClinicalTrials.gov

    2014-04-03

    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; Prolymphocytic Leukemia; 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 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 Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  3. Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-08-16

    Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  4. Interleukin-2 or Observation Following Radiation Therapy, Combination Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Recurrent Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-02-27

    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 Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma

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

    ClinicalTrials.gov

    2016-03-21

    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

  6. ATM deficiency promotes development of murine B-cell lymphomas that resemble diffuse large B-cell lymphoma in humans

    PubMed Central

    Hathcock, Karen S.; Padilla-Nash, Hesed M.; Camps, Jordi; Shin, Dong-Mi; Triner, Daniel; Shaffer, Arthur L.; Maul, Robert W.; Steinberg, Seth M.; Gearhart, Patricia J.; Staudt, Louis M.; Morse, Herbert C.; Ried, Thomas

    2015-01-01

    The serine-threonine kinase ataxia-telangiectasia mutated (ATM) plays a central role in maintaining genomic integrity. In mice, ATM deficiency is exclusively associated with T-cell lymphoma development, whereas B-cell tumors predominate in human ataxia-telangiectasia patients. We demonstrate in this study that when T cells are removed as targets for lymphomagenesis and as mediators of immune surveillance, ATM-deficient mice exclusively develop early-onset immunoglobulin M+ B-cell lymphomas that do not transplant to immunocompetent mice and that histologically and genetically resemble the activated B cell–like (ABC) subset of human diffuse large B-cell lymphoma (DLBCL). These B-cell lymphomas show considerable chromosomal instability and a recurrent genomic amplification of a 4.48-Mb region on chromosome 18 that contains Malt1 and is orthologous to a region similarly amplified in human ABC DLBCL. Of importance, amplification of Malt1 in these lymphomas correlates with their dependence on nuclear factor (NF)-κB, MALT1, and B-cell receptor (BCR) signaling for survival, paralleling human ABC DLBCL. Further, like some human ABC DLBCLs, these mouse B-cell lymphomas also exhibit constitutive BCR-dependent NF-κB activation. This study reveals that ATM protects against development of B-cell lymphomas that model human ABC DLBCL and identifies a potential role for T cells in preventing the emergence of these tumors. PMID:26400962

  7. The molecular biology of diffuse large B-cell lymphoma.

    PubMed

    Frick, Mareike; Dörken, Bernd; Lenz, Georg

    2011-12-01

    Diffuse large B-cell lymphoma (DLBCL) represents the most common type of malignant lymphoma. In the last few years, significant progress has been achieved in the understanding of the molecular pathogenesis of this entity. Gene expression profiling has identified three molecular DLBCL subtypes, termed germinal-center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma (PMBL). In this review, we summarize our current understanding of the biology of these DLBCL subtypes with a special emphasis on novel diagnostic and therapeutic approaches. PMID:23556103

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

    ClinicalTrials.gov

    2016-09-06

    Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  9. MicroRNA signatures in B-cell lymphomas

    PubMed Central

    Di Lisio, L; Sánchez-Beato, M; Gómez-López, G; Rodríguez, M E; Montes-Moreno, S; Mollejo, M; Menárguez, J; Martínez, M A; Alves, F J; Pisano, D G; Piris, M A; Martínez, N

    2012-01-01

    Accurate lymphoma diagnosis, prognosis and therapy still require additional markers. We explore the potential relevance of microRNA (miRNA) expression in a large series that included all major B-cell non-Hodgkin lymphoma (NHL) types. The data generated were also used to identify miRNAs differentially expressed in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) samples. A series of 147 NHL samples and 15 controls were hybridized on a human miRNA one-color platform containing probes for 470 human miRNAs. Each lymphoma type was compared against the entire set of NHLs. BL was also directly compared with DLBCL, and 43 preselected miRNAs were analyzed in a new series of routinely processed samples of 28 BLs and 43 DLBCLs using quantitative reverse transcription-polymerase chain reaction. A signature of 128 miRNAs enabled the characterization of lymphoma neoplasms, reflecting the lymphoma type, cell of origin and/or discrete oncogene alterations. Comparative analysis of BL and DLBCL yielded 19 differentially expressed miRNAs, which were confirmed in a second confirmation series of 71 paraffin-embedded samples. The set of differentially expressed miRNAs found here expands the range of potential diagnostic markers for lymphoma diagnosis, especially when differential diagnosis of BL and DLBCL is required. PMID:22829247

  10. Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2016-06-17

    B-Cell Prolymphocytic Leukemia; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  11. Tetanus toxoid reactive lymphadenopathy masquerading as T-cell lymphoma.

    PubMed

    White, Christine K; Al-Saleem, Tahseen; Skarbnik, Alan Pz; Smith, Mitchell R

    2012-05-01

    We report a case in which a patient with persistent reactive lymphadenopathy post-tetanus toxoid vaccination was initially diagnosed as having T-cell lymphoma/leukemia. A florid CD4+ T-cell proliferation and pathology interpretation, in the absence of complete clinical information, that these cells co-expressed CD8 led to the initial diagnosis. Better integration of the clinical and pathologic data may have led more rapidly to the final diagnosis. Postvaccination responses can mimic lymphoma.

  12. Mimicking Neural Stem Cell Niche by Biocompatible Substrates

    PubMed Central

    Regalado-Santiago, Citlalli; Juárez-Aguilar, Enrique; Olivares-Hernández, Juan David; Tamariz, Elisa

    2016-01-01

    Neural stem cells (NSCs) participate in the maintenance, repair, and regeneration of the central nervous system. During development, the primary NSCs are distributed along the ventricular zone of the neural tube, while, in adults, NSCs are mainly restricted to the subependymal layer of the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. The circumscribed areas where the NSCs are located contain the secreted proteins and extracellular matrix components that conform their niche. The interplay among the niche elements and NSCs determines the balance between stemness and differentiation, quiescence, and proliferation. The understanding of niche characteristics and how they regulate NSCs activity is critical to building in vitro models that include the relevant components of the in vivo niche and to developing neuroregenerative approaches that consider the extracellular environment of NSCs. This review aims to examine both the current knowledge on neurogenic niche and how it is being used to develop biocompatible substrates for the in vitro and in vivo mimicking of extracellular NSCs conditions. PMID:26880934

  13. NK/T cell lymphoma associated with peripheral eosinophilia.

    PubMed

    Yap, E; Wan Jamaluddin, W F; Tumian, N R; Mashuri, F; Mohammed, F; Tan, G C; Masir, N; Abdul Wahid, F S

    2014-12-01

    NK/T cell lymphoma, nasal type is an aggressive and uncommon malignancy. Disease that occurs outside of the aerodigestive tract exhibits an even more aggressive clinical behaviour and does not respond as well to conventional therapy compared to its nasal counterpart. We report such a case of NK/T cell lymphoma, nasal type, that presented as an anterior chest wall mass, arising from the left pectoralis muscle. An interesting feature we wish to highlight is the associated eosinophilia that corresponded to disease activity, exhibiting fluctuations with surgical resection and chemotherapy. To the best of our knowledge this is the third reported case of NK/T cell lymphoma that is associated with peripheral eosinophilia. Our case highlights the role of certain NK cell subsets that play a major role in eosinophilic activation in NK/T lymphomas and calls for more research into further classification of this disease by virtue of its NK cell subsets. PMID:25500520

  14. B-Cell Lymphoma of the Mandible: A Case Report

    PubMed Central

    Adouani, Ali; Bouguila, Jed; Jeblaoui, Yassine; Ben Aicha, Mehdi; Abdelali, Mouhamed Ali; Hellali, Mouna; Zitouni, Karima; Amani, Landolsi; Issam, Zairi

    2008-01-01

    Summary Introduction The mandible is an infrequent localisation of primary osseous non-Hodgkin’s lymphomas. Few cases of mandibular non-Hodgkin’s lymphomas (NHL) have been reported. Case report A rare condition of primary malignant non-Hodgkin’s lymphoma of the mandible in 53-year-old man, was reported at the Department of Maxillofacial and Plastic Surgery in Charles Nicolle Hospital (Tunis, Tunisia). Histologic and Immunohistochemical (IHC) examination Confirmed a B-Cell lymphoma. Discussion The purpose of this report is to describe this rare case of NHL of the mandible, explore the diagnosis and workup, and discuss treatment strategies. In this localisation, neither the clinical features nor the radiologic appearances are often pathognomonic. Conclusion Particular care must be taken to consider lymphoma in the differential diagnosis because this uncommon lesion can pose significant diagnostic problems and is frequently misdiagnosed. PMID:21892315

  15. Mycosis Fungoides Associated with Kaposi's Sarcoma, T-cell Rich B-cell Lymphoma, and T-cell Lymphoma with Angioimmunoblastic Features.

    PubMed

    Samuelov, Liat; Gat, Andrea; Bergman, Reuven; Sprecher, Eli; Goldberg, Ilan

    2016-08-01

    A patient with mycosis fungoides (MF), Kaposi's sarcoma, T-cell rich B-cell lymphoma, and T-cell lymphoma with angioimmunoblastic features is described. The appearance of multiple malignancies in this patient may have been caused by previous exposure to radiation in the Chernobyl accident and/or systemic chemotherapy for the initial T-cell rich B-cell lymphoma which he underwent. PMID:27663924

  16. Relation of CD30 expression to survival and morphology in large cell B cell lymphomas.

    PubMed Central

    Noorduyn, L A; de Bruin, P C; van Heerde, P; van de Sandt, M M; Ossenkoppele, G J; Meijer, C J

    1994-01-01

    AIMS--To investigate whether CD30 expression is correlated with anaplastic morphology, and whether this correlated with a better survival in large cell B cell lymphomas, as has been described for T cell lymphomas. METHODS--CD30 expression was investigated using frozen sections in a series of 146 large cell B cell lymphomas. Clinical data and follow up information were collected from 25 lymphomas with strong CD30 expression, 30 lymphomas with partial CD30 expression, and a control group of 25 lymphomas which did not express CD30. RESULTS--Morphological distinction between anaplastic and non-anaplastic tumours was difficult. Of the cases with an anaplastic morphology, 50% were CD30 positive, as were 24% of the polymorphic centroblastic B cell lymphomas. Only 65% of the morphologically non-anaplastic tumours were completely CD30 negative. There was no difference in survival among patients with lymphomas expressing CD30 and those that did not. Patients with morphologically anaplastic B cell lymphomas did not differ in their survivals from those with other high grade B cell lymphomas. Clinical stage at presentation was the only variable that was significantly associated with survival. CONCLUSIONS--CD30 expression occurs frequently in large cell B cell lymphomas and is poorly related to anaplastic morphology. Morphological distinction between anaplastic and non-anaplastic tumours is difficult. In contrast to T cell lymphomas, CD30 positive B cell lymphomas do not show a relatively favourable clinical course. The results presented here raise serious doubts as to whether large cell B cell lymphoma, based on the expression of CD30 or anaplastic morphology, can really be termed a separate entity. Images PMID:8132806

  17. Diffuse Large B-Cell Lymphoma Version 1.2016.

    PubMed

    Zelenetz, Andrew D; Gordon, Leo I; Wierda, William G; Abramson, Jeremy S; Advani, Ranjana H; Andreadis, C Babis; Bartlett, Nancy; Byrd, John C; Fayad, Luis E; Fisher, Richard I; Glenn, Martha J; Habermann, Thomas M; Lee Harris, Nancy; Hernandez-Ilizaliturri, Francisco; Hoppe, Richard T; Horwitz, Steven M; Kaminski, Mark S; Kelsey, Christopher R; Kim, Youn H; Krivacic, Susan; LaCasce, Ann S; Lunning, Matthew; Nademanee, Auayporn; Porcu, Pierluigi; Press, Oliver; Rabinovitch, Rachel; Reddy, Nishitha; Reid, Erin; Roberts, Kenneth; Saad, Ayman A; Sokol, Lubomir; Swinnen, Lode J; Vose, Julie M; Yahalom, Joachim; Zafar, Nadeem; Dwyer, Mary; Sundar, Hema

    2016-02-01

    Diffuse large B-cell lymphomas (DLBCL) are now considered a heterogeneous group of distinct molecular subtypes (germinal center B-cell DLBCL, activated B-cell DLBCL, and primary mediastinal large B-cell lymphoma (PMBL) with varied natural history and response to therapy. In addition, a subset of patients with DLBCL have concurrent MYC and/or BCL2 gene rearrangements (double-hit lymphomas; DHL) and others have a dual expression of both MYC and BCL2 proteins (double-expressing DLBCL; DEL). The standard of care for the treatment of patients with PMBL, DHL, or DEL has not been established. Adequate immunophenotyping and molecular testing (in selected circumstances) are necessary for the accurate diagnosis of different subtypes of DLBCL. The NCCN Guidelines included in this issue, part of the NCCN Guidelines for non-Hodgkin's lymphomas, address the diagnosis and management of DLBCL and its subtypes. PMID:26850490

  18. Molecular Targeted Approaches in Mantle Cell lymphoma.

    PubMed Central

    Weniger, Marc A.; Wiestner, Adrian

    2011-01-01

    Mantle cell lymphoma (MCL) is a malignancy of mature B cells characterized by the translocation t(11;14) that leads to aberrant expression of cyclin D1. Response to first-line chemotherapy is good but most patients relapse resulting in a median survival of 5-7 years. The important PI3K/AKT/mTOR pathway can be targeted with small molecules. mTOR inhibitors have clinical activity and temsirolimus has been approved in Europe. Second generation mTOR inhibitors and the PI3K inhibitor CAL-101 offer additional means to target the pathway. Promising results with the BTK inhibitor PCI-32765 suggest that B-cell receptor signaling could play a role. For unknown reasons, MCL appears to be particularly sensitive to disruption of protein homeostasis. The proteasome inhibitor bortezomib achieves responses in up to 50% of relapsed patients. Much work has been done in elucidating the mechanism of its cytotoxicity, its incorporation into combination therapies, and the development of second generation proteasome inhibitors. Deacetylase and HSP90 inhibitors are also promising classes of drugs that can synergize with proteasome inhibitors. Finally, BH3 mimetics are emerging as tools to sensitize tumor cells to chemotherapy. Participation in clinical trials offers patients an immediate chance to benefit from these advances and is essential to maintain the momentum of progress. PMID:21782064

  19. Signet-ring Cell Lymphoma-a Case Report.

    PubMed

    Masir, N; Cheong, S K; Noordin, K

    2001-01-01

    A case of signet-ring cell lymphoma diagnosed initially by fine needle aspiration cytology is reported. This rare tumor is a variant of follicular lymphoma, which closely resembles metastatic adenocarcinoma and other tumors which exhibit signet-ring cell appearance. Correct diagnosis can be achieved by careful morphologic analysis together with positive reactivity with lymphoid markers. The cytohistologic, immunohistochemical and electron microscopic features are described, and the differ ential diagnostic considerations are discussed in the report. PMID:27420125

  20. Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma

    ClinicalTrials.gov

    2016-10-06

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; 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; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

  1. [Monoclonal gammopathy and primary colonic mantle cell lymphoma].

    PubMed

    Mohamed, G; Kochlef, A; Gargouri, D; Kilani, A; Elloumi, H; Ouakaa, A; Belhadj, N; Romani, M; Kharrat, J; Ghorbel, A

    2009-03-01

    The association of a monoclonal gammopathy (MG) with a B cell non-Hodgkin's lymphoma (NHL) is a well-known phenomenon. It has been recognized in many subtypes of primary gastrointestinal lymphoma but its association with primary colonic mantle cell lymphoma has never been yet described. We report a 65-year-old man who presented with an exudative ascites and constipation. Serum electrophoresis showed a monoclonal peak in the gamma region of 45g/L and immunoelectrophoresis confirmed the presence of monoclonal gammopathy of IgM kappa type. Bone marrow aspirate was normal. Radiologic and endoscopic investigations evidenced a primary colonic mantle cell lymphoma. Although the association of an MG with an NHL and, in particular, to a primitive digestive location appears a rare phenomenon, endoscopic investigations in patients with MG appears legitimate in the presence of any digestive sign.

  2. Langerhans Cell Histiocytosis Followed by Hodgkin Lymphoma: A Case Report

    PubMed Central

    Safaei, Akbar; Bagheri, Mandana; Shahryari, Jahanbanoo; Noori, Sadat; Esmailzade, Elmira

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare neoplasm defined as the proliferation of bone marrow langerhans cells, which is a kind of dendritic cells. The major pathological features of LCH are expression of CD1a and S100 as well as Birbeck granules. Its presentation can differ from a mild bone lesion to a multi-systemic evolved malignant neoplasm; however, the latter outcome is almost rare. Thus, LCH is mostly known as a benign neoplasm. In this study, we present a case of LCH followed by Hodgkin lymphoma (HL). Accompaniment of this disease with malignant lymphoma is rare and considered as case report. Several cases in which malignant lymphoma occurred prior to LCH are reported; however, few cases can be found with LCH followed by malignant lymphomas. PMID:25999631

  3. B Cell Lymphoma, Unclassifiable, Transformed from Follicular Lymphoma: A Rare Presentation with Review of the Literature

    PubMed Central

    Kanna, Anila; Agrawal, Swati; Jayant, Kumar; Kumar Pala, Varun; Altujjar, Mohammad; Hadid, Tarik; Khurram, Muhammad

    2015-01-01

    B cell lymphoma, unclassifiable, with features of diffuse large B cell lymphoma and classical Hodgkin's lymphoma (BCLu-DLBCL/CHL) is more commonly known as gray zone lymphoma. These cases more often present with mediastinal disease. In this report, we present a very rare case of BCLu-DLBCL/CHL without mediastinal involvement, transformed from follicular lymphoma (FL) to BCLu-DLBCL/CHL. This patient initially presented with a mass in the right neck; biopsy of the lymph node showed predominantly nodular, follicular pattern. Immunohistochemical (IHC) staining of tumor cells expressed positivity for mature B cell markers CD20, CD19, CD10, CD23, CD45, and CD38 but negative for CD5,11c. Hence, diagnosed with FL, he was given rituximab, cyclophosphamide, vincristine, and prednisone (RCVP) regimen, followed by maintenance rituximab. He showed good response. After 2 years, he presented again with a mass in the right side of the neck. Although the needle core biopsy of this mass was suggestive of B cell lymphoma, excisional biopsy showed morphological features of DLBCL as well as foci of histological pattern of CHL. IHC staining expressed positivity for CD20, CD79a, PAX5, and CD15 and CD30 consistent with DLBCL and CHL. He was diagnosed with BCLu-DLBCL/CHL. The patient received “ACVBP” (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) followed by radiation. BCLu-DLBCL/CHL is clinically an aggressive tumor with poorer outcomes, but our case showed complete response to ACVBP regimen with tumor regression. PMID:26380128

  4. Melanoma Stem Cells and Metastasis: Mimicking Hematopoietic Cell Trafficking?

    PubMed Central

    Lee, Nayoung; Barthel, Steven R.; Schatton, Tobias

    2014-01-01

    Malignant melanoma is a highly metastatic cancer that bears responsibility for the majority of skin cancer-related deaths. Amidst the research efforts to better understand melanoma progression, there has been increasing evidence that hints at a role for a subpopulation of virulent cancer cells, termed malignant melanoma stem or initiating cells (MMICs), in metastasis formation. MMICs are characterized by their preferential ability to initiate and propagate tumor growth and their selective capacity for self-renewal and differentiation into less tumorigenic melanoma cells. The frequency of MMICs has been shown to correlate with poor clinical prognosis in melanoma. Additionally, MMICs are enriched among circulating tumor cells (CTCs) in the peripheral blood of cancer patients, suggesting that MMICs may be a critical player in the metastatic cascade. Although these links exist between MMICs and metastatic disease, the mechanisms by which MMICs may advance metastatic progression are only beginning to be elucidated. Recent studies have shown that MMICs express molecules critical for hematopoietic cell maintenance and trafficking, providing a possible explanation for how circulating MMICs could drive melanoma dissemination. We therefore propose that MMICs might fuel melanoma metastasis by exploiting homing mechanisms commonly utilized by hematopoietic cells. Here we review the biological properties of MMICs and the existing literature on their metastatic potential. We will discuss possible mechanisms by which MMICs might initiate metastases in the context of established knowledge of cancer stem cells (CSCs) in other cancers and of hematopoietic homing molecules, with a particular focus on selectins, integrins, chemokines, and chemokine receptors known to be expressed by melanoma cells. Biological understanding of how these molecules might be utilized by MMICs to propel the metastatic cascade could critically impact the development of more effective therapies for advanced

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

    ClinicalTrials.gov

    2016-10-11

    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

  6. New Molecular Targets in Mantle Cell lymphoma

    PubMed Central

    Parekh, Samir; Weniger, Marc A.; Wiestner, Adrian

    2011-01-01

    Mantle cell lymphoma (MCL) is a malignancy of mature B cells characterized by aberrant expression of cyclin D1 due to the translocation t(11;14). Epigenomic and genomic lesions in pathways regulating B-cell activation, cell cycle progression, protein homeostasis, DNA damage response, cell proliferation and apoptosis contribute to its pathogenesis. While patients typically respond to first-line chemotherapy, relapse is the rule resulting in a median survival of 5–7 years. The PI3K/AKT/mTOR appears as a key pathway in the pathogenesis and can be targeted with small molecules. Most experience is with mTOR inhibitors of the rapamycin class. Second-generation mTOR inhibitors and the PI3K inhibitor CAL-101 are novel options to more effectively target this pathway. Bruton’s tyrosine kinase inhibition by PCI-32765 has promising activity and indicates immunoreceptor signaling as a novel therapeutic target. Up to 50% of relapsed patients respond to the proteasome inhibitor bortezomib suggesting that MCL may be particularly sensitive to disruption of protein homeostasis and/or induction of oxidative stress. Recent work has focused on elucidating the mechanism of bortezomib-induced cytotoxicity and the development of second-generation proteasome inhibitors. DNA hypomethylating agents and histone deacetylase inhibitors effect epigenetic de-repression of aberrantly silenced genes. These epigenetic pharmaceuticals and HSP90 inhibitors can synergize with proteasome inhibitors. Finally, BH3 mimetics are emerging as tools to sensitize tumor cells to chemotherapy. Participation in clinical trials offers patients a chance to benefit from these advances and is essential to maintain the momentum of progress. Innovative trial designs may be needed to expedite the clinical development of these targeted agents. PMID:21945517

  7. Prospective Isolation of Clonogenic Mantle Cell Lymphoma Initiating Cells

    PubMed Central

    Chen, Zheng; Ayala, Paul; Wang, Michael; Fayad, Luis; Katz, Ruth L.; Romaguera, Jorge; Caraway, Nancy; Neelapu, Sattva S.; Kwak, Larry W.; Simmons, Paul J.; McCarty, Nami

    2010-01-01

    Here, we have prospectively isolated and characterized, for the first time, clonogenic cells with self-renewal capacities from mantle cell lymphoma (MCL), a particularly deadly form of Non-Hodgkin’s Lymphoma (NHL). Self-renewal and tumorigenic activities were enriched in MCL cell fractions that lacked expression of the prototypic B cell surface marker, CD19. CD45+CD19− cells represented a relatively small fraction of the total MCL tumor cells, however, they recapitulated the heterogeneity of original patient tumors upon transplantation into immunodeficient mice. As few as 100 of these cells displayed self-renewal capacities in secondary and tertiary recipient mice by in vivo limiting dilution assays. Similar to leukemic stem cells, CD45+CD19− MCL cells also displayed a quiescent status as determined by dye efflux assays. In summary, this study is the first to isolate subpopulations of MCL cells that have self-renewal and tumorigenic capacities. Identification and characterization of MCL-ICs is an important first step toward understanding how self-renewal and tumorigenicity are regulated in MCL and designing targeted therapies against MCL-ICs will ultimately lead to improved outcomes for MCL patients. PMID:20851072

  8. Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2016-09-08

    Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  9. S0349 Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Oblimersen in Treating Patients With Advanced Diffuse Large B-Cell Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-04

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  10. Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia

    ClinicalTrials.gov

    2016-10-24

    Childhood B Acute Lymphoblastic Leukemia; Childhood Burkitt Leukemia; Childhood Diffuse Large Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma

  11. Clonal relationships in recurrent B-cell lymphomas.

    PubMed

    Lee, Seung Eun; Kang, So Young; Yoo, Hae Yong; Kim, Seok Jin; Kim, Won Seog; Ko, Young Hyeh

    2016-03-15

    Immunoglobulin (Ig) gene rearrangements remain largely unmodified during the clonal expansion of neoplastic cells. We investigated the clonal relationships between lymphoma components at diagnosis and at relapse by analyzing Ig gene rearrangements. A BIOMED-2 multiplex polymerase chain reaction (PCR) assay was performed in 27 patients using formalin-fixed paraffin embedded tissues, with subsequent cloning and sequencing of the amplified Ig genes in 17 patients. All 27 cases of primary and corresponding relapsed tumors showed monoclonal rearrangements of the Ig genes by BIOMED-2 PCR. Whereas IgVH or IgVK fragment lengths were identical in 8/27 pairs (30%), fragment lengths differed in 19/27 pairs (70%). In 17 cases analyzed by sequencing, an identical VDJ gene rearrangement was confirmed in 4/4 pairs (100%) with the same fragment lengths and in 10/13 pairs (77%) with different fragment lengths. Four of 17 primary lymphomas had multiple VDJ rearrangements, and three of them showed an unrelated relapse. Unrelated relapse was observed in 1/8 mantle cell lymphomas, 1/5 diffuse large B-cell lymphomas, and a large B cell lymphoma developed in a patient with a small lymphocytic lymphoma. Unrelated relapses developed after a longer disease-free interval and tended to show poorer outcome compared with related relapse. In summary, relapse of a lymphoma from an unrelated clone is uncommon, but can occur in B-cell lymphomas. Clonal relationships should be determined by sequencing of the Ig genes, and not just by comparing the PCR product size. PMID:26848863

  12. Lenalidomide as Maintenance Therapy After Combination Chemotherapy With or Without Rituximab and Stem Cell Transplant in Treating Patients With Persistent or Recurrent Non-Hodgkin Lymphoma That is Resistant to Chemotherapy

    ClinicalTrials.gov

    2014-12-02

    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; 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 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 Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic 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 Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic 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

  13. B-cell leukemia/lymphoma panel

    MedlinePlus

    ... Elsevier Saunders; 2016:chap 183. Bierman PJ, Armitage JO. Non-Hodgkin lymphomas. In: Goldman L, Schafer AI, ... cytometry in oncologic diagnosis. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's ...

  14. Primary splenic B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: A case report

    PubMed Central

    Shi, Feng; Zhou, Quan; Gao, Ying; Cui, Xiang-Qing; Chang, Hong

    2016-01-01

    B-cell lymphoma (BCL), unclassifiable, with features intermediate between diffuse large BCL (DLBCL) and classical Hodgkin's lymphoma (CHL), is a novel entity to the World Health Organization classification system. These tumors are rare aggressive lymphomas that have a poor prognosis. The present study reports the case of a patient with one such lymphoma that occurred in the spleen, which expressed cluster of differentiation (CD)20, CD79α, melanoma associated antigen (mutated) 1, BCL6, CD15 and CD30. Polymerase chain reaction analysis demonstrated a clonal rearrangement of the genes coding for immunoglobulin heavy chains. The tumor cells demonstrated a negative reaction in the Epstein-Barr virus-encoded small RNA assay. Following the diagnosis of unclassifiable BCL, with intermediate features between DLBCL and CHL, the patient received 7 cycles of the CHOP regimen, and so far, has been in good general condition and tumor-free for 17 months. PMID:27602118

  15. Advances and issues in mantle cell lymphoma research: report of the 2014 Mantle Cell Lymphoma Consortium Workshop.

    PubMed

    Kahl, Brad S; Gordon, Leo I; Dreyling, Martin; Gascoyne, Randy D; Sotomayor, Eduardo M

    2015-01-01

    Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma characterized by the t(11;14) chromosomal translocation and cyclin D1 over-expression. A biologically and clinically heterogeneous lymphoma, MCL, remains clinically challenging, with no proven curative therapy and no established standard of care. However, there have been considerable advances in the last several years in the treatment and understanding of MCL with the FDA approval of lenalidomide and ibrutinib, the development of other potentially active novel agents and the identification of recurrent mutations through new genomic sequencing approaches that may contribute to the biology of MCL and to therapeutic resistance. At the Lymphoma Research Foundation's 11th MCL Workshop, researchers gathered to discuss recent studies and current issues related to the biology of MCL, novel therapeutic targets and new treatment strategies. The presentations are summarized in this manuscript, which is intended to highlight areas of active investigation and identify topics for future research.

  16. KLF4 is a tumor suppressor in B-cell non-Hodgkin lymphoma and in classic Hodgkin lymphoma.

    PubMed

    Guan, Hanfeng; Xie, Linka; Leithäuser, Frank; Flossbach, Lucia; Möller, Peter; Wirth, Thomas; Ushmorov, Alexey

    2010-09-01

    The transcription factor KLF4 may act both as an oncogene and a tumor suppressor in a tissue-depending manner. In T- and pre-B-cell lymphoma, KLF4 was found to act as tumor suppressor. We found the KLF4 promoter methylated in B-cell lymphoma cell lines and in primary cases of B-cell lymphomas, namely, follicular lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma, and in classic Hodgkin lymphoma (cHL) cases. Promoter hypermethylation was associated with silencing of KLF4 expression. Conditional overexpression of KLF4 in Burkitt lymphoma cell lines moderately retarded proliferation, via cell-cycle arrest in G(0)/G(1). In the cHL cell lines, KLF4 induced massive cell death that could partially be inhibited with Z-VAD.fmk. A quantitative reverse-transcribed polymerase chain reaction array revealed KLF4 target genes, including the proapoptotic gene BAK1. Using an shRNA-mediated knock-down approach, we found that BAK1 is largely responsible for KLF4-induced apoptosis. In addition, we found that KLF4 negatively regulates CXCL10, CD86, and MSC/ABF-1 genes. These genes are specifically up-regulated in HRS cells of cHL and known to be involved in establishing the cHL phenotype. We conclude that epigenetic silencing of KLF4 in B-cell lymphomas and particularly in cHL may favor lymphoma survival by loosening cell-cycle control and protecting from apoptosis. PMID:20519630

  17. Human T cell lymphotropic virus-associated leukemia/lymphoma

    PubMed Central

    Ratner, Lee

    2009-01-01

    Purpose of review This article summarizes the current pathophysiologic basis for human T cell lymphotropic virus-associated leukemia/lymphoma as well as past, present, and future therapeutic options. Recent findings New studies have been published on allogeneic stem cell transplantation, arsenic trioxide, and bortezomib for this condition. Summary Studies of the molecular biology of human T cell lymphotropic virus-1-induced T cell leukemia/lymphoma have defined a critical role for oncoprotein, Tax, and activation of nuclear factor κB transcription pathways, which have provided rational approaches to improved therapy for T cell leukemia/lymphoma as well as a model for other hematopoietic malignancies characterized by nuclear factor κB activation. PMID:16093798

  18. Diffuse large B cell lymphoma with chronic granulomatous inflammation.

    PubMed

    Nyunt, W W T; Wong, Y P; Wan Jamaludin, W F; Abdul Wahid, S F S

    2016-04-01

    Non-necrotic epithelioid granulomas have been reported in association with neoplasms including Hodgkin and non-Hodgkin lymphoma. We report a case of diffuse large B cell lymphoma with chronic granulomatous inflammation to highlight awareness of obscure tumour cells within the granuloma, to avoid delay in diagnosis and management of lymphoma. A 39-year-old Malay lady with no past medical history, presented with a 2-month history of progressive worsening of difficulty in breathing, cough, low-grade fever, loss of weight and loss of appetite. Chest X-ray showed an anterior mediastinal mass and computed tomography (CT)-guided biopsy was reported as chronic granulomatous inflammation suggestive of tuberculosis. After 2 months of anti-TB treatment, her symptoms were not relieved. The patient underwent another CT-guided biopsy of the anterior mediastinal mass in another hospital and the histopathology revealed diffuse large B cell lymphoma. The patient was referred for treatment. On histopathological review, the first sample showed noncaseating granulomas engulfing tumour cells and large abnormal lymphoid cells which were CD20 positive and with high Ki-67 proliferative index. The patient was diagnosed with diffuse large B cell lymphoma stage IV B IPSS score 3. She underwent chemotherapy (R-EPOCH) and responded well to treatment. PMID:27126666

  19. Candidate genes contributing to the aggressive phenotype of mantle cell lymphoma

    PubMed Central

    Henson, Sarah E.; Morford, Travis; Stein, Mary-Pat; Wall, Randolph; Malone, Cindy S.

    2012-01-01

    Mantle cell lymphoma and small lymphocytic lymphoma are lymphocyte cancers that have similar morphologies and a common age of onset. Mantle cell lymphoma is generally an aggressive B cell lymphoma with a short median survival time, whereas small lymphocytic lymphoma is typically an indolent B cell lymphoma with a prolonged median survival time. Using primary tumor samples in bidirectional suppression subtractive hybridization, we identified genes with differential expression in an aggressive mantle cell lymphoma versus an indolent small lymphocytic lymphoma. “Virtual” Northern blot analyses of multiple lymphoma samples confirmed that a set of genes was preferentially expressed in aggressive mantle cell lymphoma compared to indolent small lymphocytic lymphoma. These analyses identified mantle cell lymphoma-specific genes that may be involved in the aggressive behavior of mantle cell lymphoma and possibly other aggressive human lymphomas. Interestingly, most of these differentially-expressed genes have not been identified using other techniques, highlighting the unique ability of suppression subtractive hybridization to identify potentially rare or low expression genes. PMID:21145576

  20. Epiglottic diffuse B-cell malignant lymphoma: A case report

    PubMed Central

    CHANG, HUNG-MIN; LI, CHIUNG-CHON; TSAI, STELLA CHIN-SHAW; TSAO, TANG-YI

    2016-01-01

    A 55-year-old male patient was admitted to our department with complaints of dysphagia and throat soreness for 2 months. A tumor of the left epiglottis, with an irregular surface, was identified by video laryngoscopy. The diagnosis of malignant lymphoma was confirmed by biopsy during laryngomicrosurgery. The atypical diffuse lymphocytic lymphoma was positive for CD20 and Bcl-2, and negative for CD3, CD10 and Bcl-1. The diagnosis was diffuse large B-cell malignant lymphoma. The patient was treated with eight cycles of rituximab with cyclophosphamide + doxorubicin + vincristine + prednisolone (R-CHOP regimen). This is a rare case of extranodal non-Hodgkin lymphoma occurring in the epiglottis. PMID:26870358

  1. Autoimmune haemolytic anaemia associated with mantle cell lymphoma.

    PubMed

    Eve, Heather E; Rule, Simon A J

    2010-03-01

    Autoimmune haemolytic anaemia (AIHA) is a well-recognised complication of lymphoproliferative disorders, and has been reported in association with all B and T cell non-Hodgkin lymphoma subtypes with the exception of mantle cell lymphoma (MCL). We describe herein a case of MCL diagnosed in an initially asymptomatic 66-year-old woman who developed transfusion-dependent AIHA 6 months later coincident with lymphoma progression. The AIHA failed to respond satisfactorily to conventional treatment (high-dose oral prednisolone) but rapidly resolved following commencement of non-rituximab-containing combination chemotherapy in parallel with complete remission of the lymphoma. This is the first of such cases to be described in the literature and confirms that the immune environment of MCL can predispose to AIHA in the same way as in other lymphoma subtypes. Despite this being an infrequent occurrence, clinicians should be aware that AIHA is a potential complication of MCL and may be more successfully controlled by treating the underlying lymphoma rather than relying on conventional anti-haemolytic strategies such as steroids.

  2. TLR9 Agonist SD-101, Ipilimumab, and Radiation Therapy in Treating Patients With Low-Grade Recurrent B-cell Lymphoma

    ClinicalTrials.gov

    2016-04-23

    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 Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  3. TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma

    PubMed Central

    Horlad, Hasita; Ohnishi, Koji; Ma, Chaoya; Fujiwara, Yukio; Niino, Daisuke; Ohshima, Koichi; Jinushi, Masahisa; Matsuoka, Masao; Takeya, Motohiro; Komohara, Yoshihiro

    2016-01-01

    Adult T-cell leukemia/lymphoma (ATLL), an aggressive type of malignant lymphoma, is highly resistant to chemotherapy. However, the detailed mechanisms of the chemoresistance of ATLL have never been elucidated. We previously demonstrated that direct cell-cell interaction between macrophages and lymphoma cells was significantly associated with lymphoma progression in patients with ATLL. The present study aimed to further analyze the effects of cell-cell interaction between macrophages and ATLL cells by means of cell culture studies and immunohistochemical analysis using human ATLL samples. It was found that direct co-culture with macrophages induced chemoresistance in the ATLL ATN-1 cell line, but not in other cell lines, including TL-Mor, ED and ATL-2S. It was also found that expression of the T cell Ig and mucin domain-containing molecule-3 (TIM-3) was induced in ATN-1 cells by their long-term co-culture with macrophages. TIM-3 gene transfection induced chemoresistance in the ATN-1 cells. Immunostaining of ATLL tissues showed TIM-3 expression in 25 out of 58 ATLL cases. Although TIM-3 expression was not associated with overall survival or T classification, it was associated with resistance to chemotherapy. TIM-3 expression is therefore considered to be a marker for predicting the efficacy of chemotherapy, and TIM-3-associated signals may be a therapeutic target for patients with ATLL. PMID:27446463

  4. Differential expression of aurora-A kinase in T-cell lymphomas

    PubMed Central

    Kanagal-Shamanna, Rashmi; Lehman, Norman L; O’Donnell, James P; Lim, Megan S; Schultz, Daniel S; Chitale, Dhananjay A; Bueso-Ramos, Carlos E; Medeiros, L Jeffrey; Inamdar, Kedar V

    2016-01-01

    Aurora-A is a mitotic kinase implicated in oncogenesis and is known to be overexpressed in B-cell lymphomas and plasma cell myeloma. The expression of Aurora-A kinase (henceforth referred to as Aurora-A) in T-cell lymphomas is not well characterized. In this study, we assessed Aurora-A expression by immunohistochemical analysis in 100 lymphomas encompassing a variety of T-cell lymphomas as categorized in the World Health Organization classification. Aurora-A expression was highest in anaplastic large-cell lymphomas and variably expressed in other types of T-cell lymphomas. In addition, the pattern of Aurora-A expression was predominantly cytoplasmic in ALK-positive anaplastic large-cell lymphoma and was nuclear in ALK-negative anaplastic large-cell lymphoma and other T-cell lymphomas, suggesting altered biochemical mechanisms of Aurora-A nuclear transport in ALK-positive anaplastic large-cell lymphoma. Reverse transcriptase-PCR analysis showed that Aurora-A is more highly expressed in ALK-positive anaplastic large-cell lymphoma than in ALK-negative anaplastic large-cell lymphoma, and is relatively lower in peripheral T-cell lymphomas. Using western blot analysis and the DEL cell line (derived from ALK-positive anaplastic large-cell lymphoma), we showed that Aurora-A expression is decreased after treatment with either MYC or MEK inhibitors, consistent with the MYC and MAP kinase signaling pathways being involved in driving Aurora-A expression; the greatest decrease was observed after MYC inhibition. These findings provide insights into the possible importance of Aurora-A overexpression in anaplastic large-cell lymphoma pathogenesis, and also suggest that Aurora-A inhibition could be a potential therapeutic approach for patients with anaplastic large-cell lymphoma. PMID:23411487

  5. Pediatric B-Cell Lymphoma With Lymphoblastic Morphology, TdT Expression, MYC Rearrangement, and Features Overlapping With Burkitt Lymphoma.

    PubMed

    Meznarich, Jessica; Miles, Rodney; Paxton, Christian N; Afify, Zeinab

    2016-05-01

    Burkitt lymphoma (BL) and B-lymphoblastic lymphoma are subtypes of pediatric non-Hodgkin lymphoma with different presenting features, treatment, and outcomes. This case report documents a 5-year-old female who presented with B-cell lymphoma with lymphoblastic morphology, terminal deoxynucleotidyl transferase expression, MYC rearrangement, and features overlapping with BL. Genomic microarray analysis identified a gain on the long arm of chromosome 1 without other definitive changes. She was treated according to a BL protocol and remains in remission 16-months after initial diagnosis. PMID:26785246

  6. Primary Central Nervous System Anaplastic Large T-cell Lymphoma

    PubMed Central

    Splavski, Bruno; Muzevic, Dario; Ladenhauser-Palijan, Tatjana; Jr, Brano Splavski

    2016-01-01

    Introduction: Primary central nervous system lymphoma (PCNSL) of T-cell origin is an exceptionally rare, highly malignant intracranial neoplasm. Although such a tumor typically presents with a focal mass lesion. Case report: Past medical history of a 26-year-old male patient with a PCNS lymphoma of T-cell origin was not suggestive of intracranial pathology or any disorder of other organs and organic systems. To achieve a gross total tumor resection, surgery was performed via osteoplastic craniotomy using the left frontal transcortical transventricular approach. Histological and immunohistochemical analyses of the tissue removed described tumor as anaplastic large cell lymphoma of T-cells (T-ALCL). Postoperative and neurological recovery was complete, while control imaging of the brain showed no signs of residual tumor at a six-month follow-up. The patient, who did not appear immunocompromized, was referred to a hematologist and an oncologist where corticosteroids, the particular chemotherapeutic protocol and irradiation therapy were applied. Conclusion: Since PCNS lymphoma is a potentially curable brain tumor, we believe that proper selection of the management options, including early radical tumor resection for solitary PCNS lymphoma, may be proposed as a major treatment of such a tumor in selected patients, resulting in a satisfactory outcome. PMID:27703297

  7. The Anaplastic Lymphoma Kinase controls cell shape and growth of Anaplastic Large Cell Lymphoma through Cdc42 activation

    PubMed Central

    Ambrogio, Chiara; Voena, Claudia; Manazza, Andrea D.; Martinengo, Cinzia; Costa, Carlotta; Kirchhausen, Tomas; Hirsch, Emilio; Inghirami, Giorgio; Chiarle, Roberto

    2008-01-01

    Anaplastic Large Cell Lymphoma (ALCL) is a Non-Hodgkin Lymphoma (NHL) that originates from T cells and frequently expresses oncogenic fusion proteins derived from chromosomal translocations or inversions of the Anaplastic Lymphoma Kinase (ALK) gene. Proliferation and survival of ALCL cells are determined by the ALK activity. Here we show that the kinase activity of the Nucleophosmin (NPM)-ALK fusion regulated the shape of ALCL cells and F-actin filaments assembly in a pattern similar to T-Cell Receptor (TCR) stimulated cells. NPM-ALK formed a complex with the Guanine Exchange Factor (GEF) VAV1, enhancing its activation through phosphorylation. VAV1 increased Cdc42 activity and, in turn, Cdc42 regulated the shape and the migration of ALCL cells. In vitro knock-down of VAV1 or Cdc42 by sh-RNA, as well as pharmacological inhibition of Cdc42 activity by secramine, resulted in a cell-cycle arrest and apoptosis of ALCL cells. Importantly, the concomitant inhibition of Cdc42 and NPM-ALK kinase acted synergistically to induce apoptosis of ALCL cells. Finally, Cdc42 was necessary for the growth as well as for the maintenance of already established lymphomas in vivo. Thus, our data open perspectives for new therapeutic strategies by revealing a mechanism of regulation of ALCL cells growth through Cdc42. PMID:18974134

  8. Molecular mechanisms of angioimmunoblastic T-cell lymphoma development.

    PubMed

    Sakata-Yanagimoto, Mamiko; Chiba, Shigeru

    2016-08-01

    The molecular pathogenesis of peripheral T-cell lymphoma (PTCL) has gradually been clarified in terms of genomic abnormalities. Insights into these genomic abnormalities have provided clues to understanding the pathogenesis of PTCL. Furthermore, the origins of lymphoma cells have been clarified by investigating the distribution of genomic abnormalities in tumor cells and non-tumor blood cells. Multistep tumorigenesis has been suggested to be a fundamental mechanism underlying the development of angioimmunoblastic T-cell lymphoma (AITL), a distinct subtype of PTCL: premalignant cells evolve from hematopoietic progenitors via mutations in epigenetic regulators. These cells then further differentiate into tumor cells via the addition of tumor-specific G17V RHOA mutations. Meanwhile, AITL are composed of various infiltrating cells as well as tumor cells. Most notably, AITL tissues are characterized by massive infiltration of B cells partially infected by Epstein-Barr virus, follicular dendritic cells, and high endothelial venules. Infiltration of these cell types has been thought to be a reactive process, promoted by cytokines and chemokines released from tumor cells. Considering the multistep mechanisms of AITL allows us to analyze whether these infiltrating cells are also derived from premalignant cells. Indeed, the mechanisms underlying massive infiltration of bystander cells might be more complicated than previously imagined. PMID:27599421

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

    PubMed Central

    Dunleavy, Kieron

    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. PMID:25499450

  10. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2016-11-02

    Adult T Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Stage II Adult T-Cell Leukemia/Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Contiguous Adult Lymphoblastic Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-Cell Leukemia/Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-Cell Leukemia/Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  11. A Case Report: Systemic Lymph Node Tuberculosis Mimicking Lymphoma on 18F-FDG PET/CT.

    PubMed

    Wang, Qingxuan; Chen, Endong; Cai, Yefeng; Zhang, Xiangjian; Li, Quan; Zhang, Xiaohua

    2016-03-01

    F-fluorodeoxyglucose positron emission tomography--an established modality for evaluating malignancies--exhibits increased uptake under inflammatory conditions. A 21-year-old man came to our hospital with persistent pain in his right lower quadrant of abdomen for more than 1 month, but had no diarrhea, fever, chills, weight loss, or other constitutional symptoms. Colonoscopy analysis showed no organic diseases in his colorectum. Ultrasound results revealed multiple enlarged lymph nodes in the bilateral neck, axilla, and groin. Positron emission tomography analysis was performed and showed intense ¹⁸F-fluorodeoxyglucose accumulation in the bilateral neck, supraclavicular, pulmonary hilar, mediastinum, gastric paracardial, and mesenterium lymph node. These findings were considered typical for lymphoma. To confirm the diagnosis, we obtained a diagnostic biopsy in the left supraclavicular lymph node. The diagnosis of tuberculosis was confirmed in the final pathology. This uncommon case underscores the necessity of considering lymph node tuberculosis as a possible differential diagnosis in lymphoma. PMID:26945389

  12. Pruritus in Cutaneous T-cell Lymphoma: A Review

    PubMed Central

    Ahern, Kristen; Gilmore, Elaine S.; Poligone, Brian

    2012-01-01

    Background Pruritus can be a distressing and even debilitating symptom for patients with cutaneous T-cell lymphoma (CTCL). To date, few studies have evaluated the pathophysiology of this symptom. Due to this, therapy for pruritus in CTCL has mainly relied on those therapies that target and treat the lymphoma. For patients living with CTCL that relapses or becomes refractory to treatment, and who continue to experience severe itch, this lymphoma-targeted treatment may not be enough to combat their pruritus. Therefore, other itch-targeted therapies are needed for use in this disease Objective Evaluate the current evidence regarding the mechanism of action and treatments for pruritus associated with cutaneous T-cell lymphoma. Methods An explicit and thorough search was restricted to all peer-reviewed literature available through MEDLINE (1950 to September 2011) and pubmed.org. Search terms used were pruritus, cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF), and Sézary Syndrome (SS). All studies that involved pruritus in either CTCL, MF, or SS were evaluated by all three authors. Results The current literature helps to identify therapies and possible mechanisms for treating patients with CTCL associated pruritus. . Limitation Most studies were pre-clinical. Only studies involving mechanisms of action or treatment were included Conclusion A guideline is necessary to assist in the treatment of pruritus in CTCL and additional studies are necessary to uncover the exact mechanism(s) of action. PMID:22285672

  13. Primary nodal peripheral T-cell lymphomas: diagnosis and therapeutic considerations

    PubMed Central

    Lage, Luis Alberto de Pádua Covas; Cabral, Tamara Carvalho dos Santos; Costa, Renata de Oliveira; Gonçalves, Marianne de Castro; Levy, Debora; Zerbini, Maria Cláudia Nogueira; Pereira, Juliana

    2015-01-01

    Nodal peripheral T-cell lymphomas are a rare group of neoplasms derived from post-thymic and activated T lymphocytes. A review of scientific articles listed in PubMed, Lilacs, and the Cochrane Library databases was performed using the term “peripheral T-cell lymphomas”. According to the World Health Organization classification of hematopoietic tissue tumors, this group of neoplasms consists of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase positive (ALCL-ALK+), and a provisional entity called anaplastic large cell lymphoma-anaplastic lymphoma kinase negative (ALCL-ALK−). Because the treatment and prognoses of these neoplasms involve different principles, it is essential to distinguish each one by its clinical, immunophenotypic, genetic, and molecular features. Except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, which has no adverse international prognostic index, the prognosis of nodal peripheral T-cell lymphomas is worse than that of aggressive B-cell lymphomas. Chemotherapy based on anthracyclines provides poor outcomes because these neoplasms frequently have multidrug-resistant phenotypes. Based on this, the current tendency is to use intensified cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) regimens with the addition of new drugs, and autologous hematopoietic stem cell transplantation. This paper describes the clinical features and diagnostic methods, and proposes a therapeutic algorithm for nodal peripheral T-cell lymphoma patients. PMID:26190436

  14. Primary T-cell lymphoblastic lymphoma in the middle ear.

    PubMed

    Li, Bo; Liu, Shixi; Yang, Hui; Wang, Weiya

    2016-03-01

    T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma characterized by precursor T-cell malignancy and lymphadenopathy or mediastinal involvement. We present the case of an 11-year-old boy with a diagnosis of middle ear T-LBL, which manifested as a headache, hearing loss and peripheral facial paralysis. The child was given intensive chemotherapy and had a complete response. To our knowledge, this is the first case reported in the literature of T-LBL originating in the middle ear. This case aims to help clinicians to be vigilant about the possibility of primary lesions at atypical sites in some special diseases.

  15. Primary cutaneous blastoid mantle cell lymphoma-case report.

    PubMed

    Estrozi, Bruna; Sanches, José A; Varela, Paulo C S; Bacchi, Carlos E

    2009-06-01

    Mantle cell lymphoma (MCL) commonly involves extranodal sites, usually as a manifestation of disseminated disease. In rare cases, MCLs may arise as a primary tumor in the skin. Blastoid mantle cell lymphoma (BV-MCL) is a rare variant and has a more aggressive clinical course. The phenotype of BV-MCL is characterized as CD20+, CD5+, cyclin D1+, CD23-, and CD10-. Interphase fluorescence in situ hybridization shows a characteristic t(11;14) fusion pattern. We report a case of a BV-MCL arising in skin as primary cutaneous MCL with the characteristic immunophenotype and translocation.

  16. Primary T-Cell Non-Hodgkin Lymphoma of the Vagina

    PubMed Central

    Herraiz, J. L.; Llueca, A.; Maazouzi, Y.; Piquer, D.; Palmeiro, A.; Calpe, E.

    2015-01-01

    The primary vaginal T-cell non-Hodgkin lymphoma is a rare form of lymphoma. Most of the previously published cases were about B-cell non-Hodgkin lymphomas. We present the case of a vaginal mass in an 82-year-old patient presenting vaginal bleeding. The results of the immunohistological studies of the mass revealed the presence of a cytotoxic T-cell non-Hodgkin lymphoma, which is the least common subtype. PMID:26101677

  17. An Open-Label, Multicenter, Phase 1/2 Study of E7438 (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas

    ClinicalTrials.gov

    2016-09-01

    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

  18. The immune microenvironment in Hodgkin lymphoma: T cells, B cells, and immune checkpoints

    PubMed Central

    Vardhana, Santosha; Younes, Anas

    2016-01-01

    Classical Hodgkin lymphoma is curable in the majority of cases with chemotherapy and/or radiation. However, 15–20% of patients ultimately relapse and succumb to their disease. Pathologically, classical Hodgkin lymphoma is characterized by rare tumor-initiating Reed-Sternberg cells surrounded by a dense immune microenvironment. However, the role of the immune microenvironment, particularly T and B cells, in either promoting or restricting Classical Hodgkin lymphoma growth remains undefined. Recent dramatic clinical responses seen using monoclonal antibodies against PD-1, a cell surface receptor whose primary function is to restrict T cell activation, have reignited questions regarding the function of the adaptive immune system in classical Hodgkin lymphoma. This review summarizes what is known regarding T cells, B cells, and immune checkpoints in classical Hodgkin lymphoma. PMID:27365459

  19. Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2014-08-04

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; 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 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; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  20. Dose-Escalation Trial of Carfilzomib With and Without Romidepsin in Cutaneous T-Cell Lymphoma

    ClinicalTrials.gov

    2015-11-10

    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; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

  1. Analysis of FOXO1 mutations in diffuse large B-cell lymphoma | Office of Cancer Genomics

    Cancer.gov

    Abstract: Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of newly diagnosed lymphomas and has an overall cure rate of approximately 60%. Previously, we observed FOXO1 mutations in non-Hodgkin lymphoma patient samples. To explore the effects of FOXO1 mutations, we assessed FOXO1 status in 279 DLBCL patient samples and 22 DLBCL-derived cell lines.

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

    PubMed

    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. PMID:27427148

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

    PubMed Central

    Cortez, Afonso José Pereira; Dulley, Frederico Luiz; Saboya, Rosaura; Mendrone Júnior, Alfredo; Amigo Filho, Ulisses; Coracin, Fabio Luiz; Buccheri, Valéria; Linardi, Camila da Cruz Gouveia; Ruiz, Milton Artur; Chamone, Dalton de Alencar Fischer

    2011-01-01

    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 been previously reported

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

    PubMed

    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. PMID:21590365

  5. B-cell markers in malignant B-cell lymphoma with scleroderma-like manifestation.

    PubMed

    Van Joost, T; Stolz, E; Blog, F B; Van der Kwast, T H; Vuzevski, V D; Van Dongen, J M

    1984-12-01

    A case is described of malignant B-cell lymphoma with scleroderma-like manifestation. Using different monoclonals as B-cell markers the tumor appeared to be positive for surface immunoglobulins (SmIg) and for B2-antigen, but negative for intracytoplasmic immunoglobulin (CIg), BA2- and FMC7-antigens. Therefore, the tumor could be determined as a highly differentiated Sm-positive early B-cell type of B-cell lymphoma. In this clinically rare manifestation of cutaneous B-cell lymphoma aspects of the cell morphology and of cellular mediated immunity are briefly discussed.

  6. T-cell leukemia 1 expression in nodal Epstein-Barr virus-negative diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma.

    PubMed

    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2010-09-01

    The physiologic expression of the product of the proto-oncogene TCL1 (T-cell leukemia 1) is primarily restricted to early embryonic cells. In nonneoplastic B cells, the expression of TCL1 is determined by the differentiation step with silencing at the germinal center stage. TCL1 protein is overexpressed in a wide variety of human diseases. It has been shown that TCL1 is a powerful B-cell oncogene, which has been implicated in the pathogenesis of various types of mature B-cell lymphomas. There is no comparative information in the literature addressing the expression of TCL1 in pediatric and adult nodal diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma. We studied 55 cases of adult and pediatric diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma to analyze the phenotypic profile of these lymphomas, including TCL1 expression, and its relationship with clinical outcome in different age groups. The cases were analyzed by immunohistochemistry for the expression of TCL1, CD10, BCL-2, BCL-6, and MUM1. We also evaluated c-MYC translocation by fluorescence in situ hybridization. TCL1 was observed in 11 cases, 5 pediatric and 6 adult cases, all but one diffuse large B-cell lymphoma. Pediatric cases showed a significant association between TCL1 expression, high proliferative index, and presence of c-MYC translocation. TCL1 positivity was predominantly found in germinal center phenotype diffuse large B-cell lymphoma. Overall survival was worse in adult TCL1-positive cases than pediatric ones. Primary mediastinal large B-cell lymphomas infrequently expressed TCL1 in both age groups.

  7. Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers.

    PubMed

    Hopp, Lydia; Nersisyan, Lilit; Löffler-Wirth, Henry; Arakelyan, Arsen; Binder, Hans

    2015-01-01

    We systematically studied the expression of more than fifty histone and DNA (de)methylating enzymes in lymphoma and healthy controls. As a main result, we found that the expression levels of nearly all enzymes become markedly disturbed in lymphoma, suggesting deregulation of large parts of the epigenetic machinery. We discuss the effect of DNA promoter methylation and of transcriptional activity in the context of mutated epigenetic modifiers such as EZH2 and MLL2. As another mechanism, we studied the coupling between the energy metabolism and epigenetics via metabolites that act as cofactors of JmjC-type demethylases. Our study results suggest that Burkitt's lymphoma and diffuse large B-cell Lymphoma differ by an imbalance of repressive and poised promoters, which is governed predominantly by the activity of methyltransferases and the underrepresentation of demethylases in this regulation. The data further suggest that coupling of epigenetics with the energy metabolism can also be an important factor in lymphomagenesis in the absence of direct mutations of genes in metabolic pathways. Understanding of epigenetic deregulation in lymphoma and possibly in cancers in general must go beyond simple schemes using only a few modes of regulation. PMID:26506391

  8. Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers

    PubMed Central

    Hopp, Lydia; Nersisyan, Lilit; Löffler-Wirth, Henry; Arakelyan, Arsen; Binder, Hans

    2015-01-01

    We systematically studied the expression of more than fifty histone and DNA (de)methylating enzymes in lymphoma and healthy controls. As a main result, we found that the expression levels of nearly all enzymes become markedly disturbed in lymphoma, suggesting deregulation of large parts of the epigenetic machinery. We discuss the effect of DNA promoter methylation and of transcriptional activity in the context of mutated epigenetic modifiers such as EZH2 and MLL2. As another mechanism, we studied the coupling between the energy metabolism and epigenetics via metabolites that act as cofactors of JmjC-type demethylases. Our study results suggest that Burkitt’s lymphoma and diffuse large B-cell Lymphoma differ by an imbalance of repressive and poised promoters, which is governed predominantly by the activity of methyltransferases and the underrepresentation of demethylases in this regulation. The data further suggest that coupling of epigenetics with the energy metabolism can also be an important factor in lymphomagenesis in the absence of direct mutations of genes in metabolic pathways. Understanding of epigenetic deregulation in lymphoma and possibly in cancers in general must go beyond simple schemes using only a few modes of regulation. PMID:26506391

  9. Genetic lesions in diffuse large B-cell lymphomas

    PubMed Central

    Testoni, M.; Zucca, E.; Young, K. H.; Bertoni, F.

    2015-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults, accounting for 35%–40% of all cases. The combination of the anti-CD20 monoclonal antibody rituximab with anthracycline-based combination chemotherapy (R-CHOP, rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) lead to complete remission in most and can cure more than half of patients with DLBCL. The diversity in clinical presentation, as well as the pathologic and biologic heterogeneity, suggests that DLBCL comprises several disease entities that might ultimately benefit from different therapeutic approaches. In this review, we summarize the current literature focusing on the genetic lesions identified in DLBCL. PMID:25605746

  10. Primary Malignant B-cell Lymphoma of the Epididymis

    PubMed Central

    Suh, Jungyo; Jeong, Hyeon; Kim, Young A.

    2015-01-01

    Primary epididymal lymphomas are very rare condition, only 6 case report was published. In 4 of them, initial presentation was non-tender, continuous growth of testis. It can be misdiagnosed with epididymitis, 5 of them was treated by antibiotics before surgery. One patients treated by surgery another 5 makes neoadjuvant therapy, 2 of radiotherapy 3 of chemotherapy. Only one man died after treatment. This case is about 54-year male patients, diagnosed by diffuse large B-cell lymphoma, who treated by surgery and neoadjuvant chemotherapy combined with radiotherapy. PMID:26793572

  11. Bilateral conjunctival extranodal marginal zone B-cell lymphoma.

    PubMed

    Kram, David E; Brathwaite, Carole D; Khatib, Ziad A

    2010-12-15

    Extranodal marginal zone B-cell lymphomas (EMZLs), while relatively common in adults, are rare entities in the pediatric population. A subclass of the typically aggressive non-Hodgkin lymphomas, the few reported pediatric cases indicate that, as in adults, these tumors tend to be indolent. We present a case of EMZL arising in the conjunctivae in a 9-year-old male with bilateral disease. The patient was treated with surgical excision alone and has remained disease-free 6 years after the operation. PMID:20981695

  12. Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-02-16

    Follicular Lymphoma; Marginal Zone Lymphoma; Mantle Cell Lymphoma; Small Lymphocytic Lymphoma; Lymphoplasmacytic Lymphoma; Low Grade B-cell Lymphoma, Not Otherwise Specified; Diffuse Large B-cell Lymphoma; Peripheral T-cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Anaplastic Large-cell Lymphoma

  13. The Histological Classification of Diffuse Large B-cell Lymphomas

    PubMed Central

    Xie, Yi; Pittaluga, Stefania; Jaffe, Elaine S.

    2015-01-01

    Diffuse large B cell lymphomas (DLBCLs) are aggressive B-cell neoplasms with considerable clinical, biologic and pathologic diversity, in part reflecting the functional diversity of the B-cell system and multiple pathways of transformation. In recent years, the advent of new high-throughput genomic technologies has provided new insights into the biology of DLBCL, leading to the identification of distinct molecular identities and novel pathogenetic pathways. This increasing complexity had led to an expanding number of entities in the WHO classification. Using a multi-modality approach, the updated 2008 classification delineated some new subgroups, including DLBCLs associated with particular age groups or specific anatomic sites, as well as two borderline categories: tumors at the interface between classical Hodgkin lymphoma (cHL) and DLBCL as well as between Burkitt Lymphoma (BL) and DLBCL. This article reviews the histopathologic features of the various aggressive B-cell lymphoma subtypes included in the 2008 classification, with emphasis on some of the new entities as well as areas of diagnostic challenge. PMID:25805585

  14. Primary cutaneous T-cell lymphomas: a review.

    PubMed

    Sidiropoulos, Konstantinos G; Martinez-Escala, M Estela; Yelamos, Oriol; Guitart, Joan; Sidiropoulos, Michael

    2015-12-01

    Primary cutaneous T-cell lymphomas (CTCLs) represent a number of extranodal lymphomas arising from a malignant population of lymphocytes in the skin, with the most common type being mycosis fungoides (MF) representing half of all primary CTCLs. Despite advances in immunohistochemistry and molecular methodology, significant diagnostic challenges remain due to phenotypic overlap of primary CTCLs with several inflammatory dermatoses, secondary lymphomas, among other conditions. Clinical features such as presentation and morphology, staging, histology, immunophenotype and molecular features must be considered in detail before a diagnosis is made in order to minimise false-positive, false-negative and indeterminate diagnoses. Herein, we review primary CTCLs, including epidemiological data, a brief summary of clinical presentations, immunophenotype, molecular signatures and differential diagnoses. PMID:26602417

  15. Genetically Engineered Lymphocyte Therapy in Treating Patients With B-Cell Leukemia or Lymphoma That is Resistant or Refractory to Chemotherapy

    ClinicalTrials.gov

    2015-07-31

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; 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; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  16. Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma arising in a patient with hypersensitivity to mosquito bites.

    PubMed

    Kang, Jin Hee; Lee, Ji Hae; Kim, Miri; Cho, Baik Kee; Song, Chan Hee; Ock, Sun Myeong; Park, Hyun Jeong

    2015-01-01

    Hypersensitivity to mosquito bites is defined as the appearance of intense skin reactive lesions and systemic symptoms subsequent to mosquito bites. Most cases of hypersensitivity to mosquito bites reported thus far have been associated with chronic Epstein-Barr virus infection or natural killer cell leukemia/lymphoma. In this study, we describe the case of an 18-year-old Korean boy who had hypersensitivity to mosquito bites associated with primary systemic anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. After a mosquito bite, the patient developed a progressive cutaneous nodule on his left lower leg and regional lymphadenopathy in the left inguinal area. The histopathological and immunohistochemical findings suggested anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. Positron emission tomography-computed tomography revealed increased fluorodeoxyglucose uptake in the left T4 vertebrae, left external iliac lymph nodes, left inguinal lymph nodes, and lateral subcutaneous region of the left lower leg. According to the clinical, histopathological, and immunohistochemical findings, as well as the imaging data, the patient was diagnosed with primary systemic anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. Consequently, the patient received a total of 6 cycles of cyclophosphamide + doxorubicin + vincristine + prednisolone chemotherapy at 3-week intervals, after which the lesions regressed.

  17. CD44 variant expression in cutaneous T-cell lymphoma.

    PubMed

    Orteu, C H; Li, W; Allen, M H; Smith, N P; Barker, J N; Whittaker, S J

    1997-07-01

    Expression of the lymphocyte homing receptor CD44 and its splice variants have been linked to tumour dissemination and poor prognosis in non-Hodgkin's lymphoma. Specifically, the in vitro expression of variant exon V6 confers metastatic potential in rat pancreatic carcinoma cell lines. In this study, we investigated the expression of CD44 splice variants in cutaneous T-cell lymphomas, including patients with mycosis fungoides (MF), Sezary syndrome (SS), large-cell anaplastic lymphoma (LCAL) and HTLV1-associated cutaneous lymphoma. In addition, 4 involved lymph nodes from 2 patients with MF and 1 patient with SS were examined. Inflammatory dermatoses, lichen planus and psoriasis, and normal skin were also studied. Immunohistochemistry was performed using a panel of monoclonal antibodies, including those with specificity for CD44H (standard isoform) and variant exons V3, V6 and V8-9. Normal epidermal keratinocytes were consistently CD44H and CD44 V3, V6 and V8-9 positive. In all the different clinicopathological subtypes and stages of cutaneous T-cell lymphomas, including involved lymph nodes, tumour cells consistently expressed CD44H, but were CD44 V3 and V6 negative. CD44 V8-9 was expressed on a majority of tumour cells in 2/5 LCAL and on occasional tumour cells in 2/5 LCAL. Occasional V8-9 positive tumour cells were also identified in 6/13 MF, 1/4 SS and 3/4 HTLV1. In 2/3 lymph node samples from 2 patients with tumour-stage MF, CD44 V8-9 expression was found on a small percentage of atypical mononuclear cells. Scattered V8-9 positive dermal mononuclear cells were present in sections of lichen planus and psoriasis. We have found no evidence to suggest that the metastasis-associated CD44 variant exon (V6) is expressed in cutaneous T-cell lymphoma, or that CD44H expression is associated with an adverse prognostic group. It is not clear whether the strong expression of CD44 V8-9 in 2 patients with CD30 positive LCAL reflects activation status or metastatic potential.

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

    PubMed

    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.

  19. Fluidic and air-stable supported lipid bilayer and cell-mimicking microarrays.

    PubMed

    Deng, Yang; Wang, Yini; Holtz, Bryan; Li, Jingyi; Traaseth, Nathan; Veglia, Gianluigi; Stottrup, Benjamin J; Elde, Robert; Pei, Duanqing; Guo, Athena; Zhu, X-Y

    2008-05-14

    As drug delivery, therapy, and medical imaging are becoming increasingly cell-specific, there is a critical need for high fidelity and high-throughput screening methods for cell surface interactions. Cell membrane-mimicking surfaces, i.e., supported lipid bilayers (SLBs), are currently not sufficiently robust to meet this need. Here we describe a method of forming fluidic and air-stable SLBs through tethered and dispersed cholesterol groups incorporated into the bottom leaflet. Achieving air stability allows us to easily fabricate SLB microarrays from direct robotic spotting of vesicle solutions. We demonstrate their application as cell membrane-mimicking microarrays by reconstituting peripheral as well as integral membrane components that can be recognized by their respective targets. These demonstrations establish the viability of the fluidic and air-stable SLB platform for generating content microarrays in high throughput studies, e.g., the screening of drugs and nanomedicine targeting cell surface receptors.

  20. The horse that was a zebra: primary lymphoma of bone mimicking shoulder strain in an elderly male

    PubMed Central

    Keyes, Warren J; Morgan, Christopher; Pulinec, Andrew

    2000-01-01

    Primary malignant tumours of the extremities are rarely seen in chiropractic clinics. A case is presented of an eighty year old male who had complained of pain in the right shoulder of several days duration. History and clinical examination were consistent with mechanical joint pain. Following an appropriate course of conservative care the patient continued to improve until a re-injury occurred 3 months later. At that time, radiographs revealed an ill-defined moth-eaten lesion in the proximal humeral head. Subsequent evaluation demonstrated it to be a rare histologic sub-type of lymphoma. This case highlights several important issues ranging from clinical presentation to case management. ImagesFigure 1Figure 2

  1. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

    SciTech Connect

    Hoshiba, Takashi; Tanaka, Masaru

    2013-09-20

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

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

    PubMed

    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. PMID:26819049

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

    PubMed Central

    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

    2016-01-01

    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. PMID:26819049

  4. [F-18]-Fluoro-2-deoxy-D-glucose positron emission tomography as a tool for early detection of immunotherapy response in a murine B cell lymphoma model

    PubMed Central

    Chaise, Coralie; Itti, Emmanuel; Petegnief, Yolande; Wirquin, Evelyne; Copie-Bergman, Christiane; Farcet, Jean-Pierre; Delfau-Larue, Marie-Hélène; Meignan, Michel; Talbot, Jean-Noël; Molinier-Frenkel, Valérie

    2007-01-01

    [F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is a non-invasive imaging technique which has recently been validated for the assessment of therapy response in patients with aggressive non-Hodgkin’s lymphoma. Our objective was to determine its value for the evaluation of immunotherapy efficacy in immunocompetent Balb/c mice injected with the A20 syngeneic B lymphoma cell line. The high level of in vitro FDG uptake by A20 cells validated the model for further imaging studies. When injected intravenously, the tumour developed as nodular lesions mostly in liver and spleen, thus mimicking the natural course of an aggressive human lymphoma. FDG-PET provided three-dimensionnal images of tumour extension including non palpable lesions, in good correlation with ex-vivo macroscopic examination. When mice were pre-immunized with an A20 cell lysate in adjuvant before tumour challenge, their significantly longer survival, compared to control mice, was associated with a lower incidence of lymphoma visualized by PET at different time points. Estimation of tumour growth and metabolism using the calculated tumour volumes and maximum standardized uptake values respectively, also demonstrated delayed lymphoma development and lower activity in the vaccinated mice. Thus, FDG-PET is a sensitive tool relevant for early detection and follow-up of internal tumours, allowing discrimination between treated and non-treated small animal cohorts without invasive intervention. PMID:17171356

  5. A Single Mass Forming Colonic Primary Mantle Cell Lymphoma

    PubMed Central

    Assi, Hazem I.; Karaoui, Walid; El Cheikh, Jean; Bannoura, Sami; Nassif, Samer

    2016-01-01

    Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin's lymphoma (NHL) comprising around 7% of adult NHL. It is characterized by a chromosomal translocation t(11:14) and overexpression of Cyclin D1. The incidence of secondary gastrointestinal tract involvement in MCL ranges from 10 to 28% in various series. However primary gastrointestinal MCL is very rare, accounting for only 1 to 4% of primary gastrointestinal lymphomas. The most common endoscopic feature of primary intestinal MCL is multiple lymphomatous polyposis. In rare cases it presents as protruded lesions or superficial lesions. Single colonic mass presentation is an extremely infrequent presentation. MCL has an aggressive course with quick progression, and most cases are discovered in the advanced stages. Colonic biopsies with histologic examination and specific immunohistochemical staining are the gold standard for a proper diagnosis. We report a case of a single mass forming mantle cell lymphoma of the ascending colon in a 57-year-old female patient with unusual colonoscopic and radiologic features and describe the therapy the patient received, thereby adding to the spectrum of clinical presentations of this aggressive lymphoproliferative disorder. PMID:27579189

  6. A Single Mass Forming Colonic Primary Mantle Cell Lymphoma.

    PubMed

    Daniel, Fady; Assi, Hazem I; Karaoui, Walid; El Cheikh, Jean; Bannoura, Sami; Nassif, Samer

    2016-01-01

    Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin's lymphoma (NHL) comprising around 7% of adult NHL. It is characterized by a chromosomal translocation t(11:14) and overexpression of Cyclin D1. The incidence of secondary gastrointestinal tract involvement in MCL ranges from 10 to 28% in various series. However primary gastrointestinal MCL is very rare, accounting for only 1 to 4% of primary gastrointestinal lymphomas. The most common endoscopic feature of primary intestinal MCL is multiple lymphomatous polyposis. In rare cases it presents as protruded lesions or superficial lesions. Single colonic mass presentation is an extremely infrequent presentation. MCL has an aggressive course with quick progression, and most cases are discovered in the advanced stages. Colonic biopsies with histologic examination and specific immunohistochemical staining are the gold standard for a proper diagnosis. We report a case of a single mass forming mantle cell lymphoma of the ascending colon in a 57-year-old female patient with unusual colonoscopic and radiologic features and describe the therapy the patient received, thereby adding to the spectrum of clinical presentations of this aggressive lymphoproliferative disorder. PMID:27579189

  7. DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma

    SciTech Connect

    Wang, Lei; Nishihara, Hiroshi; Kimura, Taichi; Kato, Yasutaka; Tanino, Mishie; Nishio, Mitsufumi; Obara, Masato; Endo, Tomoyuki; Koike, Takao; Tanaka, Shinya

    2010-04-23

    DOCK2; a member of the CDM protein family, regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells and plays a pivotal role in the modulation of the immune system. Here we demonstrated the alternative function of DOCK2 in hematopoietic tumor cells, especially in terms of its association with the tumor progression. Immunostaining for DOCK2 in 20 cases of human B cell lymphoma tissue specimens including diffuse large B cell lymphoma and follicular lymphoma revealed the prominent expression of DOCK2 in all of the lymphoma cells. DOCK2-knockdown (KD) of the B cell lymphoma cell lines, Ramos and Raji, using the lentiviral shRNA system presented decreased cell proliferation compared to the control cells. Furthermore, the tumor formation of DOCK2-KD Ramos cell in nude mice was significantly abrogated. Western blotting analysis and pull-down assay using GST-PAK-RBD kimeric protein suggested the presence of DOCK2-Rac-ERK pathway regulating the cell proliferation of these lymphoma cells. This is the first report to clarify the prominent role of DOCK2 in hematopoietic malignancy.

  8. Picropodophyllin inhibits proliferation and survival of diffuse large B-cell lymphoma cells.

    PubMed

    Strömberg, Thomas; Feng, Xiaoying; Delforoush, Maryam; Berglund, Mattias; Lin, Yingbo; Axelson, Magnus; Larsson, Olle; Georgii-Hemming, Patrik; Lennartsson, Johan; Enblad, Gunilla

    2015-07-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. Although chemotherapy in combination with anti-CD20 antibodies results in a cure rate of 60-70 %, novel treatment approaches are warranted for the remaining patients. The insulin-like growth factor-1 receptor (IGF-1R) and its principal ligands IGF-1 and IGF-2 have been suggested to play pivotal roles in different cancers. However, in DLBCL the importance of this system is less well understood. To assess whether interference with IGF-1R-mediated signaling may represent a therapeutic option for this malignancy, we used a panel of eight DLBCL cell lines together with primary tumor cells derived from lymph nodes in four DLBCL patients. The cells were treated with the cyclolignan picropodophyllin (PPP), a small molecule compound initially described to selectively inhibit the IGF-1R. PPP dose-dependently inhibited proliferation/survival in all cell lines and primary cell preparations. In parallel experiments, the IGF-1R inhibitor NVP-AEW541 and the microtubule-destabilizing compounds podophyllotoxin (PPT) and colchicine were demonstrated to also inhibit growth of the cell lines. Linear regression analysis showed that the responses of the cell lines to PPP correlated with their responses to the microtubule inhibitors PPT and colchicine, but not with the response to NVP-AEW541 or the expression level of surface IGF-1R. Analysis of cell cycle phase distribution revealed that treatment with PPP for only 1 h induced a clear accumulation of cells in the G2/M-phase with a corresponding depletion of the G0/G1-phase. Interestingly, these cell cycle effects could be closely mimicked by using PPT or colchicine. Treatment with PPP led to increased apoptotic cell death in the SU-DHL-6 and U-2932 cell lines, whereas the DB and U-2940 did not undergo apoptosis. However, the DB cells were still killed by PPP, suggesting another mode of cell death for this cell line. The U-2940 cells responded to PPP mainly by

  9. Study of Alisertib (MLN8237) in Adults With Aggressive Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-11-15

    Diffuse Large B-cell Lymphoma; Mantle Cell Lymphoma; Burkitt's Lymphoma; Precursor B-lymphoblastic Leukemia/Lymphoma; T-cell Lymphoma, Excluding Primary Cutaneous T-cell Lymphoma; Transformed Follicular Lymphoma With ≥ 50% Diffuse Large Cell Component

  10. Obatoclax and Bortezomib in Treating Patients With Aggressive Relapsed or Recurrent Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-12-03

    Adult Non-Hodgkin 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

  11. Myeloid cell nuclear differentiation antigen is expressed in a subset of marginal zone lymphomas and is useful in the differential diagnosis with follicular lymphoma.

    PubMed

    Metcalf, Ryan A; Monabati, Ahmad; Vyas, Monika; Roncador, Giovanna; Gualco, Gabriela; Bacchi, Carlos E; Younes, Sheren F; Natkunam, Yasodha; Freud, Aharon G

    2014-08-01

    The diagnosis of marginal zone lymphomas (MZL) is challenged by the lack of specific markers that distinguish them from other low-grade non-Hodgkin B-cell lymphomas. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein that labels myelomonocytic cells as well as B lymphocytes that localize to the marginal zone areas of splenic white pulp. We evaluated MNDA expression in a large series of B-cell lymphomas to assess the sensitivity and specificity of this antigen for the characterization of MZL. A total of 440 tissue sections containing extramedullary B-cell lymphomas and 216 bone marrow biopsies containing atypical or neoplastic lymphoid infiltrates were stained for MNDA by immunohistochemistry. Among the extramedullary lymphoma cases, approximately 67% of nodal MZL, 61% of extranodal MZL, and 24% of splenic MZL expressed MNDA. MNDA was also infrequently expressed in other B-cell neoplasms including mantle cell lymphoma (6%), chronic lymphocytic leukemia/small lymphocytic lymphoma (13%), follicular lymphoma (FL) (4%), lymphoplasmacytic lymphoma (25%), and diffuse large B-cell lymphoma (3%). In contrast, MNDA was only expressed in 2.3% of all bone marrow biopsies involved by lymphoid infiltrates, including 2 cases of FL and one case of MZL. Collectively, these data support the inclusion of MNDA in the diagnostic evaluation of extramedullary B-cell lymphomas, particularly those in which the differential diagnosis is between low-grade FL and MZL.

  12. Clinicopathological features of aggressive B-cell lymphomas including B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell and Burkitt lymphomas: a study of 44 patients from Argentina.

    PubMed

    Bürgesser, María Virginia; Gualco, Gabriela; Diller, Ana; Natkunam, Yasodha; Bacchi, Carlos E

    2013-06-01

    Aggressive B-cell lymphomas incorporate a wide spectrum of lymphomas that pose challenges in diagnosis as well as treatment. We evaluated the clinicopathological features of 44 patients with aggressive B-cell lymphomas which were classified into 3 groups based on the World Health Organization 2008 classification as follows: including 30 cases of diffuse large B-cell lymphoma (DLBCL), 8 cases of Burkitt lymphoma (BL) and 6 cases of B-cell lymphoma, unclassifiable, with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (BCLU). Male predominance was observed in BL and BCLU groups and the mean age varied from 29 years in BL, 61 years in DLBCL and 70 years in BCLU. Patients with BCLU presented at more advanced stages and had a higher international prognostic index. By immunohistochemistry, they shared characteristics of both BL (including more frequent expression of SOX11) and DLBCL. FISH analyses showed three cases with more than one rearrangement: one MYC/BCL2 and two BCL2/BCL6, in addition to which one case with BCL2/IGH translocation and another with MYC rearrangement were also detected. The mean follow-up survival time of BCLU was 6.6 months, which was significantly shorter in comparison to DLBCL (31 months) and BL (30 months), respectively. The importance of recognizing this BCLU group relies on its different clinical course, poor prognosis and shorter survival than DLBCL and BL. An accurate diagnosis is critical for risk stratification and to improve therapeutic approaches and outcomes.

  13. Detection of an early adult T-cell leukemia-lymphoma clone in lymph nodes with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma involvement.

    PubMed

    Tokunaga, Masahito; Yoshida, Noriaki; Nakano, Nobuaki; Kubota, Ayumu; Takeuchi, Shogo; Takatsuka, Yoshifusa; Seto, Masao; Utsunomiya, Atae

    2016-04-01

    A 58-year-old man was admitted to our hospital with systemic lymphadenopathy and was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL) by lymph node biopsy. Although he was a human T-cell leukemia virus type I (HTLV-1) carrier, Southern blot analysis of the lymph node did not show monoclonal integration of HTLV-1 provirus deoxyribonucleic acid (DNA). He achieved complete remission after chemotherapy and subsequently, autologous peripheral blood stem cell transplantation (auto-PBSCT) was performed. Fifteen months after the auto-PBSCT, abnormal lymphocytes in the peripheral blood gradually increased. Southern blot analysis revealed monoclonal integration of HTLV-1 provirus DNA and monoclonal rearrangement of TRB. He was diagnosed with chronic type adult T-cell leukemia-lymphoma (ATL), which immediately progressed to the acute type. He died of tumor progression despite intensive chemotherapy. We analyzed genomic alterations of the ALCL and ATL cells using array comparative genomic hybridization. We found that the genomic alteration pattern differed between the two diseases. T-cell receptor clonality analysis using polymerase chain reaction (PCR) showed that the T-cell clone of the ATL was present in the lymph nodes with ALCL involvement, but not in peripheral blood. This finding suggests that lymph nodes can serve as a niche for ATL development.

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

    PubMed

    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. PMID:25023849

  15. Histiocytic necrotising lymphadenitis in mediastinum mimicking thymoma or lymphoma - case presentation and literature review of Kikuchi Fujimoto disease.

    PubMed

    Błasiak, P; Jeleń, M; Rzechonek, A; Marciniak, M; Pawełczyk, K; Cianciara, J; Kołodziej, J; Muszczyńska-Bernhard, B

    2016-03-01

    Kikuchi Fujimoto disease (KFD) as a rare self-limiting lymphadenopathy of short and benign course concerns most frequently the lymph nodes of the neck. The most common symptoms are painfulness of the diseased area, fever and night sweating. The etiology is not well understood, but in the role of pathogenesis viral, autoimmune and genetic factors are taken into account. In the presented case of 37-year-old female it was necessary to exclude diseases such as lymphoma or thymoma because of atypical mediastinal location of Kikuchi Fujimoto disease. After multidisciplinary consultation the lymph node was resected from the mediastinum with videothoracoscopic approach. The diagnosis was difficult for the pathologist because of the large percentage of necrosis of the lymph node but the image was typical for histiocytic necrotizing lymphadenitis. Two cases of patients with KFD limited to the mediastinum have been previously reported in the literature. This article presents the world's first reported case of this disease in the topographic location of the thymus. Furthermore, a review of current literature was made. PMID:27179280

  16. Cyclin Dl expression in B-cell non Hodgkin lymphoma.

    PubMed

    Aref, Salah; Mossad, Y; El-Khodary, T; Awad, M; El-Shahat, E

    2006-10-01

    Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over-expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the effect of its expression on clinical behavior and outcome in B-cell Non-Hodgkin lymphoma (NHL). In this study, we investigated the expression of cyclin Dl in group of patients with NHL and correlated the results with the clinical and laboratory data. The degree of expression of cyclin Dl protein was evaluated by flow cytometry in a group of NHL patients (n = 46) and in normal control group (n = 10). Cyclin Dl over expression was detected in 10 out of 46 (21.7%) patients; they were 5/5-mantle cell lymphoma (MCL) (100%) and 5/28 large B-cell lymphoma (17.8%). All other NHL subtypes showed normal cyclin D1 expression. The clinical signs (hepatomegaly, splenomegaly and B-symptoms, clinical staging) and laboratory data (hemoglobin, white cell count (WBCs), platelet count, and bone marrow infiltration) were not significantly different between NHL subgroup with cyclin Dl over expression and that with normal cyclin Dl expression. Serum lactic dehydrogenase (LDH) levels and lymphadenopathy were significantly higher in NHL group with cyclin D1 over expression as compared to those without. Also, cyclin D1 over expression is associated with poor outcome of NHL patients. Cyclin Dl over expression was evident among all cases of MCL and few cases of large B-cell lymphoma. Cyclin Dl over expression might be used as adjuvant tool for diagnosis of MCL; has role in NHL biology and is bad prognostic index in NHL. PMID:17607588

  17. Optimizing Management of Patients with Adult T Cell Leukemia-Lymphoma

    PubMed Central

    Yared, Jean A.; Kimball, Amy S.

    2015-01-01

    Adult T cell leukemia-lymphoma is a rare disease with a high mortality rate, and is challenging for the clinician. Early allogeneic stem cell transplant can confer durable remission. As novel therapeutic agents become available to treat T cell malignancies, it is increasingly important that medical oncologists, hematologists, and hematopathologists recognize and accurately diagnose adult T cell leukemia-lymphoma. There is no uniform standard of treatment of adult T cell leukemia-lymphoma, and clinical trials remain critical to improving outcomes. Here we present one management approach based on the recent advances in treatment for adult T cell leukemia-lymphoma patients. PMID:26610571

  18. Value of fine needle aspiration cell blocks in the diagnosis and classification of lymphoma

    PubMed Central

    Zhang, Shuhong; Yu, Xiaomeng; Zheng, Yuanyuan; Yang, Yan; Xie, Jianlan; Zhou, Xiaoge

    2014-01-01

    Fine needle aspiration biopsy (FNAB) is a simple yet accurate diagnostic procedure. However, the role of FNAB in lymphoma diagnosis and classification remains controversial. This study aimed to evaluate the value of FNAB cell blocks in the diagnosis and classification of lymphoma using our patented aspirator in a pencil-grip operation manner and a simplified cell block preparation method. We retrospectively reviewed 177 cases of lymph node and extranodal lymphoproliferative disorders that were diagnosed with cytomorphology, morphology, and immunohistochemistry of cell blocks. Of these, 83 were primary lymphoma; 14 were recurrent lymphoma; 8 were suspected as lymphoma, and 72 were benign reactive hyperplasia (BRH). Our analysis indicated 99.0% sensitivity, 95.9% specificity, 97.1% positive predictive value, and 98.6% negative predictive value in discriminating among primary/recurrent lymphoma and BRH. The diagnostic accuracy for sub-classification of lymphoma was 86.6% (84/97), with 77.8% (7/9) for classical Hodgkin’s lymphoma and 87.5% (77/88) for non-Hodgkin’s lymphoma. Our results implicated cell blocks as a reliable and useful adjunct to FNAB for the diagnosis and classification of lymphoma. Cytomorphology, morphology, and immunohistochemical studies of cell blocks offered very high accuracy in the diagnosis of lymphoma and allowed further sub-classification in many cases. Thus, patients with a definitive diagnosis and classification might avoid invasive and expensive surgical biopsy procedures. PMID:25550808

  19. Hepatitis C virus - associated B cell non-Hodgkin's lymphoma

    PubMed Central

    Mihăilă, Romeo-Gabriel

    2016-01-01

    The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin’s lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin’s lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Post-transplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they

  20. Hepatitis C virus - associated B cell non-Hodgkin's lymphoma.

    PubMed

    Mihăilă, Romeo-Gabriel

    2016-07-21

    The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin's lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin's lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Post-transplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they seem to

  1. Cystic granular cell tumor mimicking Rathke cleft cyst.

    PubMed

    Mumert, Michael L; Walsh, Michael T; Chin, Steven S; Couldwell, William T

    2011-02-01

    Symptomatic granular cell tumors of the neurohypophysis are a rarely reported entity. To the authors' knowledge, they report the first fully described case of a symptomatic granular cell tumor with a large cystic component. A 31-year-old woman presented with headaches and visual complaints with imaging findings confirming a cystic sellar and suprasellar mass. The lesion was resected, and histological examination confirmed the diagnosis. The literature has shown that granular cell tumors are rarely reported as being symptomatic but may actually be a fairly common finding in autopsy studies. The authors review the literature with a specific focus on radiographic findings in patients with symptomatic granular cell tumors.

  2. Hemophagocytic Lymphohistiocytosis in Association with Primary Cutaneous Anaplastic Large Cell Lymphoma

    PubMed Central

    Basheer, Aneesh; Padhi, Somanath; Nagarajan, Ramesh; Boopathy, Vinoth; Mookkappan, Sudhagar; Iqbal, Nayyar

    2014-01-01

    Hemophagocytic lymphohistiocytosis (HLH) has a well known association with lymphomas, especially of T cell origin. Prognosis of lymphoma associated HLH is very poor, especially in T cell lymphomas; and, therefore, early diagnosis might alter the outcome. Though association of HLH with systemic anaplastic large cell lymphoma (ALCL) is known, its occurrence in primary cutaneous ALCL (C-ALCL) is distinctly rare. We aim to describe a case of C-ALCL (anaplastic lymphoma kinase (ALK)−) in an elderly male who succumbed to the complication of associated HLH, which was possibly triggered by coexistent virus infection. We briefly present the literatures on lymphoma associated HLH and discuss the histopathological differentials of cutaneous CD30+ lymphoproliferative disorders. We do suggest that HLH may pose diagnostic challenges in the evaluation of an underlying lymphoma and hence warrants proper evaluation for the underlying etiologies and/or triggering factors. PMID:25405042

  3. Primary and secondary T-cell lymphomas of the breast: clinico-pathologic features of 11 cases.

    PubMed

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

    2009-07-01

    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 non otherwise specified type. Breast T-cell lymphomas are very infrequent and are morphologically and clinically heterogeneous.

  4. Mimicking the niche: cytokines expand muscle stem cells.

    PubMed

    Quarta, Marco; Rando, Thomas A

    2015-07-01

    Muscle stem cells (MuSCs) have long been considered to be potential therapeutic vehicles for diseases of muscle such as muscular dystrophies. A recent study published in Cell Research by Fu et al. reveals that recapitulating in vitro the in vivo microenvironment of MuSCs that occurs during muscle regeneration might be a major step towards translation.

  5. Diffuse Large B Cell Lymphoma with Extensive Cutaneous Relapse

    PubMed Central

    Malkan, Umit Yavuz; Gunes, Gursel; Yayar, Okan; Demiroglu, Haluk

    2015-01-01

    Herein, we aimed to report a diffuse large B cell lymphoma (DLBCL) case that had extensive cutaneous relapse with no skin involvement previously. A 59-year-old man presented to hospital in April 2014 with fatigue, anorexia, fever, and anemia. Cervical lymph node biopsy revealed CD20+, BCL2+, MUM1+, BCL6+ high grade B lymphoproliferative neoplasm. After FISH investigation, he was diagnosed as DLBCL. He was given 7 cycles of R-CHOP and achieved remission. However, in November 2014, he had emerging skin lesions that cover nearly all of his body. A control PET-CT revealed diffuse cutaneous involvement. CD20+, BCL2+, MUM1+, BCL6+ high grade B cell lymphoma infiltration was detected with skin biopsy. He was diagnosed as relapse lymphoma, so 2 cycles of R-DHAP were given. There was no treatment response; therefore, R-ICE regimen was started. The patient had achieved second complete remission and his skin lesions were completely regressed. The involvement of skin with CD20+ cells after 7 cycles of rituximab therapy favors that there is a rituximab resistant disease which tends to involve the skin. To conclude, DLBCL may relapse extensively with cutaneous involvement and the best treatment option in these patients is salvage chemotherapy followed by autologous peripheral blood stem cell transplantation. PMID:26457084

  6. Romidepsin for the Treatment of Peripheral T-Cell Lymphoma.

    PubMed

    Barbarotta, Lisa; Hurley, Kristen

    2015-01-01

    Peripheral T-cell lymphomas (PTCLs) are a rare, heterogeneous group of T-cell- or natural killer cell-derived non-Hodgkin lymphomas. The majority of patients with PTCL experience an aggressive disease course and poor overall survival. Historically, PTCL has been treated with chemotherapy regimens used to treat B-cell lymphomas; however, a lack of durable responses to frontline therapies and few effective options for salvage treatment have led to the development of newer therapies. Romidepsin is a structurally unique, potent, bicyclic class 1 selective histone deacetylase (HDAC) inhibitor that has demonstrated durable clinical responses in patients with relapsed/refractory PTCL, leading to its approval by the US Food and Drug Administration in 2011 for the treatment of PTCL in patients who have received at least one prior therapy. Here, the authors provide an overview of PTCL, review the role of HDAC inhibitors as anticancer agents, discuss romidepsin use in PTCL, and highlight considerations for advanced practitioners (including the management of side effects).

  7. Mimicking Retinal Development and Disease With Human Pluripotent Stem Cells.

    PubMed

    Sinha, Divya; Phillips, Jenny; Joseph Phillips, M; Gamm, David M

    2016-04-01

    As applications of human pluripotent stem cells (hPSCs) continue to be refined and pursued, it is important to keep in mind that the strengths and weaknesses of this technology lie with its developmental origins. The remarkable capacity of differentiating hPSCs to recapitulate cell and tissue genesis has provided a model system to study stages of human development that were not previously amenable to investigation and experimentation. Furthermore, demonstration of developmentally appropriate, stepwise differentiation of hPSCs to specific cell types offers support for their authenticity and their suitability for use in disease modeling and cell replacement therapies. However, limitations to farming cells and tissues in an artificial culture environment, as well as the length of time required for most cells to mature, are some of the many issues to consider before using hPSCs to study or treat a particular disease. Given the overarching need to understand and modulate the dynamics of lineage-specific differentiation in stem cell cultures, this review will first examine the capacity of hPSCs to serve as models of retinal development. Thereafter, we will discuss efforts to model retinal disorders with hPSCs and present challenges that face investigators who aspire to use such systems to study disease pathophysiology and/or screen for therapeutics. We also refer readers to recent publications that provide additional insight and details on these rapidly evolving topics. PMID:27116663

  8. PARP activation promotes nuclear AID accumulation in lymphoma cells.

    PubMed

    Tepper, Sandra; Jeschke, Julia; Böttcher, Katrin; Schmidt, Angelika; Davari, Kathrin; Müller, Peter; Kremmer, Elisabeth; Hemmerich, Peter; Pfeil, Ines; Jungnickel, Berit

    2016-03-15

    Activation-induced cytidine deaminase (AID) initiates immunoglobulin diversification in germinal center B cells by targeted introduction of DNA damage. As aberrant nuclear AID action contributes to the generation of B cell lymphoma, the protein's activity is tightly regulated, e.g. by nuclear/cytoplasmic shuttling and nuclear degradation. In the present study, we asked whether DNA damage may affect regulation of the AID protein. We show that exogenous DNA damage that mainly activates base excision repair leads to prevention of proteasomal degradation of AID and hence its nuclear accumulation. Inhibitor as well as knockout studies indicate that activation of poly (ADP-ribose) polymerase (PARP) by DNA damaging agents promotes both phenomena. These findings suggest that PARP inhibitors influence DNA damage dependent AID regulation, with interesting implications for the regulation of AID function and chemotherapy of lymphoma.

  9. PARP activation promotes nuclear AID accumulation in lymphoma cells

    PubMed Central

    Böttcher, Katrin; Schmidt, Angelika; Davari, Kathrin; Müller, Peter; Kremmer, Elisabeth; Hemmerich, Peter; Pfeil, Ines; Jungnickel, Berit

    2016-01-01

    Activation-induced cytidine deaminase (AID) initiates immunoglobulin diversification in germinal center B cells by targeted introduction of DNA damage. As aberrant nuclear AID action contributes to the generation of B cell lymphoma, the protein's activity is tightly regulated, e.g. by nuclear/cytoplasmic shuttling and nuclear degradation. In the present study, we asked whether DNA damage may affect regulation of the AID protein. We show that exogenous DNA damage that mainly activates base excision repair leads to prevention of proteasomal degradation of AID and hence its nuclear accumulation. Inhibitor as well as knockout studies indicate that activation of poly (ADP-ribose) polymerase (PARP) by DNA damaging agents promotes both phenomena. These findings suggest that PARP inhibitors influence DNA damage dependent AID regulation, with interesting implications for the regulation of AID function and chemotherapy of lymphoma. PMID:26921193

  10. Transitional cell bladder carcinoma with presentation mimicking ovarian carcinoma.

    PubMed

    Erickson, D R; Dabbs, D J; Olt, G J

    1996-05-01

    In the case described here, the patient's initial presentation suggested ovarian carcinoma. She had recurrent ascites, a pelvic mass, elevated CA-125, and extensive peritoneal carcinomatosis with transitional cell histology. The presence of hematuria prompted a cystoscopy, which revealed the true site of origin to be the urinary bladder rather than ovaries. This presentation is extremely rare for bladder cancer. Since transitional cell tumors from the bladder have a much worse prognosis than those of ovarian origin, it is important to identify the primary site correctly. Therefore, cystoscopy is essential for patients with hematuria, and should be considered in cases of apparent primary peritoneal carcinoma with transitional cell histology.

  11. Association of Epstein-Barr virus with sinonasal angiocentric T cell lymphoma.

    PubMed Central

    O'Leary, G; Kennedy, S M

    1995-01-01

    AIM--To investigate whether non-Hodgkin's lymphomas arising in the sinonasal region or Waldeyer's ring contain the Epstein-Barr virus (EBV) genome in lesional tissue. METHOD--Sections from paraffin wax blocks of 22 lymphoid proliferations arising in the sinonasal region or Waldeyer's ring were studied with EBV encoded RNAs (EBER-1 and -2) using in situ hybridisation. RESULTS--EBV was detected in nuclei of tumour cells of five of seven T cell lymphomas and in nuclei of two of seven diffuse, large cell immunoblastic lymphomas of B phenotype in the sinonasal region. Of tumours arising in Waldeyer's ring, two of 10 non-Hodgkin's lymphomas (both large cell) were positive, as was a single case of Hodgkin's disease. Lymphoma of other types, including Western type Burkitt's lymphoma, and nodular and diffuse small cleaved cell lymphoma, were negative. CONCLUSION--EBV is highly associated with large cell lymphomas especially T cell lymphomas of sinonasal origin in the indigenous Irish population, underlining the importance of this virus in nasopharyngeal lymphomas in Northern European as well as Asian populations. Images PMID:8537496

  12. Bortezomib, Rituximab, and Dexamethasone With or Without Temsirolimus in Treating Patients With Untreated or Relapsed Waldenstrom Macroglobulinemia or Relapsed or Refractory Mantle Cell or Follicular Lymphoma

    ClinicalTrials.gov

    2016-07-11

    Cognitive Side Effects of Cancer Therapy; Fatigue; Neurotoxicity Syndrome; 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; Therapy-Related Toxicity; Waldenstrom Macroglobulinemia

  13. Cell-based microfluidic platform for mimicking human olfactory system.

    PubMed

    Lee, Seung Hwan; Oh, Eun Hae; Park, Tai Hyun

    2015-12-15

    Various attempts have been made to mimic the human olfactory system using human olfactory receptors (hORs). In particular, OR-expressed cell-based odorant detection systems mimic the smell sensing mechanism of humans, as they exploit endogenous cellular signaling pathways. However, the majority of such cell-based studies have been performed in the liquid phase to maintain cell viability, and liquid odorants were used as detection targets. Here, we present a microfluidic device for the detection of gaseous odorants which more closely mimics the human olfactory system. Cells expressing hOR were cultured on a porous membrane. The membrane was then flipped over and placed between two compartments. The upper compartment is the gaseous part where gaseous odorants are supplied, while the lower compartment is the aqueous part where viable cells are maintained in the liquid medium. Using this simple microfluidic device, we were able to detect gaseous odorant molecules by a fluorescence signal. The fluorescence signal was generated by calcium influx resulting from the interaction between odorant molecules and the hOR. The system allowed detection of gaseous odorant molecules in real-time, and the findings showed that the fluorescence responses increased dose-dependently in the range of 0-2 ppm odorant. In addition, the system can discriminate among gaseous odorant molecules. This microfluidic system closely mimics the human olfactory system in the sense that the submerged cells detect gaseous odorants.

  14. Strategies for Treating Cutaneous T-Cell Lymphoma

    PubMed Central

    Heald, Peter

    2009-01-01

    In this article, the management of cutaneous T-cell lymphoma will be presented in terms of the strategies that guide treatment. With the strategies and goals in mind, treatment options to achieve a measurable goal will be presented. The treatments presented in this article are those utilized to reliably achieve a remission. If remission is not achieved, a patient’s management plan must be changed. The landmarks that help guide the therapy plan will be discussed. PMID:20729945

  15. A case of mantle cell lymphoma presenting with ascites.

    PubMed

    Al-Nabulsi, Majdi; Basnet, Alina; Salerno, Vincent; Cholankeril, Michelle

    2016-04-01

    Ascites with the finding of peritoneal carcinomatosis is considered an unusual presentation for mantle cell lymphoma (MCL) and has been rarely described in literature. This case reflects the importance of cytological analysis of peritoneal fluid in a patient with intractable ascites not contributing from other comorbidities. In the event a bone marrow (BM) analysis cannot be made, this may serve as an alternative method for diagnosing MCL taking into consideration the good concordance between peritoneal fluid and BM cytological markers.

  16. Novel therapeutic agents for cutaneous T-Cell lymphoma

    PubMed Central

    2012-01-01

    Mycosis fungoides (MF) and Sezary Syndrome (SS) represent the most common subtypes of primary Cutaneous T-cell lymphoma (CTCL). Patients with advanced MF and SS have a poor prognosis leading to an interest in the development of new therapies with targeted mechanisms of action and acceptable safety profiles. In this review we focus on such novel strategies that have changed the treatment paradigm of this rare malignancy. PMID:22594538

  17. Other Chemotherapeutic Agents in Cutaneous T-Cell Lymphoma.

    PubMed

    Chung, Catherine G; Poligone, Brian

    2015-10-01

    Traditional chemotherapies, interleukins, phosphorylase inhibitors, and proteasome inhibitors are important therapies available to patients with cutaneous T-cell lymphoma (CTCL). Traditional chemotherapies, both in combination and as single agents, are commonly used in relapsed, refractory CTCLs that behave in an aggressive manner. Interleukins, phosphorylase inhibitors, and proteasome inhibitors are less commonly used but data support a role in patients with more refractory disease. PMID:26433850

  18. Abdominal varices mimicking an acute gastrointestinal hemorrhage during technetium-99m red blood cell scintigraphy

    SciTech Connect

    Moreno, A.J.; Byrd, B.F.; Berger, D.E.; Turnbull, G.L.

    1985-04-01

    Abdominal varices consisting of a caput medusae and dilated mesenteric veins resulted in pooling of Tc-99m tagged red blood cells (RBC) within these dilated vessels in a 57-year-old man with severe Laennec's cirrhosis. The atypical radiotracer localization within the abdomen mimicked an acute gastrointestinal hemorrhage. Clinical suspicion and careful evaluation of scintigraphic gastrointestinal bleeding studies will avoid false-positive interpretations.

  19. Pathobiology of primary mediastinal B-cell lymphoma.

    PubMed

    Pileri, Stefano A; Zinzani, Pier L; Gaidano, Gianluca; Falini, Brunangelo; Gaulard, Philippe; Zucca, Emanuele; Sabattini, Elena; Ascani, Stefano; Rossi, Maura; Cavalli, Franco

    2003-01-01

    Controversy still exists over the response to therapy and prognosis of patients with primary mediastinal B-cell lymphoma (PMBL). Recent data from the International Extranodal Lymphoma Study Group (IELSG) suggest that a MACOP-B (methotrexate, adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin) chemotherapy regimen followed by radiotherapy may be a better induction strategy than other previously used treatments. Although the pathobiology of PMBL has been widely studied, its precise histology, phenotype, and molecular characteristics are still not clear. To date, phenotypic analysis has revealed the following phenotype: positivity for CD45 and CD20, but negativity for CD3, CD10, CD21, Class I/II major histocompatibility antigens, and a variety of other immunohistochemical markers. CD79a is generally detected, despite an absence of surface immunoglobulins (Igs). CD30 staining is observed in most cases, but is weaker and less homogeneous than in classic Hodgkin's lymphoma or anaplastic large cell lymphoma. BCL-2 protein is usually expressed but there are few data describing the expression of MUM1/IRF4, PAX5/BSAP, BCL-6, or the B-cell transcription factors BOB.1, Oct-2, and PU.1. Cytogenetic studies reveal gains in segments of chromosome 9p, including amplification of the REL proto-oncogene and the tyrosine kinase gene JAK2. Other molecular findings include: C-myc mutations or rearrangements, p53 mutations, IgV(H), gene mutations, and bcl-2 and mal over-expression. bcl-6 mutations and bcl-2 gene rearrangements are generally absent, suggesting that PMBL is of pre-germinal center (GC) origin. However, two recent reports show isotype-switched Ig genes with a high frequency of somatic hypermutations as well as variants in the 5' noncoding region of the bcl-6 gene. The IELSG collected 137 PMBL cases for extensive pathologic review. Histologically, the lymphomatous growth was predominantly diffuse with sclerosis that induced compartmentalized cell aggregation. It

  20. A case of Primary Bone Anaplastic Large Cell Lymphoma

    PubMed Central

    Kim, Kyung Hyun; Jung, Yun Hwa; Han, Chi Wha; Woo, In Sook; Son, Jong ho

    2016-01-01

    Patient: Female, 52 Final Diagnosis: Primary bone anaplastic large cell lymphoma Symptoms: Bone pain Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: Anaplastic large cell lymphoma (ALCL) is a relatively rare subtype of non-Hodgkin’s lymphoma (NHL). Like other types of NHL, ALCL primarily involves the nodal area, and sometimes it can involve several extra-nodal sites such as skin, soft tissue, and lungs. However, extensive bone involvement in cases of ALCL is very rare whether it is primary or secondary. Without nodular involvement, ALCL can be misdiagnosed as bone tumor or metastatic carcinoma such as lung, breast, or prostate cancer, which frequently spread to bone. Case Report: A 52-year-old woman with generalized pain and 2 months of fever of unknown origin presented to our institution. After extensive evaluation, only multiple osteolytic bone lesions with periosteal soft tissue reaction were identified. Repeated core needle biopsy revealed only inflammatory cells with histiocytic reactions. After pathologic and chromosomal analysis of sufficient tissue, which was acquired from incisional biopsy, primary bone ALCL was confirmed. Conclusions: Clinicians should keep in mind that ALCL can present with extensive bone involvement without nodal involvement. PMID:27729639

  1. Dominant neurologic symptomatology in intravascular large B-cell lymphoma.

    PubMed

    Kubisova, K; Martanovic, P; Sisovsky, V; Tomleinova, Z; Steno, A; Janega, P; Rychly, B; Babal, P

    2016-01-01

    Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal large B-cell lymphoma and it is characterized by selective intravascular proliferation of malignant cells. Typical features of the disease include aggressive behavior, rapid and frequently fatal course. Clinical picture is non-specific and heterogeneous, depending on the affected organ. It is not uncommon that this unique type of lymphoma is diagnosed post mortem. Herein, we report two cases of IVLBCL with neurologic symptomatology. In our clinical study patient 1 was an 80-year-old male with mixed paraparesis of lower extremities and difficulties with sphincter control. Patient 2 (56-year-old male) had vision malfunction, mental status changes and defect in phatic and motor functions. In both cases definite diagnosis was established by histological examination of necroptic material. We propose to include IVLBCL in differential diagnostic considerations in patients presenting with gradually impairing neurological status and spinal cord damage of unknown etiology (Fig. 2, Ref. 9). PMID:27546361

  2. [Angiogenesis and lymphangiogenesis in primary cutaneous T-cell lymphomas].

    PubMed

    Jankowska-Konsur, Alina; Kobierzycki, Christopher; Dzięgiel, Piotr

    2015-01-01

    Primary cutaneous T-cell lymphomas are a group of rare hematologic malignancies, derived from mature T lymphocytes and initially developing only in the skin. The most common lymphomas representing this group are mycosis fungoides and Sezary syndrome. Mycosis fungoides is an indolent disease with a chronic course and characteristic evolution of the skin lesions from erythematous patches, through plaques to tumors. Sezary syndrome is characterized by an aggressive course and a triad of symptoms (erythroderma, generalized lymphadenopathy, and the presence of atypical cells in the skin, lymph nodes and peripheral blood). The etiopathogenesis of cutaneous lymphomas is not fully understood, but a few studies on angiogenesis and lymphangiogenesis in these malignancies indicate a significant role in their development and progression. Angiogenesis is a process of formation of new blood vessels from existing ones. Lymphangiogenesis is a similar process concerning lymphatic vasculature. Development of new vessels is a complex process composed of several successive stages: migration, proliferation, and differentiation of endothelial cells, extracellular matrix degradation and formation and stabilization of new vessels, regulated by growth factors, cytokines and other proteins. Both phenomena are essential in the development and progression of solid tumors and hematological malignancies. Therapeutic strategies involving the inhibition of tumor angiogenesis and lymphangiogenesis are a promising new direction of studies in antitumor therapy, requiring further experiments. PMID:26561847

  3. Identification of Highly Methylated Genes across Various Types of B-Cell Non-Hodgkin Lymphoma

    PubMed Central

    Bethge, Nicole; Honne, Hilde; Hilden, Vera; Trøen, Gunhild; Eknæs, Mette; Liestøl, Knut; Holte, Harald; Delabie, Jan; Smeland, Erlend B.; Lind, Guro E.

    2013-01-01

    Epigenetic alterations of gene expression are important in the development of cancer. In this study, we identified genes which are epigenetically altered in major lymphoma types. We used DNA microarray technology to assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs. We identified 233 genes with upregulated expression in treated cell lines and with downregulated expression in B-cell lymphoma patient samples (n = 480) when compared to normal B cells (n = 5). The top 30 genes were further analyzed by methylation specific PCR (MSP) in 18 lymphoma cell lines. Seven of the genes were methylated in more than 70% of the cell lines and were further subjected to quantitative MSP in 37 B-cell lymphoma patient samples (diffuse large B-cell lymphoma (activated B-cell like and germinal center B-cell like subtypes), follicular lymphoma and Burkitt`s lymphoma) and normal B lymphocytes from 10 healthy donors. The promoters of DSP, FZD8, KCNH2, and PPP1R14A were methylated in 28%, 67%, 22%, and 78% of the 36 tumor samples, respectively, but not in control samples. Validation using a second series of healthy donor controls (n = 42; normal B cells, peripheral blood mononuclear cells, bone marrow, tonsils and follicular hyperplasia) and fresh-frozen lymphoma biopsies (n = 25), confirmed the results. The DNA methylation biomarker panel consisting of DSP, FZD8, KCNH2, and PPP1R14A was positive in 89% (54/61) of all lymphomas. Receiver operating characteristic analysis to determine the discriminative power between lymphoma and healthy control samples showed a c-statistic of 0.96, indicating a possible role for the biomarker panel in monitoring of lymphoma patients. PMID:24260260

  4. Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

    ClinicalTrials.gov

    2016-10-24

    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 Acute Lymphoblastic Leukemia; 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 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 Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

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

    PubMed

    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.

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

    PubMed Central

    Savsek, Lina; Opaskar, Tanja Ros

    2016-01-01

    Background 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. Case report 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, 8th 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. Conclusions 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. PMID

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

    PubMed

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

    PubMed

    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. PMID:19055573

  9. SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype

    PubMed Central

    Mozos, Ana; Royo, Cristina; Hartmann, Elena; De Jong, Daphne; Baró, Cristina; Valera, Alexandra; Fu, Kai; Weisenburger, Dennis D.; Delabie, Jan; Chuang, Shih-Sung; Jaffe, Elaine S.; Ruiz-Marcellan, Carmen; Dave, Sandeep; Rimsza, Lisa; Braziel, Rita; Gascoyne, Randy D.; Solé, Francisco; López-Guillermo, Armando; Colomer, Dolors; Staudt, Louis M.; Rosenwald, Andreas; Ott, German; Jares, Pedro; Campo, Elias

    2009-01-01

    Background Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors. Design and Methods The microarray database of 238 mature B-cell neoplasms was re-examined. SOX11 protein expression was investigated immunohistochemically in 12 cases of cyclin D1-negative mantle cell lymphoma, 54 cases of conventional mantle cell lymphoma, and 209 additional lymphoid neoplasms. Results SOX11 mRNA was highly expressed in conventional and cyclin D1-negative mantle cell lymphoma and in 33% of the cases of Burkitt’s lymphoma but not in any other mature lymphoid neoplasm. SOX11 nuclear protein was detected in 50 cases (93%) of conventional mantle cell lymphoma and also in the 12 cyclin D1-negative cases of mantle cell lymphoma, the six cases of lymphoblastic lymphomas, in two of eight cases of Burkitt’s lymphoma, and in two of three T-prolymphocytic leukemias but was negative in the remaining lymphoid neoplasms. Cyclin D2 and D3 mRNA levels were significantly higher in cyclin D1-negative mantle cell lymphoma than in conventional mantle cell lymphoma but the protein expression was not discriminative. The clinico-pathological features and outcomes of the patients with cyclin D1-negative mantle cell lymphoma identified by SOX11 expression were similar to those of patients with conventional mantle cell lymphoma. Conclusions SOX11 mRNA and nuclear protein expression is a highly specific marker for both cyclin D1-positive and negative mantle cell lymphoma. PMID:19880778

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

    PubMed

    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. PMID:26189744

  11. High Expression of Intestinal Homing Receptor CD103 in Adult T-Cell Leukemia/Lymphoma, Similar to 2 Other CD8+ T-Cell Lymphomas.

    PubMed

    Ishibashi, Hideki; Nimura, Satoshi; Ishitsuka, Kenji; Mihashi, Yasuhito; Mizoguchi, Mikio; Nakamura, Shotaro; Okamura, Seiichi; Momosaki, Seiya; Aoyagi, Kunihiko; Sakisaka, Shotaro; Takeshita, Morishige

    2016-04-01

    We investigated the expression of the αEβ7 integrin (CD103)-intestinal homing receptor of T-intraepithelial lymphocytes (IELs) in 130 cases of adult T-cell leukemia/lymphoma (ATLL). We detected CD103 lymphoma cells in 55% (31/56) of mainly gastrointestinal (GI)-involved ATLL cases. Among them, lymphoma cells of 18 cases located in other involved organs had similar CD103 expression patterns. Histologically, we found (a) increased reactive IELs in non-neoplastic mucosal layers in 28% (5/18) of surgical and mucosal resection cases, (b) preserved epithelial glands, and (c) numerous small intraepithelial ATLL nests in involved lesions in 36 (69%) and 21 (40%), respectively, of the 52 examined cases. These 3 patterns were common in intestinal type II enteropathy-associated T-cell lymphoma but were rare in intestinal EBV nasal-type/like T/natural killer (NK)-cell lymphoma. We detected CD103 tumor cells in 41% (16/39) of lymph node-involved ATLL, in 31% (11/35) of skin-involved ATLL, in 68% (21/31) of type II CD4 enteropathy-associated T-cell lymphoma cases, in 36% (8/22) of primary gastric T/NK-cell lymphomas, and in 77% (7/9) of CD8 epidermotropic mycosis fungoides. CD103 ATLL prefers involving the GI tract over the skin (P<0.05). CD103 expression in GI-involved and/or total ATLL cases was significantly higher than in other 9 T/NK-cell lymphoma groups (P<0.05 or 0.01). Only ATLL cases were commonly CD103 in CD4 T/NK-cell lymphoma groups (P<0.05 or 0.01). Human T-lymphotropic virus-1-infected CD103 T-IELs and mucosal T cells may be important sources of ATLL. PMID:26813744

  12. Mimicking the Interfacial Dynamics of Flowing White Blood Cells

    NASA Astrophysics Data System (ADS)

    Santore, Maria

    2015-03-01

    The rolling of particles on surfaces, facilitated by hydrodynamic forces combined with localized surface interactions of the appropriate strengths, spatial arrangements, and ranges, is a technologically useful means of transporting and manipulating particles. One's intuition for the rolling of a marble or a car tire cannot be extrapolated down to microparticle length scales because the microparticle interactions are dominated by electrostatic, van der Waals, and hydrogen bonding interactions rather than a friction that depends on an imposed normal force. Indeed, our microparticle rolling systems are inspired by the rolling of white blood cells on the inner walls of venules as part of the innate immune response: Selectin molecules engage with their counterparts on the opposing surfaces to slow cell motion relative to that for freely flowing cells. In the resulting rolling signature, ligand-receptor binding and crack closing on the front of the cell are balanced with molecular dis-bonding and crack opening at the rear. The contact region is relatively static, allowing other interactions (for instance signaling) to occur for a finite duration. Thus, achieving particle rolling in synthetic systems is important because it facilitates particle-surface interactions in a continuous nonfouling fashion where the contact surface is continually renewed. In developing a synthetic model for this system, we employ polymers to modify flowing particles and /or planar collectors, producing heterogeneous interfaces which can support rolling or produce other motion signatures such as skipping, arrest, or free flow. We identify, in the synthetic system, combinations of variables that produce rolling and demonstrate how the distinction between rolling and arrest is not a simple matter of the adhesion strength between the particles and the collector. Rolling is a cooperative process and the coordination of binding in one location with dis-bonding in another requires appropriate length

  13. Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma

    ClinicalTrials.gov

    2016-08-22

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; 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; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  14. Disseminated T-cell lymphoma in a bonobo (Pan paniscus).

    PubMed

    Gibson-Corley, Katherine N; Haynes, Joseph S

    2012-01-01

    Disseminated lymphoma was diagnosed in an 8-year-old male bonobo (Pan paniscus). The male bonobo presented with a 4-6 week history of dyspnea and facial swelling around the eyes; thoracic radiographs and computed tomography scan indicated a craniodorsal mediastinal soft tissue mass. Upon gross examination, there was a large, cream to white mass expanding the mediastinum and pericardial sac. The mass extended along the thoracic aorta and cranial vena cava, through the thoracic inlet, along and encircling the trachea, and bilaterally into the thyroid glands. Microscopically, neoplastic lymphocytes were present in the thymus, trachea, lungs, kidney, heart, and numerous other tissues. Immunohistochemical staining of neoplastic lymphocytes revealed diffuse immunoreactivity for cluster of differentiation (CD)3 indicating T-cell lymphoma. Routine viral screening was negative via polymerase chain reaction.

  15. Anaplastic large cell lymphoma in paediatric and young adult patients.

    PubMed

    Turner, Suzanne D; Lamant, Laurence; Kenner, Lukas; Brugières, Laurence

    2016-05-01

    Anaplastic large cell lymphoma (ALCL) is a heterogeneous disease of debateable origin that, in children, is largely anaplastic lymphoma kinase (ALK) positive with aberrant ALK activity induced following the formation of chromosomal translocations. Whilst the survival rates for this disease are relatively high, a significant proportion (20-40%) of patients suffer disease relapse, in some cases on multiple occasions and therefore suffer the toxic side-effects of combination chemotherapy. Traditionally, patients are treated with a combination of agents although recent data from relapse patients have suggested that low risk patients might benefit from single agent vinblastine and, going forward, the addition of ALK inhibitors to the therapeutic regimen may have beneficial consequences. There are also a plethora of other drugs that might be advantageous to patients with ALCL and many of these have been identified through laboratory research although the decision as to which drugs to implement in trials will not be trivial. PMID:26913827

  16. Differential cytokine expression in EBV positive peripheral T cell lymphomas.

    PubMed Central

    Ho, J W; Liang, R H; Srivastava, G

    1999-01-01

    AIM: To investigate whether specific cytokines are secreted locally at the tumour site in Epstein-Barr virus (EBV) positive peripheral T cell lymphoma (PTCL). METHODS: An RNase protection assay system was used to study the differential expression of 21 cytokines in parallel in eight cases of EBV positive non-nasal PTCL, and compared with 11 EBV negative non-nasal PTCLs and three EBV positive nasal natural killer (NK) cell lymphomas. RESULTS: Among the eight EBV positive cases, interferon gamma (IFN-gamma), lymphotoxin beta (LT beta), interleukin 10 (IL-10), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta 1 (TGF-beta 1), and IL-1 receptor a (IL-Ra) were frequently detectable. IL-15, IL-6, IL-4, IL-1 beta, TNF-beta, and IL-9 were sporadically detectable. Of the frequently detectable cytokines, IFN-gamma and LT beta were commonly detected in the EBV negative cases. For cases with > 50% EBV encoded small non-polyadenylated RNA (EBER) positive cells, IL-10, TNF-alpha, and TGF-beta 1 were detected in three of three cases, and IL-1Ra in two of three cases. For cases with < 20% EBER positive cells, IL-10 was detected in three of five cases, TNF-alpha in two of four cases, but TGF-beta 1 and IL-1Ra were not detected. Interestingly, IL-6 was detected in two of three cases with > 50% EBER positive cells, but only in one of five cases with < 20% EBER positive cells. For comparison, in NK cell lymphomas, IL-10, TNF-alpha, IL-1Ra, and IL-6 were all detectable, but TGF-beta 1 was not detected at all. Immunohistochemical staining revealed IL-10 in many cells; in contrast, EBV latent membrane protein 1 (LMP1) was only found to be positive in isolated cells. CONCLUSIONS: Certain cytokines, such as IL-10 and TNF-alpha, might be expressed preferentially in EBV positive peripheral T cell lymphomas. It is likely that such a cytokine environment enhances EBV infection and contributes towards tumorigenesis. PMID:10748876

  17. Mechanisms of Dihydroartemisinin and Dihydroartemisinin/Holotransferrin Cytotoxicity in T-Cell Lymphoma Cells

    PubMed Central

    Zhao, Xindong; Zhao, Chunting; Zhao, Hongguo; Huo, Lanfen

    2015-01-01

    The validated therapeutic effects of dihydroartemisinin (DHA) in solid tumors have encouraged us to explore its potential in treating T-cell lymphoma. We found that Jurkat cells (a T-cell lyphoma cell line) were sensitive to DHA treatment with a IC50 of dihydroartemisinin. The cytotoxic effect of DHA in Jurkat cells showed a dose- and time- dependent manner. Interestingly, the cytotoxic effect of DHA was further enhanced by holotransferrin (HTF) due to the high expression of transferrin receptors in T-cell lymphoma. Mechanistically, DHA significantly increased the production of intracellular reactive oxygen species, which led to cell cycle arrest and apoptosis. The DHA treatment also inhibited the expression of protumorgenic factors including VEGF and telomerase catalytic subunit. Our results have proved the therapeutic effect of DHA in T-cell lymphoma. Especially in combination with HTF, DHA may provide a novel efficient approach in combating the deadly disease. PMID:26502166

  18. B-cell and T-cell lymphomas of the breast: clinical--pathological features of 53 cases.

    PubMed

    Gualco, Gabriela; Bacchi, Carlos E

    2008-10-01

    Breast involvement by non-Hodgkin lymphomas is rare. We studied the morphological, immunophenotypical, and clinical features of 53 cases of malignant lymphomas involving the breast in a population of Brazilian patients. Most of the cases were of B-cell phenotype. Four of the patients with primary breast lymphomas had T-cell lymphomas, 3 had CD30-positive anaplastic large cell lymphomas, and 1 had panniculitis-like T-cell lymphoma. Most patients presented with an incidental breast mass. Secondary breast lymphoma was seen in 19 patients and most commonly occurred as part of widespread nodal disease. Two patients presented with bilateral breast involvement. The most prevalent histological subtype was also diffuse large B-cell lymphoma, followed by follicular lymphoma. This study shows that the broad morphological and immunophenotypical spectrum of malignant lymphoma of the breast occurring in a large series of Brazilian patients has many similarities with that seen in Western countries, with a higher proportion of high-grade lymphomas in both primary and secondary cases.

  19. [Nasal type natural killer/T cell lymphoma: case series and literature review].

    PubMed

    Düzlü, Mehmet; Ant, Ayça; Tutar, Hakan; Karamert, Recep; Şahin, Melih; Sayar, Erolcan; Cesur, Nesibe

    2016-01-01

    Nasal type natural killer/T-cell lymphoma is a rare type of extranodal non-Hodgkin lymphoma which originates from nasal cavity and paranasal sinuses. Exact diagnosis of nasal natural killer/T-cell lymphoma, which is a rapidly progressive clinical condition, may be established by immunohistochemical analysis on biopsy material after clinical suspicion. In this article, we report four cases of nasal natural killer/T-cell lymphoma who were followed-up in our clinic and discuss the diagnosis and treatment of the disease in light of the literature data. PMID:27405082

  20. Gingival squamous cell carcinoma mimicking as a desquamative lesion

    PubMed Central

    Keshava, Abbayya; Gugwad, Sushma; Baad, Rajendra; Patel, Rufi

    2016-01-01

    Oral squamous cell carcinoma (SCC) is the most frequently encountered neoplasm in the oral cavity, which accounts for more than 90% of all cancers. Except for carcinoma of the lip vermilion, the most common sites of oral SCC are the tongue and floor of mouth, followed at a lower frequency by the soft palate, gingiva, and buccal mucosa. Clinically, it may be misdiagnosed because of its variable appearances. This case report presents a case of well-differentiated SCC of gingiva. A 48-year-old male patient reported to the Department of Periodontology, School of Dental Sciences, Karad, with a 1-year history of burning sensation and painful lesion on the gingiva from 35 to 37 (mandibular) regions. On clinical examination, desquamated gingival lesion was seen with no purulent exudation. Clinical characteristics and differential diagnosis indicated the lesion for an excisional biopsy. Histopathological examination confirmed the lesion to be a well-differentiated SCC. The patient was referred for the treatment consisting of surgical excision of the lesion. Since an early diagnosis and treatment was possible in this case, it resulted in a good prognosis. In these instances, dentist plays an important role in early detection of gingival SCC. PMID:27041843

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

    PubMed

    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. PMID:26940273

  2. MicroRNAs in diffuse large B-cell lymphoma

    PubMed Central

    NI, HUIYUN; TONG, RONG; ZOU, LINQING; SONG, GUOQI; CHO, WILLIAM C.

    2016-01-01

    The aberrant expression of microRNAs (miRs) has a significant impact on the biological characteristics of lymphocytes, and is important in the pathogenesis of diffuse large B-cell lymphoma (DLBCL). It has been demonstrated, using miR profiling and detecting distinct miR signatures, that certain miRs may accurately distinguish different subtypes and prognostic classifications of DLBCL, as well as distinguish DLBCL from other more indolent lymphomas, including follicular lymphoma. miRs are excellent biomarkers for cancer diagnosis and prognosis. In DLBCL, specific miR expression profiles in the tissues of patients are associated with prognosis and clinical outcome. Over the past decade, there has been substantial investigation concerning the pathogenetic, diagnostic and prognostic roles of miRs in DLBCL. The aim of the present review is to describe the aberrant expression of miRs in DLBCL, and the functions, potential clinical use and possible therapeutic targets of miRs in this disease. PMID:26893730

  3. Management of relapsed mantle cell lymphoma: still a treatment challenge.

    PubMed

    Ruan, Jia; Coleman, Morton; Leonard, John P

    2009-07-01

    Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma that remains incurable, and is associated with a median survival of approximately 5 years. Management of patients with relapsed or refractory disease is challenging. The major therapeutic goal in MCL management is to improve survival and quality of life whenever possible. Progress has been made in MCL therapy in the past decade based on clinical experimentation with novel agents and combinations. There is a growing list of conventional and novel agents in our armamentarium, consisting of not only additional chemotherapy combinations including high-dose approaches, but also biologically targeted reagents such as the monoclonal antibody rituximab, the proteasome inhibitor bortezomib, the mTOR inhibitor temsirolimus, immunomodulatory and antiangiogenic agents including thalidomide and lenalidomide, and cyclin-dependent kinase inhibitors, as well as a renewed interest in older compounds such as bendamustine and metronomic regimens. Efficacy evaluations for individual agents and rational combinations are in various stages of development, while treatment selection based on molecular and clinical prognostic scores is yet to be tested. In the absence of evidence demonstrating relative survival advantages of various second-line options, management of relapsed and refractory disease should be individualized. Involvement of a lymphoma center participating in clinical trials of novel MCL treatments is encouraged.

  4. Induction of lymphomas on implantation of human oral squamous cell carcinomas in nude mice.

    PubMed

    Teni, T R; Saranath, D; Mahale, A M; Pai, S A; Ahire, S D; Ingle, A D

    2001-02-01

    Cancer cells from five oral cancer patients and pleomorphic adenoma cells from one individual were inoculated as single cell suspension into subcutis of 30 Swiss nude mice and tail vein of additional 30 mice. Further, tumor tissue pieces from three oral cancer patients were xenografted s.c. in 18 nude mice, and 10 mice were kept as controls. In animals implanted with tumor pieces, 7/18 (39%) mice, developed squamous cell carcinoma at the site of inoculation within 8-15 days, while tumors were not observed in mice inoculated with single cell suspension, up to 60/90 days. In 8/68 (12%) mice, white foci were observed in several tissues, with hepatomegaly and splenomegaly noted in 27/68 (39%) mice. Histopathological examination of various tissues revealed presence of large cell lymphoma in several organs in 14/68 (21%) mice. No regional or distant metastasis of the implanted oral tumor cells was detected. Mice injected with cells from pleomorphic adenoma, also demonstrated large cell lymphoma in 2/10 (20%) mice, whereas none of the 10 control animals showed any gross abnormalities or microscopic abnormalities in several organs. 2/16 (12%) lymphomas exhibited positive reaction with mouse B cell antibodies illustrating the murine origin of the lymphomas, and these were immunophenotyed as B cell lymphomas. The lymphomas were also examined with mouse T cell antibodies and none reacted positively with the mouse T cell antibodies. The lymphomas also failed to react with human T cell, B cell and human Leucocyte common antigen (LCA) antibodies, indicating that the induced lymphomas were not of human origin. The tumor specimens from seven of eight oral cancer patients and the pleomorphic adenoma patient induced lymphomas in nude mice. Thus it appears that xenografting oral tumor cells into nude mice may cause induction of the murine lymphomas, and this needs further investigation.

  5. Investigation of the cytotoxic effect of flavopiridol in canine lymphoma cell lines.

    PubMed

    Ema, Y; Igase, M; Takeda, Y; Yanase, T; Umeki, S; Hiraoka, H; Okuda, M; Mizuno, T

    2016-08-01

    The cyclin-dependent kinase (CDK) inhibitor, flavopiridol, was tested as a potential new cancer therapeutic agent to treat canine lymphoma by examining its effect on cell growth of canine lymphoma cell lines in vitro. Flavopiridol induced profound cell death in all eight lymphoma cell lines at 400 nM, and in all cases cell death was due to apoptosis. Apoptosis was inhibited by caspase inhibitor, despite the variable sensitivities between cell lines. Analysis of the mechanism of flavopiridol-induced apoptosis showed that Rb phosphorylation was inhibited, possibly due to CDK4 or CDK6 inhibition. There was also decreased expression of Rb protein and anti-apoptotic proteins, Mcl-1 and XIAP, possibly through transcriptional regulation by inhibition of CDK7 or CDK9 activation. Canine lymphoma cell line-xenotransplanted mice were then treated with flavopiridol and profound tumour shrinkage was observed. This study describes a new therapeutic approach using flavopiridol for canine lymphoma treatment. PMID:25623777

  6. B-cell lymphomas with concurrent MYC and BCL2 abnormalities other than translocations behave similarly to MYC/BCL2 double-hit lymphomas.

    PubMed

    Li, Shaoying; Seegmiller, Adam C; Lin, Pei; Wang, Xuan J; Miranda, Roberto N; Bhagavathi, Sharathkumar; Medeiros, L Jeffrey

    2015-02-01

    Large B-cell lymphomas with IGH@BCL2 and MYC rearrangement, known as double-hit lymphoma (DHL), are clinically aggressive neoplasms with a poor prognosis. Some large B-cell lymphomas have concurrent abnormalities of MYC and BCL2 other than coexistent translocations. Little is known about patients with these lymphomas designated here as atypical DHL. We studied 40 patients of atypical DHL including 21 men and 19 women, with a median age of 60 years. Nine (23%) patients had a history of B-cell non-Hodgkin lymphoma. There were 30 diffuse large B-cell lymphoma (DLBCL), 7 B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma, and 3 DLBCL with coexistent follicular lymphoma. CD10, BCL2, and MYC were expressed in 28/39 (72%), 33/35 (94%), and 14/20 (70%) cases, respectively. Patients were treated with standard (n=14) or more aggressive chemotherapy regimens (n=17). We compared the atypical DHL group with 76 patients with DHLand 35 patients with DLBCL lacking MYC and BCL2 abnormalities. The clinicopathologic features and therapies were similar between patients with atypical and typical DHL. The overall survival of patients with atypical double-hit lymphoma was similar to that of patients with double-hit lymphoma (P=0.47) and significantly worse than that of patients with DLBCL with normal MYC and BCL2 (P=0.02). There were some minor differences. Cases of atypical double-hit lymphoma more often have DLBCL morphology (P<0.01), less frequently expressed CD10 (P<0.01), and patients less often had an elevated serum lactate dehydrogenase level (P=0.01). In aggregate, these results support expanding the category of MYC/BCL2 DHL to include large B-cell lymphomas with coexistent MYC and BCL2 abnormalities other than concurrent translocations. PMID:25103070

  7. Immunopathogenesis and therapy of cutaneous T cell lymphoma

    PubMed Central

    Kim, Ellen J.; Hess, Stephen; Richardson, Stephen K.; Newton, Sara; Showe, Louise C.; Benoit, Bernice M.; Ubriani, Ravi; Vittorio, Carmela C.; Junkins-Hopkins, Jacqueline M.; Wysocka, Maria; Rook, Alain H.

    2005-01-01

    Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of lymphoproliferative disorders caused by clonally derived, skin-invasive T cells. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of CTCLs and are characterized by malignant CD4+/CLA+/CCR4+ T cells that also lack the usual T cell surface markers CD7 and/or CD26. As MF/SS advances, the clonal dominance of the malignant cells results in the expression of predominantly Th2 cytokines, progressive immune dysregulation in patients, and further tumor cell growth. This review summarizes recent insights into the pathogenesis and immunobiology of MF/SS and how these have shaped current therapeutic approaches, in particular the growing emphasis on enhancement of host antitumor immune responses as the key to successful therapy. PMID:15841167

  8. [Role of radiotherapy in the treatment of NK/T-cell nasal type and primary cerebral lymphomas].

    PubMed

    Boros, A; Michot, J-M; Hoang-Xuan, K; Mazeron, R

    2016-10-01

    The head and neck are common sites for extranodal non-Hodgkin lymphomas. Radiotherapy plays an important role in the treatment of low-grade lymphomas, with curative or palliative intent. In the case of high-grade lymphomas, its combination with chemotherapy is debated. Its role is however undeniable in two specific entities: NK/T-cell lymphoma NK/T nasal type, and primary central nervous system lymphomas, which are the subject of this review. PMID:27614517

  9. Primary anaplastic large-cell lymphoma associated with breast implants

    PubMed Central

    Popplewell, Leslie; Thomas, Sandra H.; Huang, Qin; Chang, Karen L.; Forman, Stephen J.

    2012-01-01

    Primary T-cell anaplastic large cell lymphoma (ALCL) of the breast is a rare entity, which has been reported in association with breast implants. In a retrospective analysis of the City of Hope pathology database, we uncovered nine such patients, eight of whom had breast implants proximal to primary ALCL. The diagnosis of ALCL in the implant capsule occurred at a median of 7 years (range 5–30) following implant surgery, and median patient age was 45.5 years (range 32–62). Malignancy was effusion-associated in 2 cases and tissue-associated in 6. Seven patients were negative for anaplastic large-cell kinase (ALK) and one patient was positive. Treatment and follow-up data were available for four patients, all tissue-associated cases: two patients were lost to follow-up after failing to mobilize stem cells and two patients were in remission, 6 years and 7.5 years post autologous transplant. These cases represent 24% of reported primary ALCL cases associated with breast implants. Our review of these cases and the literature suggest that 1) there is a strong skew in primary breast lymphomas associated with implant capsules toward T-cell, ALCL ALK-, and 2) the disease course for tissue-associated cases is not always indolent, with four patients requiring multiple treatment regimens PMID:21699454

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

    PubMed Central

    Narwal, Anjali; Yadav, Achla Bharti; Prakash, Sant; Gupta, Shally

    2016-01-01

    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. PMID:27041916

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

    PubMed

    Narwal, Anjali; Yadav, Achla Bharti; Prakash, Sant; Gupta, Shally

    2016-01-01

    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. PMID:27041916

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

    PubMed

    Narwal, Anjali; Yadav, Achla Bharti; Prakash, Sant; Gupta, Shally

    2016-01-01

    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.

  13. Patient-reported outcomes of brentuximab vedotin in Hodgkin lymphoma and anaplastic large-cell lymphoma

    PubMed Central

    Chen, Robert; Allibone, Suzanne; Bartlett, Nancy L; Brice, Pauline; Chen, Andy; Pose, Katrina; Rich, Lynn; Bonthapally, Vijay; Garfin, Phillip M; Fanale, Michelle

    2016-01-01

    Background Patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) or R/R systemic anaplastic large-cell lymphoma (sALCL) treated with brentuximab vedotin (BV) experienced high remission rates in two Phase II trials. With increased response rates and survival times, patient-reported outcomes (PROs) and health-related quality of life (HRQoL) are becoming increasingly important and can help inform treatment decisions to enhance care of cancer patients. Objective The objective was to qualitatively assess HRQoL in long-term survivors treated with BV. Methods An eight-question survey assessing PRO-related aspects was developed and fielded to a subset of patients with HL or sALCL who remained in long-term follow-up after completing BV treatment in the two pivotal studies. Results The survey was completed by 25 of 38 patients (12 with HL, 13 with sALCL). The majority of patients reported that their energy level, outlook on life, difficulties with daily activities, ability to participate in physical activities, and overall HRQoL improved compared to those before BV treatment. Limitations Small sample size and lack of a baseline questionnaire or validated assessment instrument limit broad applicability of these findings to large populations of patients with HL or sALCL. Conclusion This is the first report of BV PRO data in R/R HL and sALCL. Given the patients’ poor prognostic outcomes before stem cell transplant, these encouraging results warrant formal evaluation of PRO end points in BV trials. PMID:27103829

  14. Pyrvinium selectively induces apoptosis of lymphoma cells through impairing mitochondrial functions and JAK2/STAT5.

    PubMed

    Xiao, Meifang; Zhang, Liming; Zhou, Yizheng; Rajoria, Pasupati; Wang, Changfu

    2016-01-15

    Targeting mitochondrial respiration has emerged as an attractive therapeutic strategy in blood cancer due to their unique metabolic dependencies. In this study, we show that pyrvinium, a FDA-approved anthelmintic drug, selectively targets lymphoma T-cells though inhibition of mitochondrial functions and JAK2/STAT5. Pyrvinium induces apoptosis of malignant T-cell line Jurkat and primary T-cells from lymphoma patients while sparing T-cells from healthy donors. Increased level of active caspase-3 and decreased levels of Bcl-2 and Mcl-1 were also observed in Jurkat and lymphoma T-cells but not normal T-cells treated with pyrvinium. In addition, pyrvinium impairs mitochondrial functions by inhibit mitochondrial respiration, suppressing mitochondrial respiratory complex I activity, increasing ROS and decreasing ATP levels. However, the effects of pyrvinium were abolished in mitochondrial respiration-deficient Jurkat ρ(0) cells, confirming that pyrvinium acts on lymphoma T-cells via targeting mitochondrial respiration. We further show that lymphoma T-cells derived from patients depend more on mitochondrial respiration than normal T-cells, and this explains the selective toxicity of pyrvinium in lymphoma versus normal T-cells. Finally, we demonstrate that pyrvinium also suppresses JAK2/STAT5 signaling pathway in Jurkat cells. Our study suggests that pyrvinium is a useful addition to T-cell lymphoma treatment, and emphasizes the potential therapeutic value of the differences in the mitochondrial characteristics between malignant and normal T-cells in blood cancer.

  15. An Unusual Presentation of B-Cell Lymphoma as a Large Isolated Epiglottic Mass: Case Report and Literature Review

    PubMed Central

    Liu, Changxing; Brown, Tamara N.

    2016-01-01

    Extranodal presentation of B-cell lymphoma is uncommon. Isolated primary epiglottic B-cell lymphoma is even rarer. To our knowledge, there has been only one description of isolated B-cell lymphoma presenting as a large epiglottic mass. We report an unusual type of B-cell lymphoma of the epiglottis, as it could not be subtyped based on routine staining and hybridization. The lymphoma presented as a large isolated globular mass pedicled to the epiglottis, occupying most of the oropharynx, but did not have any ball-valving effect or increased respiratory efforts. Initial radiographic findings were nonspecific. The diagnosis of B-cell lymphoma was determined by transoral incisional biopsy under local anesthesia. The condition was treated successfully with chemoradiation. The current standard of treatment for high grade B-cell lymphoma is concurrent chemoradiotherapy, with excellent prognosis. Although rare, B-cell lymphoma should be considered when investigating pedunculated hypopharyngeal masses. PMID:27213065

  16. MOLECULAR ANALYSIS OF MUTATIONS INDUCED BY MUTAGENS IN THE TK GENE OF MOUSE LYMPHOMA CELLS

    EPA Science Inventory

    MOLECULAR ANALYSIS OF MUTATIONS INDUCED BY BROMATE AND N- ETHYL-N-NITROSOUREA IN THE TK GENE OF MOUSE L YMPHOMA CELLS

    The mouse lymphoma assay is widely used to identify chemical mutagens The Tk +1- gene located on an autosome in mouse lymphoma cells may recover a wide ra...

  17. Solitary (primary) uveal T-cell lymphoma in a horse.

    PubMed

    Trope, Gareth D; McCowan, Christina I; Tyrrell, Dayle; Lording, Peter M; Maggs, David J

    2014-03-01

    A 22-year-old Australian stockhorse gelding was presented with anterior uveitis in the right eye which was nonresponsive to anti-inflammatory therapy. Clinical examination revealed corneal edema and vascularization, marked hypopyon, and thickening of the dorsal iris, which was confirmed by ultrasonography. Hematologic and biochemical analyses, abdominal and thoracic ultrasonography, and abdominocentesis with cytologic and biochemical analysis revealed no significant abnormalities. Cytological examination of an aqueous humor sample revealed a population of predominantly large lymphoblasts with high nuclear-to-cytoplasmic ratio, round or irregular nuclei, clumped nuclear chromatin, multiple large prominent nucleoli, and a small volume of basophilic cytoplasm. The cytologic diagnosis was intraocular lymphoma. Biopsy of the right submandibular lymph node revealed no evidence of neoplastic invasion. Euthanasia and a complete necropsy were performed and revealed no evidence of neoplasia in any tissue other than the right eye, which had an extensive, well-defined infiltrate of neoplastic lymphocytes expanding the ciliary body and iris, infiltrating the ciliary epithelium, and extending into the pars plana and peripheral choroid. Immunohistochemistry confirmed that neoplastic cells expressed the T-cell marker CD3. To the authors' knowledge, this is the first description of primary, solitary uveal T-cell lymphoma in a horse. Although apparently rare, lymphoma should be considered in horses with uveitis, even when inflammation is unilateral and in the absence of extraocular signs of neoplasia. Aqueocentesis and cytological examination provided an antemortem diagnosis in this case and should be considered as a diagnostic tool for investigation of uveal thickening and hypopyon. PMID:23802547

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

    ClinicalTrials.gov

    2016-04-18

    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

  19. Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells.

    PubMed

    Polo, Jose M; Dell'Oso, Tania; Ranuncolo, Stella Maris; Cerchietti, Leandro; Beck, David; Da Silva, Gustavo F; Prive, Gilbert G; Licht, Jonathan D; Melnick, Ari

    2004-12-01

    The BTB/POZ transcriptional repressor and candidate oncogene BCL6 is frequently misregulated in B-cell lymphomas. The interface through which the BCL6 BTB domain mediates recruitment of the SMRT, NCoR and BCoR corepressors was recently identified. To determine the contribution of this interface to BCL6 transcriptional and biological properties, we generated a peptide that specifically binds BCL6 and blocks corepressor recruitment in vivo. This inhibitor disrupts BCL6-mediated repression and establishment of silenced chromatin, reactivates natural BCL6 target genes, and abrogates BCL6 biological function in B cells. In BCL6-positive lymphoma cells, peptide blockade caused apoptosis and cell cycle arrest. BTB domain peptide inhibitors may constitute a novel therapeutic agent for B-cell lymphomas. PMID:15531890

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

    ClinicalTrials.gov

    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

  1. Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer.

    PubMed

    Zhu, Bo; Luo, Shyh-Chyang; Zhao, Haichao; Lin, Hsing-An; Sekine, Jun; Nakao, Aiko; Chen, Chi; Yamashita, Yoshiro; Yu, Hsiao-Hua

    2014-01-01

    Although electrically stimulated neurite outgrowth on bioelectronic devices is a promising means of nerve regeneration, immunogenic scar formation can insulate electrodes from targeted cells and tissues, thereby reducing the lifetime of the device. Ideally, an electrode material capable of electrically interfacing with neurons selectively and efficiently would be integrated without being recognized by the immune system and minimize its response. Here we develop a cell membrane-mimicking conducting polymer possessing several attractive features. This polymer displays high resistance towards nonspecific enzyme/cell binding and recognizes targeted cells specifically to allow intimate electrical communication over long periods of time. Its low electrical impedance relays electrical signals efficiently. This material is capable to integrate biochemical and electrical stimulation to promote neural cellular behaviour. Neurite outgrowth is enhanced greatly on this new conducting polymer; in addition, electrically stimulated secretion of proteins from primary Schwann cells can also occur on it. PMID:25060339

  2. [Breast implant-associated anaplastic large-cell lymphoma].

    PubMed

    Jarjis, Reem Dina; Matzen, Steen Henrik

    2015-11-23

    Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare entity. Due to the lack of awareness of BIA-ALCL, patients with prior history of breast implants who present with non-specific implant-related complications might experience a delay in diagnosis and appropriate treatment of this distinct condition. There are still no evidence-based guidelines on how this condition should be diagnosed, treated or followed because of the rarity of available data. We review current literature in order to raise awareness and discuss management options of this unique clinical entity. PMID:26617170

  3. Radiation Therapy for Cutaneous T-Cell Lymphomas.

    PubMed

    Tandberg, Daniel J; Craciunescu, Oana; Kelsey, Chris R

    2015-10-01

    Radiation therapy is an extraordinarily effective skin-directed therapy for cutaneous T-cell lymphomas. Lymphocytes are extremely sensitive to radiation and a complete response is generally achieved even with low doses. Radiation therapy has several important roles in the management of mycosis fungoides. For the rare patient with unilesional disease, radiation therapy alone is potentially curative. For patients with more advanced cutaneous disease, radiation therapy to local lesions or to the entire skin can effectively palliate symptomatic disease and provide local disease control. Compared with other skin-directed therapies, radiation therapy is particularly advantageous because it can effectively penetrate and treat thicker plaques and tumors. PMID:26433843

  4. Primary diffuse large B-cell lymphoma of the corpora cavernosa presented as a perineal mass

    PubMed Central

    Carlos, González-Satué; Ivanna, Valverde Vilamala; Gustavo, Tapia Melendo; Joan, Areal Calama; Javier, Sanchez Macias; Luis, Ibarz Servio

    2012-01-01

    Primary male genital lymphomas may appear rarely in testis, and exceptionally in the penis and prostate, but there is not previous evidence of a lymphoma arising from the corpora cavernosa. We report the first case in the literature of a primary diffuse cell B lymphoma of the corpora cavernosa presented with low urinary tract symptoms, perineal pain and palpable mass. Diagnosis was based on trucut biopsy, histopathological studies and computed tomographic images. PMID:22919138

  5. Kuttner's tumor of salivary glands resembling marginal zone B-cell lymphoma of the MALT type: a histopathologic and immunohistochemical study of 7 cases.

    PubMed

    Kojima, Masaru; Nakamura, Shigeo; Itoh, Hideaki; Yamane, Yuko; Shimizu, Kazuhiko; Masawa, Nobuhide

    2004-10-01

    Kuttner's tumor is a benign inflammatory process of the submandibular gland that presents as a hard mass mimicking a malignant neoplasm clinically. The histologic feature varies according to stage of evolution and severity of inflammation. We report here 7 cases of Kuttner's tumor that morphologically resemble primary salivary gland marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Histologically, the lobular architecture was distorted and the septa showed sclerosis. There was a dense lymphoplasmacytoid infiltration with lymphoid follicle formation accompanied by loss of acini and ducts. In 4 cases, a few salivary gland ducts contained the lymphoid cells within the epithelium. However, a true lymphoepithelial lesion was observed in none of the 7 cases. Immunohistochemical study demonstrated a disrupted follicular dendritic cell network, which is a characteristic finding of follicular colonization of MALT-type lymphoma. In 6 cases, there were a few small foci of lymphocytes somewhat resembling centrocyte-like cells of MALT-type lymphoma. However, immunohistological study demonstrated the mixed nature of the cells resembling centrocyte-like cells. Moreover, the polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction.

  6. Paraneoplastic retinopathy associated with systemic follicular cell lymphoma.

    PubMed

    Bhavsar, Kavita V; Hedges, Thomas; Thirkill, Charles E; Reichel, Elias

    2015-03-01

    The authors describe two rare cases of autoimmune retinopathy associated with follicular cell lymphoma, including a 54-year-old man who experienced nyctalopia for 1 year (patient 1) and a 59-year-old man who had bilateral loss of central vision for 6 months (patient 2). Visual field testing of patient 1 revealed nonspecific defects, and multifocal electroretinogram (ERG) testing showed mildly subnormal amplitudes more pronounced in the left than the right eye. Serologic testing detected antibodies against a 47-kD protein, presumed to be alpha-enolase. Goldmann perimetry of patient 2 showed dense central scotomas, and a full-field ERG revealed reduced amplitudes of bright scotopic responses. Serological testing yielded anti-bipolar cell antibodies. A variable presentation of autoimmune retinopathy can occur in the setting of follicular cell lymphoma. Disparate serum autoantibodies may have mediated the pathogenesis of retinal degeneration in these two patients and could explain the difference in course and severity of retinopathy. PMID:25835308

  7. My Treatment Approach to Patients With Diffuse Large B-Cell Lymphoma

    PubMed Central

    Armitage, James O.

    2012-01-01

    My favored treatment approach for patients with diffuse large B-cell lymphoma continues to evolve. Diffuse large B-cell lymphoma can now be cured in more than 50% of patients. This is a result of improved definitions of the disease, improved diagnostic capabilities, better staging and restaging techniques, a useful prognostic index to guide therapeutic decisions, and the development of increasingly effective therapies. Positron emission tomographic scans have improved the accuracy of both staging and restaging. Findings on a positron emission tomographic scan at the end of therapy are the best predictors of a good treatment outcome. Numerous subtypes of diffuse large B-cell lymphoma have been identified that require specific treatment approaches. For example, plasmablastic lymphoma typically lacks CD20 and does not benefit from treatment with rituximab. Diffuse large B-cell lymphoma originating in specific extranodal sites such as the central nervous system, testes, and skin presents special problems and requires specific treatment approaches. A subgroup of diffuse large B-cell lymphoma with a very high proliferative rate seems to have a poor outcome when treated with CHOP-R and does better with regimens used for patients with Burkitt lymphoma. New insights into the biology of these disorders are likely to further change treatment approaches. Recognition that diffuse large B-cell lymphoma is not one disease, but a variety of clinicopathologic syndromes provides the opportunity to further improve our ability to benefit patients. PMID:22305028

  8. My treatment approach to patients with diffuse large B-cell lymphoma.

    PubMed

    Armitage, James O

    2012-02-01

    My favored treatment approach for patients with diffuse large B-cell lymphoma continues to evolve. Diffuse large B-cell lymphoma can now be cured in more than 50% of patients. This is a result of improved definitions of the disease, improved diagnostic capabilities, better staging and restaging techniques, a useful prognostic index to guide therapeutic decisions, and the development of increasingly effective therapies. Positron emission tomographic scans have improved the accuracy of both staging and restaging. Findings on a positron emission tomographic scan at the end of therapy are the best predictors of a good treatment outcome. Numerous subtypes of diffuse large B-cell lymphoma have been identified that require specific treatment approaches. For example, plasmablastic lymphoma typically lacks CD20 and does not benefit from treatment with rituximab. Diffuse large B-cell lymphoma originating in specific extranodal sites such as the central nervous system, testes, and skin presents special problems and requires specific treatment approaches. A subgroup of diffuse large B-cell lymphoma with a very high proliferative rate seems to have a poor outcome when treated with CHOP-R and does better with regimens used for patients with Burkitt lymphoma. New insights into the biology of these disorders are likely to further change treatment approaches. Recognition that diffuse large B-cell lymphoma is not one disease, but a variety of clinicopathologic syndromes provides the opportunity to further improve our ability to benefit patients. PMID:22305028

  9. Incidental Detection of Hairy Cell Leukaemia with Herpes Simplex Virus (HSV) Related Lip Ulcer Mimicking Carcinoma.

    PubMed

    Agrawal, Pallavi; Bhartiya, Richa; Singh, Ran Vijoy Narayan

    2016-08-01

    Hairy cell leukemia is a chronic lympho-proliferative disease. It is indolent but progressive in nature. It arises from B-cell lineage. We report an incidentally detected case of Hairy Cell Leukaemia (HCL) in a 55-year-old male patient with Herpes simplex virus (HSV) - related lip ulcer mimicking squamous cell carcinoma. Clinically the patient presented with lip ulceration without pain. He was found to have moderate hepatosplenomegaly and pancytopenia on general examination. Bone marrow aspiration and flow cytometric immunophenotyping revealed HCL. The oral lesion resolved after antiviral therapy. The intriguing possibility of a combined pathogenesis for the two disorders is considered, as HCL is known to be associated with immunosuppression, second malignancies and the production of cytokines promoting epithelial growth. PMID:27656454

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

    ClinicalTrials.gov

    2016-10-10

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Mediastinal Lymphoma; Recurrent Adult Burkitt 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

  11. Transformation of follicular lymphoma to double hit B-cell lymphoma causing hypercalcemia in a 69-year-old female: a case report and review of the literature.

    PubMed

    Kapur, Sakshi; Levin, Miles B

    2014-01-01

    Double hit B-cell lymphomas are rare tumors that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, mainly a t(14;18)(q32;q21) involving BCL2. These tumors mostly occur in adults and carry a very poor prognosis. Double hit lymphomas can occur de novo, or arise from transformation of follicular lymphoma. We report a case of a 69-year-old female with abdominal distention and progressively worsening weakness over six months. Patient presented with severe hypercalcemia and multiple intra-abdominal/pelvic masses. Histopathology results of the abdominal mass were compatible with a double hit B-cell lymphoma. However, bone marrow biopsy results showed a low grade follicular lymphoma, thus suggesting peripheral transformation of follicular lymphoma to double hit B-cell lymphoma. Patient was transferred to a tertiary care center and was started on combination chemotherapy (EPOCH: doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone). Our paper highlights not only transformation of follicular lymphoma to double hit B-cell lymphoma and the challenges encountered in diagnosing and treating these aggressive tumors, but also the association of new onset/worsening hypercalcemia in such patients.

  12. Transformation of Follicular Lymphoma to Double Hit B-Cell Lymphoma Causing Hypercalcemia in a 69-Year-Old Female: A Case Report and Review of the Literature

    PubMed Central

    2014-01-01

    Double hit B-cell lymphomas are rare tumors that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, mainly a t(14;18)(q32;q21) involving BCL2. These tumors mostly occur in adults and carry a very poor prognosis. Double hit lymphomas can occur de novo, or arise from transformation of follicular lymphoma. We report a case of a 69-year-old female with abdominal distention and progressively worsening weakness over six months. Patient presented with severe hypercalcemia and multiple intra-abdominal/pelvic masses. Histopathology results of the abdominal mass were compatible with a double hit B-cell lymphoma. However, bone marrow biopsy results showed a low grade follicular lymphoma, thus suggesting peripheral transformation of follicular lymphoma to double hit B-cell lymphoma. Patient was transferred to a tertiary care center and was started on combination chemotherapy (EPOCH: doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone). Our paper highlights not only transformation of follicular lymphoma to double hit B-cell lymphoma and the challenges encountered in diagnosing and treating these aggressive tumors, but also the association of new onset/worsening hypercalcemia in such patients. PMID:25161781

  13. Concanavalin A-induced agglutination of human leukemic and lymphoma cells.

    PubMed

    Maca, R D

    1976-04-01

    With a newly developed turbidometric method, concanavalin A was shown to agglutinate normal lymphocytes, lymphoma cells, and leukemic cells from chronic lymphocytic leukemia and from acute myelocytic and lymphocytic leukemia. However, there was a marked difference in the kinetics of this agglutination process. Leukemic blast cells and cells from a patient with convoluted lymphoma agglutinated poorly in this system. Conversely, the degree of agglutination for chronic lymphocytic leukemia cells was greater than that for the blast cells and also slightly greater than that for normal lymphocytes. Cultured cells from a Burkitt's lymphoma (Raji) and from a patient with poorly differentiated lymphoma agglutinated very rapidly with concanavalin A. Prior incubation of all cell types with neuraminidase markedly enhanced the agglutination process similar to that of trypsinization. Thus, these studies illustrate the usefulness of this method in quantitating the kinetics of agglutination of various human neoplastic cell types by concanavalin A. PMID:1063062

  14. Diffuse large B cell lymphoma of the spermatic cord: a case report and literature review.

    PubMed

    Joshi, Shivam; Mansour, Ahmed M; Eldefrawy, Ahmed; Soloway, Mark S

    2012-12-01

    Primary lymphoma of the spermatic cord is rare. We report a case of primary lymphoma of the spermatic cord and review the literature. A 77-year-old man presented with a 5 month history of an enlarging right inguino-scrotal mass. On physical exam, the mass involved the spermatic cord. Computerized tomography and magnetic resonance imaging revealed a 10 cm x 4 cm inguinoscrotal mass related to the spermatic cord. A right inguinal orchidectomy with wide local excision was performed. Pathological and immunohistochemical evaluation identified the tumor as a diffuse large B cell lymphoma of the spermatic cord. Postoperatively, patient began a chemoradiotherapy regimen consistent with metastatic lymphoma.

  15. Interferon alpha-2a in cutaneous T-cell lymphoma.

    PubMed

    Vegna, M L; Papa, G; Defazio, D; Pisani, F; Coppola, G; De Pità, O; Puddu, P; Ferranti, G; Simoni, R; Mandelli, F

    1990-01-01

    23 newly diagnosed patients affected by cutaneous T-cell lymphoma were treated with sub-cutaneous interferon alpha-2a to evaluate the therapeutic efficacy and the toxicity of this agent. IFN was administered daily with dose escalation from 3 to 18 million units for 12 weeks; thereafter, patients induced into complete (CR) or partial (PR) remission were given IFN at maximal tolerated dose 3 times weekly for 6 or 9 months. The objective tumor response was observed in 17 patients (74%): 8 (35%) were CR and 9 (39%) were PR. A 74-yr-old patient died because of neutropenia and sepsis at the end of induction phase, while receiving IFN at dose of 18 million units. Disease stage is the initial feature predictive of response to IFN therapy. The dose schedule of this study was well tolerated: only 3 patients developed liver toxicity, while leukopenia was evident in 6 patients. Only 2 CR patients have relapsed, 18 and 24 months from response; the remaining 6 CR patients are in continuous complete remission with a median follow-up of 41.8 months. 6 PR patients have progressed from 8 to 17 months after response, and in the 3 PR patients not yet progressed the response duration ranges from 20 to 24 months. In conclusion, interferon alpha-2a is a very effective agent in therapy of untreated cutaneous T-cell lymphoma with an overall response rate of 74%.

  16. Romidepsin: in the treatment of T-cell lymphoma.

    PubMed

    Yang, Lily P H

    2011-07-30

    Romidepsin is a histone deacetylase inhibitor with high inhibitory activity for class I histone deacetylases. Intravenous romidepsin is indicated in the US for the treatment of adult patients with cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL) who have received at least one prior systemic therapy. The clinical efficacy of romidepsin has been demonstrated in two noncomparative, multicentre, phase II trials in patients with relapsed, refractory or advanced CTCL. In both trials, therapy with intravenous romidepsin was associated with an overall response (i.e. both complete response and partial response) rate of 34% and a complete response rate of 6%. The efficacy of romidepsin was also evaluated in patients with relapsed or refractory PTCL in two noncomparative, multicentre, phase II trials. Intravenous romidepsin therapy was associated with overall response rates of 38% and 26% and a complete response rate of 18% and 13% in these trials. Romidepsin had an acceptable tolerability profile in clinical trials in patients with CTCL or PTCL. The most common adverse events of grade 3 or 4 severity considered at least possibly related to romidepsin were haematological or asthenic in nature, and included leukopenia, lymphopenia, granulocytopenia, thrombocytopenia, fatigue and anaemia.

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

    ClinicalTrials.gov

    2016-09-20

    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. Aberrant Circulating Th17 Cells in Patients with B-Cell Non-Hodgkin's Lymphoma.

    PubMed

    Lu, Ting; Yu, Shuang; Liu, Yan; Yin, Congcong; Ye, Jingjing; Liu, Zhi; Ma, Daoxin; Ji, Chunyan

    2016-01-01

    Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of neoplasm in which 90% are B-cell lymphomas and 10% T-cell lymphomas. Although T-helper 17 (Th17) cells have been implicated to be essential in the pathogenesis of autoimmune and inflammatory diseases, its role in B-cell non-Hodgkin's lymphoma (B-NHL) remains unknown. In this study, we observed a significantly decreased frequency of Th17 cells in peripheral blood from B-NHL patients compared with healthy individuals, accompanied with increased Th1 cells. IL-17AF plasma levels were remarkably decreased in B-NHL patients, accompanied with undetectable IL-17FF and unchangeable IL-17AA. Moreover, Th17 and Th1 cells became normalized after one or two cycles of chemotherapy. Interestingly, in B-NHL, circulating Th17 cells frequencies were significantly higher in relapsed patients than those in untreated patients or normal individuals. Meanwhile, there was no statistical difference regarding the frequencies of Th1 cells between relapsed and untreated patients. Taken these data together, circulating Th17 subset immune response may be associated with the response of patients to treatment and with different stages of disease. PMID:26812681

  19. Non-Hodgkin Lymphoma

    MedlinePlus

    ... Lymphoma? A lymphoma is a cancer of the lymphatic system . The lymphatic system is a part of the body's immune system. ... non-Hodgkin lymphoma, cancer cells form in the lymphatic system and start to grow. Most of the time, ...

  20. Single-agent cytarabine is insufficient for the treatment of human mantle cell lymphoma in mouse xenograft model.

    PubMed

    Klanova, M; Soukup, T; Molinsky, J; Lateckova, L; Vockova, P; Alam, M; Zivny, J; Trneny, M; Klener, P

    2016-01-01

    Mantle cell lymphoma is an aggressive type of B-cell non-Hodgkin lymphoma with adverse prognosis. It was demonstrated that alternation of CHOP and DHAP chemotherapy improved outcome of mantle cell lymphoma patients. However, which components of DHAP, cisplatin, cytarabine, or both, were responsible for the improved outcome remained unclear. To answer this question, antitumor efficacies of equally toxic doses of cytarabine, cisplatin, and three different combinations were compared in vivo using mouse xenograft models of mantle cell lymphoma. We demonstrated that cisplatin, alone or with cytarabine, is significantly superior to single-agent cytarabine in both eliminating lymphoma cells and suppressing their proliferation rate. PMID:27468882

  1. Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge.

    PubMed

    Khan, Maria S; McCubbin, Mark; Nand, Sucha

    2014-01-01

    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, and about 65% are

  2. [Mediastinal lymphomas].

    PubMed

    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. PMID:27507160

  3. B-cell non-Hodgkin lymphoma linked to Coxiella burnetii.

    PubMed

    Melenotte, Cléa; Million, Matthieu; Audoly, Gilles; Gorse, Audrey; Dutronc, Hervé; Roland, Gauthier; Dekel, Michal; Moreno, Asuncion; Cammilleri, Serge; Carrieri, Maria Patrizia; Protopopescu, Camelia; Ruminy, Philippe; Lepidi, Hubert; Nadel, Bertrand; Mege, Jean-Louis; Xerri, Luc; Raoult, Didier

    2016-01-01

    Bacteria can induce human lymphomas, whereas lymphoproliferative disorders have been described in patients with Q fever. We observed a lymphoma in a patient with Q fever that prompted us to investigate the association between the 2 diseases. We screened 1468 consecutive patients of the 2004 to 2014 French National Referral Center for Q fever database. The standardized incidence ratios (SIRs) of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were calculated comparatively to the 2012 Francim Registry. The presence of Coxiella burnetii was tested using immunofluorescence and fluorescence in situ hybridization using a specific 16S ribosomal RNA probe and genomic DNA probe. Seven patients (0.48%) presented mature B-cell lymphoma consisting of 6 DLBCL and 1 FL. An excess risk of DLBCL and FL was found in Q fever patients compared with the general population (SIR [95% confidence interval], 25.4 [11.4-56.4] and 6.7 [0.9-47.9], respectively). C burnetii was detected in CD68(+) macrophages within both lymphoma and lymphadenitis tissues but localization in CD123(+) plasmacytoid dendritic cells (pDCs) was found only in lymphoma tissues. Q fever patients with persistent focalized infection were found more at risk of lymphoma (hazard ratio, 9.35 [1.10-79.4]). Interleukin-10 (IL10) overproduction (P = .0003) was found in patients developing lymphoma. These results suggest that C burnetii should be added to the list of bacteria that promote human B-cell non-Hodgkin lymphoma, possibly by the infection of pDCs and IL10 overproduction. Screening for early lymphoma diagnosis should be considered in the management of patients with Q fever, especially those with persistent focalized infections. PMID:26463422

  4. Primary Cutaneous Lymphoma-Associated Pseudoepitheliomatous Hyperplasia Masquerading as Squamous Cell Carcinoma in a Young Adult.

    PubMed

    Ansari, Mahsa; Azmoodeh Ardalan, Farid; Najafi, Masoumeh; Goodarzi, Azadeh; Ghanadan, Alireza

    2015-12-01

    Primary cutaneous anaplastic large cell lymphoma is a T-cell malignancy with atypical CD30 positive lymphocytes. Pseudoepitheliomatous hyperplasia is an uncommon finding in primary cutaneous anaplastic large cell lymphoma, and may mimic squamous cell carcinoma as pseudomalignancy. Careful attention of a pathologist to correct diagnosis of pseudoepitheliomatous hyperplasia and its underlying causes will help physicians to avoid inappropriate management. Here, we present a 22-year-old man referred to our hospital with a solitary nodule persistent on his forearm which was diagnosed as squamous cell carcinoma in the first biopsy. The lesion recurred after two months and histopathologic and immunohistochemistry examination revealed anaplastic large cell lymphoma with florid pseudoepitheliomatous hyperplasia which masquerading as well-differentiated squamous cell carcinoma. Diagnosis of pseudoepitheliomatous hyperplasia must guide the pathologist to search for underlying causes, such as primary cutaneous lymphoma. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and this can result in inappropriate diagnosis and management. PMID:26749237

  5. Nuclear overexpression of lymphoid-enhancer-binding factor 1 identifies chronic lymphocytic leukemia/small lymphocytic lymphoma in small B-cell lymphomas.

    PubMed

    Tandon, Bevan; Peterson, Loann; Gao, Juehua; Nelson, Beverly; Ma, Shuo; Rosen, Steven; Chen, Yi-Hua

    2011-11-01

    Lymphoid-enhancer-binding factor 1 (LEF1), coupling with β-catenin, functions as a key nuclear mediator of WNT/β-catenin signaling, which regulates cell proliferation and survival. LEF1 has an important role in lymphopoiesis, and is normally expressed in T and pro-B cells but not mature B cells. However, gene expression profiling demonstrates overexpression of LEF1 in chronic lymphocytic leukemia, and knockdown of LEF1 decreases the survival of the leukemic cells. So far, the data on LEF1 expression in B-cell lymphomas are limited. This study represents the first attempt to assess LEF1 by immunohistochemistry in a large series (290 cases) of B-cell lymphomas. Strong nuclear staining of LEF1 was observed in virtually all neoplastic cells in 92 of 92 (100%) chronic lymphocytic leukemia/small lymphocytic lymphomas including two CD5- cases, with strongest staining in cells with Richter's transformation. LEF1 also highlighted the morphologically inconspicuous small lymphocytic lymphoma component in three composite lymphomas. All 53 mantle cell lymphomas, 31 low-grade follicular lymphomas and 31 marginal zone lymphomas, including 3 CD5+ cases, were negative. In 12 grade 3 follicular lymphomas, LEF1 was positive in a small subset (5-15%) of cells. Diffuse large B-cell lymphoma, however, demonstrated significant variability in LEF1 expression with overall positivity in 27 of 71 (38%) cases. Our results demonstrate that nuclear overexpression of LEF1 is highly associated with chronic lymphocytic leukemia/small lymphocytic lymphoma, and may serve as a convenient marker for differential diagnosis of small B-cell lymphomas. The expression of β-catenin, the coactivator of LEF1 in WNT signaling, was examined in 50 chronic lymphocytic leukemia/small lymphocytic lymphomas, of which 44 (88%) showed negative nuclear staining. The findings of universal nuclear overexpression of LEF1 but lack of nuclear β-catenin in the majority of chronic lymphocytic leukemia/small lymphocytic

  6. [Diffuse large B-cell lymphoma of the testis relapsed 16 years after achieving complete response].

    PubMed

    Nagasaka, Isao; Mitsui, Takeki; Ishizaki, Takuma; Koiso, Hiromi; Yokohama, Akihiko; Saitoh, Takayuki; Hirato, Junko; Igarashi, Tadahiko; Kojima, Masaru; Tsukamoto, Norifumi; Nojima, Yoshihisa; Murakami, Hirokazu; Handa, Hiroshi

    2015-12-01

    Testicular lymphoma is a rare disease, accounting for 1-2% of non-Hodgkin lymphoma and 5-9% of all testicular tumors, and has a high relapse rate with a poor prognosis. We report a patient with testicular diffuse large B-cell lymphoma (DLBCL) who relapsed after being in remission for 16 years. He had undergone orchiectomy of the right testis and was diagnosed as having DLBCL (stage IAE) at 49 years of age. After 3 cycles of CHOP, he achieved a complete remission. Orchiectomy was performed because of a left testicular tumor, and he was again diagnosed with DLBCL at the age of 65. VH3-21 was detected in lymphoma cells at the times of both the first diagnosis and the relapse based on analysis of the variable region of the immunoglobulin heavy chain. Accordingly, the lymphoma cells at relapse were confirmed to be the same clone as that which had been documented at the first diagnosis.

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

    PubMed Central

    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. PMID:25973119

  8. Anti-CD22 CAR-T Therapy for CD19-refractory or Resistant Lymphoma Patients

    ClinicalTrials.gov

    2016-08-22

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage III/IV Adult Diffuse Large Cell Lymphoma; Stage III/IV Follicular Lymphoma; Stage III/IV Mantle Cell Lymphoma

  9. Arsenic trioxide rewires mantle cell lymphoma response to bortezomib.

    PubMed

    Zhao, Ling-Ling; Liu, Yuan-Fang; Peng, Li-Jun; Fei, Ai-Mei; Cui, Wen; Miao, Sheng-Chao; Hermine, Olivier; Gressin, Remy; Khochbin, Saadi; Chen, Sai-Juan; Wang, Jin; Mi, Jian-Qing

    2015-11-01

    Although most of the mantle cell lymphoma (MCL) patients initially responded well to bortezomib (BTZ), the dose-dependent toxicities have greatly limited the application of BTZ to MCL. To investigate the efficacy and mechanism of arsenic trioxide (ATO) with BTZ in inducing apoptosis of MCL cells, two MCL cell lines, along with primary cells from MCL patients (n = 4), were used. Additionally, the NOD-SCID mice xenograft model of Jeko-1 cells was established to study the anti-MCL mechanisms in an in vivo setting. ATO treatment highly improved BTZ capacity to inhibit proliferation and induce apoptosis of MCL cells. Furthermore, the interaction of Noxa and Mcl-1 leads Bak to release from Mcl-1 or from Bcl-xl, which could further activate Bak and Bax and then induce cell apoptosis. We also found that when lower doses of BTZ were used in combination with ATO, more effective proapoptotic effects in both the cell lines and the primary cells were obtained compared to the effects of BTZ used alone at higher doses. Simultaneously, the combination of these two drugs delayed the tumor growth in mice more effectively than BTZ alone. The cooperative anti-MCL effects of this combination therapy both in vitro and in vivo strongly provided a new strategy to the clinical treatment of MCL. PMID:26310857

  10. Comparative proteomic profiling of Hodgkin lymphoma cell lines.

    PubMed

    Vergara, D; Simeone, P; De Matteis, S; Carloni, S; Lanuti, P; Marchisio, M; Miscia, S; Rizzello, A; Napolitano, R; Agostinelli, C; Maffia, M

    2016-01-01

    Classical Hodgkin lymphoma (cHL) is a malignancy with complex pathogenesis. The hallmark of the disease is the presence of large mononucleated Hodgkin and bi- or multinucleated Reed/Sternberg (H/RS) cells. The origin of HRS cells in cHL is controversial as these cells show the coexpression of markers of several lineages. Using a proteomic approach, we compared the protein expression profile of cHL models of T- and B-cell derivation to find proteins differentially expressed in these cell lines. A total of 67 proteins were found differentially expressed between the two cell lines including metabolic proteins and proteins involved in the regulation of the cytoskeleton and/or cell migration, which were further validated by western blotting. Additionally, the expression of selected B- and T-cell antigens was also assessed by flow cytometry to reveal significant differences in the expression of different surface markers. Bioinformatics analysis was then applied to our dataset to find enriched pathways and networks, and to identify possible key regulators. In the present study, a proteomic approach was used to compare the protein expression profiles of two cHL cell lines. The identified proteins and/or networks, many of which not previously related to cHL, may be important to better define the pathogenesis of the disease, to identify novel diagnostic markers, and to design new therapeutic strategies. PMID:26588820

  11. [A case of pulmonary low-grade B cell lymphoma (MALT type) presenting seven years after gastric lymphoma resection].

    PubMed

    Tojima, Hirokazu; Shimura, Ryuhi; Nishiwaki, Tetsu; Kawabata, Yoshinori

    2003-02-01

    A 71-year-old man was admitted to our hospital because of systemic edema and exertional dyspnea. Chest radiographs revealed infiltrative shadows in both lung fields, pleural effusion, and pericardial effusion. Seven years before, he had undergone gastric surgery for a gastric ulcer with lymphoid hyperplasia. In the pathologic diagnosis based on the percutaneous lung biopsy, hyalinizing granuloma was suspected. For a more thorough diagnosis, the patient was subjected to an open lung biopsy, and the final diagnosis was low-grade B-cell lymphoma of the MALT (mucosa-associated lymphoid tissue) type. Gallium scintigraphy showed accentuated accumulation in the left neck and hypothyroidism was present. Histologic re-examination of the resected stomach revealed infiltration of centrocyte-like cells and lymphoepithelial lesions, compatible with the pathologic features of MALT lymphoma. We considered that the gastric neoplasm and the pulmonary, pleural, and thyroid tumors of MALT lymphoma had occurred seven years apart in this case. Thyroid hormone replacement and CHOP therapy improved the symptoms and decreased the lung tumor size by 73%. MALT lymphomas tend to remain localized for a long period. The multiorgan involvement seen in this case is rather rare. PMID:12722333

  12. Managing Patients with Cutaneous B-Cell and T-Cell Lymphomas Other Than Mycosis Fungoides.

    PubMed

    Kheterpal, Meenal; Mehta-Shah, Neha; Virmani, Pooja; Myskowski, Patricia L; Moskowitz, Alison; Horwitz, Steven M

    2016-06-01

    Cutaneous lymphomas (CL) are a heterogeneous group of neoplasms characterized with clinical and histopathological variation, as well as overlap with benign dermatoses. Diagnosis and treatment of CLs is challenging and often requires a multidisciplinary approach. However, prognostic knowledge of these conditions and awareness of treatment options can help optimize appropriate use of available regimens, thereby improving care for patients. Here, we review the most recent literature and outline treatment themes for managing patients with cutaneous B-cell and T-cell lymphomas other than mycosis fungoides.

  13. Pathophysiology and molecular aspects of diffuse large B-cell lymphoma

    PubMed Central

    Gouveia, Gisele Rodrigues; Siqueira, Sheila Aparecida Coelho; Pereira, Juliana

    2012-01-01

    Diffuse large B-Cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the West. In Brazil, it is the fifth cause of cancer, with more than 55,000 cases and 26,000 deaths per year. At Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, diffuse large B-Cell lymphoma represents 49.7% of all non-Hodgkin lymphoma cases. Initially, the classification of non-Hodgkin lymphoma was based on morphology, but advances in immunology and molecular medicine allowed the introduction of a biological classification for these diseases. As for other cancers, non-Hodgkin lymphoma involves patterns of multifactorial pathogenesis with environmental factors, as well as genetic, occupational and dietary factors, contributing to its development. Multiple lesions involving molecular pathways of B-cell proliferation and differentiation may result in the activation of oncogenes such as the BCL2, BCL6, and MYC genes and the inactivation of tumor suppressor genes such as p53 and INK4, as well as other important transcription factors such as OCT-1 and OCT-2. A dramatic improvement in survival was seen after the recent introduction of the anti-CD20 monoclonal antibody. The association of this antibody to the cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (CHOP) regimen has increased overall survival of diffuse large B-Cell lymphoma and follicular lymphoma patients by 20%. However, 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment. Thus, it is important to know and understand the key factors and molecular pathways involved in the pathogenesis of diffuse large B-Cell lymphoma. PMID:23323070

  14. Primary Cutaneous Peripheral T-Cell Lymphoma Not Otherwise Specified: A Rapidly Progressive Variant of Cutaneous T-Cell Lymphoma

    PubMed Central

    Aderhold, Kimberly; Carpenter, Lisa; Brown, Krysta; Donato, Anthony

    2015-01-01

    Primary Cutaneous Peripheral T-Cell Lymphoma NOS (PTL-NOS) is a rare, progressive, fatal dermatologic disease that presents with features similar to many common benign plaque-like skin conditions, making recognition of its distinguishing features critical for early diagnosis and treatment (Bolognia et al., 2008). A 78-year-old woman presented to ambulatory care with a single 5 cm nodule on her shoulder that had developed rapidly over 1-2 weeks. Examination was suspicious for malignancy and a biopsy was performed. Biopsy results demonstrated CD4 positivity, consistent with Mycosis Fungoides with coexpression of CD5, CD47, and CD7. Within three months her cancer had progressed into diffuse lesions spanning her entire body. As rapid progression is usually uncharacteristic of Mycosis Fungoides, her diagnosis was amended to PTL-NOS. Cutaneous T-Cell Lymphoma (CTCL) should be suspected in patients with patches, plaques, erythroderma, or papules that persist or multiply despite conservative treatment. Singular biopsies are often nondiagnostic, requiring a high degree of suspicion if there is deviation from the anticipated clinical course. Multiple biopsies are often necessary to make the diagnosis. Physicians caring for patients with rapidly progressive, nonspecific dermatoses with features described above should keep more uncommon forms of CTCL in mind and refer for early biopsy. PMID:26380134

  15. Primary Cutaneous Peripheral T-Cell Lymphoma Not Otherwise Specified: A Rapidly Progressive Variant of Cutaneous T-Cell Lymphoma.

    PubMed

    Aderhold, Kimberly; Carpenter, Lisa; Brown, Krysta; Donato, Anthony

    2015-01-01

    Primary Cutaneous Peripheral T-Cell Lymphoma NOS (PTL-NOS) is a rare, progressive, fatal dermatologic disease that presents with features similar to many common benign plaque-like skin conditions, making recognition of its distinguishing features critical for early diagnosis and treatment (Bolognia et al., 2008). A 78-year-old woman presented to ambulatory care with a single 5 cm nodule on her shoulder that had developed rapidly over 1-2 weeks. Examination was suspicious for malignancy and a biopsy was performed. Biopsy results demonstrated CD4 positivity, consistent with Mycosis Fungoides with coexpression of CD5, CD47, and CD7. Within three months her cancer had progressed into diffuse lesions spanning her entire body. As rapid progression is usually uncharacteristic of Mycosis Fungoides, her diagnosis was amended to PTL-NOS. Cutaneous T-Cell Lymphoma (CTCL) should be suspected in patients with patches, plaques, erythroderma, or papules that persist or multiply despite conservative treatment. Singular biopsies are often nondiagnostic, requiring a high degree of suspicion if there is deviation from the anticipated clinical course. Multiple biopsies are often necessary to make the diagnosis. Physicians caring for patients with rapidly progressive, nonspecific dermatoses with features described above should keep more uncommon forms of CTCL in mind and refer for early biopsy. PMID:26380134

  16. Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-08-11

    Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom's Macroglobulinaemia; Lymphoma,T-cell Cutaneous; Lymphoma, T-Cell, Peripheral

  17. Clinical and Pathologic Studies in Non-Hodgkin's Lymphoma Patients Receiving Antibody Treatment

    ClinicalTrials.gov

    2011-05-31

    Lymphoma, Non-Hodgkin; Lymphomas: Non-Hodgkin; Lymphomas: Non-Hodgkin Cutaneous Lymphoma; Lymphomas: Non-Hodgkin Diffuse Large B-Cell; Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell; Lymphomas: Non-Hodgkin Mantle Cell; Lymphomas: Non-Hodgkin Marginal Zone; Lymphomas: Non-Hodgkin Peripheral T-Cell; Lymphomas: Non-Hodgkin Waldenstr Macroglobulinemia

  18. Bortezomib for the treatment of mantle cell lymphoma: an update.

    PubMed

    Hambley, Bryan; Caimi, Paolo F; William, Basem M

    2016-08-01

    Bortezomib is a first in class proteasome inhibitor, initially approved by the US Food and Drug Administration for the treatment of plasma cell myeloma. Bortezomib has been approved for the treatment of relapsed and refractory mantle cell lymphoma (MCL) and, more recently, in the upfront setting as well. Treatment algorithms for MCL have rapidly evolved over the past two decades, and the optimal regimen remains to be defined. The choice of treatment regimen is based on disease risk stratification models, the expected toxicity of antineoplastic agents, the perceived patient ability to tolerate the planned treatments and the availability of novel agents. As new drugs with novel mechanisms of action and variable toxicity profiles come into use, treatment decisions for a given patient have become increasingly complex. This article provides an overview of the evolving use of bortezomib in the rapidly changing management landscape of MCL.

  19. Bortezomib for the treatment of mantle cell lymphoma: an update

    PubMed Central

    Hambley, Bryan; Caimi, Paolo F.; William, Basem M.

    2016-01-01

    Bortezomib is a first in class proteasome inhibitor, initially approved by the US Food and Drug Administration for the treatment of plasma cell myeloma. Bortezomib has been approved for the treatment of relapsed and refractory mantle cell lymphoma (MCL) and, more recently, in the upfront setting as well. Treatment algorithms for MCL have rapidly evolved over the past two decades, and the optimal regimen remains to be defined. The choice of treatment regimen is based on disease risk stratification models, the expected toxicity of antineoplastic agents, the perceived patient ability to tolerate the planned treatments and the availability of novel agents. As new drugs with novel mechanisms of action and variable toxicity profiles come into use, treatment decisions for a given patient have become increasingly complex. This article provides an overview of the evolving use of bortezomib in the rapidly changing management landscape of MCL PMID:27493710

  20. Bortezomib for the treatment of mantle cell lymphoma: an update.

    PubMed

    Hambley, Bryan; Caimi, Paolo F; William, Basem M

    2016-08-01

    Bortezomib is a first in class proteasome inhibitor, initially approved by the US Food and Drug Administration for the treatment of plasma cell myeloma. Bortezomib has been approved for the treatment of relapsed and refractory mantle cell lymphoma (MCL) and, more recently, in the upfront setting as well. Treatment algorithms for MCL have rapidly evolved over the past two decades, and the optimal regimen remains to be defined. The choice of treatment regimen is based on disease risk stratification models, the expected toxicity of antineoplastic agents, the perceived patient ability to tolerate the planned treatments and the availability of novel agents. As new drugs with novel mechanisms of action and variable toxicity profiles come into use, treatment decisions for a given patient have become increasingly complex. This article provides an overview of the evolving use of bortezomib in the rapidly changing management landscape of MCL. PMID:27493710

  1. Human immunodeficiency virus (HIV)-associated extranodal T cell non-Hodgkin lymphoma of the oral cavity.

    PubMed

    Wood, Neil H; Feller, Liviu; Raubenheimer, Erich J; Jadwat, Yusuf; Meyerov, Robin; Lemmer, Johan

    2008-04-01

    T cell non-Hodgkin lymphoma is characterized by uncontrolled cellular proliferation of immature malignant clones. HIV-associated T cell non-Hodgkin lymphoma comprises a heterogeneous group of lymphoproliferative neoplastic entities classified according to morphological, immunological, genetic and clinical features. Extranodal T cell non-Hodgkin lymphoma of the oral cavity is uncommon. A case is presented with extranodal T cell non-Hodgkin lymphoma as an initial sign of HIV-infection. The characteristics of HIV-associated non-Hodgkin lymphoma are discussed. PMID:18689348

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

    PubMed

    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.

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

    PubMed

    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. PMID:25817451

  4. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses

    PubMed Central

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G.

    2016-01-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  5. Molecular characterization of primary mediastinal B cell lymphoma.

    PubMed

    Tsang, P; Cesarman, E; Chadburn, A; Liu, Y F; Knowles, D M

    1996-06-01

    Primary mediastinal B cell lymphoma (PMBL) is a diffuse large B cell lymphoma (DLCL) postulated to arise from noncirculating thymic B lymphocytes. Because of its distinctive clinical and morphological features and putative unique cellular origin, PMBL is generally considered a distinct clinicopathological entity. Little is known, however, about the molecular characteristics of PMBL. Therefore, we analyzed 16 PMBLs for molecular alterations involving the bcl-1, bcl-2, bcl-6, c-myc, H-ras, K-ras, N-ras, and p53 genes and for Epstein-Barr virus infection, which are commonly involved in lymphoid neoplasia. Employing a combination of Southern blotting and/or polymerase chain reaction and single-strand conformation polymorphism assays, we detected genetic alterations in 7 of the 16 (44%) PMBLs. Whereas the bcl-6 gene is rearranged in up to 45% of DLCLs, rearrangement of the bcl-6 gene was detected in only 1 of these 16 (6%) PMBLS. Point mutations of the 5' noncoding region of the c-myc gene were demonstrated in 3 other cases (19%), although c-myc gene rearrangements were not seen by Southern blotting. Missense point mutations of the p53 gene were identified in 3 additional PMBLs (19%). Alterations of the bcl-1, bcl-2, or ras genes and evidence of Epstein-Barr virus infection were not observed. In conclusion, a variety of molecular lesions occur in PMBLs and may be involved in their pathogenesis. This molecular genetic pattern bears little resemblance to that known for other B cell malignancies, including DLCL. In particular, the infrequent occurrence of bcl-6 gene rearrangement in PMBLs distinguishes them from other DLCLs of B cell origin, suggesting that PMBLs do not represent a distinct subtype of DLCL. PMID:8669486

  6. Molecular characterization of primary mediastinal B cell lymphoma.

    PubMed Central

    Tsang, P.; Cesarman, E.; Chadburn, A.; Liu, Y. F.; Knowles, D. M.

    1996-01-01

    Primary mediastinal B cell lymphoma (PMBL) is a diffuse large B cell lymphoma (DLCL) postulated to arise from noncirculating thymic B lymphocytes. Because of its distinctive clinical and morphological features and putative unique cellular origin, PMBL is generally considered a distinct clinicopathological entity. Little is known, however, about the molecular characteristics of PMBL. Therefore, we analyzed 16 PMBLs for molecular alterations involving the bcl-1, bcl-2, bcl-6, c-myc, H-ras, K-ras, N-ras, and p53 genes and for Epstein-Barr virus infection, which are commonly involved in lymphoid neoplasia. Employing a combination of Southern blotting and/or polymerase chain reaction and single-strand conformation polymorphism assays, we detected genetic alterations in 7 of the 16 (44%) PMBLs. Whereas the bcl-6 gene is rearranged in up to 45% of DLCLs, rearrangement of the bcl-6 gene was detected in only 1 of these 16 (6%) PMBLS. Point mutations of the 5' noncoding region of the c-myc gene were demonstrated in 3 other cases (19%), although c-myc gene rearrangements were not seen by Southern blotting. Missense point mutations of the p53 gene were identified in 3 additional PMBLs (19%). Alterations of the bcl-1, bcl-2, or ras genes and evidence of Epstein-Barr virus infection were not observed. In conclusion, a variety of molecular lesions occur in PMBLs and may be involved in their pathogenesis. This molecular genetic pattern bears little resemblance to that known for other B cell malignancies, including DLCL. In particular, the infrequent occurrence of bcl-6 gene rearrangement in PMBLs distinguishes them from other DLCLs of B cell origin, suggesting that PMBLs do not represent a distinct subtype of DLCL. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8669486

  7. Laser Light Induced Photosensitization Of Lymphomas Cells And Normal Bone Marrow Cells

    NASA Astrophysics Data System (ADS)

    Gulliya, Kirpal S.; Pervaiz, Shazib; Nealon, Don G.; VanderMeulen, David L.

    1988-06-01

    Dye mediated, laser light induced photosensitization was tested in an in vitro model for its efficacy in eliminating the contaminating tumor cells for ex vivo autologous bone marrow purging. Daudi and U-937 cells (3 x 106/ml) in RPMI-1640 supplemented with 0.25% human albumin were mixed with 20 µg/ml and 25 µg/ml of MC-540, respectively. These cell-dye mixtures were then exposed to 514 nm argon laser light. Identical treatment was given to the normal bone marrow cells. Viability was determined by the trypan blue exclusion method. Results show that at 31.2 J/cm2 irradiation, 99.9999% Daudi cells were killed while 87% of the normal bone marrow cells survived. No regrowth of Daudi cells was observed for 30 days in culture. However, a light dose of 93.6 J/cm2 was required to obtain 99.999% U-937 cell kill with 80% normal bone marrow cell survival. Mixing of irradiated bone marrow cells with an equal number of lymphoma cells did not interfere with the photodynamic killing of lymphoma cells. Exposure of cells to low doses of recombinant interferon-alpha prior to photodynamic therapy increased the viability of lymphoma cells.

  8. Biomembrane-mimicking lipid bilayer system as a mechanically tunable cell substrate

    PubMed Central

    Lin, C. Y.; Auernheimer, V.; Naumann, C.; Goldmann, W. H.; Fabry, B.

    2014-01-01

    Cell behavior such as cell adhesion, spreading, and contraction critically depends on the elastic properties of the extracellular matrix. It is not known, however, how cells respond to viscoelastic or plastic material properties that more closely resemble the mechanical environment that cells encounter in the body. In this report, we employ viscoelastic and plastic biomembrane-mimicking cell substrates. The compliance of the substrates can be tuned by increasing the number of polymer-tethered bilayers. This leaves the density and conformation of adhesive ligands on the top bilayer unaltered. We then observe the response of fibroblasts to these property changes. For comparison, we also study the cells on soft polyacrylamide and hard glass surfaces. Cell morphology, motility, cell stiffness, contractile forces and adhesive contact size all decrease on more compliant matrices but are less sensitive to changes in matrix dissipative properties. These data suggest that cells are able to feel and respond predominantly to the effective matrix compliance, which arises as a combination of substrate and adhesive ligand mechanical properties. PMID:24439398

  9. Cilengitide (EMD 121974) in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-01-23

    AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; 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 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; 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 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 Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2

  10. Proposed Pharmacological Countermeasures Against Apoptotic Cell Death in Experimental Models Mimicking Space Environment Damage

    NASA Astrophysics Data System (ADS)

    Lulli, Matteo; Papucci, Laura; Witort, Ewa; Donnini, Martino; Lapucci, Andrea; Lazzarano, Stefano; Mazzoni, Tiziano; Simoncini, Madine; Falciani, Piergiuseppe; Capaccioli, Sergio

    2008-06-01

    Several damaging agents have been suggested to affect human vision during long term space travels. Recently, apoptosis induced by DNA-damaging agents has emerged as frequent pathogenetic mechanism of ophthalmologic pathologies. Here, we propose two countermeasures: coenzyme Q10 and bcl-2 downregulation preventing antisense oligoribonucleotides (ORNs), aimed to inhibit cellular apoptotic death. Our studies have been carried out on retina and neuronal cultured cells treated with the following apoptotic stimuli mimicking space environment: a several-day exposure to either 3H-labeled tymidine or to the genotoxic drug doxorubicin, UV irradiation, hypoxia and glucose/growth factor starvation (Locke medium). The preliminary results clearly indicate that CoQ10, as well as bcl-2 down-regulation preventing ORNs, significantly counteract apoptosis in response to different DNA damaging agents in cultured eye and in neuronal cells. This supports the possibility that both could be optimal countermeasures against ophthalmologic lesions during space explorations.

  11. Human lymphoma-lymphoma hybrids and lymphoma-leukemia hybrids. I. Isolation, characterization, cell surface markers, and B-cell markers.

    PubMed

    Zeuthen, J; Klein, G; Ber, R; Masucci, G; Bisballe, S; Povey, S; Terasaki, P; Ralph, P

    1982-02-01

    Four new somatic cell hybrids were obtained by fusion of various Burkitt's lymphoma (BL)-derived cell lines that had different selective markers: Raji-P3HR-1, Daudi-Raji, and a P3HR-1-P3HR-1 "autohybrid" derived from two P3HR-1 sublines. In addition, a hybrid was obtained between the Daudi (BL) line and the human leukemia cell line K562. The hybrids were extensively characterized by means of chromosome, isozyme, and HLA surface markers. The phenotypic differences between the parent cell lines allowed some conclusions with respect to the expression of latent Epstein-Barr virus (EBV) genomes, C3 and EBV receptors, and of immunoglobulin and beta 2-microglobulin-HLA expression as well as the influence of the leukemia cell (K562) genome on B-cell properties in the Daudi-K562 hybrid. B-cell and differentiated markers of these hybrids were characterized. High-level expression dominated for the marker C3 and EBV receptors, which showed a good correlation coefficient of 0.84, as was true for Fc receptors and surface immunoglobulin. The Daudi-K562 hybrid showed loss of all B-cell markers but retention of the leukemia cell markers (e.g., hemoglobin synthesis).

  12. Tumor-associated macrophages promote tumor cell proliferation in nasopharyngeal NK/T-cell lymphoma

    PubMed Central

    Liu, Yixiong; Fan, Linni; Wang, Yingmei; Li, Peifeng; Zhu, Jin; Wang, Lu; Zhang, Weichen; Zhang, Yuehua; Huang, Gaosheng

    2014-01-01

    Objective: To explore the relationship between the number of tumor-associated macrophages (TAMs) and proliferative activity of tumor cells and the relationship between two macrophage biomarkers CD68 and CD163 in nasopharyngeal NK/T-cell lymphoma. Methods: Immunohistochemistry was used to reconfirm the diagnosis of nasal NK/T-cell lymphoma and detect the numbers of TAMs and the ki-67 label index of the tumor cells in all 31 cases. In addition, 12 cases of inflammatory cases were collected as controls, for which the immunostaining of CD68 and CD163 were done as well. Then staining results were analyzed with Pearson correlation and t test. Results: The number of TAMs was positively correlated with tumor proliferative activity (P = 0.024) in nasopharyngeal NK/T-cell lymphoma. The expression of CD68 and CD163 was closely related (P = 0.009), and the positive rate of CD68 was generally higher than CD163, however there is no statistical significance. Conclusion: The increase in numbers of TAMs in nasopharyngeal NK/T-cell lymphoma is related to higher proliferative index, indicating the TAMs play an important role in tumor proliferation. Meanwhile both CD68 and CD163 might be the markers for TAMs but CD163 would be the better one. PMID:25337185

  13. Epstein-Barr virus in a CD8-positive T-cell lymphoma.

    PubMed Central

    Richel, D. J.; Lepoutre, J. M.; Kapsenberg, J. G.; Ooms, E. C.; Boom, W. R.; Boucher, C. A.; Kluin, P. M.

    1990-01-01

    In contrast to its role in B-lymphomagenesis, Epstein-Barr Virus (EBV) only incidentally has been associated with T-cell lymphomas. In the present report we describe a fourth patient with EBV-related T-cell lymphoma. The patient presented with an angio-immunoblastic lymphadenopathy (AILD)-like T-cell lymphoma. Serology was compatible with chronic Epstein-Barr (EBV) infection. After a 1-year period of waxing and waning lymphadenopathy, this lymphoma evolved to an aggressive CD8+ Immunoblastic T-cell lymphoma. A relationship with the chronic EBV infection was indicated by the finding of EBV genome in the tumor tissue by Southern blot analysis. Moreover, EBV nuclear antigen (EBNA) was detected in situ within individually defined CD8+ tumor cells by two-color immunofluorescence. Two alternative possibilities, namely that EBV primarily played a role in lymphomagenesis of the AILD-like T-cell lymphoma or that the virus was an additional oncogenic event in the final process of tumor progression to the immunoblastic lymphoma, are discussed. Images Figure 1 Figure 2 Figure 4 Figure 3 Figure 5 PMID:2161617

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

    SciTech Connect

    Fernandez, Margarita; Manso, Rebeca; Bernaldez, Flavia; Lopez, Pilar; Martin-Duce, Antonio; Alemany, Susana

    2011-08-12

    Highlights: {yields} We show here that ALCL lymphoma cell lines present high levels of Cot (MAP3K8). {yields} We show that Cot mediates the constitutive Erk1/2 activation in SUDHL-1 cells. {yields} Inhibition of Cot activity reduces the number of cell divisions in SUDHL-1 cells. {yields} Cot controls the activation state of p70 S6K and JunB expression in SUDHL-1 cells. -- Abstract: 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.

  15. Expression of perforin in nasal lymphoma. Additional evidence of its natural killer cell derivation.

    PubMed Central

    Mori, N.; Yatabe, Y.; Oka, K.; Kinoshita, T.; Kobayashi, T.; Ono, T.; Asai, J.

    1996-01-01

    Eight patients with nasal lymphoma in whom fresh-frozen tissues were available were studied to elucidate the nature of the lymphoma cells. Two cases were diagnosed as diffuse, large cell lymphoma, and the remaining six cases as diffuse, mixed cell types. Immunohistochemical studies revealed that all of the cases were positive for perforin, which is a specific marker for cytotoxic T or natural killer (NK) cells. As all of the cases were CD8 negative, the perforin-positive finding further confirmed the concept that nasal lymphoma is a distinct neoplastic entity derived from NK or NK-related cells. Light microscopic immunohistochemical studies revealed that these nasal lymphoma cases could be classified into Leu19(CD56)+Leu4(CD3)+ (two cases) and Leu19(CD56)+Leu4(CD3)- (six cases) types according to the phenotypes of the proliferating cells. However, simultaneous staining for perforin and Leu4 (CD3) using immunoelectron microscopy on the Leu19+Leu4+ cases showed that the perforin-positive cells were different from the Leu4-positive cells. This finding suggests that the Leu4-positive cells are not neoplastic NK cells but reactive T cells. Six cases were positive for EBER-1 by in situ hybridization analysis. This finding reconfirms the previous studies that Epstein-Barr virus plays a significant role in the pathogenesis of nasal lymphoma. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8702007

  16. Immune evasion of mantle cell lymphoma: expression of B7-H1 leads to inhibited T-cell response to and killing of tumor cells

    PubMed Central

    Wang, Lijuan; Qian, Jianfei; Lu, Yong; Li, Haiyan; Bao, Hanying; He, Donghua; Liu, Zhiqiang; Zheng, Yuhuan; He, Jin; Li, Yi; Neelapu, Sattva; Yang, Jing; Kwak, Larry W.; Yi, Qing; Cai, Zhen

    2013-01-01

    Clinical trials of immunotherapy in mantle cell lymphoma have not yet delivered desirable results, partly because of the inhibitory machinery of the tumor and its microenvironment. Here we investigated the role of B7-H1, a member of the B7 family of co-stimulatory/co-inhibitory ligands, in mantle cell lymphoma-mediated immunosuppression. Allogeneic CD3+, CD4+ and CD8+ T cells were purified and co-cultured with irradiated mantle cell lymphoma cells. Mantle cell lymphoma-reactive T-cell lines from HLA-A*0201+ healthy blood donors were generated after in vitro restimulation, and were subjected to functional tests. We found that B7-H1 expressed on mantle cell lymphoma cells was able to inhibit T-cell proliferation induced by the tumor cells, impair the generation of antigen-specific T-cell responses, and render mantle cell lymphoma cells resistant to T-cell-mediated cytolysis. Blocking or knocking down B7-H1 on mantle cell lymphoma cells enhanced T-cell responses and restored tumor-cell sensitivity to T-cell-mediated killing in vitro and in vivo. Knocking down B7-H1 on mantle cell lymphoma cells primed more CD4+ or CD8+ memory effector T cells. Our study demonstrates for the first time that lymphoma cell-expressed B7-H1 may lead to the suppression of host anti-tumor immune responses in mantle cell lymphoma and targeting tumor cell B7-H1 may represent a novel approach to improve the efficacy of immunotherapy in patients with mantle cell lymphoma. PMID:23508008

  17. Integrated molecular analysis of adult T cell leukemia/lymphoma.

    PubMed

    Kataoka, Keisuke; Nagata, Yasunobu; Kitanaka, Akira; Shiraishi, Yuichi; Shimamura, Teppei; Yasunaga, Jun-Ichirou; Totoki, Yasushi; Chiba, Kenichi; Sato-Otsubo, Aiko; Nagae, Genta; Ishii, Ryohei; Muto, Satsuki; Kotani, Shinichi; Watatani, Yosaku; Takeda, June; Sanada, Masashi; Tanaka, Hiroko; Suzuki, Hiromichi; Sato, Yusuke; Shiozawa, Yusuke; Yoshizato, Tetsuichi; Yoshida, Kenichi; Makishima, Hideki; Iwanaga, Masako; Ma, Guangyong; Nosaka, Kisato; Hishizawa, Masakatsu; Itonaga, Hidehiro; Imaizumi, Yoshitaka; Munakata, Wataru; Ogasawara, Hideaki; Sato, Toshitaka; Sasai, Ken; Muramoto, Kenzo; Penova, Marina; Kawaguchi, Takahisa; Nakamura, Hiromi; Hama, Natsuko; Shide, Kotaro; Kubuki, Yoko; Hidaka, Tomonori; Kameda, Takuro; Nakamaki, Tsuyoshi; Ishiyama, Ken; Miyawaki, Shuichi; Yoon, Sung-Soo; Tobinai, Kensei; Miyazaki, Yasushi; Takaori-Kondo, Akifumi; Matsuda, Fumihiko; Takeuchi, Kengo; Nureki, Osamu; Aburatani, Hiroyuki; Watanabe, Toshiki; Shibata, Tatsuhiro; Matsuoka, Masao; Miyano, Satoru; Shimoda, Kazuya; Ogawa, Seishi

    2015-11-01

    Adult T cell leukemia/lymphoma (ATL) is a peripheral T cell neoplasm of largely unknown genetic basis, associated with human T cell leukemia virus type-1 (HTLV-1) infection. Here we describe an integrated molecular study in which we performed whole-genome, exome, transcriptome and targeted resequencing, as well as array-based copy number and methylation analyses, in a total of 426 ATL cases. The identified alterations overlap significantly with the HTLV-1 Tax interactome and are highly enriched for T cell receptor-NF-κB signaling, T cell trafficking and other T cell-related pathways as well as immunosurveillance. Other notable features include a predominance of activating mutations (in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7) and gene fusions (CTLA4-CD28 and ICOS-CD28). We also discovered frequent intragenic deletions involving IKZF2, CARD11 and TP73 and mutations in GATA3, HNRNPA2B1, GPR183, CSNK2A1, CSNK2B and CSNK1A1. Our findings not only provide unique insights into key molecules in T cell signaling but will also guide the development of new diagnostics and therapeutics in this intractable tumor. PMID:26437031

  18. MORAb-004 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2016-01-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/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; 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 Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved 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; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  19. Investigation of Tumor Cell Behaviors on a Vascular Microenvironment-Mimicking Microfluidic Chip

    PubMed Central

    Huang, Rong; Zheng, Wenfu; Liu, Wenwen; Zhang, Wei; Long, Yunze; Jiang, Xingyu

    2015-01-01

    The extravasation of tumor cells is a key event in tumor metastasis. However, the mechanism underlying tumor cell extravasation remains unknown, mainly hindered by obstacles from the lack of complexity of biological tissues in conventional cell culture, and the costliness and ethical issues of in vivo experiments. Thus, a cheap, time and labor saving, and most of all, vascular microenvironment-mimicking research model is desirable. Herein, we report a microfluidic chip-based tumor extravasation research model which is capable of simultaneously simulating both mechanical and biochemical microenvironments of human vascular systems and analyzing their synergistic effects on the tumor extravasation. Under different mechanical conditions of the vascular system, the tumor cells (HeLa cells) had the highest viability and adhesion activity in the microenvironment of the capillary. The integrity of endothelial cells (ECs) monolayer was destroyed by tumor necrosis factor-α (TNF-α) in a hemodynamic background, which facilitated the tumor cell adhesion, this situation was recovered by the administration of platinum nanoparticles (Pt-NPs). This model bridges the gap between cell culture and animal experiments and is a promising platform for studying tumor behaviors in the vascular system. PMID:26631692

  20. Hybrid vitronectin-mimicking polycaprolactone scaffolds for human retinal progenitor cell differentiation and transplantation.

    PubMed

    Lawley, Elodie; Baranov, Petr; Young, Michael

    2015-01-01

    Many advances have been made in an attempt to treat retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa. The irreversible loss of photoreceptors is common to both, and currently no restorative clinical treatment exists. It has been shown that retinal progenitor and photoreceptor precursor cell transplantation can rescue the retinal structure and function. Importantly, retinal progenitor cells can be collected from the developing neural retina with further expansion and additional modification in vitro, and the delivery into the degenerative host can be performed as a single-cell suspension injection or as a complex graft transplantation. Previously, we have described several polymer scaffolds for culture and transplantation of retinal progenitor cells of both mouse and human origin. This tissue engineering strategy increases donor cell survival and integration. We have also shown that biodegradable poly(ɛ-caprolactone) induces mature photoreceptor differentiation from human retinal progenitor cells. However, poor adhesive properties limit its use, and therefore it requires additional surface modification. The aim of this work was to study vitronectin-mimicking oligopeptides (Synthemax II-SC) poly(ɛ-caprolactone) films and their effects on human retinal progenitor cell adhesion, proliferation, and differentiation. Here, we show that the incorporation of vitronectin-mimicking oligopeptide into poly(ɛ-caprolactone) leads to dose-dependent increases in cell adhesion; the optimum dose identified as 30 µg/ml. Inhibition of human retinal progenitor cells proliferation was seen on poly(ɛ-caprolactone) and was maintained with the hybrid scaffold. This has been shown to be beneficial for driving cell differentiation. Additionally, we observed equal expression of Nrl, rhodopsin, recoverin, and rod outer membrane 1 after differentiation on the hybrid scaffold as compared to the standard fibronectin coating of poly

  1. Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-04-19

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin 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 Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; Waldenström Macroglobulinemia

  2. A Case of p63 Positive Diffuse Large B Cell Lymphoma of the Bladder

    PubMed Central

    Jones, Carol

    2016-01-01

    Diffuse large B cell lymphoma (DLBCL), currently the most common type of non-Hodgkin lymphoma (NHL), is an aggressive B cell neoplasm that typically presents in older adults as a rapidly enlarging mass. The enlarging mass typically represents a lymph node, although extranodal disease can occur in a significant percentage (40%) of cases. The most common extranodal sites of involvement include the gastrointestinal tract and skin; primary bladder lymphoma represents only 0.2% of extranodal non-Hodgkin lymphomas. We report a case of diffuse large B cell lymphoma occurring in the bladder of an 83-year-old gentleman with an initial presentation of hematuria. This neoplasm displayed large, atypical cells with vesicular chromatin and prominent nucleoli that involved the bladder mucosa with invasion into muscularis propria, prostate, and urethra. Positive staining for p63 initially raised suspicion for poorly differentiated urothelial carcinoma; however, lack of staining for pancytokeratin and positive staining for LCA, CD20, CD79a, and PAX-5 confirmed the diagnosis of diffuse large B cell lymphoma. Though it does not occur in all cases, p63 can be positive in a significant percentage of cases of DLBCL; therefore, a diagnosis of lymphoma remains an important entity on the differential diagnosis of aggressive and particularly poorly differentiated neoplasms. PMID:27648316

  3. A Case of p63 Positive Diffuse Large B Cell Lymphoma of the Bladder

    PubMed Central

    Jones, Carol

    2016-01-01

    Diffuse large B cell lymphoma (DLBCL), currently the most common type of non-Hodgkin lymphoma (NHL), is an aggressive B cell neoplasm that typically presents in older adults as a rapidly enlarging mass. The enlarging mass typically represents a lymph node, although extranodal disease can occur in a significant percentage (40%) of cases. The most common extranodal sites of involvement include the gastrointestinal tract and skin; primary bladder lymphoma represents only 0.2% of extranodal non-Hodgkin lymphomas. We report a case of diffuse large B cell lymphoma occurring in the bladder of an 83-year-old gentleman with an initial presentation of hematuria. This neoplasm displayed large, atypical cells with vesicular chromatin and prominent nucleoli that involved the bladder mucosa with invasion into muscularis propria, prostate, and urethra. Positive staining for p63 initially raised suspicion for poorly differentiated urothelial carcinoma; however, lack of staining for pancytokeratin and positive staining for LCA, CD20, CD79a, and PAX-5 confirmed the diagnosis of diffuse large B cell lymphoma. Though it does not occur in all cases, p63 can be positive in a significant percentage of cases of DLBCL; therefore, a diagnosis of lymphoma remains an important entity on the differential diagnosis of aggressive and particularly poorly differentiated neoplasms.

  4. A Case of p63 Positive Diffuse Large B Cell Lymphoma of the Bladder.

    PubMed

    Deel, Chelsey D; Jones, Carol; Scordino, Teresa

    2016-01-01

    Diffuse large B cell lymphoma (DLBCL), currently the most common type of non-Hodgkin lymphoma (NHL), is an aggressive B cell neoplasm that typically presents in older adults as a rapidly enlarging mass. The enlarging mass typically represents a lymph node, although extranodal disease can occur in a significant percentage (40%) of cases. The most common extranodal sites of involvement include the gastrointestinal tract and skin; primary bladder lymphoma represents only 0.2% of extranodal non-Hodgkin lymphomas. We report a case of diffuse large B cell lymphoma occurring in the bladder of an 83-year-old gentleman with an initial presentation of hematuria. This neoplasm displayed large, atypical cells with vesicular chromatin and prominent nucleoli that involved the bladder mucosa with invasion into muscularis propria, prostate, and urethra. Positive staining for p63 initially raised suspicion for poorly differentiated urothelial carcinoma; however, lack of staining for pancytokeratin and positive staining for LCA, CD20, CD79a, and PAX-5 confirmed the diagnosis of diffuse large B cell lymphoma. Though it does not occur in all cases, p63 can be positive in a significant percentage of cases of DLBCL; therefore, a diagnosis of lymphoma remains an important entity on the differential diagnosis of aggressive and particularly poorly differentiated neoplasms. PMID:27648316

  5. Primary non-Hodgkin's lymphoma of the salivary gland: a spectrum of lymphoepithelial sialadenitis, low-grade B-cell lymphoma of mucosa-associated lymphoid tissue with transformation to high-grade lymphoma.

    PubMed

    Agale, Shubhangi Vinayak; D'Costa, Grace Francis; Hastak, Meenal Shirish; Shedge, Rakesh Tukaram

    2010-01-01

    Lymphoid infiltrates of the salivary gland can be either reactive or neoplastic. The reactive lesion, lymphoepithelial sialadenitis (LESA) may be associated with Sjogren's syndrome (SS) or may occur as an isolated salivary gland enlargement. Patients with LESA/SS have a particularly high risk of subsequently developing lymphoma, which is a low-grade mucosa-associated lymphoid tissue (MALT) type lymphoma of the salivary gland. We document a rare case of primary non-Hodgkin's lymphoma of the parotid gland arising in the background of LESA and with a rare example of transformation from low grade to high-grade B cell lymphoma of MALT type. PMID:20551561

  6. Methotrexate and etanercept-induced primary cutaneous CD4 positive small/medium-sized pleomorphic T-cell lymphoma*

    PubMed Central

    MA, Han; Qiu, Shu; Lu, Rongbiao; Feng, Peiying; Lu, Chun

    2016-01-01

    Immunosuppressive drugs and biological agents may represent a potential risk of lymphoma development in patients with rheumatoid arthritis. But most cases are diffuse, large B-cell lymphomas. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, a provisional entity in the 2005 WHO-EORTC classification of cutaneous lymphomas, is only described in a limited number of reports. To our knowledge, our case is a rare instance of primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, after associated treatment with methotrexate and etanercept, in a patient with moderate rheumatoid arthritis who had undergone an orchidectomy incorrectly. PMID:27438209

  7. Methotrexate and etanercept-induced primary cutaneous CD4 positive small/medium-sized pleomorphic T-cell lymphoma.

    PubMed

    Ma, Han; Qiu, Shu; Lu, Rongbiao; Feng, Peiying; Lu, Chun

    2016-01-01

    Immunosuppressive drugs and biological agents may represent a potential risk of lymphoma development in patients with rheumatoid arthritis. But most cases are diffuse, large B-cell lymphomas. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, a provisional entity in the 2005 WHO-EORTC classification of cutaneous lymphomas, is only described in a limited number of reports. To our knowledge, our case is a rare instance of primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, after associated treatment with methotrexate and etanercept, in a patient with moderate rheumatoid arthritis who had undergone an orchidectomy incorrectly. PMID:27438209

  8. Diffuse large B-cell lymphoma of the cauda equina

    PubMed Central

    Broen, Martijn; Draak, Tim; Riedl, Robert G; Weber, Wim E J

    2014-01-01

    Primary central nervous system (CNS) lymphoma is a rare form of non-Hodgkin's lymphoma. The clinical presentation is variable, depending on its localisation within the nervous system. Only 1% of primary CNS lymphoma emerges in the spinal cord, and the prevalence of primary lymphoma of the cauda equina is unknown, but probably even rarer. Diagnosing primary lymphoma of the cauda equina is difficult, since it can mimic other more common disorders such as a herniated disc, especially in its early stages. Here we present two cases of primary cauda equina lymphoma in which diagnostic work up took a long time, as the final diagnosis was only reached after a nerve root biopsy. PMID:25368124

  9. A Mendelian predisposition to B-cell lymphoma caused by IL-10R deficiency.

    PubMed

    Neven, Bénédicte; Mamessier, Emilie; Bruneau, Julie; Kaltenbach, Sophie; Kotlarz, Daniel; Suarez, Felipe; Masliah-Planchon, Julien; Billot, Katy; Canioni, Danielle; Frange, Pierre; Radford-Weiss, Isabelle; Asnafi, Vahid; Murugan, Dhaarini; Bole, Christine; Nitschke, Patrick; Goulet, Olivier; Casanova, Jean-Laurent; Blanche, Stéphane; Picard, Capucine; Hermine, Olivier; Rieux-Laucat, Frederic; Brousse, Nicole; Davi, Frederic; Baud, Véronique; Klein, Christoph; Nadel, Bertrand; Ruemmele, Frank; Fischer, Alain

    2013-11-28

    Monogenic interleukin-10 (IL-10) and IL-10 receptor (IL-10R) deficiencies cause very early onset severe inflammatory bowel disease. Here, we report that 5 patients with an IL-10R1 (n = 1) or IL-10R2 (n = 4) deficiency developed B-cell non-Hodgkin lymphoma between the ages of 5 and 6 years (which was recurrent in 1 patient). These lymphomas had some of the characteristics of diffuse large B-cell lymphomas and contained monoclonal, Epstein-Barr virus-negative germinal center B cells. The tumors displayed a remarkably homogeneous signature, with original activation of the nuclear factor κB pathway and a decrease in intratumor T-cell infiltration. Hence, IL-10R deficiency is associated with a high risk of developing B-cell lymphoma. Our results revealed an unexpected role of the IL-10R pathway in lymphomagenesis. PMID:24089328

  10. Anaplastic Large Cell Lymphoma Involving Anterior Segment of the Eye

    PubMed Central

    Park, Choul Yong; Hwang, Sang Won; Kim, Do Yeun; Huh, Hee Jin

    2014-01-01

    A 36-year-old woman was diagnosed with anaplastic large cell lymphoma (ALCL) by excisional biopsy of a left frontal skin lesion. During the first cycle of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone), the patient complained of right ocular pain and inflammation. Cytologic examination using aqueous humor revealed atypical lymphocytes, suggesting intraocular ALCL involvement. Acute angle closure developed in the anterior chamber due to rapid progression of ALCL, causing pupillary block. Laser and surgical interventions were attempted but failed to relieve the pupillary block. Finally, radiation therapy resolved the pupillary block to restore the anterior chamber and normalize intraocular pressure. This is the first case in the English literature of ALCL involving the iris to cause acute secondary angle closure. PMID:24505208

  11. Primary cutaneous anaplastic large-cell lymphoma: a case report.

    PubMed

    Cao, Can; Zeng, Kang; Wang, Menglei; Han, Kai; Peng, Yusheng; Xiong, Hao; Wang, Qi; Li, Qian; Wang, Qian; Li, Li

    2016-07-01

    Primary cutaneous anaplastic large-cell lymphoma (PCALCL) is a part of the spectrum of CD30+ lymphoproliferative cutaneous processes. The characteristics include single or multifocal nodules that ulcerate as skin lesion, slow disease progression, autoregressive, and recurrent in few years. The present study report the case of a 16-year-old boy presenting PCALCL with single nodules, ulcer, keloid, and scab in his right-side face. He showed a good response to the treatment with systemic chemotherapy and dermatoplasty, and regained confidence after the appearance of recovery. There is no relapse of the primary lesion and organs involved till now. The chemotherapy combining with surgical excision and dermatoplasty is a good method for PCALCL, per the lesion biopsy and positron emission tomography-computed tomography before and after treatment. PMID:26970422

  12. A very unusual cause of dysphagia: mantle cell lymphoma

    PubMed Central

    Zullo, Angelo; Cerro, Paola; Chios, Anastassios; Andriani, Alessandro; Balsamo, Giuseppina; Francesco, Vincenzo De; Bruzzese, Vincenzo

    2016-01-01

    Dysphagia is an alarm symptom requiring a prompt investigation. Different benign and malignant diseases may present such a symptom. We describe a case of a 79-year-old patient who complained of fluctuating dysphagia episodes following solid food ingestion in the previous 5 months with mild weight loss. No other gastrointestinal symptoms were present. The patient was referred by the General Practitioner for a videofluoroscopic swallow examination which revealed nodularity of mucosa surface in the oropharynx, esophagus, fundus, and gastric body. Upper endoscopy confirmed the feature, also showing a normal mucosa of the antrum and duodenum. The histological examination revealed a mantle cell lymphoma (MCL). A stage III, MCL involving the esophagus and proximal stomach was eventually diagnosed. Esophageal MCL localization is extremely rare, and this is the first report showing a clinical onset with dysphagia. PMID:27366047

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

    PubMed

    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. PMID:26642249

  14. Menus for Managing Patients With Cutaneous T-Cell Lymphoma

    PubMed Central

    Poligone, Brian; Heald, Peter

    2013-01-01

    In the management of patients with cutaneous T-cell lymphoma (CTCL), there are numerous distinct therapy options. Each of these therapies is discussed in terms of when to use it, what factors limit the success of the treatment, and what to expect. A menu is defined as a list of items from which to choose. The treatments for CTCL are presented in various menus where they are options for a particular goal in a particular setting of CTCL. The best recognized clinical scenarios of CTCL are those recognized by the staging system: limited patch plaque (T1), disseminated patch plaque (T2), erythroderma (T4), and tumor (T3). Each phase of the disease will have the menu of therapy options presented for a given goal of management. PMID:22361286

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

    PubMed

    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.

  16. Rapidly Progressive Acute Pustular Secondary Cutaneous Anaplastic Large Cell Lymphoma.

    PubMed

    Mordorski, Breanne; Friedman, Adam; Han, George

    2016-09-01

    Cutaneous anaplastic large cell lymphoma (ALCL) is an uncommon diagnosis that may either present as a primary cutaneous process or develop secondary to systemic disease. It is imperative to distinguish between these two entities due to differences in treatment recommendations and prognosis. Here, their salient features will be reviewed. It is also important that clinicians recognize atypical clinical morphologies of cutaneous ALCL, including pustular lesions, which may masquerade as infectious or other inflammatory conditions, thereby delaying the onset of treatment. In this report, we present a case of secondary cutaneous ALCL associated with an atypical pustular morphology and an aggressive, fatal course.

    J Drugs Dermatol. 2016;15(9):1132-1135. PMID:27602978

  17. Bortezomib in the treatment of mantle cell lymphoma.

    PubMed

    Robak, Tadeusz

    2015-01-01

    Mantle cell lymphoma (MCL) is a hematological malignancy with unfavorable prognosis. Bortezomib, a potent, selective and reversible inhibitor of the 26S proteasome, was shown to be active in MCL and is currently implemented in therapeutic combinations. Single-agent bortezomib has demonstrated clinical efficacy in relapsed and refractory MCL with objective response in up to 47% of the patients. However, complete remission rates are low and duration of response is relatively short. In previously untreated patients, the addition of bortezomib to induction chemotherapy is also promising. Further evaluation of bortezomib alone or in combination with other drugs for the treatment of MCL is warranted to improve the quality of life and survival of patients. This review explores bortezomib as therapy in patients with MCL.

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

    PubMed

    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

    2016-10-01

    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 (TFH) 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.

  19. Tetraspanin CD37 protects against the development of B cell lymphoma.

    PubMed

    de Winde, Charlotte M; Veenbergen, Sharon; Young, Ken H; Xu-Monette, Zijun Y; Wang, Xiao-Xiao; Xia, Yi; Jabbar, Kausar J; van den Brand, Michiel; van der Schaaf, Alie; Elfrink, Suraya; van Houdt, Inge S; Gijbels, Marion J; van de Loo, Fons A J; Bennink, Miranda B; Hebeda, Konnie M; Groenen, Patricia J T A; van Krieken, J Han; Figdor, Carl G; van Spriel, Annemiek B

    2016-02-01

    Worldwide, B cell non-Hodgkin lymphoma is the most common hematological malignancy and represents a substantial clinical problem. The molecular events that lead to B cell lymphoma are only partially defined. Here, we have provided evidence that deficiency of tetraspanin superfamily member CD37, which is important for B cell function, induces the development of B cell lymphoma. Mice lacking CD37 developed germinal center-derived B cell lymphoma in lymph nodes and spleens with a higher incidence than Bcl2 transgenic mice. We discovered that CD37 interacts with suppressor of cytokine signaling 3 (SOCS3); therefore, absence of CD37 drives tumor development through constitutive activation of the IL-6 signaling pathway. Moreover, animals deficient for both Cd37 and Il6 were fully protected against lymphoma development, confirming the involvement of the IL-6 pathway in driving tumorigenesis. Loss of CD37 on neoplastic cells in patients with diffuse large B cell lymphoma (DLBCL) directly correlated with activation of the IL-6 signaling pathway and with worse progression-free and overall survival. Together, this study identifies CD37 as a tumor suppressor that directly protects against B cell lymphomagenesis and provides a strong rationale for blocking the IL-6 pathway in patients with CD37- B cell malignancies as a possible therapeutic intervention. PMID:26784544

  20. Tetraspanin CD37 protects against the development of B cell lymphoma

    PubMed Central

    de Winde, Charlotte M.; Veenbergen, Sharon; Young, Ken H.; Xu-Monette, Zijun Y.; Wang, Xiao-xiao; Xia, Yi; Jabbar, Kausar J.; van den Brand, Michiel; van der Schaaf, Alie; Elfrink, Suraya; van Houdt, Inge S.; Gijbels, Marion J.; van de Loo, Fons A.J.; Bennink, Miranda B.; Hebeda, Konnie M.; Groenen, Patricia J.T.A.; van Krieken, J. Han; Figdor, Carl G.; van Spriel, Annemiek B.

    2016-01-01

    Worldwide, B cell non-Hodgkin lymphoma is the most common hematological malignancy and represents a substantial clinical problem. The molecular events that lead to B cell lymphoma are only partially defined. Here, we have provided evidence that deficiency of tetraspanin superfamily member CD37, which is important for B cell function, induces the development of B cell lymphoma. Mice lacking CD37 developed germinal center–derived B cell lymphoma in lymph nodes and spleens with a higher incidence than Bcl2 transgenic mice. We discovered that CD37 interacts with suppressor of cytokine signaling 3 (SOCS3); therefore, absence of CD37 drives tumor development through constitutive activation of the IL-6 signaling pathway. Moreover, animals deficient for both Cd37 and Il6 were fully protected against lymphoma development, confirming the involvement of the IL-6 pathway in driving tumorigenesis. Loss of CD37 on neoplastic cells in patients with diffuse large B cell lymphoma (DLBCL) directly correlated with activation of the IL-6 signaling pathway and with worse progression-free and overall survival. Together, this study identifies CD37 as a tumor suppressor that directly protects against B cell lymphomagenesis and provides a strong rationale for blocking the IL-6 pathway in patients with CD37– B cell malignancies as a possible therapeutic intervention. PMID:26784544

  1. Combination Chemotherapy, Rituximab, and Ixazomib Citrate in Treating Patients With Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-08-19

    Adult Burkitt Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Diffuse Large B-Cell Lymphoma; MYC Gene Mutation; Plasmablastic Lymphoma

  2. Mediastinal large-cell lymphoma with sclerosis (MLCLS).

    PubMed Central

    Rohatiner, A. Z.; Whelan, J. S.; Ganjoo, R. K.; Norton, A. J.; Wilson, A.; Lister, T. A.

    1994-01-01

    In a retrospective analysis encompassing a 14 year period (1978-92), 22 patients (age range 19-71, median 30 years) were identified as having mediastinal large-cell lymphoma with sclerosis on the basis of clinical and pathological features. At presentation, 15/22 had 'bulky' disease and 11/22 had evidence of superior vena caval obstruction. Thirteen patients had stage II disease (6,II; 7,IIE), nine presented with stage IV disease. Complete remission (CR) was achieved in only 4/22 patients with the initial adriamycin-containing regimen. 'Good partial remission' (no clinical evidence of disease, minimal abnormalities of uncertain significance on radiological investigation) was achieved in a further seven patients and 'poor partial remission' (a reduction in measurable disease > 50%) in four, giving an overall response rate of 15/22 (68%). One patient died within 48 h of arrival at the hospital; 16 of the 17 remaining patients in whom anything less than CR was achieved subsequently received additional, alternative treatment (one chemotherapy, six mediastinal radiotherapy, nine both treatment modalities) but in only 2/16 did this result in any further degree of response. With a median follow-up of 5 1/2 years, 10/22 patients remain well without progression between 6 months and 14 years (5/6 in whom CR was eventually achieved and 5/11 in whom only partial remission was ever documented). The seven patients in whom the initial treatment demonstrably failed have all died. These results suggest that a proportion of patients with this rare subtype of high-grade B-cell lymphoma may be cured by chemotherapy alone and that the presence of a residual mediastinal mass after treatment does not necessarily imply treatment failure. However, patients in whom the initial chemotherapy fails have a very grave prognosis. PMID:8123496

  3. Primary Cutaneous Diffuse Large B-Cell Lymphoma With a MYC-IGH Rearrangement and Gain of BCL2: Expanding the Spectrum of MYC/BCL2 Double-Hit Lymphomas.

    PubMed

    Testo, Natalia; Olson, Luke C; Subramaniyam, Shivakumar; Hanson, Ty; Magro, Cynthia M

    2016-10-01

    Aggressive extracutaneous B-cell lymphomas span the various stages of B-cell ontogeny and include B-cell lymphoblastic lymphoma, Burkitt lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas represent the most common histologic subtype of non-Hodgkin lymphomas, comprising 30% of adult non-Hodgkin lymphomas in the United States. A distinctive form of diffuse large B-cell lymphoma is the double-hit lymphoma, with most cases exhibiting a combined MYC and BCL2 rearrangement, leading some hematopathologists to propose the term MYC/BCL2 lymphoma. More recently, MYC rearrangement with multiple copies/gain of BCL2 or multiple copies/gain of MYC with a BCL2 rearrangement have been described and exhibit a very similar clinical course to conventional double-hit lymphomas. We report the seventh case of diffuse large B-cell lymphoma exhibiting this distinct cytogenetic abnormality and the first reported case in the skin. The patient's clinical course was aggressive, succumbing to disease 18 months after his initial presentation. PMID:27391453

  4. Methylesterase behaviour is related to polysaccharide organisation in model systems mimicking cell walls.

    PubMed

    Bonnin, Estelle; Mutic, Jelena; Nikolic, Jasna; Burr, Sally; Robert, Paul; Crépeau, Marie-Jeanne

    2015-06-25

    Pectin gels and pectin-cellulose binary gels were used as cell wall-mimicking systems to investigate the diffusion ability of a fungal pectin methylesterase. Increasing content of cellulose in the gel appears to result: (i) in longer demethylated blocks thus favouring AaPME processivity, and (ii) in accelerated enzyme kinetics. To better understand this unexpected behaviour, a method was set up to investigate the gel porosity as a function of the cellulose content by following the passive diffusion of three pullulans having different hydrodynamic volumes. Like the enzyme, the pullulans diffused more efficiently in the gels containing the highest proportions of cellulose. Altogether, these results suggest that the gel settled differently during formation according to the respective proportions of the two polysaccharides. With cellulose present, a fraction of pectin would form close interactions with the microfibrils resulting in a larger volume accessible to diffusing molecules. This volume would be related to the cellulose concentration. PMID:25839794

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

    ClinicalTrials.gov

    2016-04-18

    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

  6. Cholestatic hepatitis C after chemotherapy containing rituximab in diffuse large B cell lymphoma.

    PubMed

    Pellicelli, Adriano M; D'Ambrosio, Cecilia; Dessanti, Maria L; Villani, Roberto; Fondacaro, Lucia; Miglioresi, Lucia; Grillo, Lucia R; Andreoli, Arnaldo

    2015-01-01

    Rituximab is a chimeric anti-CD20 monoclonal antibody that is a widely used for the treatment of B cells non-Hodgkin lymphoma. The use of chemotherapy regimens containing rituximab in HCV-positive patients with non-Hodgkin lymphoma has been associated with liver dysfunction, but no cases of cholestatic hepatitis C were described. To our knowledge, this is the first case of cholestatic hepatitis C in an HCV-positive patient with diffuse large B-cell lymphoma describes in the literature. We discuss the pathogenetic mechanisms underlying this severe form of hepatitis and describe its evolution after antiviral treatment.

  7. Angioimmunoblastic T-Cell Lymphoma in a Patient with Klinefelter Syndrome

    PubMed Central

    Park, Yong Tae; Park, Chan-Ho; Bae, Mi Ae; Jung, Hwa Sik; Lee, Youn Im; Lim, Ji-Hun; Cha, Hee Jeong; Seo, Min Jung; Park, Seol Hoon; Choi, Yunsuk; Kim, Hawk; Jo, Jae-Cheol

    2016-01-01

    Patient: Male, 61 Final Diagnosis: AITL in Klinefelter syndrome Symptoms: — Medication: — Clinical Procedure: Chemotherapy Specialty: Hematology Objective: Rare disease Background: Although patients with Klinefelter syndrome have elevated risk and incidence rates for several solid cancers, reports on the incidence of hematological malignancies have been equivocal. Case Report: We report a patient diagnosed with angioimmunoblastic T-cell lymphoma in whom Klinefelter syndrome was newly detected. Moreover, we discuss the development of a variety of lymphomas in patients with Klinefelter syndrome. Conclusions: This is the first case describing angioimmunoblastic T-cell lymphoma in a patient with Klinefelter syndrome who was treated with chemotherapy. PMID:27452959

  8. Gall Bladder and Extrahepatic Bile Duct Lymphomas: Clinicopathological observations and biological implications

    PubMed Central

    Mani, Haresh; Climent, Fina; Colomo, Lluís; Pittaluga, Stefania; Raffeld, Mark; Jaffe, Elaine S.

    2010-01-01

    Lymphomas of the gall bladder and extrahepatic bile ducts are exceedingly rare. We present the clinicopathological features of 19 cases from our files; 14 patients had primary lymphoma (13 involving gall bladder and one involving common hepatic duct), while five had systemic lymphoma on further work-up. Most patients presented with symptoms mimicking cholecystitis. The most common primary lymphoma types were diffuse large B-cell lymphoma (DLBCL), extranodal marginal zone lymphoma (EMZL), B-lymphoblastic lymphoma (B-LBL) and follicular lymphoma (FL). Two cases had features of lymphomatous polyposis, one a case of FL and the second a case of mantle cell lymphoma (MCL), with disease limited to the mantle zones, so-called in situ MCL. Other rare lymphoma subtypes not previously described in this site included the extracavitary variant of primary effusion lymphoma (PEL) and plasmablastic lymphoma (PBL). Patients with DLBCL and EMZL were older (mean age 75.8 years) than those with other subtypes (mean age 47 years) and more likely to have gallstones (60% vs. 12.5%). A comprehensive literature review revealed 36 primary gall bladder and 16 primary extrahepatic bile duct lymphomas. When compared to primary gall bladder lymphomas, those involving the extrahepatic bile ducts present at a younger age (47 years vs. 63 years) usually with obstructive jaundice, and are less often associated with gallstones (17% vs. 50%) or regional lymph node involvement (6% vs. 31%). In conclusion, primary lymphomas of the gall bladder and extrahepatic bile ducts show a broad spectrum of disease types, but in many respects mirror the spectrum of primary lymphomas of the gastrointestinal tract. PMID:20679881

  9. A case of primary pulmonary NK/T cell lymphoma presenting as pneumonia.

    PubMed

    Lee, Sangho; Shin, Bongkyung; Yoon, Hyungseok; Lee, Jung Yeon; Chon, Gyu Rak

    2016-01-01

    Primary pulmonary lymphoma, particularly non-B cell lymphomas involving lung parenchyma, is very rare. A 46-year-old male was admitted to the hospital with fever and cough. Chest X-ray showed left lower lobe consolidation, which was considered pneumonia. However, because the patient showed no response to empirical antibiotic therapy, bronchoscopic biopsy was performed for proper diagnosis. The biopsied specimen showed infiltrated atypical lymphocytes with angiocentric appearance. On immunohistochemical staining, these atypical cells were positive for CD3, CD30, CD56, MUM-1, and granzyme B, and labeled for Epstein-Barr virus encoded RNA in situ hybridization. These findings were consistent with NK/T cell lymphoma. We report on a case of primary pulmonary NK/T cell lymphoma presenting as pneumonic symptoms and review the literature on the subject.

  10. Antigen selection in B-cell lymphomas--tracing the evidence.

    PubMed

    Sutton, Lesley-Ann; Agathangelidis, Andreas; Belessi, Chrysoula; Darzentas, Nikos; Davi, Frederic; Ghia, Paolo; Rosenquist, Richard; Stamatopoulos, Kostas

    2013-12-01

    While signaling through the B cell receptor (BcR) facilitates B cell development and maintenance, it also carries intertwined risks for the development of lymphomas since malignant B cells can exploit these pathways in order to trigger and fuel clonal expansion. This corruption of the normal B cell response to antigens, leading to sustained BcR signaling, has given great impulse to investigate in detail the role of antigen in lymphomas. Suffice it to conclude from such studies, largely immunogenetics based, that the evidence implicating antigens (exogenous or self) in lymphoma development is substantial and that lymphomagenesis is functionally driven and dynamic, rather than a simple stochastic process. As the paradigm of antigen-driven lymphoma evolves, further investigation will be paramount to the identification of the inciting agent(s) that may be responsible for immunoproliferative neoplasms and also for the development of therapeutic agents targeting effectors of the BcR signaling pathway.

  11. SERS detection and targeted ablation of lymphoma cells using functionalized Ag nanoparticles

    NASA Astrophysics Data System (ADS)

    Yao, Qian; Cao, Fei; Feng, Chao; Zhao, Yan; Wang, Xiuhong

    2016-03-01

    Lymphoma is a heterogeneous group of malignancies of the lymphoid tissue, and is prevalent worldwide affecting both children and adults with a high mortality rate. There is in dire need of accurate and noninvasive approaches for early detection of the disease. Herein, we report a facile way to fabricate silver nanoparticle based nanoprobe by incorporating the corner-stone immunotherapeutic drug Rituxan for simultaneous detection and ablation of lymphoma cells in vitro. The fabricated nanoprobe can detect CD20 positive single lymphoma cell by surface enhanced Raman scattering technique with high specificity. The engineered nanoprobe retains the same antibody property as intact drug via Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) analysis. The nanoprobe efficiently eradicates lymphoma cells in vitro. By integrating the advantages of sensitive SERS detection with targeted ablation capabilities of immunotherapeutic drug through site specificity, this nanoprobe can be applied as outstanding tools in living imaging, cancer diagnosis and treatment.

  12. Functional role of regulatory T cells in B cell lymphoma and related mechanisms.

    PubMed

    Wu, Wei; Wan, Jun; Xia, Ruixiang; Huang, Zhenqi; Ni, Jing; Yang, Mingzhen

    2015-01-01

    B cell lymphoma (BCL) has a higher degree of malignancy and complicated pathogenic mechanism. Regulatory T cells (Treg cells) are known to exert certain immune suppression functions, in addition to immune mediating effects. Recent studies have revealed the role of Treg cells in pathogenesis and progression of multiple malignant tumors. This study therefore investigated the functional role and related mechanism of Treg cells in BCL. A cohort of thirty patients who were diagnosed with BCL in our hospital between January 2013 and December 2014. Another thirty healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were separated and analyzed for the ratio of CD4+/CD25+ Treg cells. The mRNA expression levels of Foxp3, transforming growth factor (TGF)-β1 and interleukin (IL)-10 genes were quantified by real-time PCR, while their serum levels were determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile all laboratory indexes for patients were monitored during the complete remission (CR) stage. BCL patients significantly elevated ratio of CD4+/CD25+ Treg cells, which were decreased at CR stage. mRNA levels of Foxp3, TGF-β1 and IL-10, in addition to protein levels of TGF-β1 and IL-10 were potentiated in lymphoma patients but decreased in CR patients (P<0.05 in all cases). CD4+/CD25+ Treg cells exert immune suppressing functions in BCL via regulating cytokines, thereby facilitating the pathogenesis and progression of lymphoma. PMID:26464657

  13. Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

    PubMed Central

    Ford, Catriona A.; Petrova, Sofia; Pound, John D.; Voss, Jorine J.L.P.; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L.; Gallimore, Awen M.; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E.; Dunbar, Donald R.; Murray, Paul G.; Ruckerl, Dominik; Allen, Judith E.; Hume, David A.; van Rooijen, Nico; Goodlad, John R.; Freeman, Tom C.; Gregory, Christopher D.

    2015-01-01

    Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. PMID:25702581

  14. Ultrasonographic thickening of the muscularis propria in feline small intestinal small cell T-cell lymphoma and inflammatory bowel disease.

    PubMed

    Daniaux, Lise A; Laurenson, Michele P; Marks, Stanley L; Moore, Peter F; Taylor, Sandra L; Chen, Rachel X; Zwingenberger, Allison L

    2014-02-01

    Gastrointestinal lymphoma is the most common form of lymphoma in the cat. More recently, an ultrasonographic pattern associated with feline small cell T-cell gastrointestinal lymphoma has been recognized as a diffuse thickening of the muscularis propria of the small intestine. This pattern is also described with feline inflammatory bowel disease. To evaluate the similarities between the diseases, we quantified the thickness of the muscularis propria layer in the duodenum, jejunum and ileum of 14 cats affected by small cell T-cell lymphoma and inflammatory bowel disease (IBD) and 19 healthy cats. We found a significantly increased thickness of the muscularis propria in cats with lymphoma and IBD compared with healthy cats. The mean thickness of the muscularis propria in cats with lymphoma or IBD was twice the thickness of that of healthy cats, and was the major contributor to significant overall bowel wall thickening in the duodenum and jejunum. A muscularis to submucosa ratio >1 is indicative of an abnormal bowel segment. Colic lymph nodes in cats with lymphoma were increased in size compared with healthy cats. In cats with gastrointestinal lymphoma and histologic transmural infiltration of the small intestines, colic or jejunal lymph nodes were rounded, increased in size and hypoechoic.

  15. A Novel Chip for Cyclic Stretch and Intermittent Hypoxia Cell Exposures Mimicking Obstructive Sleep Apnea

    PubMed Central

    Campillo, Noelia; Jorba, Ignasi; Schaedel, Laura; Casals, Blai; Gozal, David; Farré, Ramon; Almendros, Isaac; Navajas, Daniel

    2016-01-01

    Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), plays a critical role in the pathogenesis of OSA-associated morbidities, especially in the cardiovascular and respiratory systems. Oxidative stress and inflammation induced by IH are suggested as main contributors of end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, implementation of experimental in vitro cell-based systems capable of inducing high-frequency IH would be highly desirable. Here, we describe the design, fabrication, and validation of a versatile chip for subjecting cultured cells to fast changes in gas partial pressure and to cyclic stretch. The chip is fabricated with polydimethylsiloxane (PDMS) and consists of a cylindrical well-covered by a thin membrane. Cells cultured on top of the membrane can be subjected to fast changes in oxygen concentration (equilibrium time ~6 s). Moreover, cells can be subjected to cyclic stretch at cardiac or respiratory frequencies independently or simultaneously. Rat bone marrow-derived mesenchymal stem cells (MSCs) exposed to IH mimicking OSA and cyclic stretch at cardiac frequencies revealed that hypoxia-inducible factor 1α (HIF-1α) expression was increased in response to both stimuli. Thus, the chip provides a versatile tool for the study of cellular responses to cyclical hypoxia and stretch. PMID:27524971

  16. A Novel Chip for Cyclic Stretch and Intermittent Hypoxia Cell Exposures Mimicking Obstructive Sleep Apnea.

    PubMed

    Campillo, Noelia; Jorba, Ignasi; Schaedel, Laura; Casals, Blai; Gozal, David; Farré, Ramon; Almendros, Isaac; Navajas, Daniel

    2016-01-01

    Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), plays a critical role in the pathogenesis of OSA-associated morbidities, especially in the cardiovascular and respiratory systems. Oxidative stress and inflammation induced by IH are suggested as main contributors of end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, implementation of experimental in vitro cell-based systems capable of inducing high-frequency IH would be highly desirable. Here, we describe the design, fabrication, and validation of a versatile chip for subjecting cultured cells to fast changes in gas partial pressure and to cyclic stretch. The chip is fabricated with polydimethylsiloxane (PDMS) and consists of a cylindrical well-covered by a thin membrane. Cells cultured on top of the membrane can be subjected to fast changes in oxygen concentration (equilibrium time ~6 s). Moreover, cells can be subjected to cyclic stretch at cardiac or respiratory frequencies independently or simultaneously. Rat bone marrow-derived mesenchymal stem cells (MSCs) exposed to IH mimicking OSA and cyclic stretch at cardiac frequencies revealed that hypoxia-inducible factor 1α (HIF-1α) expression was increased in response to both stimuli. Thus, the chip provides a versatile tool for the study of cellular responses to cyclical hypoxia and stretch. PMID:27524971

  17. Lipidoid nanoparticle mediated silencing of Mcl-1 induces apoptosis in mantle cell lymphoma.

    PubMed

    Knapp, Christopher M; He, Jia; Lister, John; Whitehead, Kathryn A

    2016-05-01

    Conventional chemo-immunotherapy fails to cure the majority of mantle cell lymphoma patients and causes substantial toxicity. Resistant mantle cell lymphoma cells commonly overexpress and are dependent on the anti-apoptotic protein, Mcl-1, for survival. In this study, we use potent lipidoid nanoparticles to deliver siRNA to silence Mcl-1 expression. Studies were conducted using two different mantle cell lymphoma cell lines, a normal (JeKo-1) and an aggressive (MAVER-1) line, to assess the ability of lipidoid nanoparticles to be used broadly in the treatment of mantle cell lymphoma. Mcl-1 mRNA silencing and protein knockdown was observed as early as one day after treatment and the lipidoid nanoparticles achieved sustained silencing of Mcl-1 mRNA for at least four days in both JeKo-1 and MAVER-1 cells. Eighty percent silencing was achieved at three days post-transfection in JeKo-1 cells while 50% silencing was achieved in MAVER-1 cells, which are more resistant to transfection. Interestingly, silencing of Mcl-1 induced apoptosis in nearly 30% of both JeKo-1 and MAVER-1 cells three days post-transfection. Additionally, Mcl-1 silencing and the resultant apoptosis in mantle cell lymphoma cells were dose dependent. These data suggest that lipidoid nanoparticles siRNA therapy targeting Mcl-1 has potential as a new treatment modality for mantle cell lymphoma and many other cancers that overexpress Mcl-1. The combination of anti-Mcl-1 lipidoid nanoparticles with other forms of targeted therapy offers hope for reducing or replacing cytotoxic chemotherapy as standard treatment for mantle cell lymphoma. PMID:27022142

  18. Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma

    PubMed Central

    Lauenborg, Britt; Christensen, Louise; Ralfkiaer, Ulrik; Kopp, Katharina L.; Jønson, Lars; Dabelsteen, Sally; Bonefeld, Charlotte M.; Geisler, Carsten; Gjerdrum, Lise Mette R.; Zhang, Qian; Wasik, Mariusz A.; Ralfkiaer, Elisabeth; Ødum, Niels; Woetmann, Anders

    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. PMID:25915535

  19. Reduction of Myeloid-derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid

    PubMed Central

    Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

    2016-01-01

    Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A’s anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen presentation and CD4+ T cell recognition of lymphoma in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. PMID:25142864

  20. Immunomodulation therapy with lenalidomide in follicular, transformed and diffuse large B cell lymphoma: current data on safety and efficacy

    PubMed Central

    2013-01-01

    Lenalidomide is an immunomodulatory agent which has been approved for multiple myeloma. Lenalidomide is also effective in and tolerated well by patients with follicular lymphoma, diffuse large B-cell lymphoma, and transformed large cell lymphoma. This review summarizes the results of current preclinical and clinical studies of lenalidomide, alone or in combination with the monoclonal antibody rituximab, as a therapeutic option for these three lymphoma types. This review will serve as a tool guiding future clinical investigations to improve survival rates for these three lymphomas. PMID:23915913

  1. Oxaliplatin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-22

    Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; 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 Immunoblastic 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 Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Waldenström Macroglobulinemia

  2. The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma.

    PubMed

    Spaccarelli, Natalie; Rook, Alain H

    2015-10-01

    Interferons are polypeptides that naturally occur in the human body as a part of the innate immune response. By harnessing these immunomodulatory functions, synthetic interferons have shown efficacy in combating various diseases including cutaneous T-cell lymphoma. This article closely examines the qualities of interferon alfa and interferon gamma and the evidence behind their use in the 2 most common types of cutaneous T-cell lymphomas, namely, mycosis fungoides and Sézary syndrome.

  3. Clinical Significance of sIL-2R Levels in B-Cell Lymphomas

    PubMed Central

    Yoshida, Noriaki; Oda, Miyo; Kuroda, Yoshiaki; Katayama, Yuta; Okikawa, Yoshiko; Masunari, Taro; Fujiwara, Megumu; Nishisaka, Takashi; Sasaki, Naomi; Sadahira, Yoshito; Mihara, Keichiro; Asaoku, Hideki; Matsui, Hirotaka; Seto, Masao; Kimura, Akiro; Arihiro, Koji; Sakai, Akira

    2013-01-01

    Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R α chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B-lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas. PMID:24236041

  4. T-cell non-Hodgkin's lymphoma after radiotherapy and chemotherapy for Hodgkin's disease

    SciTech Connect

    Lowenthal, R.M.; Harlow, R.W.H.; Mead, A.E.; Tuck, D.; Challis, D.R.

    1981-10-01

    A rapidly fatal T-cell lymphoma developed in a 25-year-old man who, over a period of seven years, had been treated with radiotherapy and combination chemotherapy for Hodgkin's disease (HD). Non-Hodgkin's lymphoma (NHL) is increasingly being recognized as a late sequel of therapy for HD, but this is the first case in which NHL of T-cell type has been identified in such circumstances.

  5. The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma.

    PubMed

    Spaccarelli, Natalie; Rook, Alain H

    2015-10-01

    Interferons are polypeptides that naturally occur in the human body as a part of the innate immune response. By harnessing these immunomodulatory functions, synthetic interferons have shown efficacy in combating various diseases including cutaneous T-cell lymphoma. This article closely examines the qualities of interferon alfa and interferon gamma and the evidence behind their use in the 2 most common types of cutaneous T-cell lymphomas, namely, mycosis fungoides and Sézary syndrome. PMID:26433845

  6. A case of diffuse large B-cell lymphoma misdiagnosed as an erysipelas of the face.

    PubMed

    Teresiak-Mikołajczak, Ewa; Szymańska, Magdalena; Czarnecka-Operacz, Magdalena

    2013-08-01

    We report a case of a woman with diffuse large B-cell lymphoma (DLBCL). Primary cutaneous lymphomas (PCLs) represent distinct clinical and histopathologic subtypes of extranodal T- and B-cell lymphomas. Cutaneous B-cell lymphomas comprise 20-25% of all primary cutaneous lymphomas. The patient presented an erythematous tumour mass of the left nasolabial fold, nose and left cheek as well as disseminated infiltrative plagues on the trunk, arms and left lower leg. Skin biopsy revealed a diffuse infiltrate of lymphocytes around hair follicles and blood vessels within dermis and subcutaneous tissue. An immunohistochemistry showed a diffuse infiltrate of large non-cleaved B-cells, with a high proportion of centroblast-like cells within dermis. Tumor cells expressed CD20, bcl-2 protein and did not express CD10. The patient was misdiagnosed as the erysipelas of the face and unsuccessfully treated with long-term antibiotic therapy by a laryngologist and a dermatologist. The correct diagnosis was delayed and established after 6 months' history of DLBCL lesions. Therefore, we would like to strongly stress the importance of considering diagnosis of cutaneous lymphomas in chronic skin lesions non-responsive to adequate therapies.

  7. Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta.

    PubMed

    Farcet, J P; Gaulard, P; Marolleau, J P; Le Couedic, J P; Henni, T; Gourdin, M F; Divine, M; Haioun, C; Zafrani, S; Goossens, M

    1990-06-01

    Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells. PMID:2140703

  8. Cationic chlorophyl derivatives with SOD mimicking activity suppress the proliferation of human ovarian cancer cells.

    PubMed

    Kobayashi, Y; Maniki, M; Nakamura, K

    1996-06-01

    Derivatives of chlorophyl, e.g. Fe-chlorin e6-Na, alpha, beta, gamma, delta-Tetraphenylporphine-tetrasulfonic acid disulfonic acid salt tetrahydrate (Fe-TPPTS) and alpha, beta, gamma, delta-Tetrakis (4-N-trimethylaminophenyl) porphine, tetra (p-toluensulfonate (Fe-TTMAPP), express SOD mimicking activity. Examination was made of suppressive effects of human cancer cell lines by derivatives of chlorophyl. Fe-TPPTS and Fe-TTMAPP suppressed proliferation of the human ovarian cancer cell lines but Fe-chlorin e6-Na failed to suppress the proliferation. Lipid peroxide was increased by application of Fe-TPPTS and Fe-TTMAPP, but decreased by application of Fe-chlorin e6-Na. SOD activity of the cancer cells did not change by application of these drugs. TPPTS and TTMAPP have a cationic charge but Fe-chlorin e6-Na has an anionic charge. It is suggested that charge of these drugs relates to the suppressive effects of the cancer cell proliferation. PMID:10851538

  9. Three dimensional microfluidic cell arrays for ex vivo drug screening with mimicked vascular flow.

    PubMed

    Dereli-Korkut, Zeynep; Akaydin, H Dogus; Ahmed, A H Rezwanuddin; Jiang, Xuejun; Wang, Sihong

    2014-03-18

    Currently, there are no reliable ex vivo models that predict anticancer drug responses in human tumors accurately. A comprehensive method of mimicking a 3D microenvironment to study effects of anticancer drugs on specific cancer types is essential. Here, we report the development of a three-dimensional microfluidic cell array (3D μFCA), which reconstructs a 3D tumor microenvironment with cancer cells and microvascular endothelial cells. To mimic the in vivo spatial relationship between microvessels and nonendothelial cells embedded in extracellular matrix, three polydimethylsiloxane (PDMS) layers were built into this array. The multilayer property of the device enabled the imitation of the drug delivery in a microtissue array with simulated blood circulation. This 3D μFCA system may provide better predictions of drug responses and identification of a suitable treatment for a specific patient if biopsy samples are used. To the pharmaceutical industry, the scaling-up of our 3D μFCA system may offer a novel high throughput screening tool. PMID:24568664

  10. The Histological and Biological Spectrum of Diffuse Large B-cell Lymphoma in the WHO Classification

    PubMed Central

    Menon, Madhu P.; Pittaluga, Stefania; Jaffe, Elaine S.

    2012-01-01

    Diffuse large B cell lymphomas (DLBCL) are aggressive B-cell lymphomas that are clinically, pathologically and genetically diverse, in part reflecting the functional diversity of the B-cell system. The focus in recent years has been towards incorporation of clinical features, morphology, immunohistochemistry and ever evolving genetic data into the classification scheme. The 2008 WHO classification reflects this complexity with the addition of several new entities and variants. The discovery of distinct subtypes by gene expression profiling (GEP) heralded a new era with a focus on pathways of transformation as well as a promise of more targeted therapies, directed at specific pathways. Some DLBCLs exhibit unique clinical characteristics with a predilection for specific anatomic sites; the anatomic site often reflects underlying biological distinctions. Recently, the spectrum of EBV-driven B-cell proliferations in patients without iatrogenic or congenital immunosuppression has been better characterized; most of these occur in patients of advanced age, and include EBV-positive large B-cell lymphoma of the elderly. HHV-8 is involved in the pathogenesis of primary effusion lymphoma, which can present as a “solid variant.” Two borderline categories were created; one deals with tumors at the interface between classical Hodgkin lymphoma (cHL) and DLBCL. The second confronts the interface between Burkitt Lymphoma (BL) and DLBCL, so called “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma” in the 2008 classification. Most cases harbor both MYC and BCL2 translocations, and are highly aggressive. Another interesting entity is ALK+ DLBCL, which renders itself potentially targetable by ALK inhibitors. Ongoing investigations at the genomic level, with both exome and whole genome sequencing, are sure to reveal new pathways of transformation in the future. PMID:23006945

  11. Peripheral T-cell lymphomas of follicular helper T-cell type frequently display an aberrant CD3(-/dim)CD4(+) population by flow cytometry: an important clue to the diagnosis of a Hodgkin lymphoma mimic.

    PubMed

    Alikhan, Mir; Song, Joo Y; Sohani, Aliyah R; Moroch, Julien; Plonquet, Anne; Duffield, Amy S; Borowitz, Michael J; Jiang, Liuyan; Bueso-Ramos, Carlos; Inamdar, Kedar; Menon, Madhu P; Gurbuxani, Sandeep; Chan, Ernest; Smith, Sonali M; Nicolae, Alina; Jaffe, Elaine S; Gaulard, Philippe; Venkataraman, Girish

    2016-10-01

    Nodal follicular helper T-cell-derived lymphoproliferations (specifically the less common peripheral T-cell lymphomas of follicular type) exhibit a spectrum of histologic features that may mimic reactive hyperplasia or Hodgkin lymphoma. Even though angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma of follicular type share a common biologic origin from follicular helper T-cells and their morphology has been well characterized, flow cytometry of peripheral T-cell lymphomas of follicular type has not been widely discussed as a tool for identifying this reactive hyperplasia/Hodgkin lymphoma mimic. We identified 10 peripheral T-cell lymphomas of follicular type with available flow cytometry data from five different institutions, including two cases with peripheral blood evaluation. For comparison, we examined flow cytometry data for 8 classical Hodgkin lymphomas (including 1 lymphocyte-rich classical Hodgkin lymphoma), 15 nodular lymphocyte predominant Hodgkin lymphomas, 15 angioimmunoblastic T-cell lymphomas, and 26 reactive nodes. Lymph node histology and flow cytometry data were reviewed, specifically for the presence of a CD3(-/dim)CD4(+) aberrant T-cell population (described in angioimmunoblastic T-cell lymphomas), besides other T-cell aberrancies. Nine of 10 (90%) peripheral T-cell lymphomas of follicular type showed a CD3(-/dim)CD4(+) T-cell population constituting 29.3% (range 7.9-62%) of all lymphocytes. Five of 10 (50%) had nodular lymphocyte predominant Hodgkin lymphoma or lymphocyte-rich classical Hodgkin lymphoma-like morphology with scattered Hodgkin-like cells that expressed CD20, CD30, CD15, and MUM1. Three cases had a nodular growth pattern and three others exhibited a perifollicular growth pattern without Hodgkin-like cells. Epstein-Barr virus was positive in 1 of 10 cases (10%). PCR analysis showed clonal T-cell receptor gamma gene rearrangement in all 10 peripheral T-cell lymphomas of follicular type. By flow cytometry, 11 of 15 (73

  12. Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    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

  13. Intravascular large B-cell lymphoma with hemophagocytic syndrome (Asian variant) in a Caucasian patient.

    PubMed

    Fung, Kar-Ming; Chakrabarty, Jennifer H; Kern, William F; Magharyous, Hany; Gehrs, Bradley C; Li, Shibo

    2012-01-01

    Intravascular lymphoma is an aggressive and extremely rare extranodal lymphoma with neoplastic lymphoid cells confined exclusively within intravascular spaces. The histopathologic findings are subtle due to the rarity of the neoplastic cells in blood vessels. Clinical presentations are non-specific and focal space-occupying lesions or lymphoadenopathy are always lacking. It is a diagnostic challenge. Secondary hemophagocytic syndrome is uncommon and is typically associated with infection, malignancy, and suppressed immune states. Intravascular lymphoma has a strong association with hemophagocytic syndrome in Asian patients, the so-called "Asian variant", but not in Western patients. We report a case of intravascular B-cell lymphoma in a Caucasian patient associated with secondary hemophagocytic syndrome. The patient was diagnosed by core liver biopsy and successfully treated. This case demonstrates the importance of high index of suspicion and astute histopathologic examination in recognition of this unusual clinical and pathologic combination.

  14. A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma

    PubMed Central

    Dutta Roy, Subhajit; Stafford, Joanna A; Scally, John; Selvachandran, S N

    2003-01-01

    Background Mantle cell lymphoma (MCL) is a rare variety of non-Hodgkin's lymphoma which originates from CD5+ B-cell population in the mantle zones of lymphoid follicles. Coexistence of such tumours in the axillary lymph nodes with invasive breast cancers without prior history of adjuvant chemotherapy or radiotherapy has not been previously reported in literature. Case report We report a rare case of breast cancer co-existing with stage I mantle cell lymphoma of the ipsilateral axillary lymph node detected fortuitously by population screening. Conclusion Though some studies have tried to prove breast carcinomas and lymphomas to share a common molecular or viral link, more research needs to be done to establish whether such a link truly exists. PMID:14664721

  15. A three-signal model of T-cell lymphoma pathogenesis.

    PubMed

    Wilcox, Ryan A

    2016-01-01

    T-cell lymphoma pathogenesis and classification have, until recently, remained enigmatic. Recently performed whole-exome sequencing and gene-expression profiling studies have significant implications for their classification and treatment. Recurrent genetic modifications in antigen ("signal 1"), costimulatory ("signal 2"), or cytokine receptors ("signal 3"), and the tyrosine kinases and other signaling proteins they activate, have emerged as important therapeutic targets in these lymphomas. Many of these genetic modifications do not function in a cell-autonomous manner, but require the provision of ligand(s) by constituents of the tumor microenvironment, further supporting the long-appreciated view that these lymphomas are dependent upon and driven by their microenvironment. Therefore, the seemingly disparate fields of genomics and immunology are converging. A unifying "3 signal model" for T-cell lymphoma pathogenesis that integrates these findings will be presented, and its therapeutic implications briefly reviewed. PMID:26408334

  16. Characterization of (123)I-iodo-alpha-methyltyrosine transport in rat lymphoma cells.

    PubMed

    Matte, Gilbert; Sangster, Shirley M; Acker, Matthew; Hudgins, Marlene; Too, Catherine K L

    2005-01-01

    (123)I-Iodo-alpha-methyltyrosine (IMT) transport into lymphomas has not been fully characterized. In rat Nb2-11C and Nb2-Sp lymphoma cell lines, linear uptake of (123)I-IMT occurred rapidly within 5-10 min. Eadie-Hoftee plots of (123)I-IMT uptake gave apparent Km's of 8.34+/-1.17 and 9.64+/-1.05 microM for Nb2-11C and Nb2-Sp cells, respectively, and involved the L and B(0,+) systems. In lymphoma-bearing rats, injected (123)I-IMT accumulated rapidly in the primary tumors but gave a low tumor-to-background ratio of 2:1. (123)I-IMT was transported rapidly into lymphoma cells both in vitro and in vivo, but low target-to-nontarget ratio may not make (123)I-IMT practical for scanning in vivo.

  17. Characterization of the novel indolylmaleimides' PDA-66 and PDA-377 effect on canine lymphoma cells

    PubMed Central

    Schmidt, Laura C.; Roolf, Catrin; Pews-Davtyan, Anahit; Rütgen, Barbara C.; Hammer, Sabine; Willenbrock, Saskia; Sekora, Anett; Rolfs, Arndt; Beller, Matthias; Brenig, Bertram; Nolte, Ingo; Junghanss, Christian

    2016-01-01

    Protein kinase inhibitors are widely used in chemotherapeutic cancer regimens. Maleimide derivatives such as SB-216763 act as GSK-3 inhibitor targeting cell proliferation, cell death and cell cycle progression. Herein, the two arylindolylmaleimide derivatives PDA-66 and PDA-377 were evaluated as potential chemotherapeutic agents on canine B-cell lymphoma cell lines. Canine lymphoma represents a naturally occurring model closely resembling the human high-grade non-Hodgkin's lymphoma (NHL). PDA-66 showed more pronounced effects on both cell lines. Application of 2.5μM PDA-66 resulted in a significant induction of apoptosis (approx. 11 %), decrease of the metabolic activity (approx. 95 %), anti-proliferative effect (approx. 85 %) and cell death within 48h. Agent induced mode of action was characterized by whole transcriptome sequencing, 12 h and 24 h post-agent exposure. Key PDA-66-modulated pathways identified were cell cycle, DNA replication and p53 signaling. Expression analyses indicated that the drug acting mechanism is mediated through DNA replication and cycle arrest involving the spindle assembly checkpoint. In conclusion, both PDA derivatives displayed strong anti-proliferation activity in canine B-cell lymphoma cells. The cell and molecular PDA-induced effect characterization and the molecular characterization of the agent acting mechanism provides the basis for further evaluation of a potential drug for canine lymphoma serving as model for human NHL. PMID:27177088

  18. Molecular Monitoring of Cell-Free Circulating Tumor DNA in Non-Hodgkin Lymphoma.

    PubMed

    Melani, Christopher; Roschewski, Mark

    2016-08-01

    The ability to precisely monitor the effectiveness of therapy for non-Hodgkin lymphoma has important clinical implications. In patients with curable lymphomas, such as diffuse large B-cell lymphoma, the eradication of all disease is necessary for cure. In patients with incurable lymphomas, such as follicular lymphoma and mantle cell lymphoma, deep and durable remissions are associated with improvements in survival. Radiographic imaging modalities such as computed tomography and positron emission tomography are the current gold standard for monitoring therapy, but they are fundamentally limited by radiation risks, costs, lack of tumor specificity, and inability to detect disease at the molecular level. Novel sequencing-based methods can detect circulating tumor DNA (ctDNA) in the peripheral blood with great sensitivity, which opens new opportunities for molecular monitoring before, during, and after therapy. Beyond monitoring, ctDNA can also be used as a "liquid biopsy" to assess for molecular changes after therapy that may identify treatment-resistant clones. ctDNA is an emerging tool that may transform our ability to offer precision therapy in non-Hodgkin lymphoma. PMID:27539624

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

    PubMed Central

    Gorodetskiy, Vadim; Klapper, Wolfram; Probatova, Natalya; Vasilyev, Vladimir

    2016-01-01

    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. PMID:26998372

  20. FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2014-01-06

    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; 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 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

  1. Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2015-08-05

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

  2. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma.

    PubMed

    Schmitz, Roland; Hansmann, Martin-Leo; Bohle, Verena; Martin-Subero, Jose Ignacio; Hartmann, Sylvia; Mechtersheimer, Gunhild; Klapper, Wolfram; Vater, Inga; Giefing, Maciej; Gesk, Stefan; Stanelle, Jens; Siebert, Reiner; Küppers, Ralf

    2009-05-11

    Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor kappaB (NF-kappaB). NF-kappaB activation through various stimuli is negatively regulated by the zinc finger protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs (44%), including missense mutations in 2 out of 16 Epstein-Barr virus-positive (EBV(+)) cHLs and a missense mutation, nonsense mutations, and frameshift-causing insertions or deletions in 14 out of 20 EBV(-) cHLs. In most mutated cases, both TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines revealed a significant decrease in transcripts of selected NF-kappaB target genes and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B cell lymphoma (PMBL), another lymphoma with constitutive NF-kappaB activity, revealed destructive mutations in 5 out of 14 PMBLs (36%). This report identifies TNFAIP3 (A20), a key regulator of NF-kappaB activity, as a novel tumor suppressor gene in cHL and PMBL. The significantly higher frequency of TNFAIP3 mutations in EBV(-) than EBV(+) cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis. PMID:19380639

  3. GBT440 Inhibits Sickling of Sickle Cell Trait Blood Under In Vitro Conditions Mimicking Strenuous Exercise

    PubMed Central

    Dufu, Kobina; Lehrer-Graiwer, Josh; Ramos, Eleanor; Oksenberg, Donna

    2016-01-01

    In sickle cell trait (SCT), hemoglobin A (HbA) and S (HbS) are co-expressed in each red blood cell (RBC). While homozygous expression of HbS (HbSS) leads to polymerization and sickling of RBCs resulting in sickle cell disease (SCD) characterized by hemolytic anemia, painful vaso-occlusive episodes and shortened life-span, SCT is considered a benign condition usually with minor or no complications related to sickling. However, physical activities that cause increased tissue oxygen demand, dehydration and/or metabolic acidosis leads to increased HbS polymerization and life-threatening complications including death. We report that GBT440, an agent being developed for the treatment of SCD, increases the affinity of oxygen for Hb and inhibits in vitro polymerization of a mixture of HbS and HbA that simulates SCT blood. Moreover, GBT440 prevents sickling of SCT blood under in vitro conditions mimicking strenuous exercise with hypoxia, dehydration and acidosis. Together, our results indicate that GBT440 may have the potential to protect SCT individuals from sickling-related complications during conditions that favor HbS polymerization. PMID:27757216

  4. Primary bilateral adrenal intravascular large B-cell lymphoma associated with adrenal failure.

    PubMed

    Fukushima, Ayumi; Okada, Yosuke; Tanikawa, Takahisa; Onaka, Takashi; Tanaka, Aya; Higashi, Takehiro; Tsukada, Junichi; Tanaka, Yoshiya

    2003-07-01

    We report a rare case of bilateral primary adrenal non-Hodgkin's lymphoma with adrenal failure. A 66-year-old woman developed symptoms of adrenal failure. The cause of adrenal failure was suspected to be malignant lymphoma based on the high levels of serum soluble interleukin-2 receptor and LDH. Bilateral adrenalectomy was performed and pathological examination showed intravascular large B-cell lymphoma (IVL). Although complete remission was achieved, recurrence occurred three months later with brain metastases. IVL should be suspected in patients with bilateral adrenal tumors who present with rapidly progressive adrenal failure.

  5. Diffuse Large B-Cell Lymphoma Presenting with Bilateral Renal Masses and Hematuria: A Case Report.

    PubMed

    Erdoğmuş, Şiyar; Aktürk, Serkan; Kendi Çelebi, Zeynep; Kiremitçi, Saba; Kaygusuz, Gülşah; Altınbaş, Namık Kemal; Üstüner, Evren; Keven, Kenan

    2016-06-01

    Renal involvement is most often seen in conjunction with multisystemic, disseminated lymphoma either by direct extension from a retroperitoneal mass or via hematogenous spread. Primary lymphoma of the kidney is not a common entity and it is a controversial issue on account of the absence of lymphatic tissues in the normal kidney. In this case report, we describe a 19-year-old male with hematuria, acute kidney injury, and bilateral renal masses due to massive lymphomatous infiltration of the kidneys, which was diagnosed as diffuse large B-cell non-Hodgkin lymphoma by Tru-Cut biopsy. PMID:27095511

  6. Rare clinical presentation of diffuse large B-cell lymphoma as otitis media and facial palsy.

    PubMed

    Siddiahgari, Sirisha Rani; Yerukula, Pallavi; Lingappa, Lokesh; Moodahadu, Latha S

    2016-01-01

    Extra nodal presentation of Non Hodgkins Lymphoma (NHL) is a rare entity, and data available about the NHL that primarily involves of middle ear and mastoid is limited. We report a case of diffuse large B cell lymphoma (DLBCL), in a 2 year 8 month old boy, who developed otalgia and facial palsy. Computed tomography revealed a mass in the left mastoid. Mastoid exploration and histopathological examination revealed DLBCL. This case highlights the importance of considering malignant lymphoma as one of the differential diagnosis in persistent otitis media and/facial palsy.

  7. Primary CNS T-cell Lymphomas: A Clinical, Morphologic, Immunophenotypic, and Molecular Analysis.

    PubMed

    Menon, Madhu P; Nicolae, Alina; Meeker, Hillary; Raffeld, Mark; Xi, Liqiang; Jegalian, Armin G; Miller, Douglas C; Pittaluga, Stefania; Jaffe, Elaine S

    2015-12-01

    Primary central nervous system (CNS) lymphomas are relatively rare with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) account for <5% of CNS lymphomas. We report the clinical, morphologic, immunophenotypic, and molecular characteristics of 18 PCNSTLs. Fifteen cases were classified as peripheral T-cell lymphoma, not otherwise specified, 2 of which were of γδ T-cell derivation and 1 was TCR silent; there was 1 anaplastic large cell lymphoma, ALK-positive and 2 anaplastic large cell lymphoma, ALK-negative. Median age was 58.5 years (range, 21 to 81 y), with an M:F ratio of 11:7. Imaging results showed that 15 patients had supratentorial lesions. Regardless of subtype, necrosis and perivascular cuffing of tumor cells were frequently observed (11/18 cases). CD3 was positive in all cases but 1; 10/17 were CD8-positive, and 5/17 were CD4-positive. Most cases studied had a cytotoxic phenotype with expression of TIA1 (13/15) and granzyme-B (9/13). Polymerase chain reaction analysis of T-cell receptor γ rearrangement confirmed a T-cell clone in 14 cases with adequate DNA quality. Next-generation sequencing showed somatic mutations in 36% of cases studied; 2 had >1 mutation, and none showed overlapping mutations. These included mutations in DNMT3A, KRAS, JAK3, STAT3, STAT5B, GNB1, and TET2 genes, genes implicated previously in other T-cell neoplasms. The outcome was heterogenous; 2 patients are alive without disease, 4 are alive with disease, and 6 died of disease. In conclusion, PCNSTLs are histologically and genomically heterogenous with frequent phenotypic aberrancy and a cytotoxic phenotype in most cases. PMID:26379152

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

    PubMed

    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.

  9. Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or Indolent Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2016-04-05

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell 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; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  10. The Genetic Basis of Diffuse Large B Cell Lymphoma

    PubMed Central

    Pasqualucci, Laura

    2014-01-01

    Purpose of review Diffuse large B cell lymphoma (DLBCL) is an aggressive disease featuring heterogeneous genetic, phenotypic and clinical characteristics. Understanding the basis for this heterogeneity represents a critical step toward further progress in the management of this disease, which remains a clinical challenge in approximately one third of patients. This review summarizes current knowledge about the molecular pathogenesis of DLBCL, and describes how recent advances in the genomic characterization of this cancer have provided new insights into its biology, revealing several potential targets for improved diagnosis and therapy. Recent findings In the past few years, the development of high-resolution technologies has provided significant help in identifying genetic lesions and/or disrupted signaling pathways that are required for DLBCL initiation and progression. These studies uncovered the involvement of cellular programs that had not been previously appreciated, including histone/chromatin remodeling and immune recognition. Alterations in these pathways could favor epigenetic reprogramming and escape from cellular immunity. Summary The identification of genetic alterations that contribute to the malignant transformation of a B cell into a DLBCL is helping to better understand the biology of this disease and to identify critical nodes driving tumor progression or resistance to therapy. The rapid pace at which these discoveries are taking place is poised to have significant impact for patients stratification based on molecular predictors and for the development of rational targeted therapies. PMID:23673341

  11. Cerebral infratentorial large B-cell lymphoma presenting as Parkinsonism.

    PubMed

    Lin, Chih-Ming; Hong, Kelvin

    2010-03-01

    Though rare, primary intracranial tumors can present with Parkinsonian symptoms, and diagnosis can be delayed unless there is a high index of suspicion. We herein present an 81-year-old man who was seen in our neurology clinic due to acute onset of unsteady gait and altered consciousness. Parkinsonism was initially diagnosed because of the typical manifestations. Levodopa was prescribed; however, there was a limited effect on his symptoms. Upon detail history and neurological examination, left sided hemiparesis was disclosed. Cerebral imaging studies revealed a solid mass over the right infratentorial para-midbrain area leading to reactive obstructive hydrocephalus. Work-up including chest and abdominal CT scanning, upper and lower GI endoscopy, and tumor marker studies failed to uncover any abnormalities. A neurosurgeon was consulted and a shunt procedure and biopsy of the infratentorial mass were performed. Histopathological examination of the biopsy tissue revealed tumor diffusely intermixed with large cells consistent with large B-cell lymphoma. The patient and his family declined further treatment. Though rare, cerebral tumors can present with Parkinsonian features and represent a diagnostic challenge. Clinicians should be aware of the possibility of cerebral neoplasms causing Parkinsonism, and include them in the differential diagnosis, especially for patients presenting with atypical Parkinsonian features, or those not responsive to initial therapy.

  12. A Gene Panel, Including LRP12, Is Frequently Hypermethylated in Major Types of B-Cell Lymphoma

    PubMed Central

    Bethge, Nicole; Honne, Hilde; Andresen, Kim; Hilden, Vera; Trøen, Gunhild; Liestøl, Knut; Holte, Harald; Delabie, Jan; Lind, Guro E.; Smeland, Erlend B.

    2014-01-01

    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. PMID:25226156

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

    PubMed

    Bethge, Nicole; Honne, Hilde; Andresen, Kim; Hilden, Vera; Trøen, Gunhild; Liestøl, Knut; Holte, Harald; Delabie, Jan; Lind, Guro E; Smeland, Erlend B

    2014-01-01

    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. PMID:25226156

  14. Renal cell carcinoma with areas mimicking renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma.

    PubMed

    Petersson, Fredrik; Grossmann, Petr; Hora, Milan; Sperga, Maris; Montiel, Delia Perez; Martinek, Petr; Gutierrez, Maria Evelyn Cortes; Bulimbasic, Stela; Michal, Michal; Branzovsky, Jindrich; Hes, Ondrej

    2013-07-01

    We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for α-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for α-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.

  15. Plasmodium Infection Promotes Genomic Instability and AID Dependent B Cell Lymphoma

    PubMed Central

    Robbiani, Davide F.; Deroubaix, Stephanie; Feldhahn, Niklas; Oliveira, Thiago Y.; Callen, Elsa; Wang, Qiao; Jankovic, Mila; Silva, Israel T.; Rommel, Philipp C.; Bosque, David; Eisenreich, Tom; Nussenzweig, André; Nussenzweig, Michel C.

    2015-01-01

    Summary Chronic infection with Plasmodium falciparum was epidemiologically associated with endemic Burkitt’s lymphoma, a mature B cell cancer characterized by chromosome translocation between the c-myc oncogene and Igh, over 50 years ago. Whether infection promotes B cell lymphoma, and if so by what mechanism remains unknown. To investigate the relationship between parasitic disease and lymphomagenesis we used Plasmodium chabaudi (Pc) to produce chronic malaria infection in mice. Pc induces prolonged expansion of germinal centers (GCs), unique compartments where B cells undergo rapid clonal expansion and express activation-induced cytidine deaminase (AID), a DNA mutator. GC B cells elicited during Pc infection suffer widespread DNA damage leading to chromosome translocations. Although infection does not change the overall rate, it modifies lymphomagenesis to favor mature B cell lymphomas that are AID dependent and show chromosome translocations. Thus, malaria infection favors mature B cell cancers by eliciting protracted AID expression in GC B cells. PMID:26276629

  16. Primary bilateral adrenal B-cell lymphoma associated with EBV and JCV infection

    PubMed Central

    Barzon, Luisa; Trevisan, Marta; Marino, Filippo; Guzzardo, Vincenza; Palù, Giorgio

    2009-01-01

    Primary lymphoma of the adrenal gland is a rare and highly aggressive disease, with only a few reports in the literature. The pathogenesis is unknown, but detection of Epstein Barr virus (EBV) genome sequences and gene expression in some cases of primary adrenal lymphomas suggested the virus might be a causative agent of the malignancy. While investigating the presence of genome sequences of oncogenic viruses in a large series of adrenal tumors, both EBV and JC polyomavirus (JCV) DNA sequences were detected in a diffuse large primary bilateral B-cell non-Hodgkin lymphoma of the adrenal gland, which was diagnosed only at postmortem examination in a 77 year-old woman with incidentally discovered adrenal masses and primary adrenal insufficiency. The presence of both EBV and JCV genome sequences suggests the relevance of EBV and JCV coinfection in the pathogenesis of this rare form of B-cell lymphoma. PMID:19146683

  17. The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment

    PubMed Central

    Gru, A. A.; Haverkos, B. H.; Freud, A. G.; Hastings, J.; Nowacki, N. B.; Barrionuevo, C.; Vigil, C. E.; Rochford, R.; Natkunam, Y.; Baiocchi, R. A.

    2015-01-01

    While Epstein-Barr virus (EBV) was initially discovered and characterized as an oncogenic virus in B cell neoplasms, it also plays a complex and multifaceted role in T/NK cell lymphomas. In B cell lymphomas, EBV-encoded proteins have been shown to directly promote immortalization and proliferation through stimulation of the NF-κB pathway and increased expression of anti-apoptotic genes. In the context of mature T/NK lymphomas (MTNKL), with the possible exception on extranodal NK/T cell lymphoma (ENKTL), the virus likely plays a more diverse and nuanced role. EBV has been shown to shape the tumor microenvironment by promoting Th2-skewed T cell responses and by increasing the expression of the immune checkpoint ligand PD-L1. The type of cell infected, the amount of plasma EBV DNA, and the degree of viral lytic replication have all been proposed to have prognostic value in T/NK cell lymphomas. Latency patterns of EBV infection have been defined using EBV-infected B cell models and have not been definitively established in T/NK cell lymphomas. Identifying the expression profile of EBV lytic proteins could allow for individualized therapy with the use of antiviral medications. More work needs to be done to determine whether EBV-associated MTNKL have distinct biological and clinical features, which can be leveraged for risk stratification, disease monitoring, and therapeutic purposes. PMID:26449716

  18. Malignant hematopoietic cell lines: in vitro models for the study of primary mediastinal B-cell lymphomas.

    PubMed

    Drexler, Hans G; Ehrentraut, Stefan; Nagel, Stefan; Eberth, Sonja; MacLeod, Roderick A F

    2015-01-01

    Primary mediastinal B-cell lymphoma (PMBL) is a highly aggressive disease with a unique set of biological, clinical, morphological, immunological and in particular genetic features that in the molecular era of defining lymphomas clearly distinguishes it as a separate entity from other diffuse large B-cell lymphomas (DLBCL). A precise molecular diagnosis of PMBL can be achieved by gene expression profiling. The signature gene expression profile of PMBL is more closely related to classic Hodgkin lymphoma (cHL) than to other DLBCL subgroups. A number of common genetic aberrations in PMBL and cHL further underscore their close relationship. To investigate the pathobiology of lymphomas in depth, many groups have turned to cell lines that are suitable models facilitating molecular studies and providing unique insights. For the purposes of the current perspective, we focus on four bona fide PMBL-derived cell lines (FARAGE, KARPAS-1106, MEDB-1, U-2940) that we identified and validated as such through hierarchical cluster analysis among a large collection of leukemia-lymphoma cell lines. These gene expression profiles showed that the four PMBL cell lines represent a distinct entity and are most similar to cHL cell lines, confirming derivation from a related cell type. A validated cell line resource for PMBL should assist those seeking druggable targets in this entity. This review aims to provide a comprehensive overview of the currently available cellular models for the study of PMBL. PMID:25480038

  19. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas.

    PubMed

    Pasqualucci, L; Neumeister, P; Goossens, T; Nanjangud, G; Chaganti, R S; Küppers, R; Dalla-Favera, R

    2001-07-19

    Genomic instability promotes tumorigenesis and can occur through various mechanisms, including defective segregation of chromosomes or inactivation of DNA mismatch repair. Although B-cell lymphomas are associated with chromosomal translocations that deregulate oncogene expression, a mechanism for genome-wide instability during lymphomagenesis has not been described. During B-cell development, the immunoglobulin variable (V) region genes are subject to somatic hypermutation in germinal-centre B cells. Here we report that an aberrant hypermutation activity targets multiple loci, including the proto-oncogenes PIM1, MYC, RhoH/TTF (ARHH) and PAX5, in more than 50% of diffuse large-cell lymphomas (DLCLs), which are tumours derived from germinal centres. Mutations are distributed in the 5' untranslated or coding sequences, are independent of chromosomal translocations, and share features typical of V-region-associated somatic hypermutation. In contrast to mutations in V regions, however, these mutations are not detectable in normal germinal-centre B cells or in other germinal-centre-derived lymphomas, suggesting a DLCL-associated malfunction of somatic hypermutation. Intriguingly, the four hypermutable genes are susceptible to chromosomal translocations in the same region, consistent with a role for hypermutation in generating translocations by DNA double-strand breaks. By mutating multiple genes, and possibly by favouring chromosomal translocations, aberrant hypermutation may represent the major contributor to lymphomagenesis.

  20. The presenting manifestations of subcutaneous panniculitis-like T-cell lymphoma and T-cell lymphoma and cutaneous γδ T-cell lymphoma may mimic those of rheumatic diseases: a report of 11 cases.

    PubMed

    Yi, Lin; Qun, Shi; Wenjie, Zheng; Wen, Zhang; Jian, Li; Yan, Zhao; Fengchun, Zhang

    2013-08-01

    This study aims to investigate the association between subcutaneous panniculitis-like T-cell lymphoma (SPTCL) or cutaneous gamma/delta T-cell lymphoma (CGDTCL) and a variety of manifestations that mimic autoimmune disorders. A retrospective chart review was made for 11 patients who were initially diagnosed as autoimmune diseases but finally turned out to be SPTCL or CGDTCL. Eleven patients were initially diagnosed with erythema nodosum, nodular panniculitis, lupus erythematosus profundus, systemic vasculitis, dermatomyositis, or pyoderma gangrenosum. The interval between presenting symptoms and the diagnosis of lymphoma was 17.5 (range, 3-84)  months on average. Nearly all cases had multiple subcutaneous nodules or plaques that were most commonly distributed on the extremities and trunk. Fever was the primary accompanying sign (9/10), followed by lymphadenopathy (6/11), splenomegaly (5/11), and hepatomegaly (3/11). Two patients developed hemophagocytic syndrome. A total of 26 biopsies involving multiple anatomic locations were performed. Antirheumatic therapy including steroids and immunosuppressive agents administered before the identification of T-cell lymphoma revealed unsustainable therapeutic effect. In contrast, seven cases gained partial response after chemotherapy, while the remaining four cases died with disease progression and disease-associated severe infections. SPTCL and CGDTCL are rare and heterogeneous which may resemble those rheumatologic diseases that are characterized by inflammation involving the skin or subcutaneous fat tissue. The diagnosis relies on the constellation of disease-specific pathologic, immunophenotypic, and T-cell receptor gene rearrangement tests. In the context of an ambiguous clinical picture demonstrating inconsistency with the initial diagnosis of benign autoimmune diseases, repeated excisional biopsies of the subcutaneous lesions may be required to uncover the underlying lymphoma. PMID:23588884

  1. Development of a Malignancy-Associated Proteomic Signature for Diffuse Large B-Cell Lymphoma

    PubMed Central

    Romesser, Paul B.; Perlman, David H.; Faller, Douglas V.; Costello, Catherine E.; McComb, Mark E.; Denis, Gerald V.

    2009-01-01

    The extreme pathological diversity of non-Hodgkin’s lymphomas has made their accurate histological assessment difficult. New diagnostics and treatment modalities are urgently needed for these lymphomas, particularly in drug development for cancer-specific targets. Previously, we showed that a subset of B cell lymphoma, diffuse large B cell lymphoma, may be characterized by two major, orthogonal axes of gene expression: one set of transcripts that is differentially expressed between resting and proliferating, nonmalignant cells (ie, a “proliferative signature”) and another set that is expressed only in proliferating malignant cells (ie, a “cancer signature”). A differential proteomic analysis of B cell proliferative states, similar to previous transcriptional profiling analyses, holds great promise either to reveal novel factors that participate in lymphomagenesis or to define biomarkers of onset or progression. Here, we use a murine model of diffuse large B cell lymphoma to conduct unbiased two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomic analyses of malignant proliferating B cells and tissue-matched, normal resting, or normal proliferating cells. We show that the expression patterns of particular proteins or isoforms across these states fall into eight specific trends that provide a framework to identify malignancy-associated biomarkers and potential drug targets, a signature proteome. Our results support the central hypothesis that clusters of proteins of known function represent a panel of expression markers uniquely associated with malignancy and not normal proliferation. PMID:19498000

  2. The unexpected evolution of a case of diffuse large B-cell non-Hodgkin lymphoma.

    PubMed

    Găman, Amelia; Bold, Adriana; Găman, G

    2011-01-01

    The diffuse large B-cell lymphoma (DLBCL) represents the most common type of aggressive non-Hodgkin's lymphoma with a heterogeneous morphology, biology and clinical presentation. Gene expression profiling studies identified three distinct molecular subtypes of DLCBL arisen from B-cells at different stages of differentiation: germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, primary mediastinal B-cell lymphoma (PMBL). The most relevant oncogenic pathways in diffuse large B-cell lymphoma are: deregulated B-cell receptor/proliferation signaling, BCL6 and NF-kB constitutive expression, defects in apoptosis and neoangiogenesis. The treatment of DLBCL has been completely modified in the last ten years by combination of anti-CD20 monoclonal antibody (rituximab) and CHOP chemotherapy, which is now the first line therapy. In the last years, there have been reported several cases of progressive multifocal leukoencephalopathy (PML) at patients with rheumatoid arthritis treated with rituximab. Progressive multifocal leukoencephalopathy is possible as an adverse reaction to rituximab at patients treated with R-CHOP for diffuse large B-cell lymphoma. PMID:21655667

  3. A probable identical Epstein-Barr virus clone-positive composite lymphoma with aggressive natural killer-cell leukemia and cytotoxic T-cell lymphoma

    PubMed Central

    Sugimoto, Kei-Ji; Shimada, Asami; Wakabayashi, Mutsumi; Imai, Hidenori; Sekiguchi, Yasunobu; Nakamura, Noriko; Sawada, Tomohiro; Ota, Yasunori; Takeuchi, Kengo; Ito, Yoshinori; Kimura, Hiroshi; Komatsu, Norio; Noguchi, Masaaki

    2014-01-01

    The patient was a 52-year old woman with a history of mosquito-bite hypersensitivity since childhood. In July 2011, she developed pyrexia, headaches, and nausea, and Epstein-Barr virus (EBV)-positive aggressive natural killer leukemia (ANKL) was diagnosed on the basis of both a peripheral blood and bone marrow examination. An inguinal lymph node biopsy, on the other hand, revealed EBV-positive cytotoxic T-cell lymphoma plus the presence of a small number of EBV-positive ANKL cells, and a diagnosis of EBV-positive composite lymphoma was made. Both the cytotoxic T-cell lymphoma and ANKL exhibited EBV terminal repeat (Southern blot analysis) monoclonal patterns, and they were almost the same size, approximately 9.0 kb. If it was the identical EBV clone, it is possible that EBV infected progenitor cells common to both NK cells and T cells, that the progenitor cells then differentiated into NK cells and T cells, a chronic active Epstein-Barr virus infection developed, and neoplastic transformation occurred. If it was not the identical EBV clone, fairly similar EBVs must have infected NK cells and T cells separately, and they then underwent neoplastic transformation. Because the mechanism by which EBV infects NK cells or T cells is still unknown, we concluded that this case is also important from the standpoint of elucidating it. We are currently in the process of conducting gene analyses to determine whether the fairly similar EBVs that infected the ANKL and cytotoxic T-cell lymphoma are the identical clone. PMID:24427365

  4. Assessment of carbonic anhydrase IX expression and extracellular pH in B-cell lymphoma cell line models

    PubMed Central

    Chen, Liu Qi; Howison, Christine M.; Spier, Catherine; Stopeck, Alison T.; Malm, Scott W.; Pagel, Mark D.; Baker, Amanda F.

    2015-01-01

    The expression of carbonic anhydrase (CA IX) and it’s relation to acidosis in lymphomas has not been widely studied. We investigated the protein expression of CA IX in a human B-cell lymphoma tissue microarray, and in Raji, Ramos, and Granta 519 lymphoma cell lines and tumor models, while also investigating the relation with hypoxia. An imaging method, acidoCEST MRI, was used to estimate lymphoma xenograft extracellular pH (pHe). Our results showed that clinical lymphoma tissues and cell line models in vitro and in vivo had moderate CA IX expression. Although in vitro studies showed that CA IX expression was induced by hypoxia, in vivo studies did not show this correlation. Untreated lymphoma xenograft tumor pHe had acidic fractions, and an Acidity Score was qualitatively correlated with CA IX expression. Therefore, CA IX is expressed in B-cell lymphomas and is qualitatively correlated with extracellular acidosis in xenograft tumor models. PMID:25130478

  5. Primary cutaneous anaplastic large cell lymphoma successfully treated with local thermotherapy using pocket hand warmers.

    PubMed

    Honma, Masaru; Hashimoto, Makoto; Iwasaki, Takeshi; Iinuma, Shin; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi; Iizuka, Hajime

    2008-11-01

    Apart from for cutaneous deep fungal or mycobacterial infections, thermotherapy has been used for various malignant tumors. We report a case of primary cutaneous anaplastic large cell lymphoma, which responded quite well to topical thermotherapy using chemical pocket hand warmers. The treatment resulted in an immediate tumor regression without recurrence. This method is simple and might be a useful tool against solitary cutaneous lymphoma, especially of elderly patients with poor performance status or with various systemic complications. PMID:19120772

  6. Immunoflow cytometry and cell block immunohistochemistry in the FNA diagnosis of lymphoma: a review of 73 consecutive cases

    PubMed Central

    Mayall, F.; Dray, M.; Stanley, D.; Harrison, B.; Allen, R.

    2000-01-01

    Aims—To review the results of 73 consecutive fine needle aspirations (FNAs) that were collected by a pathologist and analysed by immunoflow cytometry. Material for a cell block was also collected from some of these lesions. Methods—The setting was a large general hospital in rural New Zealand. The FNAs were performed by a pathologist, or a radiologist for image guided localisations. Material for immunoflow cytometry was collected into RPMI and, when required, material for a cell block was collected into formalin. Results—Of the 73 samples collected by FNA nine were inadequate. Light chain restriction could be demonstrated in most FNA samples from B cell lymphomas (28 of 30 adequate samples). The exceptions were two cases of T cell rich B cell lymphoma. Artefactual light chain restriction was seen occasionally in T cell lymphomas, presumably as a result of autoantibodies binding to the cell surfaces. It was possible to subtype most (18 of 30 adequate samples) B cell lymphomas as chronic lymphocytic leukaemia (CLL), follicle centre cell lymphoma (FCCL), or mantle cell lymphoma. The CD4 to CD8 ratio was not usually restricted in T cell lymphomas and coexpression of CD4 and CD8 was not usually found. Loss of pan-T cell antigens was seen in some T cell lymphomas. Four of the six T cell lymphomas and three of the four non-lymphoid malignancies were diagnosed with the aid of cell block immunohistochemistry. Only one of the four cases of Hodgkin's lymphoma showed Reed-Sternberg cells in the FNA smears. Conclusions—It is not always possible to characterise lymphomas as fully with FNA and immunoflow cytometry as is possible with biopsy histology and a full battery of modern investigations. Nevertheless, in the setting of a large rural general hospital immunoflow cytometry on FNA samples is a highly effective method of diagnosing and typing B cell lymphomas. Immunoflow cytometry is of little use for T cell lymphomas or Hodgkin's lymphomas. We advocate the use of cell

  7. AUY922 effectively targets against activated B cell subtype of diffuse large B-cell lymphoma and low-grade lymphoma cells harboring genetic alteration-associated nuclear factor-κB activation.

    PubMed

    Tsai, Hui-Jen; Shih, Neng-Yao; Kuo, Sung-Hsin; Cheng, Ann-Lii; Lin, Hui-You; Chen, Tsai-Yun; Chang, Kung-Chao; Lin, Sheng-Fung; Chang, Jeffrey S; Chen, Li-Tzong

    2015-01-01

    Recurrent genetic alterations that are frequently observed in some low-grade lymphomas, such as activated B cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL) and mucosa-associated lymphoid tissue type lymphoma (MALT lymphoma) are usually associated with nuclear factor-κB (NF-κB) activation and confer resistance to therapy. In this study, we investigated the therapeutic efficacy and molecular mechanisms of AUY922, a novel Hsp90 inhibitor, in representative cell lines OCI-Ly3 (ABC-DLBCL) and MA-1 (a low-grade lymphoma cell line with t(14;18)/IgH-MALT1translocation) to explore its potential use in the treatment of refractory B-cell lymphoma. Our results showed that AUY922 effectively induced growth inhibition and apoptosis of OCI-Ly3 and MA-1 cells, which were accompanied by down-regulation of the expression levels of NF-κB and Bcl-2 family proteins, as well as molecules of multiple signaling pathways involving cell proliferation, growth and survival. The growth inhibitory effect of AUY922 was further confirmed in a mouse xenograft model. These findings indicate the potential use of AUY922 in B cell lymphomas.

  8. Composite mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a clinicopathologic and molecular study.

    PubMed

    Hoeller, Sylvia; Zhou, Yi; Kanagal-Shamanna, Rashmi; Xu-Monette, Zijun Y; Hoehn, Daniela; Bihl, Michel; Swerdlow, Steven H; Rosenwald, Andreas; Ott, German; Said, Jonathan; Dunphy, Cherie H; Bueso-Ramos, Carlos E; Lin, Pei; Wang, Michael; Miranda, Roberto N; Tzankov, Alexander; Medeiros, L Jeffrey; Young, Ken H

    2013-01-01

    Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) share many features and both arise from CD5+ B-cells; their distinction is critical as MCL is a more aggressive neoplasm. Rarely, cases of composite MCL and CLL/SLL have been reported. Little is known about the nature of these cases and, in particular, the clonal relationship of the 2 lymphomas. Eleven composite MCL and CLL/SLL cases were identified. The clinical, morphologic and immunophenotypic features of the MCL and CLL/SLL were characterized. IGH (immunoglobulin heavy chain) gene analysis was performed on microdissected MCL and CLL/SLL components to assess their clonal relationship. Ten patients had lymphadenopathy, and 7 patients had bone marrow involvement. The MCL component had the following growth patterns: in situ (n = 1), mantle zone (n = 3), nodular and diffuse (n = 3), diffuse (n = 3), and interstitial in the bone marrow (the only patient without lymphadenopathy) (n = 1); 6 MCLs had blastoid or pleomorphic and 5 small lymphocytic features. The CLL/SLL component was nodular (n = 9) or diffuse (n = 2). All MCL were CD5(+) and cyclin D1(+) with t(11;14) translocation. All CLL/SLL were CD5(+), CD23(+) and negative for cyclin D1 or t(11;14). IGH gene analysis showed that the MCL and CLL/SLL components displayed different sized fragments, indicating that the MCL and CLL/SLL are likely derived from different neoplastic B-cell clones. The lack of a clonal relationship between the MCL and CLL/SLL components suggests that MCL and CLL/SLL components represent distinct disease processes and do not share a common progenitor B-cell.

  9. Hepatosplenic T Cell Lymphoma in an Immunocompetent Female Diagnosed using Flow Cytometry: A Rare Clinical Entity.

    PubMed

    Dorwal, Pranav; Sachdev, Ritesh; Pande, Amit; Jain, Dharmendra; Jha, Bhawna; Raina, Vimarsh

    2016-08-01

    Hepatosplenic T-cell lymphoma is a rare haematopoietic malignancy that comprises less than 1% of Non-Hodgkin lymphomas. We are reporting a case of a 26-year-old female, who presented with pallor, weight loss, jaundice, pancytopenia and hepatosplenomegaly. The bone marrow examination showed infiltration by lymphoid cells. These cells on flow cytometric evaluation showed the phenotype of hepatosplenic T cell lymphoma. The cells were positive for CD3, CD8, CD56 and TCR γδ and negative for CD5, CD4, CD8, CD16, CD57, TCRαβ along with B cell markers. This case is reported for being a rare clinical entity and its presence in an immunocompetent female making it rarer. PMID:27656456

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

    PubMed

    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

  11. Diffuse large B-cell lymphoma involving the central nervous system.

    PubMed

    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2011-02-01

    Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype.

  12. Expression of Epstein-Barr virus encoded latent genes in nasal T cell lymphomas.

    PubMed Central

    van Gorp, J; Brink, A; Oudejans, J J; van den Brule, A J; van den Tweel, J G; Jiwa, N M; de Bruin, P C; Meijer, C J

    1996-01-01

    AIMS: To determine the expression of Epstein-Barr (EB) virus encoded latent genes in nasal T-cell lymphomas in The Netherlands. METHODS: Seven europid (Dutch) cases of nasal T cell lymphoma were investigated for the presence of EB virus by RNA in situ hybridisation (EBER). The expression of the EB virus encoded genes BARF0, EBNA1, EBNA2, LMP1, LMP2A, LMP2B, and ZEBRA was studied at the mRNA level using reverse transcriptase polymerase chain reaction. At the protein level the expression was investigated of EBNA2 and LMP1 by immunohistochemistry. RESULTS: In all seven nasal T cell lymphomas EBER was detected in the nuclei of virtually all tumour cells. BARF0 mRNA was detected in all samples. EBNA1 mRNA was found in six cases, LMP1 mRNA in five, LMP2A mRNA in three, LMP2B mRNA in one, and ZEBRA mRNA in one. EBNA2 mRNA was not found in any case. At the protein level occasional LMP1 positive tumour cells were seen in only one case. The EBNA2 protein was not detected. CONCLUSIONS: Nasal T cell lymphomas in The Netherlands are strongly associated with EB virus. The virus shows a type II latency pattern (EBNA1+, LMP1+, EBNA2-) that seems to be similar to the EB virus associated nasal T cell lymphomas in oriental countries. Images PMID:8666691

  13. The Genetic Landscape of Diffuse Large B Cell Lymphoma

    PubMed Central

    Pasqualucci, Laura; Dalla-Favera, Riccardo

    2015-01-01

    Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in the western world, is an aggressive disease that remains incurable in approximately 30% of patients. Over the past decade, the rapid expansion of sequencing technologies allowing the genome-wide assessment of genomic and transcriptional changes has revolutionized our understanding of the genetic basis of DLBCL by providing a comprehensive and unbiased view of the genes/pathways that are disrupted by genetic alterations in this disease, and may contribute to tumor initiation and expansion. These studies uncovered the existence of several previously unappreciated alterations in key cellular pathways that may also influence treatment outcome. Indeed, a number of newly identified genetic lesions are currently being explored as markers for improved diagnosis and risk stratification, or are entering clinical trials as promising therapeutic targets. This review focuses on recent advances in the genomic characterization of DLBCL and discusses how information gained from these efforts has provided new insights into its biology, uncovering potential targets of prognostic and therapeutic relevance. PMID:25805586

  14. Epigenomic evolution in diffuse large B-cell lymphomas

    PubMed Central

    Pan, Heng; Jiang, Yanwen; Boi, Michela; Tabbò, Fabrizio; Redmond, David; Nie, Kui; Ladetto, Marco; Chiappella, Annalisa; Cerchietti, Leandro; Shaknovich, Rita; Melnick, Ari M.; Inghirami, Giorgio G.; Tam, Wayne; Elemento, Olivier

    2015-01-01

    The contribution of epigenomic alterations to tumour progression and relapse is not well characterized. Here we characterize an association between disease progression and DNA methylation in diffuse large B-cell lymphoma (DLBCL). By profiling genome-wide DNA methylation at single-base pair resolution in thirteen DLBCL diagnosis–relapse sample pairs, we show that DLBCL patients exhibit heterogeneous evolution of tumour methylomes during relapse. We identify differentially methylated regulatory elements and determine a relapse-associated methylation signature converging on key pathways such as transforming growth factor-β (TGF-β) receptor activity. We also observe decreased intra-tumour methylation heterogeneity from diagnosis to relapsed tumour samples. Relapse-free patients display lower intra-tumour methylation heterogeneity at diagnosis compared with relapsed patients in an independent validation cohort. Furthermore, intra-tumour methylation heterogeneity is predictive of time to relapse. Therefore, we propose that epigenomic heterogeneity may support or drive the relapse phenotype and can be used to predict DLBCL relapse. PMID:25891015

  15. 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

    ClinicalTrials.gov

    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

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

    PubMed

    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.

  17. Targeting protein neddylation with an NEDD8-activating enzyme inhibitor MLN4924 induced apoptosis or senescence in human lymphoma cells

    PubMed Central

    Wang, Yanchun; Luo, Zhongguang; Pan, Yongfu; Wang, Weige; Zhou, Xiaoyan; Jeong, Lak Shin; Chu, Yiwei; Liu, Jie; Jia, Lijun

    2015-01-01

    Recent studies indicate that post-translational protein neddylation is required for the maintenance of cell viability in several lymphoma cell lines, while inhibition of the neddylation pathway with an NEDD8-activating enzyme (NAE) inhibitor MLN4924 induces apoptosis in lymphoma cells. However, the mechanism by which neddylation inhibition induces apoptosis in lymphoma cells has not been fully elucidated. Moreover, it is unknown whether neddylation inhibition triggers non-apoptotic cell-killing responses, such as cell senescence, in lymphoma cells. Here, we report that MLN4924 specifically inhibited protein neddylation, inactivated cullin-RING E3 ligase (CRL), the best-known neddylation substrate, and induced the accumulation of tumor-suppressive CRL substrates in lymphoma cells. Moreover, MLN4924 potently suppressed the growth of lymphoma cells by inducing G2 cell-cycle arrest, followed by apoptosis or senescence in a cell line-dependent manner. MLN4924-induced apoptosis was mediated by intrinsic apoptotic signaling with substantial up-regulation of pro-apoptotic Bik and Noxa as well as down-regulation of anti-apoptotic XIAP, c-IAP1 and c-IAP2, while senescence induction upon neddylation inhibition seemed dependent on the expression of tumor suppressor p21/p27. Together, these findings expand our understanding on how lymphoma cells respond to neddylation inhibition and support the development of neddylation inhibitors (e.g. MLN4924) for the treatment of lymphoma. PMID:25782162

  18. Proteomics Based Identification of Proteins with Deregulated Expression in B Cell Lymphomas.

    PubMed

    Wu, Rui; Nijland, Marcel; Rutgers, Bea; Veenstra, Rianne; Langendonk, Myra; van der Meeren, Lotte E; Kluin, Philip M; Li, Guanwu; Diepstra, Arjan; Chiu, Jen-Fu; van den Berg, Anke; Visser, Lydia

    2016-01-01

    Follicular lymphoma and diffuse large B cell lymphomas comprise the main entities of adult B cell malignancies. Although multiple disease driving gene aberrations have been identified by gene expression and genomic studies, only a few studies focused at the protein level. We applied 2 dimensional gel electrophoresis to compare seven GC B cell non Hodgkin lymphoma (NHL) cell lines with a lymphoblastoid cell line (LCL). An average of 130 spots were at least two folds different in intensity between NHL cell lines and the LCL. We selected approximately 38 protein spots per NHL cell line and linked them to 145 unique spots based on the location in the gel. 34 spots that were found altered in at least three NHL cell lines when compared to LCL, were submitted for LC-MS/MS. This resulted in 28 unique proteins, a substantial proportion of these proteins were involved in cell motility and cell metabolism. Loss of expression of B2M, and gain of expression of PRDX1 and PPIA was confirmed in the cell lines and primary lymphoma tissue. Moreover, inhibition of PPIA with cyclosporine A blocked cell growth of the cell lines, the effect size was associated with the PPIA expression levels. In conclusion, we identified multiple differentially expressed proteins by 2-D proteomics, and showed that some of these proteins might play a role in the pathogenesis of NHL. PMID:26752561

  19. CD7 Positive Diffuse Large B-Cell Lymphoma Arising in a Background of Follicular Lymphoma: A Case Report and Review of the Literature

    PubMed Central

    Rashidi, Hooman H.

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of large B-lymphocytes with a diffuse growth pattern. The neoplastic cells express B-cell markers such as CD20 and PAX-5 and there may be coexpression of BCL-2, BCL-6, CD10, and MUM-1. With the exception of CD5, other T-cell markers are not commonly expressed in this neoplasm. Here, we describe the first reported case of a DLBCL with abnormal expression CD7 arising in a background of follicular lymphoma in an 81-year-old male who presented with a nontender left axillary mass. Additionally, no other T-cell antigens were expressed in this B-cell lymphoma. Expression of CD7 in DLBCL is exceptionally rare and its prognostic significance is unknown. Here, we describe this rare case with review of literature of known DLBCLs with expression of T-cell antigens.

  20. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry.

    PubMed

    Ellin, Fredrik; Landström, Jenny; Jerkeman, Mats; Relander, Thomas

    2014-09-01

    Peripheral T-cell lymphomas (PTCLs) are rare lymphomas with mostly poor outcome with current treatment. The addition of etoposide to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and upfront consolidation with autologous stem cell transplantation (auto-SCT) have shown promising results but have never been tested in randomized trials. As a complement to retrospective analyses of clinical trials, we aimed at analyzing prognostic factors and outcome in an unselected, population-based cohort. Through the Swedish Lymphoma Registry, we identified 755 PTCL patients diagnosed during a 10-year period. In addition to International Prognostic Index factors, male gender was associated with an adverse overall survival (OS) (hazard ratio [HR], 1.28; P = .011) and progression-free survival (PFS) (HR, 1.26; P = .014). In an intention-to-treat analysis in 252 nodal PTCL and enteropathy-associated T-cell lymphoma patients (excluding anaplastic lymphoma kinase-positive anaplastic large cell lymphoma), upfront auto-SCT was associated with a superior OS (HR, 0.58; P = .004) and PFS (HR, 0.56; P = .002) compared with patients treated without auto-SCT. The addition of etoposide to CHOP resulted in superior PFS in patients ≤60 years (HR, 0.49; P = .008). This study is the largest population-based PTCL cohort reported so far and provides important information on outcome in PTCL outside the setting of clinical trials.

  1. Cutaneous Epitheliotropic T-Cell Lymphoma in a Marsh Rice Rat (Oryzomys palustris)

    PubMed Central

    Taylor, Bryan F; Bekkevold, Christine M; Aguirre, J Ignacio; Andrutis, Karl; Reinhard, Mary K

    2015-01-01

    Published reports of spontaneous neoplasia in marsh rice rats (Oryzomys palustris) are sparse. We report here a case of cutaneous epitheliotropic T-cell lymphoma in a 14-mo-old marsh rice rat that involved the ear pinnae, with dissemination to the liver and spleen. Histologically, the thickened ear pinnae showed diffuse infiltration of neoplastic lymphocytes into the epidermis, dermis, and adnexal skin structures, with Pautrier microaggregations present in the epidermis. In addition, neoplastic lymphocytes were observed infiltrating and disrupting the architecture of the liver and spleen. Neoplastic lymphocytes were strongly positive for the T-cell marker CD3 but were negative for the B-cell markers CD19 and CD20. These histologic and immunohistochemical features are consistent with an epitheliotropic T-cell lymphoma, as previously reported in other species, including humans. To our knowledge, this report represents the first published case of spontaneous cutaneous epitheliotropic T-cell lymphoma in a marsh rice rat. PMID:26473345

  2. Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma.

    PubMed

    Ritz, Olga; Guiter, Chrystelle; Castellano, Flavia; Dorsch, Karola; Melzner, Julia; Jais, Jean-Philippe; Dubois, Gwendoline; Gaulard, Philippe; Möller, Peter; Leroy, Karen

    2009-08-01

    Primary mediastinal B-cell lymphoma (PMBL) is a separate entity of aggressive B-cell lymphoma, characterized by a constitutive activation of janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, also observed in Hodgkin lymphoma. Although many cancers exhibit constitutive JAK-STAT pathway activation, mutations of STAT genes have not been reported in neoplasms. Here, we show that MedB-1 PMBL-derived and L1236 Hodgkin-derived cell lines and 20 of 55 (36%) PMBL cases harbor heterozygous missense mutations in STAT6 DNA binding domain, whereas no mutation was found in 25 diffuse large B-cell lymphoma samples. In 3 cases, somatic origin was indicated by the absence of the mutations in the nontumoral tissue. The pattern of STAT6 mutations was different from the classical features of somatic hypermutations. The mutant STAT6 proteins showed a decreased DNA binding ability in transfected HEK cells, but no decrease in expression of STAT6 canonical target genes was observed in PMBL cases with a mutated STAT6 gene. Although the oncogenic properties of STAT6 mutant proteins remain to be determined, their recurrent selection in PMBL strongly argues for their involvement in the pathogenesis of this aggressive B-cell lymphoma. PMID:19423726

  3. Interleukin-12 in Treating Patients With Previously Treated Non-Hodgkin's Lymphoma or Hodgkin's Disease

    ClinicalTrials.gov

    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

  4. Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice

    PubMed Central

    Vicente-Dueñas, Carolina; Fontán, Lorena; Gonzalez-Herrero, Ines; Romero-Camarero, Isabel; Segura, Victor; Aznar, M. Angela; Alonso-Escudero, Esther; Campos-Sanchez, Elena; Ruiz-Roca, Lucía; Barajas-Diego, Marcos; Sagardoy, Ainara; Martinez-Ferrandis, Jose I.; Abollo-Jimenez, Fernando; Bertolo, Cristina; Peñuelas, Ivan; Garcia-Criado, Francisco J.; García-Cenador, María B.; Tousseyn, Thomas; Agirre, Xabier; Prosper, Felipe; Garcia-Bragado, Federico; McPhail, Ellen D.; Lossos, Izidore S.; Du, Ming-Qing; Flores, Teresa; Hernandez-Rivas, Jesus M.; Gonzalez, Marcos; Salar, Antonio; Bellosillo, Beatriz; Conde, Eulogio; Siebert, Reiner; Sagaert, Xavier; Cobaleda, Cesar; Sanchez-Garcia, Isidro; Martinez-Climent, Jose A.

    2012-01-01

    Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1+Lin− hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas. PMID:22689981

  5. Oral candidiasis mimicking an oral squamous cell carcinoma: report of a case.

    PubMed

    Pontes, Hélder Antônio Rebelo; Paiva, Helena Borges; de Freitas Silva, Brunno Santos; Fonseca, Felipe Paiva; da Silva, Fernanda Bragança Monteiro; Pontes, Flávia Sirotheau Corrêa; Dos Santos Pinto, Décio

    2012-03-01

    Oral candidiasis is a significant problem in immune-compromised patients. The most common forms of mucosal candidiasis are oropharyngeal, oesophageal and vaginal, and more than 90% of HIV positive persons will manifest at least one episode of oropharyngeal candidiasis. Local and systemic factors such as uninterrupted daily use of a prosthesis by patients, smoking habit, as well as high glucose intake may contribute to the development of the lesion. The aim of this article is to report an uncommon case of oral candidiasis presenting an aggressive clinical behaviour in a 64-year-old male patient, with a significant smoking habit and a medical history of non-controlled diabetes. The lesion affected the hard and soft palate of the right side, revealing erythematous and ulcerated areas, elevated borders and central portions resembling necrosis, mimicking the clinical features of oral squamous cell carcinoma. However, the correct diagnosis of oral candidiasis was obtained after histopathological and cytological examinations and the patient was easily treated with traditional antifungal drugs and correction of his glucose levels.

  6. European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas.

    PubMed

    Senff, Nancy J; Noordijk, Evert M; Kim, Youn H; Bagot, Martine; Berti, Emilio; Cerroni, Lorenzo; Dummer, Reinhard; Duvic, Madeleine; Hoppe, Richard T; Pimpinelli, Nicola; Rosen, Steven T; Vermeer, Maarten H; Whittaker, Sean; Willemze, Rein

    2008-09-01

    Primary cutaneous B-cell lymphomas (CBCL) represent approximately 20% to 25% of all primary cutaneous lymphomas. With the advent of the World Health Organization-European Organization for Research and Treatment of Cancer (EORTC) Consensus Classification for Cutaneous Lymphomas in 2005, uniform terminology and classification for this rare group of neoplasms were introduced. However, staging procedures and treatment strategies still vary between different cutaneous lymphoma centers, which may be because consensus recommendations for the management of CBCL have never been published. Based on an extensive literature search and discussions within the EORTC Cutaneous Lymphoma Group and the International Society for Cutaneous Lymphomas, the present report aims to provide uniform recommendations for the management of the 3 main groups of CBCL. Because no systematic reviews or (randomized) controlled trials were available, these recommendations are mainly based on retrospective studies and small cohort studies. Despite these limitations, there was consensus among the members of the multidisciplinary expert panel that these recommendations reflect the state-of-the-art management as currently practiced in major cutaneous lymphoma centers. They may therefore contribute to uniform staging and treatment and form the basis for future clinical trials in patients with a CBCL.

  7. Detection of Enhancer-Associated Rearrangements Reveals Mechanisms of Oncogene Dysregulation in B-cell Lymphoma

    PubMed Central

    Ryan, Russell J.H.; Drier, Yotam; Whitton, Holly; Cotton, M. Joel; Kaur, Jasleen; Issner, Robbyn; Gillespie, Shawn; Epstein, Charles B.; Nardi, Valentina; Sohani, Aliyah R.; Hochberg, Ephraim P.; Bernstein, Bradley E.

    2015-01-01

    B-cell lymphomas frequently contain genomic rearrangements that lead to oncogene activation by heterologous distal regulatory elements. We utilized a novel approach, termed ‘Pinpointing Enhancer-Associated Rearrangements by Chromatin Immunoprecipitation’ or PEAR-ChIP, to simultaneously map enhancer activity and proximal rearrangements in lymphoma cell lines and patient biopsies. This method detects rearrangements involving known cancer genes, including CCND1, BCL2, MYC, PDCD1LG2, NOTCH1, CIITA, and SGK1, as well as novel enhancer duplication events of likely oncogenic significance. We identify lymphoma subtype-specific enhancers in the MYC locus that are silenced in lymphomas with MYC-activating rearrangements and are associated with germline polymorphisms that alter lymphoma risk. We show that BCL6-locus enhancers are acetylated by the BCL6-activating transcription factor MEF2B, and can undergo genomic duplication, or target the MYC promoter for activation in the context of a “pseudo-double-hit” t(3;8)(q27;q24) rearrangement linking the BCL6 and MYC loci. Our work provides novel insights regarding enhancer-driven oncogene activation in lymphoma. PMID:26229090

  8. High-resolution genomic profiling reveals clonal evolution and competition in gastrointestinal marginal zone B-cell lymphoma and its large cell variant.

    PubMed

    Flossbach, Lucia; Holzmann, Karlheinz; Mattfeldt, Torsten; Buck, Michaela; Lanz, Karin; Held, Michael; Möller, Peter; Barth, Thomas F E

    2013-02-01

    We studied marginal zone B-cell lymphomas of the gastrointestinal tract including seven small cell lymphomas, eight large cell areas of composite lymphomas and 13 large cell variants using SNP array profiling. We found an increase of genomic complexity with lymphoma progression from small to large cytology, and identified gains of prominent (proto) oncogenes such as REL, BCL11A, ETS1, PTPN1, PTEN and KRAS which were found exclusively in the large cell variants. Copy numbers of ADAM3A, SCAPER and SIRPB1 were varying between the three different modes of presentation, hence suggestive for aberrations associated with progression from small to large cell lymphoma. The number of aberrations was slightly higher in the large cell part of composite lymphomas than in large cell lymphomas, suggesting that clonal selection takes place and that composite lymphomas are in a transition state. To further investigate this, we comparatively analyzed samples of two morphologically different regions of the same small cell tumor with a BIRC3-MALT1 translocation, as well as material acquired at two different time points from one composite lymphoma. We found genomic heterogeneity in both cases, supporting the theory of competing subclones in the evolution and progression of extranodal marginal zone B-cell lymphoma.

  9. Burkitt lymphoma is molecularly distinct from other lymphomas

    Cancer.gov

    Scientists have uncovered a number of molecular signatures in Burkitt lymphoma, including unique genetic alterations that promote cell survival, that are not found in other lymphomas. These findings provide the first genetic evidence that Burkitt lymphoma

  10. Detailed Functional and Proteomic Characterization of Fludarabine Resistance in Mantle Cell Lymphoma Cells

    PubMed Central

    Lorkova, Lucie; Scigelova, Michaela; Arrey, Tabiwang Ndipanquang; Vit, Ondrej; Pospisilova, Jana; Doktorova, Eliska; Klanova, Magdalena; Alam, Mahmudul; Vockova, Petra; Maswabi, Bokang

    2015-01-01

    Mantle cell lymphoma (MCL) is a chronically relapsing aggressive type of B-cell non-Hodgkin lymphoma considered incurable by currently used treatment approaches. Fludarabine is a purine analog clinically still widely used in the therapy of relapsed MCL. Molecular mechanisms of fludarabine resistance have not, however, been studied in the setting of MCL so far. We therefore derived fludarabine-resistant MCL cells (Mino/FR) and performed their detailed functional and proteomic characterization compared to the original fludarabine sensitive cells (Mino). We demonstrated that Mino/FR were highly cross-resistant to other antinucleosides (cytarabine, cladribine, gemcitabine) and to an inhibitor of Bruton tyrosine kinase (BTK) ibrutinib. Sensitivity to other types of anti-lymphoma agents was altered only mildly (methotrexate, doxorubicin, bortezomib) or remained unaffacted (cisplatin, bendamustine). The detailed proteomic analysis of Mino/FR compared to Mino cells unveiled over 300 differentially expressed proteins. Mino/FR were characterized by the marked downregulation of deoxycytidine kinase (dCK) and BTK (thus explaining the observed crossresistance to antinucleosides and ibrutinib), but also by the upregulation of several enzymes of de novo nucleotide synthesis, as well as the up-regulation of the numerous proteins of DNA repair and replication. The significant upregulation of the key antiapoptotic protein Bcl-2 in Mino/FR cells was associated with the markedly increased sensitivity of the fludarabine-resistant MCL cells to Bcl-2-specific inhibitor ABT199 compared to fludarabine-sensitive cells. Our data thus demonstrate that a detailed molecular analysis of drug-resistant tumor cells can indeed open a way to personalized therapy of resistant malignancies. PMID:26285204

  11. Internalization of Red Blood Cell-Mimicking Hydrogel Capsules with pH-Triggered Shape Responses