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Sample records for angioimmunoblastic t-cell lymphoma

  1. Angioimmunoblastic T-Cell Lymphoma

    Science.gov (United States)

    Angioimmunoblastic T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Cancerous lymphocytes can travel to ...

  2. Angioimmunoblastic T Cell Lymphoma Mimicking Chronic Urticaria

    Directory of Open Access Journals (Sweden)

    Mohleen Kang

    2016-01-01

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

  3. Angioimmunoblastic T-Cell Lymphoma with Polyarthritis Resembling Rheumatoid Arthritis.

    Science.gov (United States)

    Yachoui, Ralph; Farooq, Nouman; Amos, Jonathan V; Shaw, Gene R

    2016-12-01

    Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma (PTCL). AITL typically presents with lymphadenopathy, fever, rash, hepatosplenomegaly, and rarely polyarthritis. We report the case of a 50-year-old female who presented with lymphadenopathy, rash, and symmetric polyarthritis. She was later diagnosed with AITL and was treated with chemotherapy with resolution of arthritis. AITL should be suspected in paitents presenting with rheumatoid-like arthritis and diffuse lymphadenopathy.

  4. Angioimmunoblastic T-Cell Lymphoma: A Diagnostic Challenge

    Science.gov (United States)

    Ocampo-Garza, Jorge; Herz-Ruelas, Maira Elizabeth; González-Lopez, Elias Eugenio; Mendoza-Oviedo, Eric Eduardo; Garza-Chapa, Juana Irma; Ocampo-Garza, Sonia Sofía; Vázquez-Herrera, Norma Elizabeth; Miranda-Maldonado, Ivett; Ocampo-Candiani, Jorge

    2014-01-01

    Angioimmunoblastic T-cell lymphoma (AITL) accounts for 15–20% of all peripheral T-cell lymphomas. It is a rare subtype of CD4 T-cell peripheral lymphoma that affects aged individuals, causing B symptoms, generalized lymphadenopathy and hepatosplenomegaly. Its pathogenesis is still unclear, but in some cases it has been associated with infection, allergic reaction or drug exposure. The majority of patients are diagnosed in an advanced stage and anthracycline based regimen is considered the first-line therapy. Skin involvement is not well characterized, occurring in up to 50% of patients and presenting as nonspecific rash, macules, papules, petechiae, purpura, nodules and urticaria. We present the illustrative case of a 55-year-old woman with an AITL who presented prominent skin findings, arthritis, lymphadenopathy and hypereosinophilia. Skin biopsy reported a T-cell lymphoma and the diagnosis of AITL was confirmed by an axillary lymph node biopsy, which was also positive for Epstein-Barr virus. Chemotherapy with CHOP-21 and thalidomide was given, accomplishing complete remission after six cycles. PMID:25685133

  5. Angioimmunoblastic T-Cell Lymphoma in a Patient with Klinefelter Syndrome.

    Science.gov (United States)

    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

    2016-07-25

    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.

  6. Systemic lupus erythematosus as the concomitant manifestation of angioimmunoblastic T-cell lymphoma.

    Science.gov (United States)

    Suzuki, Akitake; Shoji, Norikazu; Aoki, Naoko; Asazuma, Naoki; Machinami, Rikuo; Kojima, Masaru; Okai, Takahiro

    2017-03-01

    Herein we report a case of the simultaneous occurrence of angioimmunoblastic T-cell lymphoma (AITL) and systemic lupus erythematosus (SLE) in a 76-year-old woman. She presented with fever, night sweats, and general malaise. A laboratory examination revealed leukopenia, anemia, polyclonal hypergammaglobulinemia, hypocomplementemia, positive results for anti-nuclear antibodies and anti-double strand DNA (anti-dsDNA) antibodies, and mild proteinuria. A computed tomography scan of the abdominal cavity showed multiple swollen intra-abdominal and intra-pelvic lymph nodes. A biopsy specimen obtained from the peri-iliac lymph node confirmed the diagnosis of AITL, while renal biopsy results were consistent with lupus nephritis, International Society of Nephrology and Renal Pathology Society class V. These results indicated that our patient developed SLE concomitantly with AITL. These findings will lead to further understanding of the pathogenic mechanism of SLE.

  7. Therapy refractory angioimmunoblastic T-cell lymphoma in complete remission with lenalidomide.

    NARCIS (Netherlands)

    Beckers, M.M.; Huls, G.A.

    2013-01-01

    The prognosis of therapy refractory angioimmunoblastic lymphoma (AITL) is very poor. In this report we describe a patient with AITL refractory to 2 lines of chemotherapy. He was treated with lenalidomide 15 mg continuously and prednisone. After 2 yr follow-up, the patient has no detectable disease.

  8. Therapy refractory angioimmunoblastic T-cell lymphoma in complete remission with lenalidomide

    NARCIS (Netherlands)

    Beckers, Marielle M.; Huls, Gerwin

    2013-01-01

    The prognosis of therapy refractory angioimmunoblastic lymphoma (AITL) is very poor. In this report we describe a patient with AITL refractory to 2 lines of chemotherapy. He was treated with lenalidomide 15 mg continuously and prednisone. After 2 yr follow-up, the patient has no detectable disease.

  9. Renal infarction due to polyarteritis nodosa in a patient with angioimmunoblastic T-cell lymphoma: a case report and a brief review of the literature

    Directory of Open Access Journals (Sweden)

    Ambrosio Maria

    2012-05-01

    Full Text Available Abstract Angioimmunoblastic T-cell lymphoma is one of the most common subtypes of peripheral T-cell lymphoma (15-20% of all cases, accounting for approximately 1-2% of all non-Hodgkin lymphomas. It often presents autoimmune phenomena including hemolytic anemia, thrombocytopenia, glomerulonephrities and circulating immune complexes. Polyarteritis nodosa is an autoimmune disease characterized by necrotizing vasculitis of medium vessels, which rarely develops in association with hematological malignant disorders. Herein we report the case of a 40-year-old man who underwent lymph node biopsy in the suspicious of sarcoidosis. On the basis of histological and immunohistochemical findings, the diagnosis of angioimmunoblastic T-cell lymphoma was performed. The patient was successfully treated with cytarabine-based regimen for 6 cycles. Three months after the initial diagnosis of angioimmunoblastic T-cell lymphoma, a whole body computed tomography showed a lesion in the lower pole of the left kidney. Renal cell carcinoma was suspected, thus a nephrectomy was carried out. The histological findings were compatible with polyarteritis nodosa. To the best of our knowledge, the association between polyarteritis nodosa and angioimmunoblastic T-cell lymphoma has been described only once. This relation may be secondary to the induction of an autoimmune phenomenon by the lymphoma with the formation of circulating immune complexes, leading to vessels walls injury. A careful evaluation is needed in the management of angioimmunoblastic T-cell lymphoma patients with signs of renal failure in order to avoid delay of treatment and organ damage.

  10. Renal infarction due to polyarteritis nodosa in a patient with angioimmunoblastic T-cell lymphoma: a case report and a brief review of the literature.

    Science.gov (United States)

    Ambrosio, Maria Raffaella; Rocca, Bruno Jim; Ginori, Alessandro; Onorati, Monica; Fabbri, Alberto; Carmellini, Mario; Lazzi, Stefano; Tripodi, Sergio

    2012-05-08

    Angioimmunoblastic T-cell lymphoma is one of the most common subtypes of peripheral T-cell lymphoma (15-20% of all cases), accounting for approximately 1-2% of all non-Hodgkin lymphomas. It often presents autoimmune phenomena including hemolytic anemia, thrombocytopenia, glomerulonephrities and circulating immune complexes. Polyarteritis nodosa is an autoimmune disease characterized by necrotizing vasculitis of medium vessels, which rarely develops in association with hematological malignant disorders. Herein we report the case of a 40-year-old man who underwent lymph node biopsy in the suspicious of sarcoidosis. On the basis of histological and immunohistochemical findings, the diagnosis of angioimmunoblastic T-cell lymphoma was performed. The patient was successfully treated with cytarabine-based regimen for 6 cycles. Three months after the initial diagnosis of angioimmunoblastic T-cell lymphoma, a whole body computed tomography showed a lesion in the lower pole of the left kidney. Renal cell carcinoma was suspected, thus a nephrectomy was carried out. The histological findings were compatible with polyarteritis nodosa. To the best of our knowledge, the association between polyarteritis nodosa and angioimmunoblastic T-cell lymphoma has been described only once. This relation may be secondary to the induction of an autoimmune phenomenon by the lymphoma with the formation of circulating immune complexes, leading to vessels walls injury. A careful evaluation is needed in the management of angioimmunoblastic T-cell lymphoma patients with signs of renal failure in order to avoid delay of treatment and organ damage.

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

    Science.gov (United States)

    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.

  12. Aberrant immunoarchitecture distinguishes hyperplastic germinal centres in pattern 1 angioimmunoblastic T-cell lymphoma from reactive follicles.

    Science.gov (United States)

    Tan, Leonard Hwan-Cheong; Tan, Soo-Yong

    2014-09-01

    We compare 30 biopsies each of Pattern 1 angioimmunoblastic T-cell lymphoma (AITL1) and reactive lymphoid hyperplasia (RLH) by immunohistology, in-situ hybridization for Epstein-Barr virus-encoded RNA and T-cell receptor-γ (TRG)-clonality. AITL1 cases, more often than RLH controls, were older [median ages 61 (range 23-79) vs 46 (range 11-59) years, p germinal centres (GCs) more often showed attenuation of CD10 [30/30 (100%) vs 11/29 (38%), p = 5.3 × 10(-8)] and CD57 [18/25 (72%) vs 4/22 (18%), p = 2.4 × 10(-4)] (respectively). GC-predominant PD-1 and ICOS immunoreactivity were more often seen in RLH [20/22 and 9/19 controls (91% and 47%)] than AITL1 [9/25 and 3/19 cases (36% and 16%), p = 1.0 × 10(-4) and 0.033, respectively]. Significant independent predictors against AITL1 were: solid GC CD10 immunoreactivity {p = 0.023, odds ratio (OR) for AITL1 0.01 [95% confidence interval (CI): 0.0002-0.529]}; lower interfollicular proliferation fraction [p = 0.047, OR for AITL1 1.1 (95% CI: 1.001-1.209) per % rise in Ki-67]; younger presenting age [p = 0.028, OR for AITL1 1.136 (95% CI: 1.014-1.272) per year older]. Hence, GCs and perifollicular zones in AITL1 are distinct from those in RLH.

  13. The IDH2 R172K mutation associated with angioimmunoblastic T-cell lymphoma produces 2HG in T cells and impacts lymphoid development

    Science.gov (United States)

    Lemonnier, François; Cairns, Rob A.; Inoue, Satoshi; Li, Wanda Y.; Dupuy, Aurélie; Broutin, Sophie; Martin, Nadine; Fataccioli, Virginie; Pelletier, Romain; Wakeham, Andrew; Snow, Bryan E.; de Leval, Laurence; Pujals, Anais; Haioun, Corinne; Paci, Angelo; Tobin, Erica R.; Narayanaswamy, Rohini; Yen, Katherine; Jin, Shengfang; Gaulard, Philippe; Mak, Tak W.

    2016-01-01

    Oncogenic isocitrate dehydrogenase (IDH)1 and IDH2 mutations at three hotspot arginine residues cause an enzymatic gain of function that leads to the production and accumulation of the metabolite 2-hydroxyglutarate (2HG), which contributes to the development of a number of malignancies. In the hematopoietic system, mutations in IDH1 at arginine (R) 132 and in IDH2 at R140 and R172 are commonly observed in acute myeloid leukemia, and elevated 2HG is observed in cells and serum. However, in angioimmunoblastic T-cell lymphoma (AITL), mutations are almost exclusively restricted to IDH2 R172, and levels of 2HG have not been comprehensively measured. In this study, we investigate the expression pattern of mutant IDH2 in the AITL tumor microenvironment and measure levels of 2HG in tissue and serum of AITL patients. We find that mutant IDH2 expression is restricted to the malignant T-cell component of AITL, and that 2HG is elevated in tumor tissue and serum of patients. We also investigate the differences between the three hotspot mutation sites in IDH1 and IDH2 using conditional knock-in mouse models. These studies show that in the lymphoid system, mutations in IDH2 at R172 produce high levels of 2HG compared with mutations at the other two sites and that lymphoid development is impaired in these animals. These data provide evidence that IDH2 R172 mutations may be the only variants present in AITL because of their capacity to produce significant amounts of the oncometabolite 2HG in the cell of origin of this disease. PMID:27956631

  14. Cyclosporine,prednisone,and high-dose immunoglobulin treatment of angioimmunoblastic T-cell lymphoma refractory to prior CHOP or CHOP-like regimen

    Institute of Scientific and Technical Information of China (English)

    Xing-Gui Chen; He Huang; Ying Tian; Cheng-Cheng Guo; Chao-Yong Liang; Yao-Ling Gong; Ben-Yan Zou; Rui-Qing Cai; Tong-Yu Lin

    2011-01-01

    Angioimmunoblastic T-cell lymphoma(AITL) is a rare,distinct subtype of peripheral T-cell lymphoma,possessing an aggressive course and poor prognosis with no standard therapy.Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine(CsA),prednisone(PDN),and monthly,high-dose intravenous immunoglobulin (HI?IVIG).The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function.All patients were examined for response,toxicity and survival.The most significant toxicities insomnia(16.7%).Discontinuation of treatment occurred in one patient(8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection.Treatment-related death was not observed.The overall response rate was 75.0%(complete response,33.3%; partial response,41.7%).With a median follow-up of 25.5 months,the median duration of response was 20 months (range,12 to 49 months) and the median progression-free survival(PFS) was 25.5 months(range,10 to 56 months).The 2-year PFS rate was 81.5%.Our findings indicate the combination of CsA,PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.

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

    Science.gov (United States)

    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

  16. 血管免疫母细胞性T细胞淋巴瘤治疗进展%Advances of treatment for angioimmunoblastic T-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    周志远; 张明智

    2013-01-01

    Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma (PTCL) with aggressive behaviour and poor prognosis.Due to the rarity of the disease,few prospective controlled randomized clinical trials were conducted,and the standard therapeutic option for AITL has not been established.Although conventional anthracycline-based chemotherapy achieves response rates of up to 50 %,most of the patients relapse,the median survival time and overall survival rate are unsatisfactory.Recent studies have demonstrated that hematopietic stem cell transplantation and cyclosporine show promising efficacy in the treatment of AITL.This current review mainly focused on the advance of treatment for AITL.%血管免疫母细胞性T细胞淋巴瘤(AITL)是一种罕见的侵袭性外周T细胞淋巴瘤,预后较差.AITL发病率较低,缺乏大样本的前瞻性临床随机对照试验,标准的治疗方案尚未明确.尽管以传统蒽环类药物为基础的化疗方案缓解率达50%,但大多数患者短期内复发,中位生存时间和总体生存率均不理想.最新研究发现造血干细胞移植、环孢素等治疗AITL显示出较好的临床疗效,义章介绍AITL的治疗进展.

  17. No survival improvement for patients with angioimmunoblastic T-cell lymphoma over the past two decades: a population-based study of 1207 cases.

    Directory of Open Access Journals (Sweden)

    Bei Xu

    Full Text Available Angioimmunoblastic T-cell lymphoma (AITL is a rare lymphoid malignancy with dismal prognosis. We conducted a large population-based study using the Surveillance, Epidemiology, and End Results (SEER database (1973-2010 to determine the temporal survival trends and prognostic factors of AITL patients. A total of 1207 patients with AITL were included in this study, with a median age at diagnosis of 69 years. At presentation, most patients (79.5% had an advanced-stage disease. Overall survival (OS probabilities at 2, 5 and 10 years were 46.8%, 32.9%, and 21.9% respectively. Two-year, 5-year, and 10-year disease-specific survival (DSS rates were 56.1%, 44.0%, and 35.9% respectively.On multivariate analysis, age older than 70 years, advanced-stage disease and male sex were identified adverse predictors for OS and DSS. We failed to find any survival differences among subgroups diagnosed in the 5 periods studied (1992 to 1998, 1999 to 2001, 2002 to 2004, 2005 to 2007, and 2008 to 2010. The current study represents the largest specific series of patients with AITL and the first investigation on temporal changes in survival of AITL patients. There has been no survival improvement for AITL patients over the past two decades. Further investigations are warranted to develop more effective treatment for AITL.

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

    Science.gov (United States)

    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

  19. T-Cell Lymphoma

    Science.gov (United States)

    Getting the Facts T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). T-cell lymphomas account for ...

  20. 506U78 in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or T-cell Lymphoma

    Science.gov (United States)

    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 T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  1. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    Getting the Facts Peripheral T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma and ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Peripheral T-cell lymphoma (PTCL) ...

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

    Science.gov (United States)

    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

  3. 48例血管免疫母性T细胞淋巴瘤治疗及预后因素分析%Treatment response and prognosis factors in 48 patients with angioimmunoblastic T cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    李佳; 刘卓刚

    2016-01-01

    Objective To explore the influencing factors of therapeutic effect and prognosis in patients with angioimmunoblastic T cell lymphoma (AITL). Methods The clinical data of 48 patients with AITL were collected in order to evaluate its therapeutic effect and the influencing factors of prognosis. Results In the 48 patients with AITL, complete remission (CR) was in 15 cases, partial remission (PR) was in 16 cases, and the total effective rate was 64.58%(31/48). The recent total effective rate in patients of international prognostic index (IPI) score ≤2 scores was significantly higher than that in patients of IPI score >2 scores: 84.00% (21/25) vs. 43.48% (10/23), and there was statistical difference (P2 scores, Ki-67 ≥ 50% and using CHOP regimen: 8/13 vs. 25.71%(9/35), 52.00% (13/25) vs. 17.39% (4/23), 55.00% (11/20) vs. 21.43% (6/28) and 48.28% (14/29) vs. 3/19, and there were statistical differences (P<0.05). Conclusions AITL is a kind of disease with poor prognosis. IPI score is the important influencing factor of recent therapeutic effect. The Ann Arbor stage, IPI score, Ki-67 levels and using contained ASP chemotherapy are the important factors of prognosis in patients with AITL.%目的:探讨影响血管免疫母性T细胞淋巴瘤(AITL)疗效和预后的因素。方法收集48例AITL患者的临床资料,评价其疗效,探讨影响其预后的因素。结果48例AITL患者,完全缓解(CR)15例,部分缓解(PR)16例,总有效率为64.58%(31/48)。国际预后指数(IPI)评分≤2分患者的近期总有效率明显优于IPI评分>2分患者[84.00%(21/25)比43.48%(10/23)],差异有统计学意义(P<0.05)。1、2、3年总生存率分别为75.00%(36/48)、52.08%(25/48)及35.42%(17/48),中位生存时间24.5个月。Ann Arbor分期Ⅰ~Ⅱ期、IPI评分≤2分、Ki-67<50%及应用CHOP联合门冬酰胺酶方案化疗患者较Ann Arbor分期Ⅲ~Ⅳ期、IPI评分>2分、Ki-67≥50%

  4. Chidamide in the treatment of peripheral T-cell lymphoma

    Science.gov (United States)

    Chan, Thomas S; Tse, Eric; Kwong, Yok-Lam

    2017-01-01

    Mature T-cell lymphomas are aggressive malignancies. Treatment outcome is poor with conventional chemotherapy. They are about twice as common in Asia as compared with other non-Asian countries. Histone proteins form the basic structure of chromatin, and their acetylation at lysine residues relaxes chromatin structure, facilitating gene transcription. Conversely, histone deacetylation, catalyzed by histone deacetylases, compacts chromatin and represses gene transcription. Histone deacetylase inhibitors are an important class of antineoplastic agents. Chidamide is a novel orally active benzamide-type histone deacetylase inhibitor that has shown in vitro activities against a wide array of neoplasms. In Phase I trials, chidamide showed preferential efficacy in mature T-cell lymphomas. In a pivotal Phase II trial of chidamide in 79 patients with relapsed or refractory mature T-cell lymphomas, an overall response rate of 28% (complete remission/complete remission unconfirmed: 14%) was achieved, with most responses occurring within the first 6 weeks of treatment. The median duration of response (DOR) was 9.9 (1.1–40.8) months. Of 22 responders, 19 patients (86%) had a DOR of ≥3 months and eight patients (36%) had a DOR of >12 months. Angioimmunoblastic T-cell lymphoma and anaplastic large cell lymphoma (anaplastic lymphoma kinase-negative) showed better response rates, with the most durable responses observed in angioimmunoblastic T-cell lymphoma patients. Safety profile was favorable, with very few cases of grade 3/4 toxicities observed. Chidamide is approved by the China Food and Drug Administration for the treatment of relapsed and refractory peripheral T-cell lymphomas. PMID:28138258

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

    Science.gov (United States)

    2016-07-12

    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

  6. Perspective research of preliminarily diagnosed angioimmunoblastic T-cell lymphoma with dose-adjusted EPOCH regimen%剂量调整的EPOCH方案治疗初治血管免疫母T细胞淋巴瘤的前瞻性研究

    Institute of Scientific and Technical Information of China (English)

    仲凯励; 苏航; 肖秀斌; 刘静; 鲁云; 陈喜林; 达永; 路春蕾; 张伟京

    2014-01-01

    Objective:The effect and side effect of the dose-adjusted EPOCH regimen were evaluated perspectively for the pre-liminarily diagnosed angioimmunoblastic T-cell lymphoma. Methods: Nine cases of untreated angioimmunoblastic T-cell lymphoma were diagnosed and enrolled in our department from September 2008 to September 2012. All patients received dose-adjusted EPOCH regimen as first-line chemotherapy. Results: The median age of 9 patients was 54 years. The male-to-female ratio was 2∶1. About 88.9%of all patients were at Ann Arbor stageⅢ/Ⅳ, and 77.8%presented with B symptoms. Anemia was found in 66.7%of 9 patients, and lactate dehydrogenase elevated in 55.6%of patients. After an average of 4.7 cycles of chemotherapy of dose-adjusted EPOCH regi-men, the complete remission rate was 22.2%, and the total response rate was 66.7%. With a median follow-up of 20 months, the 4-year progression-free survival rate was 11.1%, and the overall survival rate was 33.3%. The median survival time was 19 months. The most common adverse events of EPOCH chemotherapy were hematologic toxicity. Grades 3-4 neutropenia and thrombocytopenia were re-ported in 77.8%and 33.3%of patients. Febrile neutropenia was observed in 44.4%of patients. Non-treatment-related mortality was al-so noted. Conclusion: The results of our research showed no clear benefit of treating preliminarily diagnosed angioimmunoblastic T-cell lymphoma with dose-adjusted EPOCH regimen. The main adverse events were hematologic toxicity and could be tolerated.%目的:前瞻性研究剂量调整的EPOCH方案对初治血管免疫母T细胞淋巴瘤(AITL)患者的疗效及不良反应。方法:选择2008年9月至2012年9月中国军事医学科学院附属307医院确诊的初治AITL患者9例。全组患者均接受剂量调整的EPOCH方案一线化疗。结果:全组患者发病中位年龄54岁,男∶女为2∶1,88.9%为Ann-Arbor stageⅢ~Ⅳ期,77.8%合并B症状。初诊时伴有贫血的患者占66.7%

  7. 血管免疫母细胞性T细胞淋巴瘤伴霍奇金样细胞的临床病理分析%Clinicopathologic analysis of angioimmunoblastic T-cell lymphoma with Hodgkin/Reed-Sternberg-like cells

    Institute of Scientific and Technical Information of China (English)

    高雪; 黄文勇; 李文生; 谢建兰; 郑媛媛; 周小鸽

    2015-01-01

    Objective To study the clinicopathologic features and pathologic diagnosis and differential diagnosis of angioimmunoblastic T-cell lymphoma with HRS-like cells.Methods Six cases of angioimmunoblastic T-cell lymphoma with HRS-like cells were examined histologically and immunohistochemically ( EliVision method ) and in-situ hybridization for Epstein-Barr virus-encoded RNA (EBER), and the literature was reviewed.Results The cytologic and microscopic features of these imprints and lymph node samples showed a heterogeneous population of hematolymphoid cells , including small to intermediate lymphoid cells, immunoblasts, plasma cells, dendritic cells, and eosinophils, as well as small vessels that were surrounded by some of the abnormal cells.The neoplastic T-cells expressed CD3 and CD5 and partly positive for CD10 and bcl-6, CD21 showed expanded and irregular follicular dendritic cell ( FDC) meshworks that surrounding the high HEV.The HRS-like cells were positive for MUM-1 and Ki-67, variable intensity positive for CD30, CD20, and PAX-5, but negative for CD15.EBV-positive cells included HRS-like cells and small to large-sized neoplastic T-cells, which formed small clusters or scattering in the background of the disease.Conclusions The clinical course of angioimmunoblastic T-cell lymphoma with HRS-like cells is aggressive.Which present with histomorphology overlap with classical Hodgkin lymphoma ( CHL) , similar to CHL in EBER and immunophenotype , however, it is easy to misdiagnosis as HL.Thus, angioimmunoblastic T-cell lymphoma pathology diagnosis should comprehensive analysis of different kinds of materials , including clinical features , and histological structure , and EBER , and immunophenotype , and gene rearrangement .%目的:探讨血管免疫母细胞性T细胞淋巴瘤伴霍奇金样细胞的临床表现、病理诊断与鉴别诊断。方法对6例血管免疫母细胞性T细胞淋巴瘤伴霍奇金样细胞进行形态学观察

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

    Science.gov (United States)

    2016-12-04

    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

  9. 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.

    Science.gov (United States)

    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

  10. Cutaneous natural killer/T-cell lymphoma.

    Science.gov (United States)

    Radonich, Michael A; Lazova, Rossitza; Bolognia, Jean

    2002-03-01

    Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2 subtypes of non-Hodgkin's lymphoma that can present primarily in the skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both of which tend to be low-grade malignant neoplasms. Recently another distinct subtype of lymphoma was discovered, the natural killer (NK)/T-cell lymphoma, which can involve the skin in a primary or secondary fashion. The NK/T-cell subtype of lymphoma is characterized by the expression of the NK-cell antigen CD56. These CD56(+) lymphomas are further subdivided into nasal NK/T-cell lymphomas that commonly present as midfacial destructive disease and non-nasal NK/T-cell lymphomas that often arise in extranodal locations, including the skin. We report a case of aggressive NK-cell leukemia/lymphoma with numerous secondary cutaneous lesions and review the clinical and histopathologic spectrum of non-nasal CD56(+) lymphomas, with an emphasis on the dermatologic findings.

  11. Peripheral T-cell lymphoma: Frequency and distribution in a tertiary referral center in South India

    Directory of Open Access Journals (Sweden)

    Deepak K Burad

    2012-01-01

    Full Text Available Background and Aim: Peripheral T/NK-cell lymphomas are uncommon types of non-Hodgkin′s lymphoma (NHL with a higher frequency in Far East countries as compared to the West. This study was undertaken to ascertain the frequency and distribution pattern of peripheral T-cell lymphomas (PTCLs diagnosed in a tertiary care center in South India. Materials and Methods: This retrospective study was carried out in Department of General Pathology, Christian Medical College, Vellore. The time period was for 2 years from 1 st January 2008 till 31st December 2009. All PTCLs were reviewed and classified according to the World Health Organization (WHO 2008 classification. Results: Of a total of 1032 cases of NHL, 180 cases were PTCL, which accounted for 17.4% cases of all the NHLs. Of these, PTCL, not otherwise specified (PTCL, NOS was the most common subtype (48 cases, 26.1%, followed by anaplastic large cell lymphoma (41 cases, 22.8%, mycosis fungoides (21 cases, 11.7%, angioimmunoblastic T-cell lymphoma (16 cases, 8.9%, subcutaneous panniculitis like T-cell lymphoma (15 cases, 8.4%, extranodal NK/T-cell lymphoma, nasal type (12 cases, 6.7%, and hepatosplenic T-cell lymphoma (10 cases, 5.6%. The most common primary site of presentation was nodal accounting for 42% followed by cutaneous (34%, upper aerodigestive sites (8.9%, spleen (6.7%, and gastrointestinal tract (GIT; 3.3%. Conclusions: This is the largest single study on PTCLs in India and we document that its frequency is higher than that reported in Western literature and previous Indian studies and almost similar to that reported in some Far East studies. The frequency of mycosis fungoides, subcutaneous panniculitis like T-cell lymphoma, and hepatosplenic T-cell lymphoma was higher than that reported in the World literature and previous Indian studies. The frequency of extranodal NK/T-cell lymphoma and angioimmunoblastic T-cell lymphoma was much lower than that reported in the Far East literature.

  12. Angioimmunoblastic T-cell lymphoma:pathological features of tumor cells and the microenvironment%血管免疫母细胞性T细胞淋巴瘤肿瘤细胞及其微环境病理学特征

    Institute of Scientific and Technical Information of China (English)

    吴丽莉; 王黎; 许海敏; 李芹芹; 刘强

    2013-01-01

    Objective:To study the pathological features of tumor cells and the microenvironment in angioimmunoblastic T-cell lymphoma (AITL).Methods:Twenty cases of AITL and 20 cases of non-specific peripheral Tcell lymphoma (PTCL-NOS) were enrolled in this study.Twenty cases of lymph node reactive proliferation were served as control.Morphological observation and immunohistochemistry assay were performed for analyzing the morphological features,expressions of follicular helper T cell (TFH) related antigens,and the blood vessels,follicular dendrite cells (FDC),macrophages,B immunoblastic cells,eosinophils,and basophils proliferation in microenvironment.In situ hybridization was adopted to detect EB virus.Results:① Tumor cells with round or oval nucleus were presented in 19 cases (95%) of AITL and 6 cases (30%) of PTCL-NOS.Tumor cells with distort or collapsed nucleus were observed in 1 case (5%) of AITL and 14 cases (70%) of PTCL-NOS.Clear cells were found in 16 cases (80%) of AITL and were not seen in PTCLNOS.In a total of 20 cases of AITL,CD10,Bcl-6,CXCL13 and PD-1 expressions were found in 11 cases (55%),16 cases (80%),17 cases (85%) and 20 cases (100%),respectively.All cases expressed at least 2 TFH cell markers and 90% cases co-expressed at least 3 TFH cell markers.In 20 cases of PTCL-NOS,CD10,Bcl-6,CXCL13 and PD-1 expressions were positive in 0,2 cases (10%),2 cases (10%) and 4 cases (100%),respectively.Expression of TFH markers in AITL group was significantly higher than in PTCL-NOS group(P<0.01).② Analysis of microenvironment elements showed that irregular FDC network (19/20 cases of AITL and 1/20 cases of PTCL-NOS),vascular endothelial swelling (20/20 cases of AITL and 4/20 cases of PTCL-NOS),prominent infiltration of eosinophils (15/20 cases of AITL and 5/20 cases of PTCL-NOS),and Epstein-Barr virus infection (10/20 cases of AITL and 4/20 cases of PTCL-NOS) were different between AITL and PTCLNOS groups (P<0.05).The mean vascular

  13. Enteropathy Associated T Cell Lymphoma – A Case Report of An Uncommon Extranodal T Cell Lymphoma

    Science.gov (United States)

    V, Geetha; Kudva, Ranjini

    2014-01-01

    Enteropathy associated T cell lymphoma is a rare primary intestinal lymphoma. It is often, but not always associated with celiac disease. Intraepithelial T cells are postulated as the cell of origin. It is a rare disease accounting for fewer than 5% of all gastrointestinal tract lymphomas. Recent studies indicate that EATL consists of two diseases that are morphologically and genetically distinct and differ with respect to their frequency of association with celiac disease. Current WHO classification recognises two subtypes of EATL – type 1 (classic) and type 2, based on morphology and immunophenotype. EATL type 1 is a large cell lymphoma which is more common and is more commonly associated with celiac disease compared to type 2. Most common site of involvement is the small intestine. We report a case of EATL type 1, in a 62-year-old female patient who presented with features of intestinal obstruction. However, she did not have spruce like featutes. PMID:25478355

  14. Clinicopathologic features of intestinal natural killer/T-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    周军

    2013-01-01

    Objective To study the clinicopathologic features,diagnosis and differential diagnosis of intestinal natural killer(NK)/T-cell lymphoma.Methods The clinical features,histopathology,immunohistochemical

  15. Central nervous system involvement in T-cell lymphoma: A single center experience.

    Science.gov (United States)

    Gurion, Ronit; Mehta, Neha; Migliacci, Jocelyn C; Zelenetz, Andrew; Moskowitz, Alison; Lunning, Matthew; Moskowitz, Craig; Hamlin, Paul; Horwitz, Steven

    2016-05-01

    Background We characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T-cell lymphoma (PTCL). Methods Retrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994-2011 with a minimum six months of follow-up or an event defined as relapse or death. Results Histologies included peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B-cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16-103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III-IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10-75). Conclusions Despite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥3.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Shet Tanuja

    2010-07-01

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

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

    DEFF Research Database (Denmark)

    Lauenborg, Britt; Christensen, Louise; Ralfkiaer, Ulrik

    2015-01-01

    Lymphotoxin α (LTα) plays a key role in the formation of lymphatic vasculature and secondary lymphoid structures. Cutaneous T cell lymphoma (CTCL) is the most common primary lymphoma of the skin and in advanced stages, malignant T cells spreads through the lymphatic to regional lymph nodes...

  19. Adult T-Cell Leukemia-Lymphoma during Pregnancy

    OpenAIRE

    2013-01-01

    Adult T-cell leukemia-lymphoma (ATL) is an uncommon highly aggressive T-cell lymphoma associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. It is rarely encountered during pregnancy and is particularly challenging to treat due to its aggressive nature and because of the lack of robust data on optimal chemotherapy. We report a case of a Jamaican immigrant diagnosed with ATL during pregnancy.

  20. Adult T-Cell Leukemia-Lymphoma during Pregnancy

    Directory of Open Access Journals (Sweden)

    Martin Miguel Amor

    2013-01-01

    Full Text Available Adult T-cell leukemia-lymphoma (ATL is an uncommon highly aggressive T-cell lymphoma associated with human T-cell lymphotropic virus type 1 (HTLV-1 infection. It is rarely encountered during pregnancy and is particularly challenging to treat due to its aggressive nature and because of the lack of robust data on optimal chemotherapy. We report a case of a Jamaican immigrant diagnosed with ATL during pregnancy.

  1. T-Cell Lymphomas Presenting as Colon Ulcers and Eosinophilia

    Directory of Open Access Journals (Sweden)

    Ping-Hsiu Wu

    2015-07-01

    Full Text Available Primary gastrointestinal T-cell lymphoma is an uncommon entity and primary colon T-cell lymphoma is even rarer. The majority of enteropathy-associated T-cell lymphomas present predominantly as ulcers or strictures in the endoscopic examinations, while primary B-cell lymphomas commonly present as exophytic lesions. Ulcerative colon T-cell lymphoma may mimic Crohn's disease (CD, which is a chronic inflammatory disease of the intestines with ulcer and fistula formations difficult for clinicians to diagnose based on endoscopic observations alone. Like CD, T-cell lymphoma may be characterized by the presence of multiple skipped ulcers distributed from the terminal ileum to the descending colon. Furthermore, it is difficult to diagnose this unusual lymphoma by a single endoscopic biopsy. Typically, the histological composition of T-cell lymphoma is made of medium to large atypical cells located in the base of the ulcer with extension to the muscle layer and the adjacent mucosa. However, it is common that biopsy specimens show only mixed inflammatory changes where the lymphoma cells are hard to be identified. The differential diagnosis of malignant lymphoma must be considered when clinically diagnosed CD is refractory to the medical treatment or when its clinical behavior becomes aggressive. The current study presents a rare case of primary colon T-cell lymphoma in a 56-year-old male with marked recent weight loss, watery diarrhea and bilateral neck lymphadenopathy, who received a laboratory checkup and endoscopic workup for colon biopsy. The initial pathological report was consistent with mucosal inflammation and benign colon ulcers. Interestingly, the blood test showed a prominent eosinophilia. A biopsy of the enlarged neck lymph nodes done approximately 1 month after the colon biopsy unexpectedly showed T-cell lymphoma, which led to a review of the initial colonic biopsy specimens. Additional immunohistochemical stains were used accordingly, which

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

    Directory of Open Access Journals (Sweden)

    Kayo Tokeji

    2016-01-01

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

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

    Science.gov (United States)

    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.

  4. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas

    Science.gov (United States)

    Palomero, Teresa; Couronné, Lucile; Khiabanian, Hossein; Kim, Mi-Yeon; Ambesi-Impiombato, Alberto; Perez-Garcia, Arianne; Carpenter, Zachary; Abate, Francesco; Allegretta, Maddalena; Haydu, J. Erika; Jiang, Xiaoyu; Lossos, Izidore S.; Nicolas, Concha; Balbin, Milagros; Bastard, Christian; Bhagat, Govind; Piris, Miguel Angel; Campo, Elias; Bernard, Olivier; Rabadan, Raul; Ferrando, Adolfo

    2014-01-01

    Peripheral T-cell lymphomas (PTCLs) are a heterogeneous and poorly understood group of non Hodgkin lymphomas1,2. Here we combined whole exome sequencing of 12 tumor-normal DNA pairs, RNAseq analysis and targeted deep sequencing to identify new genetic alterations in PTCL transformation. These analyses identified highly recurrent epigenetic factor mutations in TET2, DNMT3A and IDH2 as well as a new highly prevalent RHOA p.Gly17Val (NM_001664) mutation present in 22/35 (67%) of angioimmunoblastic T-cell lymphomas (AITL) and in 8/44 (18%) not otherwise specified PTCL (PTCL NOS) samples. Mechanistically, the RHOA Gly17Val protein interferes with RHOA signaling in biochemical and cellular assays, an effect potentially mediated by the sequestration of activated Guanine Exchange Factor (GEF) proteins. In addition, we describe new and recurrent, albeit less frequent, genetic defects including mutations in FYN, ATM, B2M and CD58 implicating SRC signaling, impaired DNA damage response and escape from immune surveillance mechanisms in the pathogenesis of PTCL. PMID:24413734

  5. 506U78 in Treating Patients With Lymphoma

    Science.gov (United States)

    2013-01-15

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Small Intestine Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome

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

    Directory of Open Access Journals (Sweden)

    I. Hansenne

    2004-01-01

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

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

    LENUS (Irish Health Repository)

    Ryan, A J A

    2012-02-01

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

  8. Cutaneous T-cell lymphomas and their management strategies

    Directory of Open Access Journals (Sweden)

    S S Pandey

    2014-01-01

    Full Text Available Cutaneous T-cell lymphomas (CTCLs comprise a heterogeneous group of lymphoproliferative disorders characterized by the proliferation of skin-homing post-thymic T-cells. It is the second most common extranodal non-Hodgekin′s lymphoma. Many variants of mycosis fungoides and CTCLs are known to date, differing in clinical, histological, and immunophenotypic characteristics. Oral involvement has also been reported rarely in CTCLs. Treatment depends on the disease stage or the type of variant. New insights into the disease and the number of emerging novel therapeutic options have made it an interesting area for dermatologists and medical oncologists.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Aim: To investigate the presentation of a patch-stage cutaneous T-cell lymphoma (CTCL) using optical coherence tomography (OCT). Methods: A patient with a patch caused by CTCL was photographed digitally, OCT-scanned and biopsied. A normal skin area adjacent to the patch was OCT-scanned for compar......Aim: To investigate the presentation of a patch-stage cutaneous T-cell lymphoma (CTCL) using optical coherence tomography (OCT). Methods: A patient with a patch caused by CTCL was photographed digitally, OCT-scanned and biopsied. A normal skin area adjacent to the patch was OCT.......13 mm. A good immediate correlation was found between histology and OCT imaging of the sample. Conclusion: The aetiology of the elongated structures is thought to be lymphomatous infiltrates. Similar findings have been described in ocular lymphoma and may therefore be an important characteristic...

  11. Pulmonary Involvement of Peripheral T-cell Lymphoma, Unspecified: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jin; Shim, Hyo Sub; Ham, Seok Jin; Kim, Tae Hoon; Kim, Sang Jin [Gangnam Severance Hospital, Seoul (Korea, Republic of)

    2010-01-15

    Peripheral T-cell lymphoma is a rare type of lymphoma that's derived from postthymic lymphoid T cells. Pulmonary involvement of peripheral T-cell lymphoma of the unspecified type is very rare and the imaging findings of this illness have rarely been reported. We present here a case of peripheral T-cell lymphoma of the unspecified type with a cavitary lesion in the lung parenchyma, and we pathologically confirmed this illness by performing video-assisted thoracoscopic surgery.

  12. Composite Lymphoma : EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma A Case Report

    NARCIS (Netherlands)

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

    2009-01-01

    Composite lymphomas are rare and defined as hematopoietic neoplasms with more than I malignant lymphomatous clone showing different phenotypic features. Of all possible combinations between non-Hodgkin lymphomas, B cell or T cell, and Hodgkin lymphoma, the least frequent are the ones combining T-cel

  13. Hepatosplenic γδ T-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Shuan-Zeng Wei; Tong-Hua Liu; De-Tian Wang; Jin-Ling Cao; Yu-Feng Luo; Zhi-Yong Liang

    2005-01-01

    AIM: To investigate the clinicopathologic characteristics, immunophenotype and TCR gene rearrangements of hepatosplenic T-cell lymphoma in eight Chinese patients.METHODS: Eight Chinese patients with hepatosplenic γδ T-cell lymphomas were studied. Hematoxylin-eosin-stained slides and clinical histories were reviewed. We also carried out immunohistochemical staining for CD3, CD4,CD8, CD20, CD43, CD56, CD79a, UCHL-1, and TCR γδ. Rearrangements of TCR gamma and delta chain genes were also studied.RESULTS: The spleens were enlarged and the cut surfaces were homogeneous and red-purple in color without identifiable gross lesions or enlarged hilar lymph nodes. Histologically, lymphoma cells infiltrated the cords of Billroth and often packed the sinuses. Liver biopsy showed lymphoma cell infiltrations in the sinusoids, and three cases showed involvements of the portal tracts. Immunohistochemically lymphoma cells were positive for CD3, CD43, and CD56 in all cases. Four of eight cases were positive for CD8, and all cases were negative for CD4 (6/6). Monoclonal rearrangements of TCR γ gene were demonstrated by PCR analysis in five out of the eight cases. TCR δ gene rearrangements were detected in six out of the eight cases, which demonstrated single bands on PAGE gel, and the amplification products in two cases were confirmed by sequencing.CONCLUSION: The clinicopathology of hepatosplenic γδ T-cell lymphoma in Chinese patients is similar to what was previously reported except that the splenomegaly is not so massive, and CD8 is positive.

  14. Classification of distinct subtypes of peripheral T-cell lymphoma unspecified, identified by chemokine and chemokine receptor expression: Analysis of prognosis.

    Science.gov (United States)

    Ohshima, Koichi; Karube, Kennosuke; Kawano, Riko; Tsuchiya, Takeshi; Suefuji, Hiroaki; Yamaguchi, Takahiro; Suzumiya, Junji; Kikuchii, Masahiro

    2004-09-01

    WHO classification for malignant lymphoma was recently proposed. However, PTCL is heterogeneous. Chemokines and its receptors are closely associated with the T-cell subtypes. To clarify the T-cell subtype in PTCL, we conducted DNA chips of chemokine, its receptor (R) and cytokines. Angioimmunoblastic T-cell lymphoma (AILD, n=4), anaplastic large cell lymphoma (ALCL, n=4), adult T-cell leukemia lymphoma (ATLL, n=7), NK-cell lymphoma (NKL, n=2) and PTCL, unspecified (PTCL-U, n=6) were analyzed using DNA chips. In addition, immunological stainings were performed in 280 cases. In DNA chip, AILD, ALCL, NKL and ATLL showed a tendency for respective clusters, otherwise, PTCL-U clustered with AILD, ALCL and ATLL. From the gene expression profiling, CCR4, CCR3, MIG, CXCR3 and BLC were selected for immunohistochemistry. ATLL (n=48) expressed CCR4. ALCL (n=26) expressed CCR3, NKL (n=20) expressed MIG, and AILD (n=29) expressed CXCR3 and/or BLC. From the expression patterns, PTCL-U (n=134) were classified into three groups; CCR4 type (CCR4(+), n=42), CCR3 type (CCR3(+), n=31) and CXCR3 type (CXCR3(+) BLC(+/-), n=54). The prognosis was poor for ATLL, intermediate for AILD and favorable for ALCL (P=0.0014). Among PTCL-U, CCR4 type, CXCR3 type and CCR3 type had prognoses equivalent to ATLL, AILD and ALCL, respectively (P<0.0001).

  15. Nonmalignant T cells stimulate growth of T-cell lymphoma cells in the presence of bacterial toxins

    DEFF Research Database (Denmark)

    Woetmann, Anders; Lovato, Paola; Eriksen, Karsten W;

    2007-01-01

    Bacterial toxins including staphylococcal enterotoxins (SEs) have been implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCLs). Here, we investigate SE-mediated interactions between nonmalignant T cells and malignant T-cell lines established from skin and blood of CTCL patients...

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

    Science.gov (United States)

    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

  17. 2-chlorodeoxyadenosine treatment for cutaneous T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Malgorzata Sokolowska Wojdylo

    2010-09-01

    Full Text Available The primary cutaneous lymphomas are often indolent but difficult to treat. In the early stages psoralen and ultraviolet-A therapy is the standard treatment whereas at the tumor stage chemotherapy (e.g. pegylated doxorubicin is often used for debulking. The purine analog 2-chlorodeoxyadenosine (2CdA acts in non-Hodgkin’s lymphoma and has been used in our center for the treatment of advanced primary cutaneous T-cell lymphomas (CTCL. Here, we report on the efficacy and side effects of 2CdA in six patients with CTCL. One patient died owing to myelosuppression. Partial responses were seen in four cases but full remission was observed in only one case. We concluded that 2CdA has a limited usefulness in the management of advanced CTCL.

  18. T-cell receptor gene rearrangement analysis: cutaneous T cell lymphoma, peripheral T cell lymphoma, and premalignant and benign cutaneous lymphoproliferative disorders.

    Science.gov (United States)

    Zelickson, B D; Peters, M S; Muller, S A; Thibodeau, S N; Lust, J A; Quam, L M; Pittelkow, M R

    1991-11-01

    T-cell receptor gene rearrangement analysis is a useful technique to detect clonality and determine lineage of lymphoid neoplasms. We examined 103 patients with mycosis fungoides, Sézary syndrome, peripheral T cell lymphoma, potentially malignant lymphoproliferative disorders including pre-Sézary syndrome, large plaque parapsoriasis, lymphomatoid papulosis and follicular mucinosis, and various benign inflammatory infiltrates. A clonal rearrangement was detected in skin samples in 20 of 24 patients with mycosis fungoides and in peripheral blood samples in 19 of 21 patients with Sézary syndrome. A clonal population was also detected in seven of eight cases classified as peripheral T cell lymphoma. The potentially malignant dermatoses tended to have clonal rearrangement, with the exception of large plaque parapsoriasis, and further follow-up is needed to correlate clonality with the disease course. These studies demonstrate the value of molecular genetics as an adjunct to morphology in the examination of patients with cutaneous lymphoproliferative disease.

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

    OpenAIRE

    Kimberly Aderhold; Lisa Carpenter; Krysta Brown; Anthony Donato

    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 ...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    2015-05-06

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

  3. EBV-positive immunodeficiency lymphoma after alemtuzumab-CHOP therapy for peripheral T-cell lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke C.; Coenen, Jules L.; Boers, James E.; van Imhoff, Gustaaf W.; Rosati, Stefano

    2008-01-01

    Chemotherapy with alemtuzumab and the combination of cyclophosphamide, adriamycin, oncovin, and prednisone (CHOP) has become experimental trial therapy for aggressive T-cell lymphoma. Several multicenter phase 3 trials; will incorporate this scheme. As part of an ongoing phase 2 trial in which we re

  4. Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

    Science.gov (United States)

    2016-06-27

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin 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; 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 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; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Waldenström Macroglobulinemia

  5. Imaging Cutaneous T-Cell Lymphoma with Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Hans Christian Ring

    2012-07-01

    Full Text Available Aim: To investigate the presentation of a patch-stage cutaneous T-cell lymphoma (CTCL using optical coherence tomography (OCT. Methods: A patient with a patch caused by CTCL was photographed digitally, OCT-scanned and biopsied. A normal skin area adjacent to the patch was OCT-scanned for comparison, but not biopsied. The OCT image and the histological image were compared. Results: The OCT images illustrated a thickened and hyperreflective stratum corneum. OCT also demonstrated several elongated hyporeflective structures in the dermis. The largest structure was measured to have a width of 0.13 mm. A good immediate correlation was found between histology and OCT imaging of the sample. Conclusion: The aetiology of the elongated structures is thought to be lymphomatous infiltrates. Similar findings have been described in ocular lymphoma and may therefore be an important characteristic of cutaneous lymphoma. It may further be speculated that the differences in OCT images may reflect the biological behaviour of the infiltrate. This observation therefore suggests that OCT imaging may be a relevant tool for the in vivo investigation of mycosis fungoides and other CTCLs, but in order to verify these observed patterns in OCT imaging, further investigations will be required.

  6. The role of cytokine signaling in the pathogenesis of cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    abraham, Robert; Zhang, Qiang; Ødum, Niels

    2011-01-01

    Cutaneous T-cell lymphoma (CTCL) displays immunosuppressive properties and phenotypic plasticity. The malignant T cells in CTCL can possess features of immunomodulating regulatory T cells (Treg) and IL-17-producing helper T cells (Th17) depending on the stimuli they receive from antigen presenting...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Kimberly Aderhold

    2015-01-01

    Full Text Available 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.

  9. T cells in tumors and blood predict outcome in follicular lymphoma treated with rituximab

    DEFF Research Database (Denmark)

    Wahlin, Björn Engelbrekt; Sundström, Christer; Holte, Harald;

    2011-01-01

    T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown.......T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown....

  10. Intensified alemtuzumab-CHOP therapy for peripheral T-cell lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, H. C.; Kooy, M. van Marwijk; Lugtenburg, P. J.; van Putten, W. L. J.; Luten, M.; Oudejans, J.; van Imhoff, G. W.

    2011-01-01

    Background: The prognosis of T-cell lymphoma is poor. To explore the addition of the monoclonal antibody alemtuzumab, we studied the efficacy and tolerability of an intensified alemtuzumab-chemotherapy combination for aggressive T-cell lymphoma in a phase II study by Dutch-Belgian Hemato-Oncology Gr

  11. Utility of interim and end-of-treatment PET/CT in peripheral T-cell lymphomas: A review of 124 patients.

    Science.gov (United States)

    El-Galaly, Tarec Christoffer; Pedersen, Martin Bjerregård; Hutchings, Martin; Mylam, Karen Juul; Madsen, Jakob; Gang, Anne Ortved; Bøgsted, Martin; de Nully Brown, Peter; Loft, Annika; Nielsen, Anne Lerberg; Hendel, Helle Westergreen; Iyer, Victor; Gormsen, Lars Christian

    2015-11-01

    According to the updated guidelines for imaging in lymphoma, 18F-FDG positron emission tomography/computed tomography (PET/CT) is recommended for staging and evaluation of treatment response in FDG-avid lymphomas. The purpose of the study was to evaluate the utility of PET/CT in nodal peripheral T-cell lymphomas (PTCL). Patients with newly diagnosed nodal PTCL (peripheral T-cell lymphoma NOS, anaplastic large-cell lymphoma, or angioimmunoblastic T-cell lymphoma) seen at five Danish hematology centers during the period 2006 to 2012 were included, if they had been pretherapeutically staged with PET/CT. Medical records were reviewed for baseline clinical and follow-up information. Staging, interim (I-PET), and end-of-treatment PET/CT (E-PET) studies were centrally reviewed, and reported using the Deauville 5-point score (DS). A total of 124 patients fulfilled the inclusion criteria. The median age was 58 years, and 88% received CHOP/CHOP-like therapy. Five years PFS and OS of the study population was 36.8% (95% CI 27.3-46.4) and 49.7% (95% CI 38.9-59.6), respectively. The presence of PET/CT-ascertained lung and/or liver involvement was associated with a worse outcome. The sensitivity of PET/CT for detecting biopsy-defined bone marrow involvement was only 18% (95% CI 4-43). An interim DS >3 was not prognostic for worse OS and PFS among CHOP/CHOP-like treated patients in uni- or multivariate analyses. A DS >3 after treatment predicted a worse prognosis. In conclusion, I-PET was not predictive of outcome in CHOP/CHOP-like treated PTCL patients when using the DS. Prospective studies are needed to determine the optimal use of PET/CT in PTCL including the role of quantitative PET/CT analysis.

  12. Primary gastric T cell lymphoma mimicking marginal zone B cell lymphoma of mucosa-associated lymphoid tissue.

    Science.gov (United States)

    Holanda, Danniele; Zhao, Merry Y; Rapoport, Aaron P; Garofalo, Michael; Chen, Qing; Zhao, X Frank

    2008-07-01

    Primary gastric T cell lymphoma is rare and mostly of large cell type. In this paper, we present a case of gastric T cell lymphoma morphologically similar to the gastric marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Morphologically, the cells are small with abundant clear cytoplasm. Lymphoepithelial lesions are readily identified with diffuse destruction of gastric glands. Immunohistochemically, the neoplastic cells are CD3+/CD4+/CD8-/Granzyme B-. Molecular studies revealed monoclonal T cell receptor gamma gene rearrangement. Clinically, the patient responded initially to four cycles of R-CHOP, but then progressed. Because peripheral T cell lymphoma is usually associated with a poor prognosis, whereas marginal zone B cell lymphoma is an indolent lymphoproliferative disorder, this morphologic mimicry should be recognized and completely investigated when atypical small lymphoid infiltrates with lymphoepithelial lesions are encountered in the stomach.

  13. FOXP3+ regulatory T cells in cutaneous T-cell lymphomas: association with disease stage and survival

    DEFF Research Database (Denmark)

    Gjerdrum, L M; Woetmann, A; Odum, Niels;

    2007-01-01

    with mycosis fungoides (MF) and cutaneous T-cell lymphoma (CTCL) unspecified were analysed for the expression of FOXP3 on tumour cells and tumour-infiltrating Tregs. Labelling of above 10% of the neoplastic cells was seen in one case classified as an aggressive epidermotropic CD8+ cytotoxic CTCL...

  14. PRDM1/BLIMP1: a tumor suppressor gene in B and T cell lymphomas.

    Science.gov (United States)

    Boi, Michela; Zucca, Emanuele; Inghirami, Giorgio; Bertoni, Francesco

    2015-05-01

    The gene encoding the human BLIMP1, prdm1, is located on chromosome 6q21, a locus frequently deleted in lymphoid tumors. BLIMP1 is able to silence its target genes in a context-dependent manner through different mechanisms. BLIMP1 is expressed in both B and T cells, in which it plays important functions. In B cells, BLIMP1 acts as the master regulator of plasma cell differentiation, repressed by BCL6 and repressing both BCL6 and PAX5. In T cells, BLIMP1 is a critical factor for most terminal effector cell differentiation in both CD4+ and CD8+ T cells. BLIMP1 is frequently inactivated in a variety of lymphomas, including diffuse large B cell lymphomas, Natural Killer cell lymphoma and anaplastic large T cell lymphoma. In this review, we will summarize the role of BLIMP1 in normal cells, focusing on lymphoid cells, and on its function as tumor suppressor gene in lymphomas.

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

    Science.gov (United States)

    2015-12-03

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

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

    Science.gov (United States)

    2017-01-26

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

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

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    Impact of Growth Factor Independence 1 in Human T-Cell Lymphomas; Pathogenic Potential Identified by Insertional Mutagenesis in a Murine T-Cell Lymphoma Model. Magdalena Julia Dabrowska *,1, Karen Dybkaer *,1, Preben Johansen *,2, Hans Erik Johnsen1 and Finn Skou Pedersen *,3 1 Department...... role in the development of MLV induced lymphomas and strongly indicates that retroviral insertional mutagenesis in murine models of human NHLs can be used to identify new genes involved in lymphomagenesis and, by use of functional assays, their impact on human lymphomas can be evaluated. Disclosures...

  19. Primary anaplastic large T cell lymphoma of central nervous system

    Directory of Open Access Journals (Sweden)

    ZHANG Yan

    2013-01-01

    Full Text Available Background Primary anaplastic large T cell lymphoma (ALCL of central nervous system (CNS can occur in people of all ages, and is usually unrelated with immunodeficiency. It is often misdiagnosed as meningitis, especially tuberculous meningitis, on clinical practice and imaging examination. In pathological diagnosis, the morphological changes of primary ALCL of CNS are similar to the systemic ALCL and the anaplastic lymphoma kinase-1 (ALK-1 can be positive or negative. Being misdiagnosed as meningitis, hormone therapy with glucocorticoid before biopsy is always used, and massive necrosis and a lot of histocyte proliferation and phagocytosis can be found under histological findings. Therefore, when the material is not enough, primary ALCL of CNS is often misdiagnosed as cerebral infarction or malignant histocytosis and so on. This paper reports a case of primary ALCL of CNS and makes a review of relevant literature, so as to summarize the clinical manifestations and elevate the recognition of clinicians and pathologists on this disease. Methods and Results A 12-year-old boy was admitted because of fever, worsening headache, numbness and weakness of right limbs. MRI showed local gyri swelling and abnormal enhancement of pia mater in the right parietal lobe, expanding to the right temporal lobe, and pia mater enhancement in the left parietal lobe. The right temporo-parietal lobe lesion biopsy revealed irregularly shaped tumor cells of large size, rich and eosinophilic cytoplasm and horseshoe-shaped or kidney-shaped nuclei. Immunohistochemical examination showed tumor cells positive for CD3, CD45RO, CD30, ALK-1 and epithelial membrane antigen (EMA, and negative for CD20 and CD79a. Conclusion Primary ALCL of CNS is an extremely rare tumor which is usually misdiagnosed as meningitis according to clinical and imaging examinations. Therefore, for those patients who are considered as meningitis but with poor treatment effect and replase of illness, brain

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2009-07-01

    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.

  2. Wegener's granulomatosis simulated by a T cell lymphoma of the lung

    OpenAIRE

    1991-01-01

    A case of primary T cell lymphoma of the lung associated with antineutrophil cytoplasmic antibody simulated Wegener's granulomatosis, the patient having features compatible with but not diagnostic of Wegener's granulomatosis.

  3. Molecular analysis of T-cell receptor beta genes in cutaneous T-cell lymphoma reveals Jbeta1 bias.

    Science.gov (United States)

    Morgan, Suzanne M; Hodges, Elizabeth; Mitchell, Tracey J; Harris, Susan; Whittaker, Sean J; Smith, John L

    2006-08-01

    Molecular characterization of T-cell receptor junctional region sequences in cutaneous T-cell lymphoma had not been previously reported. We have examined in detail the features of the T-cell receptor beta (TCRB) gene rearrangements in 20 individuals with well-defined stages of cutaneous T-cell lymphoma (CTCL) comprising 10 cases with early-stage mycosis fungoides (MF) and 10 cases with late-stage MF or Sezary syndrome. Using BIOMED-2 PCR primers, we detected a high frequency of clonally rearranged TCR gamma and TCRB genes (17/20 and 15/20 cases, respectively). We carried out sequencing analysis of each complete clonal variable (V)beta-diversity (D)beta-joining(J)beta fingerprint generated by PCR amplification, and determined the primary structure of the Vbeta-Dbeta-Jbeta junctional regions. We observed considerable diversity in the T-cell receptor Vbeta gene usage and complementarity-determining region 3 loops. Although we found that TCRB gene usage in CTCL and normal individuals share common features, our analysis also revealed preferential usage of Jbeta1 genes in all cases with advanced stages of disease.

  4. Extranodal NK/T-cell lymphoma of the nasal type with predominant T-cell markers: A rare subtype of rare disease entity

    Directory of Open Access Journals (Sweden)

    Ankur Nandan Varshney

    2015-01-01

    Full Text Available Extranodal NK/T-cell Lymphoma of nasal type is a rare and comparatively a new entry among group of Non-Hodgkin lymphomas. The disease is characterized by a clinically aggressive course with involvement of upper aero-digestive tract and classical immune-phenotyping with CD2, CD3 and CD56 positivity. Being a rare entity, treatment entities are yet not formulated in guidelines. We hereby report a case of extranodal NK/T-cell lymphoma with predominant T cell markers who was initially treated with CHOP regime of non-Hodgkin lymphoma and later successfully treated with SMILE regime.

  5. Renal T-cell lymphoma with cerebral metastasis in a dog with chronic canine ehrlichiosis

    Directory of Open Access Journals (Sweden)

    E.P. Lane

    2002-07-01

    Full Text Available A renal T-cell lymphoma with exclusive cerebral metastasis was diagnosed in a 5-year-old Staffordshire bull terrier bitch euthanased for aggression. This is the first recorded case of primary renal lymphoma in a dog. Immune suppression, due to chronic canine monocytic ehrlichiosis, mayaccount for the unusual primary site and metastatic patternof the tumour.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    Ralfkiaer, Ulrik; Hagedorn, Peter; Bangsgaard, Nannie;

    2011-01-01

    Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL...

  9. Fli-1 overexpression in hematopoietic progenitors deregulates T cell development and induces pre-T cell lymphoblastic leukaemia/lymphoma.

    Directory of Open Access Journals (Sweden)

    Monique F M A Smeets

    Full Text Available The Ets transcription factor Fli-1 is preferentially expressed in hematopoietic tissues and cells, including immature T cells, but the role of Fli-1 in T cell development has not been closely examined. To address this we retrovirally overexpressed Fli-1 in various in vitro and in vivo settings and analysed its effect on T cell development. We found that Fli-1 overexpression perturbed the DN to DP transition and inhibited CD4 development whilst enhancing CD8 development both in vitro and in vivo. Surprisingly, Fli-1 overexpression in vivo eventuated in development of pre-T cell lymphoblastic leukaemia/lymphoma (pre-T LBL. Known Fli-1 target genes such as the pro-survival Bcl-2 family members were not found to be upregulated. In contrast, we found increased NOTCH1 expression in all Fli-1 T cells and detected Notch1 mutations in all tumours. These data show a novel function for Fli-1 in T cell development and leukaemogenesis and provide a new mouse model of pre-T LBL to identify treatment options that target the Fli-1 and Notch1 signalling pathways.

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

    Directory of Open Access Journals (Sweden)

    Nooshin Bagherani

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    H.A. Lopez Morra

    2007-09-01

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

  12. Salvage chemotherapy of gemcitabine, dexamethasone, and cisplatin (GDP) for patients with relapsed or refractory peripheral T-cell lymphomas: a consortium for improving survival of lymphoma (CISL) trial.

    Science.gov (United States)

    Park, Byeong-Bae; Kim, Won Seog; Suh, Cheolwon; Shin, Dong-Yeop; Kim, Jeong-A; Kim, Hoon-Gu; Lee, Won Sik

    2015-11-01

    There is no standard salvage chemotherapy for relapsed or refractory peripheral T-cell lymphomas (PTCLs). Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in the salvage setting. We investigated the efficacy and toxicity of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory PTCLs in search of a more effective and less toxic therapy. Patients with relapsed or refractory PTCLs with more than one previous regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4, and cisplatin 70 mg/m(2) i.v. on day 1, and then every 21 days. Patients could proceed to autologous stem cell transplantation (ASCT) after four cycles of GDP or receive up to six treatment cycles. Twenty-five eligible patients were evaluated for toxicity and response. The diagnoses of participants included 14 cases of PTCL-not otherwise specified (NOS) (56 %) and four cases of angioimmunoblastic T-cell lymphoma (16 %) among others. The median age of the patients was 59 years (range 20-75 years). After treatments with GDP, which delivered a median of four GDP cycles, there were 12 patients with complete responses (CR; 48 %) and six with partial responses (PR; 24 %). The overall response rate (RR) was 72 %. Four patients preceded to ASCT, and three patients finally achieved CR. The median progression free survival was 9.3 months (95 % confidence interval (CI); 4.1-14.6) with a median follow-up duration of 27.1 months. In a total of 86 cycles of GDP, grade 3 or 4 neutropenia and thrombocytopenia occurred in 16.3 and 12.8 % of cycles, respectively. Three patients (3.3 %) experienced febrile neutropenia. GDP is a highly effective and optimal salvage regimen for relapsed or refractory PTCLs and can be administered with acceptable toxicity.

  13. Concepts in mature T-cell lymphomas - highlights from an international joint symposium on T-cell immunology and oncology().

    Science.gov (United States)

    Herling, Marco; Rengstl, Benjamin; Scholtysik, René; Hartmann, Sylvia; Küppers, Ralf; Hansmann, Martin-Leo; Diebner, Hans H; Roeder, Ingo; Abken, Hinrich; Newrzela, Sebastian; Kirberg, Jörg

    2017-04-01

    Growing attention in mature T-cell lymphomas/leukemias (MTCL) is committed to more accurate and meaningful classifications, improved pathogenetic concepts and expanded therapeutic options. This requires considerations of the immunologic concepts of T-cell homeostasis and the specifics of T-cell receptor (TCR) affinities and signaling. Scientists from various disciplines established the CONTROL-T research unit and in an international conference on MTCL they brought together experts from T-cell immunity, oncology, immunotherapy and systems biology. We report here meeting highlights on the covered topics of diagnostic pitfalls, implications by the new WHO classification, insights from discovered genomic lesions as well as TCR-centric concepts of cellular dynamics in host defense, auto-immunity and tumorigenic clonal escape, including predictions to be derived from in vivo imaging and mathematical modeling. Presentations on novel treatment approaches were supplemented by strategies of optimizing T-cell immunotherapies. Work packages, that in joint efforts would advance the field of MTCL more efficiently, are identified.

  14. Ectopic expression of B-lymphoid kinase in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, Thorbjørn; Vetter-Kauczok, Claudia S; Woetmann, Anders;

    2009-01-01

    B-lymphoid kinase (Blk) is exclusively expressed in B cells and thymocytes. Interestingly, transgenic expression of a constitutively active form of Blk in the T-cell lineage of mice results in the development of T-lymphoid lymphomas. Here, we demonstrate nuclear factor-kappa B (NF......-kappaB)-mediated ectopic expression of Blk in malignant T-cell lines established from patients with cutaneous T-cell lymphoma (CTCL). Importantly, Blk is also expressed in situ in lesional tissue specimens from 26 of 31 patients with CTCL. Already in early disease the majority of epidermotropic T cells express Blk...... phosphorylated in malignant CTCL cell lines and spontaneously active in kinase assays. Furthermore, targeting Blk activity and expression by Src kinase inhibitors and small interfering RNA (siRNA) inhibit the proliferation of the malignant T cells. In conclusion, this is the first report of Blk expression...

  15. Adult T-Cell Leukemia/Lymphoma (HTLV-1)

    Science.gov (United States)

    ... against lymphoma. However, complementary therapies such as meditation, yoga, acupuncture, exercise, diet and relaxation techniques have been shown to be effective in combating some treatment side effects. Before embarking on any complementary therapies, patients should ...

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

    Science.gov (United States)

    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

  17. Critical appraisal of pralatrexate in the management of difficult-to-treat peripheral T cell lymphoma

    Directory of Open Access Journals (Sweden)

    Casanova M

    2011-10-01

    Full Text Available M Casanova, A Medina-Pérez, M Moreno-Beltran, M Mata-Vazquez, A RuedaOncohematology Service, Hospital Costa del Sol, Marbella, SpainAbstract: Aggressive T cell lymphomas are a subgroup of lymphomas with a particularly poor prognosis. This is especially true for patients with recurrent or refractory disease, who typically have limited response to salvage therapy and extremely poor overall survival. For this reason, there is a strong need to develop potentially active drugs for these malignancies. Pralatrexate is a novel antifolate designed to have high affinity for reduced folate carrier type 1. Preclinical and clinical studies have demonstrated that pralatrexate has significant activity against T cell lymphomas. The dose-limiting toxicity for pralatrexate is mucositis, which can be abrogated with folic acid and vitamin B12 supplementation. Pralatrexate is the first single agent approved for the treatment of patients with relapsed or refractory peripheral T cell lymphoma. This approval was based on an overall objective response rate observed in the pivotal study. The overall response rate was 29%, with a median duration of 10.1 months. This article reviews the biochemistry, preclinical experience, metabolism, and pharmacokinetics of pralatrexate, including the clinical experience with this agent in lymphoma. Future areas of development are now focused on identifying synergistic combinations of pralatrexate with other agents and the evaluation of predictive markers for clinical benefit.Keywords: pralatrexate, peripheral T cell lymphoma

  18. Malignant T Cells Secrete Galectins and Induce Epidermal Hyperproliferation and Disorganized Stratification in a Skin Model of Cutaneous T Cell Lymphoma

    DEFF Research Database (Denmark)

    Thode, Christenze; Andersen, Anders Woetmann; Wandall, Hans H

    2015-01-01

    Cutaneous T cell lymphomas (CTCL) are the most common primary skin lymphomas; which are characterized by an accumulation of malignant T cells in the skin. The early lesion resembles both clinically and histologically benign inflammatory disorders, which also presents with hyperproliferative...... that malignant T cells through the secretion of galectin-1 and -3 stimulate vigorous growth of keratinocytes. In parallel, malignant T cells induce disorganized keratinocyte stratification, resembling the early hyperproliferative stage of CTCL. We also observed a loss of attachment between the epithelial...

  19. Extranodal Natural Killer/T-cell lymphoma, nasal type: ‘midline lethal granuloma.’ A case report

    Directory of Open Access Journals (Sweden)

    Tlholoe Martha M

    2013-01-01

    Full Text Available Abstract Extranodal natural killer/T cell lymphoma, nasal type, is a non-Hodgkin lymphoma, most commonly affecting the nasal cavity, paranasal sinuses and nasopharynx. Clinically it is characterised by destruction of facial tissues, commencing in the midline. In most cases it arises from malignant transformation of natural killer cells (NK; sometimes from malignant transformation of cytotoxic T cells. Extranodal NK/T cell lymphoma, nasal type, is rare, but even more rare in black persons. The purpose of this article is to report a severe case of extranodal NK/T cell lymphoma, nasal type, in an elderly black male.

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

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

    2010-01-01

    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcr......CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

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

    Directory of Open Access Journals (Sweden)

    Katherine Devitt

    2014-01-01

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

  2. Diagnosis, prognosis and management of erythrodermic cutaneous T-cell lymphoma.

    Science.gov (United States)

    Moriarty, Bláithín; Whittaker, Sean

    2015-04-01

    Erythroderma describes complete or near-complete skin surface erythema of any cause. Cutaneous T-cell lymphoma accounts for a minority of cases of erythroderma and consists of erythrodermic mycosis fungoides, Sézary syndrome. Both adult T-cell leukemia/lymphoma and T-cell prolymphocytic leukemia can also rarely present with erythroderma. Diagnosis may be extremely challenging because benign disorders may have overlapping features with those of lymphoma. Prognosis is poor with median survival of approximately 2 years. The evidence base for therapeutic approaches relies on cohorts and case series and more recently Phase II trials. Improved patient selection and identification of appropriate conditioning regimens for reduced intensity allogeneic hematopoetic transplant are likely to improve survival, although a significant number of patients may not be fit for transplant because of advanced age and comorbidities.

  3. Primary central nervous system peripheral T-cell lymphoma in a child.

    Science.gov (United States)

    Gualco, Gabriela; Wludarski, Sheila; Hayashi-Silva, Luciana; Medeiros Filho, Plinio; Veras, Geni; Bacchi, Carlos Eduardo

    2010-01-01

    A 10-year-old Caucasian boy was admitted to the hospital with a 3-month history of headache, vomiting, ataxia, and right amaurosis. A magnetic resonance imaging (MRI) showed a solid, expansive, parasagittal mass in the right parietal hemisphere that extended sagitally to include the optical chiasm. The lesion was considered unresectable. Histology and immunophenotyping of biopsy tissue revealed characteristics of peripheral T-cell lymphoma. No other anatomical region, including bone marrow, was compromised. Primary T-cell lymphomas of the central nervous system are rare, especially in childhood. Here, we describe the rapidly deteriorating and fatal clinical course of a boy with a primary T-cell lymphoma in the central nervous system.

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

    Directory of Open Access Journals (Sweden)

    Li JY

    2012-03-01

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

  5. A case of primary pulmonary NK/T cell lymphoma presenting as pneumonia.

    Science.gov (United States)

    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.

  6. Biological insights into the pathogenesis of cutaneous T-cell lymphomas (CTCL).

    Science.gov (United States)

    Whittaker, Sean

    2006-02-01

    Mycosis fungoides and Sezary syndrome, collectively known as cutaneous T-cell lymphomas (CTCLs), are low-grade, indolent, clonal, non-Hodgkin's lymphomas consisting of CD4+ CD45RO+ T cells with a CLA+ CCR4+ skin-homing phenotype. There are several variants of primary CTCLs with differences in clinical behavior and prognosis. Currently, the precise etiologies of mycosis fungoides and Sezary syndrome are unknown. This article reviews our current understanding of the pathogenetic abnormalities involving genomic mutations, abnormal cDNA expression, and dysregulation of signaling pathways in CTCL.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-15

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

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

    Directory of Open Access Journals (Sweden)

    Isola V

    2012-05-01

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

  9. FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

    Science.gov (United States)

    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

  10. (18)F-FDG PET/CT in bilateral primary adrenal T-cell lymphoma.

    Science.gov (United States)

    Santhosh, Sampath; Mittal, Bhagwant Rai; Shankar, Praveen; Kashyap, Raghava; Bhattacharya, Anish; Singh, Baljinder; Das, Ashim; Bhansali, Anil

    2011-01-01

    Primary adrenal lymphoma is extremely rare. We report a young patient who presented with non- specific symptoms of fever and abdominal pain. Conventional imaging modalities demonstrated bilateral bulky adrenal masses, and whole-body fluorine-18-fluorodesoxyglucose ((18)F-FDG) positron emission tomography/computed tomography showed intense (18)F-FDG-avid bilateral adrenal masses with no evidence of extra-adrenal spread. A pathological diagnosis of non-Hodgkin lymphoma of peripheral T-cell type was made. The present case indicates that primary adrenal lymphoma should be included in the differential diagnosis of bilateral adrenal masses.

  11. Adult T-cell leukemia/lymphoma presenting multiple lymphomatous polyposis

    Institute of Scientific and Technical Information of China (English)

    Akira Hokama; Nobuyuki Takasu; Jiro Fujita; Takeaki Tomoyose; Yu-ichi Yamamoto; Takako Watanabe; Tetsuo Hirata; Fukunori Kinjo; Seiya Kato; Koichi Ohshima; Hiroshi Uezato

    2008-01-01

    Multiple lymphomatous polyposis (HLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL is reviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.

  12. Lack of Suppressive CD4+CD25+FOXP3+ T Cells in Advanced Stages of Primary Cutaneous T-Cell Lymphoma

    OpenAIRE

    Tiemessen, Machteld M.; Mitchell, Tracey J.; Hendry, Lisa; Whittaker, Sean J; Taams, Leonie S.; John, Susan

    2006-01-01

    Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls. Functional assays demonstrated a dichotomy in Treg function: in four out of 10 patients CD4+CD25+ T cells were incapabl...

  13. Splenic marginal zone lymphoma with Evans' syndrome, autoimmunity, and peripheral gamma/delta T cells

    OpenAIRE

    2008-01-01

    Splenic marginal zone lymphoma with Evans? syndrome, autoimmunity, and peripheral gamma/delta T cells (Garcia-Mu?oz, Ricardo) Hematology Service, Clinica Universitaria, University of Navarra - Pamplona - SPAIN (Garcia-Mu?oz, Ricardo) Hematology Service, Clinica Universitaria, University of Navarra - Pamplona - SPAIN (Rodriguez-Otero, Paula) Hematology Service, Clinica Universitaria, University of Navarra - Pamplona - SPAIN (Pegenaute, Carlota) Department of...

  14. Adult T-cell leukemia/lymphoma associated with HTLV-1 infection in a Brazilian adolescent

    Directory of Open Access Journals (Sweden)

    VALLE Antonio Carlos Francesconi do

    2001-01-01

    Full Text Available We present the case of a 15-year-old patient infected with HTLV-1 who developed a cutaneous T-cell lymphoma, confirmed by histopathological and immunohistochemical examination, as well as clinically and hematologically confirmed leukemia. The patient died 3 months after initial presentation of the disease. The rarity of the disease in this age group justifies the present report.

  15. Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Gniadecki, Robert; Iversen, Lars

    2015-01-01

    PURPOSE: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments...

  16. [Malignant T-cell lymphoma with osteomyelitis-like bone infiltration].

    Science.gov (United States)

    Mittelmeier, H; Schmitt, O

    1980-01-01

    After a short review on the late literature, existing about various forms of acute lymphoblastic leucemias, it is reported on a rare case of malignant T-cell-Lymphoma with ostemyelitis-like, painfull bone infiltration. The clinical symptoms, as well as differential-diagnostic criterias to other leucemias are described.

  17. Bacterial toxins fuel disease progression in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Willerslev-Olsen, Andreas; Krejsgaard, Thorbjørn; Lindahl, Lise M

    2013-01-01

    In patients with cutaneous T-cell lymphoma (CTCL) bacterial infections constitute a major clinical problem caused by compromised skin barrier and a progressive immunodeficiency. Indeed, the majority of patients with advanced disease die from infections with bacteria, e.g., Staphylococcus aureus...

  18. Cytotoxic T Cells in H. pylori-Related Gastric Autoimmunity and Gastric Lymphoma

    Directory of Open Access Journals (Sweden)

    Mathijs P. Bergman

    2010-01-01

    Full Text Available Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop gastric B-cell lymphoma, gastric autoimmunity, or other life threatening diseases, as gastric cancer or peptic ulcer. The type of host immune response against H. pylori, particularly the cytolytic effector functions of T cells, is crucial for the outcome of the infection. T cells are potentially able to kill a target via different mechanisms, such as perforins or Fas-Fas ligand interaction. In H. pylori-infected patients with gastric autoimmunity cytolytic T cells, that cross-recognize different epitopes of H. pylori proteins and H+K+-ATPase autoantigen, infiltrate the gastric mucosa and lead to gastric atrophy via long-lasting activation of Fas ligand-mediated appotosis and perforin-induced cytotoxicity. On the other hand, gastric T cells from MALT lymphoma exhibit defective perforin- and Fas-Fas ligand-mediated killing of B cells, with consequent abnormal help for B-cell proliferation, suggesting that deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support both the onset and the promotion of low-grade B-cell lymphoma.

  19. Hepatosplenic T Cell Lymphoma in an Immunocompetent Female Diagnosed using Flow Cytometry: A Rare Clinical Entity.

    Science.gov (United States)

    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.

  20. Characterization of feline T cell receptor gamma (TCRG) variable region genes for the molecular diagnosis of feline intestinal T cell lymphoma.

    Science.gov (United States)

    Moore, Peter F; Woo, Jennifer C; Vernau, William; Kosten, Sandra; Graham, Petra S

    2005-07-15

    A diagnosis of intestinal lymphoma is currently made on the basis of clinical and morphologic criteria. This can prove problematic for many reasons that include inadequate sample size, the coexistence of lymphoma and inflammation, and the inability to assess architectural integrity of all tissue compartments in biopsy specimens obtained endoscopically. The detection of a clonal population of cells in a lymphoproliferative lesion represents an important criterion for the diagnosis of neoplasia, but this has not been assessed in feline intestinal lymphoma. T cell receptor gamma (TCRG) gene rearrangement analysis using polymerase chain reaction (PCR) is a methodology that can be used to detect clonality in T cell populations. The basis of this assay depends on the assessment of the junctional diversity that results from rearrangement of TCRG V (variable) and J (joining) gene segments. Feline TCRG transcripts from normal small intestine and spleen were obtained using a rapid amplification of cDNA ends (5'RACE) method. Limited diversity of TCRG V and J gene segments was observed. The high degree of sequence homology in the TCRG V and J gene segments was exploited to develop a PCR test for the assessment of TCRG V--J junctional diversity and hence clonality determination of T cell populations in cats. Molecular clonality determination was applied to feline intestinal lymphoplasmacytic inflammatory bowel disease (IBD) (9 cats), and transmural and mucosal T cell lymphoma (28 cats). Clonal rearrangement of the TCRG V--J junction was detected in 22 of 28 intestinal T cell lymphomas, and oligoclonality was detected in 3 intestinal T cell lymphomas. This contrasted with the detection of polyclonal rearrangement in normal intestinal tissues (3 cats) and in lymphoplasmacytic IBD (9 cats). It is proposed that assessment of TCRG V--J junctional diversity for the detection of clonality represents an important adjunctive tool for the diagnosis of T cell lymphoma in the cat.

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

    Directory of Open Access Journals (Sweden)

    Petrişor Banu

    2016-04-01

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

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

    Science.gov (United States)

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

    2016-10-01

    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.

  3. Methotrexate and etanercept-induced primary cutaneous CD4 positive small/medium-sized pleomorphic T-cell lymphoma*

    Science.gov (United States)

    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

  4. Adoptive T-cell therapy improves treatment of canine non–Hodgkin lymphoma post chemotherapy

    Science.gov (United States)

    O'Connor, Colleen M.; Sheppard, Sabina; Hartline, Cassie A.; Huls, Helen; Johnson, Mark; Palla, Shana L.; Maiti, Sourindra; Ma, Wencai; Davis, R. Eric; Craig, Suzanne; Lee, Dean A.; Champlin, Richard; Wilson, Heather; Cooper, Laurence J. N.

    2012-01-01

    Clinical observations reveal that an augmented pace of T-cell recovery after chemotherapy correlates with improved tumor-free survival, suggesting the add-back of T cells after chemotherapy may improve outcomes. To evaluate adoptive immunotherapy treatment for B-lineage non-Hodgkin lymphoma (NHL), we expanded T cells from client-owned canines diagnosed with NHL on artificial antigen presenting cells (aAPC) in the presence of human interleukin (IL)-2 and IL-21. Graded doses of autologous T cells were infused after CHOP chemotherapy and persisted for 49 days, homed to tumor, and significantly improved survival. Serum thymidine kinase changes predicted T-cell engraftment, while anti-tumor effects correlated with neutrophil-to-lymphocyte ratios and granzyme B expression in manufactured T cells. Therefore, chemotherapy can be used to modulate infused T-cell responses to enhance anti-tumor effects. The companion canine model has translational implications for human immunotherapy which can be readily exploited since clinical-grade canine and human T cells are propagated using identical approaches. PMID:22355761

  5. 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

    Science.gov (United States)

    2015-10-30

    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

  6. CD1d-restricted peripheral T cell lymphoma in mice and humans

    Science.gov (United States)

    Bachy, Emmanuel; Urb, Mirjam; Chandra, Shilpi; Robinot, Rémy; Bricard, Gabriel; de Bernard, Simon; Traverse-Glehen, Alexandra; Gazzo, Sophie; Blond, Olivier; Khurana, Archana; Baseggio, Lucile; Heavican, Tayla; Ffrench, Martine; Crispatzu, Giuliano; Mondière, Paul; Schrader, Alexandra; Taillardet, Morgan; Thaunat, Olivier; Martin, Nadine; Dalle, Stéphane; Le Garff-Tavernier, Magali; Salles, Gilles; Lachuer, Joel; Hermine, Olivier; Asnafi, Vahid; Roussel, Mikael; Lamy, Thierry; Herling, Marco; Iqbal, Javeed; Buffat, Laurent; Marche, Patrice N.; Gaulard, Philippe; Kronenberg, Mitchell; Defrance, Thierry

    2016-01-01

    Peripheral T cell lymphomas (PTCLs) are a heterogeneous entity of neoplasms with poor prognosis, lack of effective therapies, and a largely unknown pathophysiology. Identifying the mechanism of lymphomagenesis and cell-of-origin from which PTCLs arise is crucial for the development of efficient treatment strategies. In addition to the well-described thymic lymphomas, we found that p53-deficient mice also developed mature PTCLs that did not originate from conventional T cells but from CD1d-restricted NKT cells. PTCLs showed phenotypic features of activated NKT cells, such as PD-1 up-regulation and loss of NK1.1 expression. Injections of heat-killed Streptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereas Escherichia coli injection did not. Gene expression profile analyses indicated a significant down-regulation of genes in the TCR signaling pathway in PTCL, a common feature of chronically activated T cells. Targeting TCR signaling pathway in lymphoma cells, either with cyclosporine A or anti-CD1d blocking antibody, prolonged mice survival. Importantly, we identified human CD1d-restricted lymphoma cells within Vδ1 TCR-expressing PTCL. These results define a new subtype of PTCL and pave the way for the development of blocking anti-CD1d antibody for therapeutic purposes in humans. PMID:27069116

  7. A Case of Malignant T-Cell Lymphoma of Gastric Origin Accompanied by Pyothorax

    Directory of Open Access Journals (Sweden)

    Naoki Asakage

    2009-06-01

    Full Text Available The patient was a 74-year-old man suffering from tuberculotic chronic pyothorax. He had hematemesis in January 2006. Hb was 6.1 g/dl. A type 2 tumor 3 cm in diameter was found in the vaulted region on the greater curvature side. It was diagnosed as a malignant lymphoma. WBC and differential count were normal, and the patient tested negative for HTVL-1 antibody. sIL2-R was elevated to 1,500 U/ml. The superficial lymph nodes were not palpable. CT examination was not remarkable for the liver and spleen. There was no generalized lymph node enlargement. Based on these findings, a diagnosis of malignant lymphoma of gastric origin was made. As the patient had respiratory disorders, too, wedge-shaped gastrectomy was performed to inhibit invasion. Pathological examination revealed CD3 positive large atypical lymphocytes diffusely, EBV positive, HP negative. As a result, a diagnosis of non-Hodgkin T-cell lymphoma was made. The tumor did not return for 1 year and 8 months after surgery, but the patient died of sudden aggravation of respiratory disorders in September 2007. Pathological anatomy was performed. The gastric remnant was left with lymphoma, and the bone marrow and systemic lymph nodes were negative for a malignant lymphoma. The possibility of stomach metastasis from the preoperative pyothorax-related malignant lymphoma was considered, but was ruled out because the lungs were devoid of a malignant lymphoma. We report a case of an extremely rare malignant T-cell lymphoma of gastric origin.

  8. Primary Testicular NK/T-Cell Lymphoma: A Study of Two Cases and Review of Literature

    Institute of Scientific and Technical Information of China (English)

    Xiao Lin; Dan Li; Peng Xie; Can Mi; Qing Lin

    2010-01-01

    Primary testicular NK/T-cell lymphoma is an extremely rare entity progressed rapidly.The aim of this study was to examine clinical and pathological features of primary testicular NK/T-cell lymphoma and to investigate the effective diagnosis and prognosis.In this paper,the two cases of primary testicular NK/T-cell lymphoma were observed by light microscopy,immunohistochemistry and examined by in situ hybridization for Epstein-Barr Virus(EBV)DNA and the literatures were reviewed.The two patients respectively present with bilateral and right-side painless testicular enlargement.The morphology of neoplastic cells of case 1 were small to medium,tumor cells of case 2 were small,medium and large mixed.The tumor cells grew diffusely with irregular and distort nuclear,destructed the organizational structure of the normal testis,and damaged blood vessels,meanwhile,coagulation necrosis was exist.Immunohistochemical staining of neoplastic cells showed positive for CD45,CD2,CD56,CD3ε(cytoplasm staining pattern),CD45RO and Granzyme B,and negative for CD57,CD20,CD79α,CD30,CK,MPO,TdT,Bcl-2 and PLAP were negative.In addition,the EBV DNA was detected in the lymphoma by In situ hybridization.In conclusion,the expression of CD56,CD3ε,and Granzyme B associated proteins and EBV examination by in situ hybridization play a vital role in diagnosis and differential diagnosis of primary testicular NK/T-cell lymphoma.

  9. Primary Testicular NK/T-Cell Lymphoma: A Study of Two Cases and Review of Literature

    Institute of Scientific and Technical Information of China (English)

    Xiao Lin; Dan Li; Peng Xie; Can Mi; Qing Lin

    2011-01-01

    Primary testicular NK/T-cell lymphoma is an extremely rare entity progressed rapidly.The aim of this study was to examine clinical and pathological features of primary testicular NK/T-cell lymphoma and to investigate the effective diagnosis and prognosis.In this paper,the two cases of primary testicular NK/T-cell lymphoma were observed by light microscopy,immunohistochemistry and examined by in situ hybridization for Epstein-Barr Virus (EBV) DNA and the literatures were reviewed.The two patients respectively present with bilateral and right-side painless testicular enlargement.The morphology of neoplastic cells of case 1 were small to medium,tumor cells of case 2 were small,medium and large mixed.The tumor cells grew diffusely with irregular and distort nuclear,destructed the organizational structure of the normal testis,and damaged blood vessels,meanwhile,coagulation necrosis was exist.Immunohistochemical staining of neoplastic cells showed positive for CD45,CD2,CD56,CD3s (cytoplasm staining pattern),CD45RO and Granzyme B,and negative for CD57,CD20,CD79a,CD30,CK,MPO,TdT,Bcl-2 and PLAP were negative.In addition,the EBV DNA was detected in the lymphoma by In situ hybridization.In conclusion,the expression of CD56,CD3e,and Granzyme B associated proteins and EBV examination by in situ hybridization play a vital role in diagnosis and differential diagnosis of primary testicularNK/T-cell lymphoma.

  10. Problems of primary T-cell lymphoma of the thyroid gland -A case report

    Directory of Open Access Journals (Sweden)

    Yokoyama Junkichi

    2012-04-01

    Full Text Available Abstract In the following report we discuss a very rare case of malignant T-cell lymphoma of the thyroid gland that developed in a 70-year-old woman with a past history of hypothyroidism due to chronic thyroiditis. The chief complaint was a rapidly growing neck mass. CT and ultrasonographic examination revealed a diffuse large thyroid gland without a nodule extending up to 13 cm. Although presence of abnormal lymphoid cells in the peripheral blood was not found, the sIL-2 Receptor antibody and thyroglobulin measured as high as 970 U/ml and 600 ng/mL respectively. Fine needle aspiration cytology diagnosed chronic thyroiditis. A preoperative diagnosis of suspicious malignant lymphoma of the thyroid gland accompanied by Hashimoto’s thyroiditis was made, and a right hemithyroidectomy was performed to definite diagnosis. Histological examination revealed diffuse small lymphocytic infiltration in the thyroid gland associated with Hashimoto’s thyroiditis. Immunohistochemical examination showed that the small lymphocytes were positive for T-cell markers with CD3 and CD45RO. The pathological diagnosis was chronic thyroiditis with atypical lymphocytes infiltration. However, Southern blot analysis of tumor specimens revealed only a monoclonal T-cell receptor gene rearrangement. Finally, peripheral T cell lymphoma was diagnosed. Therefore, the left hemithyroidectomy was also performed one month later. No adjuvant therapy was performed due to the tumor stage and its subtype. The patient is well with no recurrence or metastasis 22 months after the surgical removal of the thyroid. As malignant T-cell lymphoma of the thyroid gland with Hashimoto’s thyroiditis was difficult to diagnose, gene rearrangement examination needed to be performed concurrently.

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

    Directory of Open Access Journals (Sweden)

    Esperanza Martín-Sánchez

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

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

    Science.gov (United States)

    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. Non-tuberculous Mycobacteriosis with T-cell Lymphoma in a Red Panda (Ailurus fulgens).

    Science.gov (United States)

    Fuke, N; Hirai, T; Makimura, N; Goto, Y; Habibi, W A; Ito, S; Trang, N T; Koshino, K; Takeda, M; Yamaguchi, R

    2016-01-01

    A 9-year-old male red panda (Ailurus fulgens) became emaciated and died. Necropsy examination revealed systemic lymphadenomegaly. The liver, lungs and left kidney contained multifocal yellow nodules. Microscopical examination revealed granulomatous inflammation in the liver, lungs, kidney, spleen and lymph nodes, with numerous acid-fast bacilli. Sequencing of genetic material isolated from the tissues classified the pathogen as Mycobacterium gastri. Lymphoma was found in the liver, lungs, kidney and lymph nodes. The neoplastic cells were strongly labelled for expression of CD3, Ki67 and proliferating cell nuclear antigen by immunohistochemistry. This is the first report of M. gastri infection with T-cell lymphoma in a red panda.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Treatment of advanced cutaneous T-cell lymphomas (CTCL) is challenging because they are resistant to conventional chemotherapy. USP2 has been shown to promote resistance to chemotherapeutic agents in several cancer models.We show here USP2 is expressed in quiescent and activated T-cells and its e...... Mdm2 expression and upregulation of p53. Taken together, our findings suggest that USP2 stabilizes Mdm2 which antagonizes pro-apoptotic activity of p53 and possibly contributes to therapeutic resistance in CTCL....

  16. Primary NK/T cell lymphoma nasal type of the stomach with skin involvement: a case report

    Directory of Open Access Journals (Sweden)

    Sebastian Kobold

    2009-12-01

    Full Text Available Since nasal NK/T cell lymphoma and NK/T cell lymphoma nasal type are rare diseases, gastric involvement has seldom been seen. We report a unique case of a patient with a primary NK/T cell lymphoma nasal type of the stomach with skin involvement. The patient had no history of malignant diseases and was diagnosed with hematemesis and intense bleeding from his gastric primary site. Shortly after this event, exanthemic skin lesions appeared with concordant histology to the primary site. Despite chemotherapy, the patient died one month after the first symptomatic appearance of disease.

  17. A human T cell lymphoma secreting an immunoglobulin E specific helper factor.

    Science.gov (United States)

    Young, M C; Harfi, H; Sabbah, R; Leung, D Y; Geha, R S

    1985-06-01

    An 8-yr-old nonallergic girl with non-Hodgkin's lymphoma had markedly elevated serum IgE at presentation (greater than 10,000 IU/ml), negative skin tests to a battery of 24 common allergens, and no evidence of parasitic infestation. Serum levels of IgG, IgA, and IgM were normal. Remission after cytotoxic chemotherapy was accompanied by a marked reduction in serum IgE levels (to less than 200 IU/ml) with no change in the level of serum IgG, IgM, or IgA. Recurrence of the lymphoma 7 mo after remission was accompanied by an isotype specific rise in serum IgE (to 3,850 IU/ml). Isoelectric focusing revealed that the IgE was polyclonal. Phenotypic analysis of the lymphoma obtained during relapse revealed all (greater than 98%) cells to be T3+, T4+, and T8+. Incubation of lymphoma cells with human myeloma IgE followed by immunosorbent purified fluorescein tagged goat anti-human IgE (anti-IgE PS-adsorbed over IgE ADZ) stained 25% of the cells. In contrast, less than 1% of the cells were stained after incubation with human IgG followed by fluorescein conjugated goat anti-human IgE. Supernatants from lymphoma cells (5 X 10(6)/ml, 48 h) enhanced IgE production in B cells derived from four patients with allergic rhinitis (mean +/- SD picograms per milliliter of net IgE 930 +/- 320 in unstimulated cultures versus 2,450 +/- 650 in cultures stimulated with lymphoma supernatants; P less than 0.01) but did not induce IgE synthesis in B cells from two normal subjects that synthesized no IgE spontaneously. Lymphoma supernatants failed to enhance IgG synthesis by B cells of both allergic and nonallergic subjects. These results indicate that a T cell lymphoma comprised of cells bearing Fc receptors for IgE with a phenotype characteristic of immature T cells (i.e., T3+, T4+, T8+) exhibited IgE specific helper function. This lymphoma may represent the monoclonal expansion of a subpopulation of IgE specific helper T cells.

  18. HTLV 1 associated adult T cell lymphoma/leukemia a clinicopathologic, immunophenotypic tale of three cases from non-endemic region of south India

    Directory of Open Access Journals (Sweden)

    Faiq Ahmed

    2012-01-01

    Full Text Available Adult T cell lymphoma/leukemia is a peripheral T-cell neoplasm caused by human T-cell lymphotrophic virus-1, affects mostly adults with systemic involvement and poor prognosis. Diagnosis of adult T-Cell leukemia/Lymphoma is challenging. The clinico-pathologic and immuno-phenotypic features of the three cases will be presented.

  19. Ellipticine induces apoptosis in T-cell lymphoma via oxidative DNA damage

    DEFF Research Database (Denmark)

    Savorani, Cecilia; Manfé, Valentina; Biskup, Edyta;

    2015-01-01

    The tumor suppressor p53 is often mutated in human cancers. Restoring its antitumor activity has been shown to be a promising therapeutic approach for cancer treatment. Here we analyzed the activity and mechanism of a p53 reactivator, ellipticine, in a cellular model of cutaneous T-cell lymphoma ....... Our results provide evidence that ellipticine-induced apoptosis is exerted through DNA damage and does not require p53 activation in T-cell lymphoma....... the transcriptional activity of (G245S)p53 in SeAx. However, p53 siRNA knockdown experiments revealed that p53 was not required for ellipticine-induced apoptosis in CTCL. The lipophilic antioxidant α-tocopherol inhibited ellipticine-dependent apoptosis and we linked the apoptotic response to the oxidative DNA damage...

  20. Stenotrophomonas maltophilia with histopathological features mimicking cutaneous gamma/delta T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Natalie Kash

    2015-01-01

    Full Text Available We report a case of cutaneous Stenotrophomonas maltophilia infection which presented with clinical and histopathological findings that mimicked a gamma/delta (γδ T-cell lymphoma. In this case, tissue culture of the biopsy specimen was key to determining the diagnosis and allowing appropriate treatment with oral trimethoprim–sulfamethoxazole and topical silvadene. A prompt complete resolution of lesions was observed following antibiotic treatment, with no recurrence of disease over the last 5 years, supporting an infectious rather than malignant etiology. In our patient, radiation therapy was indicated based on the misdiagnosis of γδ T-cell lymphoma, which was supported both clinically and histopathologically. However, tissue culture in this case avoided unnecessary radiation exposure and highlights the role of tissue culture in the evaluation of the biopsy of an undiagnosed cutaneous lesion.

  1. Vorinostat approved in Japan for treatment of cutaneous T-cell lymphomas: status and prospects

    Directory of Open Access Journals (Sweden)

    Sato A

    2012-04-01

    Full Text Available Akinori SatoDepartment of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, JapanAbstract: Histone acetylation and deacetylation play important roles in the regulation of gene transcription and in the modulation of chromatin structure. The levels of histone acetylation are determined by the activities of histone acetyltransferases and histone deacetylases (HDACs. HDACs are associated with a number of oncogenes and tumor suppressor genes and can be aberrantly expressed and/or inappropriately activated in cancer cells. HDAC inhibitors have therefore recently emerged as a novel treatment modality against malignancies. They regulate gene expression by enhancing the acetylation of not only histones but also nonhistone proteins, including transcription factors, transcription regulators, signal transduction mediators, and DNA repair enzymes, and they inhibit cancer growth. Vorinostat (suberoylanilide hydroxamic acid is one of the most potent HDAC inhibitors, and was approved in Japan in 2011 for the treatment of cutaneous T-cell lymphoma. Numerous clinical trials have shown it to be effective against cutaneous T-cell lymphoma but less so against other types of cancer. Because vorinostat can overcome resistance to or enhance the efficacy of other anticancer agents, such as 5-fluorouracil, carboplatin, paclitaxel, bortezomib, and tamoxifen, combination therapies using vorinostat and these agents have been investigated. This review introduces the background and mechanism of action of vorinostat and describes the results of clinical trials using vorinostat, both as a single agent and in combination with other anticancer agents, against cutaneous T-cell lymphoma and other malignancies.Keywords: vorinostat, T-cell lymphoma, cancer, novel treatment

  2. Matrix Metalloproteinase-2 Promoter Genotype as a Marker of Cutaneous T-Cell Lymphoma Early Stage

    OpenAIRE

    Anna Vasku; Julie Bienertova Vasku; Miroslav Nečas; Vladimir Vasku

    2010-01-01

    The aim of the study was to investigate the DNA polymorphic genotype in MMP-2 promoter gene as a potential candidate region for the development of the cutaneous T-cell lymphoma (CTCL) and/or its progression. A total of 89 Czech patients with CTCL (including 23 patients with large plaque parapsoriasis) were compared to 198 controls of similar age and sex distribution, without personal or family history of chronic skin diseases and without personal history of malignancy. The three selected poly...

  3. Treatment of childhood cutaneous T-cell lymphoma with alpha-interferon plus PUVA.

    Science.gov (United States)

    Tay, Y K; Weston, W L; Aeling, J L

    1996-01-01

    All forms of cutaneous T-cell lymphoma are rare in childhood. We describe an 8-year-old boy with plaque-stage mycosis fungoides stage IIA whose cutaneous eruption had been present for 5 years. Histologic examination revealed the presence of a granulomatous infiltrate together with atypical lymphocytes within the dermis. The child had an excellent response to combination psoralen-UVA (PUVA) with interferon-alpha 2a treatment and is currently in remission.

  4. Peripheral T-cell lymphomas: A review of current approaches and hopes for the future.

    Directory of Open Access Journals (Sweden)

    Alan Pierre Skarbnik

    2013-05-01

    Full Text Available Peripheral T-cell lymphomas comprise a heterogeneous group of NHLs, with different clinical and biological behaviors, but with a common denominator of poor overall prognosis and lack of potentially curable approaches outside of the realm of stem cell transplantation. Recent data have elicited renewed hope in the treatment of this disease. The authors review the standard of care in treating PTCL, as well as novel therapeutic modalities.

  5. Recombinant interferon alfa-2a, an active agent in advanced cutaneous T-cell lymphomas.

    Science.gov (United States)

    Bunn, P A; Ihde, D C; Foon, K A

    1987-01-01

    The cutaneous T-cell lymphomas including mycosis fungoides and the Sézary syndrome, are indolent lymphomas with early systemic dissemination. Like the indolent B-cell lymphomas, they cannot be cured by currently available systemic chemotherapy so new systemic therapies need to be developed. A study of very high-dose recombinant interferon alfa-2a was, therefore, initiated in 20 patients with advanced cutaneous T-cell lymphoma (5 in stage II, 2 in stage III and 13 in stage IV). All patients were refractory to at least 2 standard therapies, including topical nitrogen mustard (18 patients), psoralens and ultraviolet A light (12 patients), total skin electron irradiation (14 patients) and systemic chemotherapy (16 patients). Nine out of 20 patients (45%; 95% confidence interval 25-69%) had either objective partial or complete responses within 3 months of starting treatment. Maximal response, however, often did not occur for at least one year. The median duration of response was 5.5 months and all complete responses lasted more than 2 years. Response frequencies were equal at both cutaneous and extracutaneous sites and in patients with or without prior chemotherapy. Toxicity was exhibited primarily as a flu-like syndrome consisting of fever, malaise, fatigue, anorexia and weight loss which necessitated dose reductions in all patients. Transient elevations in liver function and decreases in renal function and granulocyte counts occurred in some patients. It is concluded that interferon alfa-2a is highly active against advanced cutaneous T-cell lymphomas and that it should be studied in its early stages. It should also be evaluated in combination with other biological agents and with chemotherapy.

  6. MULTICENTRIC T-CELL LYMPHOMA AND CUTANEOUS HEMANGIOSARCOMA IN A CAPTIVE CHEETAH (ACINONYX JUBATUS).

    Science.gov (United States)

    Lindemann, Dana M; Carpenter, James W; Nietfeld, Jerome C; Gonzalez, Estehela; Hallman, Mackenzie; Hause, Ben M

    2015-12-01

    A 13-yr-old intact male cheetah (Acinonyx jubatus) presented for evaluation after a 4-mo history of intermittent lethargy and increased expiratory effort. The clinical signs were initially noted after the diagnosis and death of its 13-yr-old male sibling with solitary hepatic T-cell lymphoma. Physical examination findings included thin body condition, harsh lung sounds, peripheral lymphadenopathy, and a cutaneous mass on the right medial tarsus and scrotum. Excisional biopsies diagnosed well-differentiated cutaneous hemangiosarcomas. Thoracic radiographs revealed a cranial mediastinal mass. Complete blood count and serum biochemical analyses showed a leukocytosis with persistent lymphocytosis, progressive azotemia, and markedly elevated alkaline phosphatase. Because of the cheetah's declining quality of life, euthanasia was elected. Postmortem examination, histopathology, and immunohistochemical staining revealed multicentric T-cell lymphoma. Feline leukemia virus (FeLV) enzyme-linked immunosorbent assay, FeLV polymerase chain reaction (whole blood), and viral metagenomic analysis were negative. This is the first case of cutaneous hemangiosarcoma and multicentric T-cell lymphoma reported in a FeLV-negative cheetah.

  7. Angiolymphoid hyperplasia with eosinophilia developing in a patient with history of peripheral T-cell lymphoma: evidence for multicentric T-cell lymphoproliferative process

    Directory of Open Access Journals (Sweden)

    Auerbach Aaron

    2008-05-01

    Full Text Available Abstract Background Angiolymphoid hyperplasia with eosinophilia (ALHE is a vasocentric process characterized by infiltrates of lymphocytes and eosinophils, usually affecting the muscular arteries of the head and neck. Currently it is unclear whether it is a reactive or neoplastic process. Report We present a 61-year-old African American male with a twenty year history of superficial skin patches involving the head and neck region. An excisional biopsy of a right submental lymph node revealed an atypical T-cell lymphocytic process, diagnosed as peripheral T-cell lymphoma after immunophenotyping and molecular studies. Three months later the patient underwent a biopsy of a left temporal nodule that was diagnosed as ALHE. Subsequently, at two year follow-up, the patient was diagnosed with Mycosis Fungoides. Polymerase chain reaction for T cell receptor gamma showed the same T-cell receptor gene rearrangement in both the temporal mass and the right submental lymph node. Conclusion ALHE with molecular evidence of monoclonality is extremely unusual, as is the association with nodal peripheral T-cell nodal lymphoma. The findings of this case support our hypothesis that ALHE might be an early form of T-cell lymphoma.

  8. Clinical and pathological heterogeneity in cutaneous gamma-delta T-cell lymphoma: a report of three cases and a review of the literature.

    Science.gov (United States)

    Munn, S E; McGregor, J M; Jones, A; Amlot, P; Rustin, M H; Russell Jones, R; Whittaker, S

    1996-12-01

    Cutaneous gamma-delta (gamma delta) T-cell lymphoma is rare. Eleven cases have been reported to date including four cases of mycosis fungoides (MF), two of pagetoid reticulosis and five of pleomorphic cutaneous T-cell lymphoma (CTCL). We report three further cases of cutaneous gamma delta T-cell lymphoma; one of MF, one of a pleomorphic CTCL and one of a subcutaneous T-cell lymphoma. Combined data suggest that although cutaneous gamma delta T-cell lymphomas do not appear to comprise a single clinicopathological entity, they may be associated with aggressive clinical behaviour and a poor prognosis.

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

    Directory of Open Access Journals (Sweden)

    Vitor Ribeiro Paes

    2014-12-01

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

  10. A case of rapid growing colonic NK/T cell lymphoma complicated by Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Shumei Zheng; Hui Xu; Qin Ouyang; Linyun Xue; Yong Zhang; Dejun Cui

    2013-01-01

    A 37-year-old man developed abdominal pain and bloody diarrhea 11 months before admission.The colonoscopy revealed multifocal ulcers in the colon.Histology showed active chronic inflammation.Although anti-tuberculosis medication was effective,his symptoms repeated 2 months later.The subsequent colonoscopy revealed more extensive irregular ulcers than before,and he was clinically suspected with intestinal malignant lymphoma.He underwent subtotal colectomy and was histologically suggested Crohn's disease,then 5-aminosalicylic and a combination of prednisone and azathioprine were administered in succession postoperatively,but they achieved minimal relief of symptoms for a period of 7 months.The third colonoscopy showed a large irregular ulcer in the ileocolon stomas,and primary colonic NK/T cell lymphoma was diagnosed through histological and immunophenotypic studies.Malignant lymphoma should be taken into consideration when clinically diagnosed Crohn's disease was refractory to medication or when its clinical course became aggressive.

  11. Beyond the guidelines in the treatment of peripheral T-cell lymphoma: new drug development.

    Science.gov (United States)

    Chen, Andy I; Advani, Ranjana H

    2008-04-01

    Peripheral T-cell lymphomas (PTCLs) are a rare and diverse group of neoplasms with a poor prognosis. Management of these disorders has been largely extrapolated from the treatment of aggressive B-cell lymphomas; however, therapeutic responses to this approach are neither adequate nor durable for most patients with PTCL. Given the rarity of PTCL, much of the literature consists of studies with small sample size and anecdotal case reports. Therefore, no consensus exists on the best therapeutic strategy for either newly diagnosed or relapsed/refractory PTCL. This article reviews promising novel approaches in the treatment of PTCL and its subtypes. Investigation into the pathogenesis of PTCL has also identified new targets for treatment. These emerging therapies include new uses of existing agents and the development of novel agents specifically targeted against T-cell lymphoma. Results using antimetabolites, immunotherapies, and histone deacetylase inhibitors have been particularly encouraging. These novel therapies are being tested as single agents and in combination with conventional lymphoma regimens in the frontline and salvage settings. Because of the rarity and heterogeneity of PTCL, national and international cooperation is needed to conduct the clinical studies required for the development of more effective treatment paradigms. These efforts are ongoing and will hopefully guide new strategies to improve the historically poor outcome of PTCL.

  12. STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Brender, C; Nielsen, M; Kaltoft, K;

    2001-01-01

    A characteristic feature of neoplastic transformation is the loss of external control by cytokines and extracellular matrix of cellular differentiation, migration, and mitogenesis. Because suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine-induced signaling......, it has been hypothesized that an aberrant SOCS expression plays a role in neoplastic transformation. This study reports on a constitutive SOCS-3 expression in cutaneous T-cell lymphoma (CTCL) cell lines. SOCS-3 protein is constitutively expressed in tumor cell lines (but not in nonmalignant T cells......) obtained from affected skin from a patient with mycosis fungoides (MF) and from peripheral blood from a patient with Sezary syndrome (SS). In contrast, constitutive SOCS-3 expression is not found in the leukemic Jurkat T-cell line, the MOLT-4 acute lymphoblastic leukemia cell line, and the monocytic...

  13. Investigation of T-cell receptor-γ gene rearrangement in gastrointestinal lymphomas by PCR-SSCP analysis

    Institute of Scientific and Technical Information of China (English)

    Xi-Qun Han; Li He; Lan-Ying Shong; Hui-Yong Jiang; Mei-Gang Zhu; Tong Zhao

    2004-01-01

    AIM: To analyze the characterization of T-cell receptor-γ (TCR-γ) gene rearrangement in the gastrointestinal lymphomas and evaluate the value of PCR-SSCP analysis in gastrointestinal lymphomas investigation.METHODS: TCR-γgene rearrangement segments of gastrointestinal lymphomas were cloned and sequenced.Single clone plasmid and mixed clone plsamids were subsequently submitted to PCR-SSCP analysis to investigate the relationship between the number of amplified clones and band patterns of the amplified products. The PCR products of TCR-γgene rearrangement of 40 gastrointestinal lymphomas were electrophoresed on agarose gels and the positive cases on agarose gels were studied by SSCP analysis.RESULTS: The sequencing showed that TCR-γ gene rearrangement of the gastrointestinal lymphomas included functional gene and pseudogene with extensive variety in the junctional regions. In SSCP analysis, the number of the single-stranded bands was about two times of the number of amplified clones, and double-stranded band became broad with the increased number of the amplified clones. Thirteen of the 25 B-cell gastrointestinal lymphomas and 14 of the 15 gastrointestinal T-cell lymphomas were positive detected on agarose gel electrophoresis. Of the positive cases detected by SSCP analysis, 3 B-cell lymphomas and 13 T-cell lymphomas showed positive bands. The other cases showed only smears. The rearranged pattern included 13 monoallelic gene rearrangements and 3 biallelic or oligoclonal gene rearrangements.CONCLUSION: The pattern of TCR-γ, gene rearrangement in gastrointestinal lymphomas are similar to that of the nodular lymphomas. PCR-SSCP analysis for TCR-γ gene rearrangement can be applied both for adjuvant diagnosis of gastrointestinal lymphomas and analysis of the gene rearrangement pattern. The ratio of TCR-γ gene rearrangements occurred in T-cell gastrointestinal lymphomas is significantly higher than that in B-cell gastrointestinal lymphomas. The gene rearrangement

  14. Clinicopathology, immunophenotype, T cell receptor gene rearrangement, Epstein-Barr virus status and p53 gene mutation of cutaneous extranodal NK/T-cell lymphoma, nasal-type

    Institute of Scientific and Technical Information of China (English)

    WANG Ting-ting; XU Chen; LIU Shan-ling; KAN Bei; RAN Yu-ping; LIU Wei-ping; LI Gan-di

    2013-01-01

    Background Extranodal natural killer/T-cell (NK/T cell) lymphoma,nasal-type,is a rare lymphoma.Skin is the second most common site of involvement after the nasal cavity/nasalpharynx.The aim of this study was to investigate the clinicopathologic features,immunophenotype,T cell receptor (TCR) gene rearrangement,the association with Epstein-Barr virus (EBV) infection and p53 gene mutations of the lymphoma.Methods The clinicopathologic analysis,immunohistochemistry,in situ hybridization for EBER1/2,TCR gene rearrangement by polymerase chain reaction (PCR),mutations of p53 gene analyzed by PCR and sequence analysis were employed in this study.Results In the 19 cases,the tumor primarily involved the dermis and subcutaneous layer.Immunohistochemical staining showed that most of the cases expressed CD45RO,CD56,CD3ε,TIA-1 and GrB.Three cases were positive for CD3 and two cases were positive for CD30.Monoclonal TCRY gene rearrangement was found in 7 of 18 cases.The positive rate of EBER1/2 was 100%.No p53 gene mutation was detected on the exon 4-9 in the 18 cases.Fifteen cases showed Pro (proline)/Arg (arginine) single nucleotide polymorphisms (SNPs) on the exon 4 at codon 72.The expression of p53 protein was 72% (13/18) immunohistochemically.Conclusions Cutaneous NK/T-cell lymphoma is a rare but highly aggressive lymphoma with poor prognosis.No p53 gene mutation was detected on the exon 4-9,and Pro/Arg SNPs on p53 codon 72 were detected in the cutaneous NK/T-cell lymphoma.The overexpression of p53 protein may not be the result of p53 gene mutation.

  15. Histone deacetylase 1, 2, 6 and acetylated histone H4 in B- and T-cell lymphomas

    DEFF Research Database (Denmark)

    Marquard, L.; Poulsen, C.B.; Gjerdrum, L.M.;

    2009-01-01

    AIMS: Histone deacetylase (HDAC) inhibitors are novel therapeutics in the treatment of peripheral T-cell lymphoma, unspecified (PTCL) and diffuse large B-cell lymphoma (DLBCL), where, for unknown reasons, T-cell malignancies appear to be more sensitive than B-cell malignancies. The aim was to det......AIMS: Histone deacetylase (HDAC) inhibitors are novel therapeutics in the treatment of peripheral T-cell lymphoma, unspecified (PTCL) and diffuse large B-cell lymphoma (DLBCL), where, for unknown reasons, T-cell malignancies appear to be more sensitive than B-cell malignancies. The aim...... was to determine HDAC expression in DLBCL and PTCL which has not previously been investigated. METHODS AND RESULTS: The expression of HDAC1, HDAC2, HDAC6 and acetylated histone H4 was examined immunohistochemically in 31 DLBCL and 45 PTCL. All four markers showed high expression in both DLBCL and PTCL compared...

  16. T-cell receptor (TCR) phenotype of nodal Epstein-Barr virus (EBV)-positive cytotoxic T-cell lymphoma (CTL): a clinicopathologic study of 39 cases.

    Science.gov (United States)

    Kato, Seiichi; Asano, Naoko; Miyata-Takata, Tomoko; Takata, Katsuyoshi; Elsayed, Ahmed Ali; Satou, Akira; Takahashi, Emiko; Kinoshita, Tomohiro; Nakamura, Shigeo

    2015-04-01

    Among Epstein-Barr virus (EBV)-positive cytotoxic T/NK-cell lymphoma, there are only a few reports on the clinicopathologic features of patients with primary nodal presentation (nodal EBV cytotoxic T-cell lymphoma [CTL]). Here, we compared the clinicopathologic profiles of 39 patients with nodal EBV CTL with those of 27 cases of "extranasal" NK/T-cell lymphoma of nasal type (ENKTL), especially addressing their T-cell receptor (TCR) phenotype. Histologically, 22 of 39 nodal EBV CTL cases (56%) were unique in having centroblastoid appearance, which was contrasted with the lower incidence of this feature in ENKTL (15%, P=0.001). In contrast, pleomorphic appearance was more frequently seen in ENKTL than in nodal EBV CTL (67% vs. 23%, P=0.001). Thirty-three of 39 nodal EBV CTL cases (85%) were of T-cell lineage on the basis of TCR expression and/or TCRγ gene rearrangement; in detail, 18 cases (46%) were TCRβ positive (αβ T), 5 (13%) were TCRγ and/or δ positive (γδ T), and 10 (26%) were TCR-silent type with clonal TCRγ gene rearrangement but no expression of TCRβ, γ, or δ. These results were clearly contrasted by a lower incidence of T-cell lineage in ENKTL (7 cases, 26%, PEBV CTL is distinct from ENKTL.

  17. STAT5 induces miR-21 expression in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Lindahl, Lise M; Fredholm, Simon; Joseph, Claudine

    2016-01-01

    In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression...... in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR- 21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression...... T cells and cultured cytokine-dependent SS cells (SeAx). siRNA-mediated depletion of STAT5 inhibited constitutive- and IL-2- induced miR-21 expression in cytokine- independent and dependent T cell lines, respectively. IL-15 and IL-2 were more potent than IL-21 in inducing miR-21 expression...

  18. Peripheral T-cell lymphomas unspecified presenting in the skin : analysis of prognostic factors in a group of 82 patients

    NARCIS (Netherlands)

    Bekkenk, MW; Vermeer, MH; Jansen, PM; van Marion, AMW; Cunninga-van Dijk, MR; Kluin, PM; Geerts, ML; Meijer, CJLM; Willemze, R

    2003-01-01

    In the present study the clinicopathologic and immunophenotypic features of 82 patients with a CD30(-) peripheral T-cell lymphoma, unspecified, presenting in the skin were evaluated. The purpose of this study was to find out whether subdivision of these lymphomas on the basis of cell size, phenotype

  19. Staphylococcus aureus enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Willerslev-Olsen, Andreas; Krejsgaard, Thorbjørn; Lindahl, Lise Maria;

    2016-01-01

    Cutaneous T-cell lymphoma (CTCL) is characterized by proliferation of malignant T cells in a chronic inflammatory environment. With disease progression, bacteria colonize the compromised skin barrier and half of CTCL patients die of infection rather than from direct organ involvement by the malig...

  20. Ultrasonographic thickening of the muscularis propria in feline small intestinal small cell T-cell lymphoma and inflammatory bowel disease

    OpenAIRE

    2013-01-01

    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...

  1. An update on the management of peripheral T-cell lymphoma and emerging treatment options

    Directory of Open Access Journals (Sweden)

    Phillips AA

    2011-09-01

    Full Text Available Adrienne A Phillips1, Colette Owens2, Sangmin Lee1, Govind Bhagat31Division of Medical Oncology, Department of Medicine, 2Division of General Medicine, Department of Medicine, 3Department of Pathology and Cell Biology, Columbia University Medical Center and New York Presbyterian Hospital, Columbia University, New York, NY, USAAbstract: Peripheral T-cell lymphomas (PTCLs comprise a rare and heterogeneous subset of non-Hodgkin’s lymphomas (NHLs that arise from post-thymic T-cells or natural killer (NK-cells at nodal or extranodal sites. Worldwide, PTCLs represent approximately 12% of all NHLs and the 2008 World Health Organization (WHO classification includes over 20 biologically and clinically distinct T/NK-cell neoplasms that differ significantly in presentation, pathology, and response to therapy. Because of the rarity and heterogeneity of these diseases, large clinical trials have not been conducted and optimal therapy is not well defined. Most subtypes are treated with similar combination chemotherapy regimens as used for aggressive B-cell NHL, but with poorer outcomes. New treatment combinations and novel agents are currently being explored for PTCLs and this review highlights a number of options that appear promising.Keywords: treatment, non-Hodgkin’s lymphoma, novel therapy, natural-killer cells

  2. Extranodal NK/T-cell lymphoma presenting with primary cardiac involvement

    Directory of Open Access Journals (Sweden)

    Lisa M. Lepeak

    2011-08-01

    Full Text Available Primary cardiac lymphoma is extremely uncommon. We report a case of a 54 year old Caucasian male with a history of non-small cell lung cancer treated by surgical resection who presented with chest pain and dyspnea on exertion. Computerized tomography (CT imaging confirmed a 7.8¥3.8 cm right atrial soft tissue mass infiltrating the lateral wall of the right atrium, and a 5 cm pericardiophrenic mass. Echocardiography confirmed a moderate pericardial effusion without tamponade physiology. Percutaneous biopsy of the pericardiophrenic mass revealed pathologic features diagnostic of NK/T-cell lymphoma. He received CHOP chemotherapy with some improvement in symptoms, but experienced radiographic progression after 2 cycles. He received palliative involved field radiotherapy but developed new sites of progressive disease within the abdomen and died shortly after completing radiotherapy. NK/T-cell lymphomas are aggressive tumors that may present with unusual extranodal disease sites. Prompt diagnosis with consideration for referral to a specialty center with experience in treatment of these rare tumors may offer the greatest potential for improving treatment outcomes.

  3. Mogamulizumab for the treatment of adult T-cell leukemia/lymphoma

    Directory of Open Access Journals (Sweden)

    Yoshimitsu M

    2014-12-01

    Full Text Available Makoto Yoshimitsu, Naomichi Arima Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan Abstract: Adult T-cell leukemia/lymphoma (ATLL is a peripheral T-cell lymphoma caused by latent infection of human T-cell lymphotropic virus type 1. The outcome for ATLL is very poor, with a 3-year overall survival of approximately 24% with conventional chemotherapy; thus, there is an unmet need for developing new treatment options. Defucosylated humanized anti-CC chemokine receptor 4 (CCR4 antibody (KW-0761, mogamulizumab has been clinically available for the treatment of relapsed or refractory ATLL in Japan since 2012, and a Phase II study of mogamulizumab for patients with relapsed CCR4+ ATLL demonstrated a 50% objective response, a 30.8% complete response, and an acceptable safety profile. Allogeneic hematopoietic stem cell transplantation has been used to treat patients with ATLL, and mogamulizumab in combination with allogeneic hematopoietic stem cell transplantation has been used successfully in a limited number of patients to treat refractory or relapsed ATLL. The efficacy of combining mogamulizumab with standard chemotherapy (mLSG15 for patients with ATLL has also been examined, and the results have shown higher rates of complete response with the combined therapy (52% compared with for chemotherapy alone (33%. Mogamulizumab also has potential application in the treatment of human T-cell lymphotropic virus type 1-associated myelopathy/tropical paraparesis, Epstein–Barr virus-associated T-cell and natural killer-cell lymphoproliferative diseases, and peripheral and cutaneous T-cell lymphomas. Possible adverse events of mogamulizumab have been reported, such as cutaneous adverse reactions (including Stevens–Johnson syndrome, diffuse panbronchiolitis, reactivation of hepatitis B, and opportunistic infections. The treatment outcome of patients

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

    Science.gov (United States)

    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.

  5. Hydroa Vacciniforme-Like EBV-Positive Cutaneous T-Cell Lymphoma, First Report of 2 Cases in Ecuador.

    Science.gov (United States)

    Montalvo, Nelson; Redrobán, Ligia

    2016-05-01

    Hydroa vacciniforme-like cutaneous lymphoma is a very rare Epstein-Barr virus positive peripheral T-cell lymphoma affecting Asian and Hispanic children and young adults with a defective cytotoxic immune response to EBV predisposing to the development of the disease. We report on 2 Ecuadorian patients with papulovesicular and ulcerated crusted lesions on the face, upper and lower extremities and abdomen, with aggressive clinical course and, in one case, a fatal outcome. The histological and molecular profiles (immunohistochemistry and in situ hybridization) established a diagnosis of hydroa vacciniforme-like Epstein-Barr virus-encoded small RNAs + cutaneous T-cell lymphoma in both cases.

  6. Rapid progression of mediastinal tumor within a few days: A case report of T cell lymphoblastic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Tae Ran; Lee, Young Kyung; Jun, Hyun Jung; Jung, Eun Ah; Son, Jin Sung [Seoul Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    T-cell lymphoblastic lymphoma is a highly aggressive tumor derived from lymphocyte of the thymus, which accounts for 2% of non-Hodgkin's lymphoma. The disease occurs most commonly in adolescent and young adult males. It often results in respiratory emergency because of high proliferation rate. In this case, we confirmed the rapid progression of T-cell lymphoblastic lymphoma through the chest CT scan with one week interval. Three days of empirical chemotherapy resulted in substantial reduction of mediastinal mass, pleural thickening and pleural effusion.

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

    Science.gov (United States)

    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

  8. PRIMARY CUTANEOUS T-CELL LYMPHOMA - CLINICOPATHOLOGICAL FEATURES AND PROGNOSTIC PARAMETERS OF 35 CASES OTHER THAN MYCOSIS-FUNGOIDES AND CD30-POSITIVE LARGE-CELL LYMPHOMA

    NARCIS (Netherlands)

    BELJAARDS, RC; MEIJER, CJLM; VANDERPUTTE, CJ; HOLLEMA, H; GEERTS, ML; BEZEMER, PD; WILLEMZE, R

    1994-01-01

    Within the group of primary cutaneous T-cell lymphomas (CTCLs), mycosis fungoides (MF), Sezary's syndrome (SS), and CD30-positive lymphomas have been delineated as clinicopathological entities. Primary CTCLs that do not belong to one of these entities represent a heterogeneous and ill-defined group

  9. Clinical significance of T-cell clonality in mycosis fungoides and other cutaneous T-cell lymphomas

    NARCIS (Netherlands)

    Muche, Joachim Marcus

    2010-01-01

    The purpose of this thesis was to obtain more insight into T-cell clonality in blood of mycosis fungoides (MF) patients. Investigation of the frequency of blood T-cell clonality clearly indicated early dissemination of neoplastic T-cells into skin and blood as a sign of physiological recirculation.

  10. Independent Loss of Methylthioadenosine Phosphorylase (MTAP) in Primary Cutaneous T-Cell Lymphoma.

    Science.gov (United States)

    Woollard, Wesley J; Kalaivani, Nithyha P; Jones, Christine L; Roper, Catherine; Tung, Lam; Lee, Jae Jin; Thomas, Bjorn R; Tosi, Isabella; Ferreira, Silvia; Beyers, Carl Z; McKenzie, Robert C T; Butler, Rosie M; Lorenc, Anna; Whittaker, Sean J; Mitchell, Tracey J

    2016-06-01

    Methylthioadenosine phosphorylase (MTAP) and the tumor suppressor genes CDKN2A-CDKN2B are frequently deleted in malignancies. The specific role of MTAP in cutaneous T-cell lymphoma subgroups, mycosis fungoides (MF) and Sézary syndrome (SS), is unknown. In 213 skin samples from patients with MF/SS, MTAP copy number loss (34%) was more frequent than CDKN2A (12%) in all cutaneous T-cell lymphoma stages using quantitative reverse transcription PCR. Importantly, in early stage MF, MTAP loss occurred independently of CDKN2A loss in 37% of samples. In peripheral blood mononuclear cells from patients with SS, codeletion with CDKN2A occurred in 18% of samples but loss of MTAP alone was uncommon. In CD4(+) cells from SS, reduced MTAP mRNA expression correlated with MTAP copy number loss (P < 0.01) but reduced MTAP expression was also detected in the absence of copy number loss. Deep sequencing of MTAP/CDKN2A-CDKN2B loci in 77 peripheral blood mononuclear cell DNA samples from patients with SS did not show any nonsynonymous mutations, but read-depth analysis suggested focal deletions consistent with MTAP and CDKN2A copy number loss detected with quantitative reverse transcription PCR. In a cutaneous T-cell lymphoma cell line, promoter hypermethylation was shown to downregulate MTAP expression and may represent a mechanism of MTAP inactivation. In conclusion, our findings suggest that there may be selection in early stages of MF for MTAP deletion within the cutaneous tumor microenvironment.

  11. T-Cell Non-Hodgkin lymphoma associated with chronic tuberculous empyema: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ki Soon; Lee, Yul; Chung, Soo Young; Shin, Ho Seung; Park, Hee Chul; Ahn, Hye Kyung [Hallym University College of Medicine, Seoul (Korea, Republic of)

    1993-07-15

    Malignant neoplasm associated with long standing pleuritis or empyema is rare but a critical complication. Among 67 cases which were reported in English and Japanese literatures, the cause of empyema was considered to be tuberculosis in 51 cases. The most common malignant disease associated with the long standing pleural disease was non-Hodgkin lymphoma (NHL), and the majority of the malignant lymphomas were B-cell type. Detection of the malignant combined with an empyema is difficult, however, chest radiography or CT may show the evidence of malignant pleural disease. We report a case of pathologically proven T-cell type malignant NHL associated with chronic tuberculous empyema in a 66 year old male patient.

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

    Science.gov (United States)

    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

  13. T-Cell Traffic Jam in Hodgkin's Lymphoma: Pathogenetic and Therapeutic Implications.

    Science.gov (United States)

    Fozza, Claudio; Longinotti, Maurizio

    2011-01-01

    In hematologic malignancies, the microenvironment is often characterized by nonneoplastic cells with peculiar phenotypic and functional features. This is particularly true in Hodgkin's lymphoma (HL), in which T lymphocytes surrounding Hodgkin's Reed-Sternberg cells are essentially polarized towards a memory T-helper type 2 phenotype. In this paper we will first evaluate the main processes modulating T-cell recruitment towards the lymph node microenvironment in HL, especially focusing on the role played by cytokines. We will then consider the most relevant mechanisms of immune escape exerted by neoplastic cells in order to evade antitumor immunity. The potential pathogenetic and prognostic impact of regulatory T cells in such a context will be also described. We will finally overview some of the strategies of cellular immunotherapy applied in patients with HL.

  14. Advanced-Stage Primary Cutaneous T-Cell Lymphoma Treated with Bexarotene and Denileukin Diftitox

    Directory of Open Access Journals (Sweden)

    Iván Cervigón-González

    2011-02-01

    Full Text Available Advanced-stage primary cutaneous T-cell lymphoma has an unfavorable prognosis and low survival rates. Aggressive treatment with chemotherapy is not curative and causes considerable side effects. The combination of bexarotene and denileukin diftitox is associated with an acceptable safety profile and a likely synergistic effect because bexarotene is capable of modulating expression of IL-2 receptor and enhance the susceptibility of T-cell leukemia cells to denileukin diftitox. In the case reported here, the response to this combined treatment was satisfactory and well tolerated. The patient showed a complete regression of pruritus, restlessness, and insomnia. Skin lesions improved partially, and lymphadenopathy was reduced and finally disappeared completely.

  15. T-Cell Traffic Jam in Hodgkin's Lymphoma: Pathogenetic and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Claudio Fozza

    2011-01-01

    Full Text Available In hematologic malignancies, the microenvironment is often characterized by nonneoplastic cells with peculiar phenotypic and functional features. This is particularly true in Hodgkin's lymphoma (HL, in which T lymphocytes surrounding Hodgkin's Reed-Sternberg cells are essentially polarized towards a memory T-helper type 2 phenotype. In this paper we will first evaluate the main processes modulating T-cell recruitment towards the lymph node microenvironment in HL, especially focusing on the role played by cytokines. We will then consider the most relevant mechanisms of immune escape exerted by neoplastic cells in order to evade antitumor immunity. The potential pathogenetic and prognostic impact of regulatory T cells in such a context will be also described. We will finally overview some of the strategies of cellular immunotherapy applied in patients with HL.

  16. Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNalpha

    DEFF Research Database (Denmark)

    Brender, C; Lovato, P; Sommer, V H;

    2005-01-01

    Signal transducer and activator of transcription (Stat)3 is constitutively activated in cutaneous T-cell lymphoma (CTCL), where it protects tumour cells against apoptosis. The constitutive activation of Stat3 leads to a constitutive expression of suppressor of cytokine signalling (SOCS)-3....... In healthy cells, SOCS-3 is transiently expressed following cytokine stimulation and functions as a negative feedback inhibitor of the Stat3-activating kinases. Here, we attempt to resolve the apparent paradox of a simultaneous SOCS-3 expression and Stat3 activation in the same cells. We show that (i) SOCS-3...... expression in tumour cells is equal to or higher than in cytokine-stimulated nonmalignant T cells, (ii) SOCS-3 is not mutated in CTCL, (iii) overexpression of SOCS-3 blocks IFNalpha-mediated growth inhibition without affecting Stat3 activation, growth, and apoptosis, and (iv) inhibition of SOCS-3...

  17. Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol

    Directory of Open Access Journals (Sweden)

    Okudaira Taeko

    2009-01-01

    Full Text Available Abstract Background Adult T-cell leukemia/lymphoma (ATLL is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1, and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C, a naturally occurring component of Brassica vegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic and antiestrogenic properties in experimental studies. The aim of this study was to determine the potential anti-ATLL effects of I3C both in vitro and in vivo. Results In the in vitro study, I3C inhibited cell viability of HTLV-1-infected T-cell lines and ATLL cells in a dose-dependent manner. Importantly, I3C did not exert any inhibitory effect on uninfected T-cell lines and normal peripheral blood mononuclear cells. I3C prevented the G1/S transition by reducing the expression of cyclin D1, cyclin D2, Cdk4 and Cdk6, and induced apoptosis by reducing the expression of XIAP, survivin and Bcl-2, and by upregulating the expression of Bak. The induced apoptosis was associated with activation of caspase-3, -8 and -9, and poly(ADP-ribose polymerase cleavage. I3C also suppressed IκBα phosphorylation and JunD expression, resulting in inactivation of NF-κB and AP-1. Inoculation of HTLV-1-infected T cells in mice with severe combined immunodeficiency resulted in tumor growth. The latter was inhibited by treatment with I3C (50 mg/kg/day orally, but not the vehicle control. Conclusion Our preclinical data suggest that I3C could be potentially a useful chemotherapeutic agent for patients with ATLL.

  18. PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma.

    Science.gov (United States)

    Boi, Michela; Rinaldi, Andrea; Kwee, Ivo; Bonetti, Paola; Todaro, Maria; Tabbò, Fabrizio; Piva, Roberto; Rancoita, Paola M V; Matolcsy, András; Timar, Botond; Tousseyn, Thomas; Rodríguez-Pinilla, Socorro Maria; Piris, Miguel A; Beà, Sílvia; Campo, Elias; Bhagat, Govind; Swerdlow, Steven H; Rosenwald, Andreas; Ponzoni, Maurilio; Young, Ken H; Piccaluga, Pier Paolo; Dummer, Reinhard; Pileri, Stefano; Zucca, Emanuele; Inghirami, Giorgio; Bertoni, Francesco

    2013-10-10

    Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that can present as a systemic or primary cutaneous disease. Systemic ALCL represents 2% to 5% of adult lymphoma but up to 30% of all pediatric cases. Two subtypes of systemic ALCL are currently recognized on the basis of the presence of a translocation involving the anaplastic lymphoma kinase ALK gene. Despite considerable progress, several questions remain open regarding the pathogenesis of both ALCL subtypes. To investigate the molecular pathogenesis and to assess the relationship between the ALK(+) and ALK(-) ALCL subtypes, we performed a genome-wide DNA profiling using high-density, single nucleotide polymorphism arrays on a series of 64 cases and 7 cell lines. The commonest lesions were losses at 17p13 and at 6q21, encompassing the TP53 and PRDM1 genes, respectively. The latter gene, coding for BLIMP1, was inactivated by multiple mechanisms, more frequently, but not exclusively, in ALK(-)ALCL. In vitro and in vivo experiments showed that that PRDM1 is a tumor suppressor gene in ALCL models, likely acting as an antiapoptotic agent. Losses of TP53 and/or PRDM1 were present in 52% of ALK(-)ALCL, and in 29% of all ALCL cases with a clinical implication.

  19. Disseminated T-cell lymphoma in a Brazilian porcupine (Coendou prehensilis).

    Science.gov (United States)

    de Araújo, Marina Rios; Luppi, Marcela Miranda; Malta, Marcelo de Campos Cordeiro; Assumpção, Anna Luiza Facchetti Vinhaes; Langohr, Ingeborg Maria; Ecco, Roselene

    2011-01-01

    The current study describes the clinical, gross, histopathologic, and immunohistochemical findings of a T-cell lymphoma in a captive porcupine (Coendou prehensilis), a species typically seen in the tropical forests of Brazil. At necropsy, extensive neoplastic involvement was observed in the cervical lymph nodes, with extension into the salivary gland. The spleen was mildly enlarged, and neoplastic nodules were grossly evident in the liver and right kidney. Histologically, sheets of large and markedly pleomorphic round cells were observed in the cervical lymph nodes, lung, liver, spleen, and kidney. The neoplastic cells were positive for cluster of differentiation (CD)3 and negative for CD79a by immunohistochemistry.

  20. Treatment relapsed subcutaneous panniculitis-like T-cell lymphoma together HPS by Cyclosporin A

    Directory of Open Access Journals (Sweden)

    Ren'an Chen

    2010-11-01

    Full Text Available A 25-year-old man was diagnosised subcutaneous panniculitis-like T-cell lymphoma (SPTCL through biopsy of a nodule from the anterior chest. After the treatment with prednisone 90 mg 3 weeks and tapered off in 1 month, the disease released, but relapsed together with symptions of hemophagocytic syndrome eight months after the termination of prednisone. CHOEP recipe was given but with unsatisfactory result until cyclosporine was prescribed. Cyclosporine was removed 6 months later. There is no evidence of clinical relapse 1 year later. This case suggest that cyclosporine could be a selectable treatment even in relapsed SPTCL.

  1. Extranodal Natural Killer/T-Cell Lymphoma of the Nasal Type with Skin Metastases

    Directory of Open Access Journals (Sweden)

    Fadi Al Akhrass

    2016-01-01

    Full Text Available Extranodal natural killer/T-cell lymphoma (ENKL of the nasal type is a rare, clinically aggressive disease. ENKL of the nasal type is often localized in the upper aerodigestive tract, including the nasal cavity, nasopharynx, paranasal sinuses, tonsils, hypopharynx and larynx, and usually presents as stage I/II. Extranasal involvement can occur, and a common site of extranasal involvement or metastatic disease includes the skin. Identifying skin metastases is important for the appropriate staging and treatment. We report a case of ENKL of the nasal type that presented with localized disease and subsequent skin lesions that were consistent with skin metastases.

  2. CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder.

    Science.gov (United States)

    Lefèvre, Guillaume; Copin, Marie-Christine; Roumier, Christophe; Aubert, Hélène; Avenel-Audran, Martine; Grardel, Nathalie; Poulain, Stéphanie; Staumont-Sallé, Delphine; Seneschal, Julien; Salles, Gilles; Ghomari, Kamel; Terriou, Louis; Leclech, Christian; Morati-Hafsaoui, Chafika; Morschhauser, Franck; Lambotte, Olivier; Ackerman, Félix; Trauet, Jacques; Geffroy, Sandrine; Dumezy, Florent; Capron, Monique; Roche-Lestienne, Catherine; Taieb, Alain; Hatron, Pierre-Yves; Dubucquoi, Sylvain; Hachulla, Eric; Prin, Lionel; Labalette, Myriam; Launay, David; Preudhomme, Claude; Kahn, Jean-Emmanuel

    2015-08-01

    The CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3(-)CD4(+) T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome. Atypical CD4(+) T cells lymphoid infiltrates were found in 10 of 12 CD3(-)CD4(+) L-HES patients, in lymph nodes (n=4 of 4 patients), in skin (n=9 of 9) and other extra-nodal tissues (gut, lacrymal gland, synovium). Lymph nodes displayed infiltrates limited to the interfollicular areas or even an effacement of nodal architecture, associated with proliferation of arborizing high endothelial venules and increased follicular dendritic cell meshwork. Analysis of 2 fresh skin samples confirmed the presence of CD3(-)CD4(+) T cells. Clonal T cells were detected in at least one tissue in 8 patients, including lymph nodes (n=4 of 4): the same clonal T cells were detected in blood and in at least one biopsy, with a maximum delay of 23 years between samples. In the majority of cases, circulating CD3(-)CD4(+) T cells were CD2(hi) (n=9 of 14), CD5(hi) (n=12 of 14), and CD7(-)(n=4 of 14) or CD7(low) (n=10 of 14). Angio-immunoblastic T-cell lymphoma can also present with CD3(-)CD4(+) T cells; despite other common histopathological and immunophenotypic features, CD10 expression and follicular helper T-cell markers were not detected in lymphoid variant of hypereosinophilic syndrome patients, except in both patients who developed angio-immunoblastic T-cell lymphoma, and only at T-cell lymphoma diagnosis. Taken together, persistence of tissular clonal T cells and histopathological features define CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome as a peripheral indolent clonal T-cell lymphoproliferative

  3. STAT5 induces miR-21 expression in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Lindahl, Lise M; Fredholm, Simon; Joseph, Claudine;

    2016-01-01

    In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression...... in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR-21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression was inhibited...... by Tofacitinib (CP-690550), a clinical-grade JAK3 inhibitor. Chromatin immunoprecipitation (ChIP) analysis showed direct binding of STAT5 to the miR-21 promoter. Cytokine starvation ex vivo triggered a decrease in miR-21 expression, whereas IL-2 induced an increased miR-21 expression in primary SS T cells...

  4. NPM-ALK oncogenic tyrosine kinase controls T-cell identity by transcriptional regulation and epigenetic silencing in lymphoma cells.

    Science.gov (United States)

    Ambrogio, Chiara; Martinengo, Cinzia; Voena, Claudia; Tondat, Fabrizio; Riera, Ludovica; di Celle, Paola Francia; Inghirami, Giorgio; Chiarle, Roberto

    2009-11-15

    Transformed cells in lymphomas usually maintain the phenotype of the postulated normal lymphocyte from which they arise. By contrast, anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma with aberrant phenotype because of the defective expression of the T-cell receptor and other T-cell-specific molecules for still undetermined mechanisms. The majority of ALCL carries the translocation t(2;5) that encodes for the oncogenic tyrosine kinase NPM-ALK, fundamental for survival, proliferation, and migration of transformed T cells. Here, we show that loss of T-cell-specific molecules in ALCL cases is broader than reported previously and involves most T-cell receptor-related signaling molecules, including CD3epsilon, ZAP70, LAT, and SLP76. We further show that NPM-ALK, but not the kinase-dead NPM-ALK(K210R), downregulated the expression of these molecules by a STAT3-mediated gene transcription regulation and/or epigenetic silencing because this downregulation was reverted by treating ALCL cells with 5-aza-2-deoxycytidine or by knocking down STAT3 through short hairpin RNA. Finally, NPM-ALK increased the methylation of ZAP70 intron 1-exon 2 boundary region, and both NPM-ALK and STAT3 regulated the expression levels of DNA methyltransferase 1 in transformed T cells. Thus, our data reveal that oncogene-deregulated tyrosine kinase activity controls the expression of molecules that determine T-cell identity and signaling.

  5. Genetic alterations in systemic nodal and extranodal non-cutaneous lymphomas derived from mature T cells and natural killer cells.

    Science.gov (United States)

    Boi, Michela; Stathis, Anastasios; Zucca, Emanuele; Inghirami, Giorgio; Bertoni, Francesco

    2012-08-01

    Mature (peripheral) T-cell and natural killer (NK)-cell lymphomas comprise a series of rather different neoplasms. Based on morphologic, immunophenotypic, genetic, and clinical data, the World Health Organization classification recognizes more than 20 entities or provisional entities. The variable clinical presentations, the objective recognition and pathological stratification, the difficulties regarding treatment, and the hardly predictable response to therapy indicate that the management of these entities requires novel tools. In contrast to B-cell lymphomas or precursor T-cell neoplasms, few recurrent translocations have been identified so far in T-cell non-Hodgkin's and NK-cell lymphomas. Additionally, some of the entities recognized by the World Health Organization classification are very rare and very scarce molecular data are available for T-cell lymphomas. Here, we have reviewed published reports focusing on the genetic lesions and gene expression profiling underlying systemic nodal and extranodal non-cutaneous mature T-cell and NK-cell lymphomas. We also provide a summary of new agents in clinical development and outline some future directions.

  6. Emperipolesis-like invasion of neoplastic lymphocytes into hepatocytes in feline T-cell lymphoma.

    Science.gov (United States)

    Suzuki, M; Kanae, Y; Kagawa, Y; Ano, N; Nomura, K; Ozaki, K; Narama, I

    2011-05-01

    Twelve cases of feline malignant lymphoma with emperipolesis-like invasion of neoplastic lymphocytes were examined microscopically, immunohistochemically and ultrastructurally. Intracytoplasmic invasion of neoplastic cells varied in severity between the cases, between hepatic lobules and between areas within the lobules. The number of infiltrating neoplastic cells ranged from one to several per hepatocyte. Neoplastic cells exhibited widely varying morphology from case-to-case and cell-to-cell within each case, and contained eosinophilic cytoplasmic granules in four cases. Immunohistochemical examination revealed that neoplastic cells in 11 of the 12 cases expressed one or both T-cell markers (CD3 and TIA-1). Diagnosis of T-cell lymphoma was also confirmed by assessment of clonality by polymerase chain reaction. Ultrastructural analysis revealed that the neoplastic lymphocytes were contained within an invagination of the cell membrane of the hepatocyte, rather than directly infiltrating into the cytoplasm of the cell. There was no evidence that the invasive neoplastic lymphocytes had a cytotoxic effect.

  7. Ellipticine induces apoptosis in T-cell lymphoma via oxidative DNA damage.

    Science.gov (United States)

    Savorani, Cecilia; Manfé, Valentina; Biskup, Edyta; Gniadecki, Robert

    2015-03-01

    The tumor suppressor p53 is often mutated in human cancers. Restoring its antitumor activity has been shown to be a promising therapeutic approach for cancer treatment. Here we analyzed the activity and mechanism of a p53 reactivator, ellipticine, in a cellular model of cutaneous T-cell lymphoma (CTCL), a disease that is progressive, chemoresistant and refractory to treatment. We tested the effect of ellipticine in three cell lines with different p53 status: MyLa2000 (p53(wt/wt)), SeAx ((G245S)p53) and Hut-78 ((R196Stop)p53). Ellipticine caused apoptosis in MyLa2000 and SeAx and restored the transcriptional activity of (G245S)p53 in SeAx. However, p53 siRNA knockdown experiments revealed that p53 was not required for ellipticine-induced apoptosis in CTCL. The lipophilic antioxidant α-tocopherol inhibited ellipticine-dependent apoptosis and we linked the apoptotic response to the oxidative DNA damage. Our results provide evidence that ellipticine-induced apoptosis is exerted through DNA damage and does not require p53 activation in T-cell lymphoma.

  8. Nasal Type Extranodal Natural Killer/T (NK/T) Cell Lymphoma Presenting as Periorbital Cellulitis: A Case Report

    Science.gov (United States)

    Shawabkeh, Ma’in Ali Al; Sulaiti, Mansour Al; Sa’ey, Hamad Al; Ganesan, Shanmugam

    2016-01-01

    Patient: Male, 25 Final Diagnosis: Nasal type • extra nodal NK/T-cell lymphoma Symptoms: Left periorbital swelling • redness • pain for 25 days • yellowish eye discharge associated • headache • fever Medication: — Clinical Procedure: — Specialty: Otolaryngology Objective: Unusual clinical course Background: Extranodal lymphoma of the paranasal sinuses is a rare clinical entity seen in only 5–8% of extranodal lymphomas of the head and neck. Nasal natural killer/T cell lymphoma (Nasal NKTCL), which is a subtype of peripheral T cell lymphoma, constitutes about 1.4% of all lymphomas. NKTCL is usually diagnosed at a late stage because it presents with nonspecific symptoms in the early stages. Case Report: We report the case of a 25-year-old male patient who presented with periorbital swelling treated as fungal sinusitis but proven to have NKTCL. We review the literature and discuss the clinical manifestations of the disease, its relation to EBV virus, the histological and radiological characteristics, the prognostic indicators, and treatment options. This case report shows physicians that NKTCL lymphoma can present as periorbital cellulitis, although few similar cases are found in the literature. Conclusions: NKTCL is a destructive midline tumor that should be kept in mind as a differential diagnosis of paranasal sinus lesions to help in early diagnosis, which can improve the prognosis. PMID:27932776

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

    Science.gov (United States)

    Wei, Tianling; Biskup, Edyta; Gjerdrum, Lise Mette Rahbek; Niazi, Omid; Ødum, Niels; Gniadecki, Robert

    2016-07-26

    Treatment of advanced cutaneous T-cell lymphomas (CTCL) is challenging because they are resistant to conventional chemotherapy. USP2 has been shown to promote resistance to chemotherapeutic agents in several cancer models.We show here USP2 is expressed in quiescent and activated T-cells and its expression is 50% lower in CTCL cell lines (MyLa2000, SeAx and Hut-78) than in normal T-cells. USP2 is expressed in neoplastic cells in early, plaque-stage mycosis fungoides (MF) and is downregulated in advanced tumor stages. Upon treatment with psoralen with UVA (PUVA) or a p53 activator, nutlin3a, USP2 expression is significantly increased in MyLa2000 (p53wt/wt), but not in SeAx (p53mut) or Hut-78 (p53-/-). USP2 knockdown decreases MyLa2000 cell viability after PUVA by 50% but not Hut-78, suggesting that the function of USP2 in CTCL cells is p53-dependent. Furthermore, USP2 knockdown results in a decreased Mdm2 expression and upregulation of p53. Taken together, our findings suggest that USP2 stabilizes Mdm2 which antagonizes pro-apoptotic activity of p53 and possibly contributes to therapeutic resistance in CTCL.

  10. Infliximab induces clonal expansion of γδ-T cells in Crohn's disease: a predictor of lymphoma risk?

    Directory of Open Access Journals (Sweden)

    Jens Kelsen

    Full Text Available BACKGROUND: Concominant with the widespread use of combined immunotherapy in the management of Crohn's disease (CD, the incidence of hepato-splenic gamma-delta (γδ-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process resulting in the selection of malignant γδ-T cell clones. We hypothesised that repeated infusion of anti-TNF-α agents may induce clonal selection and that concurrent treatment with immunomodulators further predisposes patients to γδ-T cell expansion. METHODOLOGY/PRINCIPAL FINDINGS: We investigated dynamic changes in the γδ-T cells of patient with CD following treatment with infliximab (Remicade®; n=20 or adalimumab (Humira®; n=26 using flow cytometry. In patients with a high γδ-T cell level, the γδ-T cells were assessed for clonality. Of these 46 CD patients, 35 had a γδ-T cells level (mean 1.6% comparable to healthy individuals (mean 2.2%, and 11 CD patients (24% exhibited an increased level of γδ-T cells (5-15%. In the 18 patients also receiving thiopurines or methotrexate, the average baseline γδ-T cell level was 4.4%. In three male CD patients with a high baseline value, the γδ-T cell population increased dramatically following infliximab therapy. A fourth male patient also on infliximab monotherapy presented with 20% γδ-T cells, which increased to 25% shortly after treatment and was 36% between infusions. Clonality studies revealed an oligoclonal γδ-T cell pattern with dominant γδ-T cell clones. In support of our clinical findings, in vitro experiments showed a dose-dependent proliferative effect of anti-TNF-α agents on γδ-T cells. CONCLUSION/SIGNIFICANCE: CD patients treated with immunomodulators had constitutively high levels of γδ-T cells. Infliximab exacerbated clonal γδ-T cell expansion in vivo and induced γδ-T cell proliferation in vitro. Overall, young, male CD patients with high baseline γδ-T cell

  11. Amplification and overexpression of JUNB is associated with primary cutaneous T-cell lymphomas.

    Science.gov (United States)

    Mao, Xin; Orchard, Guy; Lillington, Debra M; Russell-Jones, Robin; Young, Bryan D; Whittaker, Sean J

    2003-02-15

    Primary cutaneous lymphomas (PCLs) represent a heterogeneous group of extranodal T- and B-cell malignancies. The underlying molecular pathogenesis of this malignancy remains unclear. This study aimed to characterize oncogene abnormalities in PCLs. Using genomic microarray, we detected oncogene copy number gains of RAF1 (3p25), CTSB (8p22), PAK1 (11q13), and JUNB (19p13) in 5 of 7 cases of mycosis fungoides (MF)/Sezary syndrome (SS) (71%), gains of FGFR1 (8p11), PTPN (20q13), and BCR (22q11) in 4 cases (57%), and gains of MYCL1 (1p34), PIK3CA (3q26), HRAS (11p15), MYBL2 (20q13), and ZNF217 (20q13) in 3 cases (43%). Amplification of JUNB was studied in 104 DNA samples from 78 PCL cases using real-time polymerase chain reaction. Twenty-four percent of cases, including 7 of 10 cases of primary cutaneous CD30(+) anaplastic large-cell lymphoma (C-ALCL), 4 of 14 MF, 4 of 22 SS, and 2 of 23 primary cutaneous B-cell lymphoma (PCBCL) showed amplification of JUNB, and high-level amplification of this oncogene was present in 3 C-ALCL and 2 MF cases. JUNB protein expression was analyzed in tissue sections from 69 PCL cases, and 44% of cases, consisting of 21 of 23 SS, 6 of 8 C-ALCL, 5 of 10 MF, and 9 of 21 PCBCL, demonstrated nuclear expression of JUNB by tumor cells. Overexpression of JUNB also was detected in 5 C-ALCL and 2 SS cases. These results have revealed, for the first time, amplification and expression patterns of JUNB in PCL, suggesting that JUNB may be critical in the pathogenesis of primary cutaneous T-cell lymphomas.

  12. Ultrasonographic thickening of the muscularis propria in feline small intestinal small cell T-cell lymphoma and inflammatory bowel disease.

    Science.gov (United States)

    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.

  13. Lack of suppressive CD4+CD25+FOXP3+ T cells in advanced stages of primary cutaneous T-cell lymphoma.

    Science.gov (United States)

    Tiemessen, Machteld M; Mitchell, Tracey J; Hendry, Lisa; Whittaker, Sean J; Taams, Leonie S; John, Susan

    2006-10-01

    Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls. Functional assays demonstrated a dichotomy in Treg function: in four out of 10 patients CD4+CD25+ T cells were incapable of suppressing autologous CD4+CD25- T-cell proliferation, whereas suppressive function was intact in the other six patients. Suppressive activity of Tregs inversely correlated with the peripheral blood tumor burden. T-plastin gene expression, used as a Sezary cell marker, confirmed that Sezary cells were heterogeneous for CD25 expression. Mixed lymphocyte reactions demonstrated that CD4+CD25- T cells from patients who lacked functional Tregs were susceptible to suppression by Tregs from healthy controls, and had not become suppressive themselves. Furthermore, we found reduced expression of Foxp3 in the CD4+CD25+ Tregs of these patients relative to the other six CTCL patients and controls. Our findings thus indicate a dysfunction of peripheral Tregs in certain CTCL patients, which correlates with tumor burden.

  14. Growth dynamics and cyclin expression in cutaneous T-cell lymphoma cell lines

    Directory of Open Access Journals (Sweden)

    Edyta Biskup

    2010-05-01

    Full Text Available We have investigated cell growth dynamics and cyclins B1 and E expression in cell lines derived from mycosis fungoides (MyLa, Sézary syndrome (SeAx, and CD30+ lympho-proliferative diseases (Mac1, Mac2a, JK. Mac1 and Mac2a had the highest growth rate (doubling time 18-28 h, >90% cycling cells whereas SeAx was proliferating slowly (doub-ling time 55 h, approximately 35% cycling cells. Expression of cyclin B1 correlated positively with doubling time whereas expression of cyclin E was unscheduled and constant across the investigated cell lines. All cell lines exhibited high expression of PCNA. Thus, we concluded that cyclin B1 could be used for rapid screening of cell proliferation in malignant lymphocytes derived from cutaneous T-cell lymphoma.

  15. Subcutaneous Panniculitis-Like T-Cell Lymphoma (SPTL in a Child with Spontaneous Resolution

    Directory of Open Access Journals (Sweden)

    Achiléa L. Bittencourt

    2011-01-01

    Full Text Available Subcutaneous panniculitis-like T-cell lymphomas (SPTLs α/β are rare in childhood. The present report refers to a case of a 7-year-old male child presenting an extensive skin lesion that began when he was 5 years of age. Two biopsies were evaluated using the CD3, CD4, CD8, CD56, βF1, and TIA markers. A dense infiltrate of CD3+, CD4−, CD8+, CD56−, βF1+, and TIA+ pleomorphic lymphocytes was found in the subcutis. The previous biopsy showed cytophagic histiocytic panniculitis with a small focus on CD8+ and βF1+ malignant cells. The lesion regressed spontaneously. This case shows that prognosis may be excellent in SPTL (α/β. On the other hand, it also serves as an alert that a biopsy performed in an area of cytophagic panniculitis may lead to misdiagnosis.

  16. Total skin electron beam irradiation for cutaneous T-cell lymphoma (mycosis fungoides)

    Energy Technology Data Exchange (ETDEWEB)

    Vloten, W.A. Van; Vroome, H. De; Noordijk, E.M. (Rijksuniversiteit Leiden (Netherlands))

    1985-06-01

    Forty patients with the cutaneous T-cell lymphoma (mycosis fungoides) were treated with total skin electron beam irradiation. The total follow-up period was up to 116 months (median 57.5 months). The patients were irradiated with a total dose of 35 Gy over 10 weeks, using the six-field technique. Ten of these patients had lymph node involvement and were subsequently treated with chemotherapy. After the initial electron irradiation complete remission of the skin lesions was obtained in 87.5% of the patients. Relapse of skin lesions occurred in 52% of the patients after 2-72 months (median 4 months). Second line therapy consisted primarily of topical nitrogen mustard. The overall survival rate at 5 years was 70%. Despite the side-effects this treatment was tolerated well by all patients.

  17. Subcutaneous panniculitis-like T-cell lymphoma in children. Literature review and case reports

    Directory of Open Access Journals (Sweden)

    D. S. Abramov

    2013-01-01

    Full Text Available Subcutaneous panniculitis-like T-cell lymphoma (SPTL is a rare tumor from αβ mature cytotoxic T-lymphocytes, which primarily affects the subcutaneous adipose tissue and has morphological manifestations similar to panniculitis. SPTL frequency is less than 1 % of all NHL. It occurs in all age groups, but only 19–20 % are patients younger 20 years. Median age of patients is 35–36 years. To date are only a few cases in children described. In this article we described 3 SPTL cases in patients 1, 10 and 17 years old with typical clinical presentation and detailed analysis.

  18. Subcutaneous panniculitis-like T-cell lymphoma in children. Literature review and case reports

    Directory of Open Access Journals (Sweden)

    D. S. Abramov

    2014-07-01

    Full Text Available Subcutaneous panniculitis-like T-cell lymphoma (SPTL is a rare tumor from αβ mature cytotoxic T-lymphocytes, which primarily affects the subcutaneous adipose tissue and has morphological manifestations similar to panniculitis. SPTL frequency is less than 1 % of all NHL. It occurs in all age groups, but only 19–20 % are patients younger 20 years. Median age of patients is 35–36 years. To date are only a few cases in children described. In this article we described 3 SPTL cases in patients 1, 10 and 17 years old with typical clinical presentation and detailed analysis.

  19. Denileukin diftitox for the treatment of cutaneous T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    David Kaminetzky

    2008-12-01

    Full Text Available David Kaminetzky1, Kenneth B Hymes21Division of Hematology/Oncology, New York University School of Medicine, New York, USA; 2New York University Cancer Institute, New York, USAAbstract: Cutaneous T-cell lymphoma/mycosis fungoides (CTCL/MF is a rare lymphoproliferative disorder which can present as an indolent or as an aggressive process involving skin, lymph nodes, and blood. In stages IA, IB and IIA, it is usually managed with topical medications and phototherapy. If there is progression despite application of these treatments, or if the patient presents with a higher stage of disease, systemic chemotherapy or retinoids, rexinoids, biologic response modifiers are often necessary. Consequently, patients are often treated with a sequence of modalities and drugs. Denileukin diftitox (DD, Ontak® is a targeted immunotoxin which has biological activity against malignancies expressing the IL-2 receptor. In addition to its unique mechanism of action, DD has a toxicity profile which does not overlap with most commonly used chemotherapeutic agents. CTCL/MF has been found be particularly susceptible to treatment with this agent. This review will describe the development DD, its proposed mechanism of action, the clinical trials which identified its utility in the treatment of CTCL/MF, the common toxicities encountered with this agent, and the management of these toxicities. In addition the incorporation of DD in the sequential treatment of CTCL/MF and data suggesting potential combination therapies employing this novel agent will be discussed.Keywords: T-cell lymphoma, mycosis fungoides, immunotoxin, cytokine therapy, denileukin diftitiox

  20. Lichen planus-like lesions as the first manifestation of adult T-cell leukaemia/lymphoma.

    Science.gov (United States)

    Sumida, Hayakazu; Sugaya, Makoto; Kamata, Masahiro; Suga, Hiraku; Miyagaki, Tomomitsu; Ohmatsu, Hanako; Fujita, Hideki; Sato, Shinichi

    2013-07-06

    Cutaneous involvement is frequent in adult T-cell leukaemia/lymphoma (ATLL), a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus type I (HTLV-I). Patients with ATLL manifest different types of skin lesions, including nodules, plaques, ulcers, erythroderma and purpura. It has been reported that this type of skin eruption is an independent prognostic factor for ATLL. We report here a rare case of a 62-year-old Japanese woman with smouldering-type ATLL, first manifested by lichen planus-like skin lesions on the lower leg. This case report highlights the multiplicity of skin manifestations in ATLL.

  1. Telomerase functions beyond telomere maintenance in primary cutaneous T-cell lymphoma.

    Science.gov (United States)

    Chevret, Edith; Andrique, Laetitia; Prochazkova-Carlotti, Martina; Ferrer, Jacky; Cappellen, David; Laharanne, Elodie; Idrissi, Yamina; Boettiger, Anna; Sahraoui, Wafa; Ruiz, Florian; Pham-Ledard, Anne; Vergier, Beatrice; Belloc, Francis; Dubus, Pierre; Beylot-Barry, Marie; Merlio, Jean-Philippe

    2014-03-20

    Telomere erosion may be counteracted by telomerase. Here we explored telomere length (TL) and telomerase activity (TA) in primary cutaneous T-cell lymphoma (CTCL) by using quantitative polymerase chain reaction and interphase quantitative fluorescence in situ hybridization assays. Samples from patients with Sézary syndrome (SS), transformed mycosis fungoides (T-MF), and cutaneous anaplastic large cell lymphoma were studied in parallel with corresponding cell lines to evaluate the relevance of TL and TA as target candidates for diagnostic and therapeutic purposes. Compared with controls, short telomeres were observed in aggressive CTCL subtypes such as SS and T-MF and were restricted to neoplastic cells in SS. While no genomic alteration of the hTERT (human telomerase catalytic subunit) locus was observed in patients' tumor cells, TA was detected. To understand the role of telomerase in CTCL, we manipulated its expression in CTCL cell lines. Telomerase inhibition rapidly impeded in vitro cell proliferation and led to cell death, while telomerase overexpression stimulated in vitro proliferation and clonogenicity properties and favored tumor development in immunodeficient mice. Our data indicate that, besides maintenance of TL, telomerase exerts additional functions in CTCL. Therefore, targeting these functions might represent an attractive therapeutic strategy, especially in aggressive CTCL.

  2. Chest HRCT findings in acute transformation of adult T-cell lymphoma/leukemia

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    Okada, Fumito; Sato, Haruka; Omeri, Ahmad Khalid; Ono, Asami; Tokuyama, Kouhei; Ando, Yumiko; Matsumoto, Akira; Mori, Hiromu [Oita University Faculty of Medicine, Department of Radiology, Yufu, Oita (Japan); Ogata, Masao; Kohno, Kazuhiro; Takano, Kuniko [Oita University Faculty of Medicine, Department of Medical Oncology and Hematology, Yufu, Oita (Japan)

    2015-06-01

    To assess chest high-resolution computed tomography (HRCT) findings in patients with acute transformation of adult T cell leukaemia/lymphoma (ATLL). We retrospectively identified 72 consecutive patients at our institution with ATLL between October 2000 and March 2014. The cases included acute type (n = 20), lymphoma type (n = 21), smouldering type (n = 24) and chronic type (n = 7). Sixteen (7 men, 9 women; aged 36-85 years, mean 63.3 years) of 31 patients (24 with smouldering and seven with chronic type; 51.6 %) developed acute transformation of ATLL, and had undergone chest HRCT examinations. Parenchymal abnormalities, enlarged lymph nodes, pericardial effusion, pleural effusion and skin lesions were evaluated on HRCT. Chest HRCT of 15 of the 16 patients showed abnormal findings, including ground-glass opacity (GGO) (n = 8), consolidation (n = 5), interlobular septal thickening (n = 5) and nodules (n = 5). Pleural effusion was found in five patients, lymph node enlargement in 10 patients and multiple skin thickening in two patients. Almost all patients with acute transformation of ATLL had abnormal findings on chest HRCT, which consisted mainly of lymph node enlargement, GGO, interlobular septal thickening, nodules and bilateral pleural effusions. (orig.)

  3. Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation.

    Science.gov (United States)

    Geskin, Larisa J; Viragova, Sara; Stolz, Donna B; Fuschiotti, Patrizia

    2015-04-30

    Cutaneous T-cell lymphomas (CTCLs) primarily affect skin and are characterized by proliferation of mature CD4(+) T-helper cells. The pattern of cytokine production in the skin and blood is considered to be of major importance for the pathogenesis of CTCLs. Abnormal cytokine expression in CTCLs may be responsible for enhanced proliferation of the malignant cells and/or depression of the antitumor immune response. Here we show that interleukin-13 (IL-13) and its receptors IL-13Rα1 and IL-13Rα2 are highly expressed in the clinically involved skin of CTCL patients. We also show that malignant lymphoma cells, identified by the coexpression of CD4 and TOX (thymus high-mobility group box), in the skin and blood of CTCL patients produce IL-13 and express both receptors. IL-13 induces CTCL cell growth in vitro and signaling through the IL-13Rα1. Furthermore, antibody-mediated neutralization of IL-13 or soluble IL-13Rα2 molecules can lead to inhibition of tumor-cell proliferation, implicating IL-13 as an autocrine factor in CTCL. Importantly, we established that IL-13 synergizes with IL-4 in inhibiting CTCL cell growth and that blocking the IL-4/IL-13 signaling pathway completely reverses tumor-cell proliferation. We conclude that IL-13 and its signaling mediators are novel markers of CTCL malignancy and potential therapeutic targets for intervention.

  4. Cytomegalovirus: its potential role in the development of cutaneous T-cell lymphoma.

    Science.gov (United States)

    Ballanger, F; Bressollette, C; Volteau, C; Planche, L; Dreno, B

    2009-06-01

    To investigate the potential role of CMV in cutaneous T-cell lymphoma (CTCL), we studied cytomegalovirus (CMV) seroprevalence in parapsoriasis (PP), mycosis fungoides (MF) and Sézary syndrome (SS) compared with healthy control patients. In cases where CMV seropositivity was observed, CMV PCR analyses were performed on skin biopsies. CMV seroprevalence was 37.1% in the control group, 50.68% in the PP + MF + SS group (P = 0.08), 56.2% in the MF + SS group (P = 0.07), 40% in the PP group (P = 0.9), 66.67% in the MF group (P = 0.009), 42.86% in the SS group (P = 0.9). CMV PCR in initial skin biopsies were all negative. However, PCR CMV was positive in two SS skin biopsies realized at an advanced stage. Our results show that latent CMV infection may play a role in the susceptibility of MF in predisposed subjects by inducing T-cell proliferation and resistance to apoptosis. Concerning SS, an immunosuppressive state may be responsible for CMV reactivation that in turn may interfere with evolution of the disease.

  5. Notch1 as a potential therapeutic target in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Biskup, Edyta; Lauenborg, Britt Thyssing;

    2010-01-01

    Deregulation of Notch signaling has been linked to the development of T-cell leukemias and several solid malignancies. Yet, it is unknown whether Notch signaling is involved in the pathogenesis of mycosis fungoides and Sézary syndrome, the most common subtypes of cutaneous T-cell lymphoma....... By immunohistochemistry of 40 biopsies taken from skin lesions of mycosis fungoides and Sézary syndrome, we demonstrated prominent expression of Notch1 on tumor cells, especially in the more advanced stages. The ¿-secretase inhibitor I blocked Notch signaling and potently induced apoptosis in cell lines derived from...... mycosis fungoides (MyLa) and Sézary syndrome (SeAx, HuT-78) and in primary leukemic Sézary cells. Specific down-regulation of Notch1 (but not Notch2 and Notch3) by siRNA induced apoptosis in SeAx. The mechanism of apoptosis involved the inhibition of nuclear factor-¿B, which is the most important...

  6. Conjunctival Involvement of T-Cell Lymphoma in a Patient with Mycosis Fungoides.

    Science.gov (United States)

    Aldrees, Sultan S; Zoroquiain, Pablo; Alghamdi, Sarah A; Logan, Patrick T; Callejo, Sonia; Burnier, Miguel N

    2016-01-01

    Background. Ocular involvement in mycosis fungoides (MF) cases occurs in one-third of patients with the eyelid being the most frequent site affected; however, conjunctival involvement is rarely reported. Herein, we report a rare case of conjunctival involvement of MF. Case Presentation. A 66-year-old man who was previously diagnosed with MF in 2010 and was treated presented in 2014 complaining of foreign body sensation and redness in both eyes. Slit lamp examination of both eyes showed erythematous conjunctival growth that extended circumferentially. Physical examination revealed erythematous skin lesions on different body parts. Conjunctival biopsy was performed and revealed a dense, highly polymorphic lymphocytic population. The immunophenotype demonstrated a neoplastic T-cell origin consistent with MF. A diagnosis of conjunctival involvement by MF was made. The conjunctiva was treated with radiotherapy resulting in tumor regression. There were no recurrences at the 6-month follow-up. Conclusion. T-cell lymphoma should be considered in patients with a history of MF presenting with conjunctival and skin lesions.

  7. Conjunctival Involvement of T-Cell Lymphoma in a Patient with Mycosis Fungoides

    Directory of Open Access Journals (Sweden)

    Sultan S. Aldrees

    2016-01-01

    Full Text Available Background. Ocular involvement in mycosis fungoides (MF cases occurs in one-third of patients with the eyelid being the most frequent site affected; however, conjunctival involvement is rarely reported. Herein, we report a rare case of conjunctival involvement of MF. Case Presentation. A 66-year-old man who was previously diagnosed with MF in 2010 and was treated presented in 2014 complaining of foreign body sensation and redness in both eyes. Slit lamp examination of both eyes showed erythematous conjunctival growth that extended circumferentially. Physical examination revealed erythematous skin lesions on different body parts. Conjunctival biopsy was performed and revealed a dense, highly polymorphic lymphocytic population. The immunophenotype demonstrated a neoplastic T-cell origin consistent with MF. A diagnosis of conjunctival involvement by MF was made. The conjunctiva was treated with radiotherapy resulting in tumor regression. There were no recurrences at the 6-month follow-up. Conclusion. T-cell lymphoma should be considered in patients with a history of MF presenting with conjunctival and skin lesions.

  8. MDM2 inhibitor nutlin-3a induces apoptosis and senescence in cutaneous T-cell lymphoma: Role of p53

    DEFF Research Database (Denmark)

    Manfé, Valentina; Biskup, Edyta Urszula; Johansen, Peter

    2012-01-01

    P53 is rarely mutated in cutaneous T-cell lymphoma (CTCL) and is therefore a promising target for innovative therapeutic approaches. Nutlin-3a is an inhibitor of MDM2 (human homolog of murine double minute 2), which disrupts its interaction with p53, leading to the stabilization and activation of p...

  9. Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway

    DEFF Research Database (Denmark)

    Krejsgaard, Thorbjørn Frej; Ralfkiær, Ulrik; Clasen-Linde, Erik;

    2011-01-01

    IL-17 is a proinflammatory cytokine that is crucial for the host's protection against a range of extracellular pathogens. However, inappropriately regulated expression of IL-17 is associated with the development of inflammatory diseases and cancer. In cutaneous T-cell lymphoma (CTCL), malignant T...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  11. Spontaneous interleukin-5 production in cutaneous T-cell lymphoma lines is mediated by constitutively activated Stat3

    DEFF Research Database (Denmark)

    Nielsen, Mette; Nissen, Mogens H; Gerwien, Jens

    2002-01-01

    Mycosis fungoides is a low-grade cutaneous T-cell lymphoma (CTCL) of unknown etiology. In advanced stages of CTCL, a shift in cytokine profile from T(H)1 to T(H)2 is observed, which coincides with eosinophilia, high levels of immunoglobulin E, and increased susceptibility to bacterial infections....

  12. Reduced Intensity Conditioning Before Partially Matched Donor Stem Cell Transplant in Treating Patients With Advanced Cutaneous T Cell Lymphoma

    Science.gov (United States)

    2016-04-11

    Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Stage IIB Mycosis Fungoides and Sezary Syndrome; Stage IIIA Mycosis Fungoides and Sezary Syndrome; Stage IIIB Mycosis Fungoides and Sezary Syndrome; Stage IVA Mycosis Fungoides and Sezary Syndrome; Stage IVB Mycosis Fungoides and Sezary Syndrome

  13. Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kim, Youn H; Duvic, Madeleine; Obitz, Erik;

    2007-01-01

    The efficacy and safety of zanolimumab in patients with refractory cutaneous T-cell lymphoma (CTCL) have been assessed in two phase 2, multicenter, prospective, open-label, uncontrolled clinical studies. Patients with treatment refractory CD4(+) CTCL (mycosis fungoides [MF], n = 38; Sézary syndro...

  14. Infliximab Induces Clonal Expansion of γδ-T Cells in Crohn’s Disease: A Predictor of Lymphoma Risk?

    DEFF Research Database (Denmark)

    Kelsen, Jens; Schwindt, Heinrich; Dige, Anders Kirch;

    2011-01-01

    Background: Concominant with the widespread use of combined immunotherapy in the management of Crohn’s disease (CD), the incidence of hepato-splenic gamma-delta (cd)-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process...

  15. Expression and prognostic value of regulatory T cells and M2 macrophages in diffuse large Bcell lymphoma tissues

    Institute of Scientific and Technical Information of China (English)

    徐原林

    2013-01-01

    Objective To explore the prognostic value of regulatory T cells (Tregs) and M2 macrophages in diffuse large B-cell lymphoma (DLBCL) tissues.Methods The expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of DLBCL,and it was

  16. In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3

    DEFF Research Database (Denmark)

    Sommer, V H; Clemmensen, O J; Nielsen, O

    2004-01-01

    A characteristic feature of neoplastic transformation is a perpetual activation of oncogenic proteins. Here, we studied signal transducers and activators of transcription (STAT) in patients with mycosis fungoides (MF)/cutaneous T-cell lymphoma (CTCL). Malignant lymphocytes in dermal infiltrates...

  17. CCR4 frameshift mutation identifies a distinct group of adult T cell leukaemia/lymphoma with poor prognosis.

    Science.gov (United States)

    Yoshida, Noriaki; Miyoshi, Hiroaki; Kato, Takeharu; Sakata-Yanagimoto, Mamiko; Niino, Daisuke; Taniguchi, Hiroaki; Moriuchi, Yukiyoshi; Miyahara, Masaharu; Kurita, Daisuke; Sasaki, Yuya; Shimono, Joji; Kawamoto, Keisuke; Utsunomiya, Atae; Imaizumi, Yoshitaka; Seto, Masao; Ohshima, Koichi

    2016-04-01

    Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology.

  18. Subcutaneous Panniculitic-Like T-Cell Lymphoma: A red alert! The role of a vigilant histopathologist

    Directory of Open Access Journals (Sweden)

    B Vijaya

    2011-01-01

    Full Text Available Subcutaneous panniculitic-like T-cell lymphoma constitutes a distinctive clinicopathologic entity derived from cytotoxic T lymphocytes. A 25-year-old female presented with fever and skin lesions over the upper limb, lower limb and trunk since 2 years. On examination, there were multiple subcutaneous, tender, erythematous, poorly circumscribed indurated plaques and nodules on the upper limbs and lower limbs. Histopathological examination revealed subcutaneous fat displaying a predominantly lobular infiltration of atypical lymphoid cells. Characteristically, there was rimming of individual fat cells by the surrounding neoplastic lymphocytes. Immunohistochemical evaluation of the neoplastic lymphocytes showed CD3 and CD5 immunoreactivity and CD30 and CD20 negativity. A diagnosis of subcutaneous panniculitic T-cell lymphoma was made. SPTCL is a rare cytotoxic lymphoma that can be misdiagnosed as benign panniculitis due to similarities in clinical and histological features between the two entities and thus cause a diagnostic hindrance.

  19. Acute spontaneous tumor lysis in anaplastic large T-cell lymphoma presenting with hyperuricemic acute renal failure.

    Science.gov (United States)

    Hsu, Hsiang-Hao; Huang, Chiu-Ching

    2004-01-01

    Acute spontaneous tumor lysis (ASTL) syndrome, an extremely rare disease, requires prompt recognition and aggressive management because it is fulminant at its outset, associated with severe metabolic derangement, and potentially reversible. We describe an unusual case in which spontaneous tumor lysis occurred in anaplastic large T-cell lymphoma associated with acute uric acid nephropathy, persistent oliguria, and shock. This case contrasts markedly with previously reported cases of ASTL syndrome, which developed mainly in the pathologic type of Burkitt lymphoma. To our knowledge, this is the first reported occurrence of ASTL syndrome associated with anaplastic large T-cell type lymphoma. This report also chronicles our successful experience with continuous renal replacement therapy in the presence of compromised hemodynamic status.

  20. Vesiculobullous variant of adult T-cell leukemia/lymphoma in a Caribbean Émigré.

    Science.gov (United States)

    Mouzakis, John; Black, William; Messina, Jane; Cherpelis, Basil

    2011-12-01

    Adult T-cell leukemia/lymphoma (ATLL) results from human T-cell lymphotropic virus (HTLV) type I infection and may present as a diverse array of cutaneous findings. Often these clinical manifestations are non-specific and overlap significantly with cutaneous T-cell lymphoma (CTCL). However, it is exceedingly rare for a patient suffering from ATLL to develop vesicular or bullous pathology and only a handful of such cases have been reported in the literature. The authors describe a patient of Jamaican descent afflicted with ATLL who developed an impressive vesiculobullous eruption. This case provides further support of the near complete clinical overlap between ATLL and CTCL. Patients from HTLV endemic areas with consistent clinical manifestations should have viral serologies drawn as the treatment and prognosis of ATLL and CTCL differ greatly.

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

    Science.gov (United States)

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

    2005-01-01

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

  2. MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Ralfkiaer, Ulrik; Lindahl, Lise M; Litman, Thomas;

    2014-01-01

    Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphoma (CTCL). MF is characterized by chronic inflammation dominated by cluster of differentiation 4-positive (CD4(+)) T-cells and T helper 2 cytokines, and as the malignant T-cell clone is initially elusive, early diagnosis...

  3. Molecular biology techniques for the diagnosis of cutaneous T-cell lymphoma.

    Science.gov (United States)

    Wood, G S; Haeffner, A; Dummer, R; Crooks, C F

    1994-04-01

    The molecular biologic analysis of TCR gene rearrangements by Southern blot analysis and various PCR-based assays has contributed significantly to the understanding of CTCL. It is now known that CTCL is a monoclonal T-cell disorder like other T-cell neoplasms and that the same tumor clone is generally present in all sites of tissue involvement. Relative to histopathologic examination, the enhanced sensitivity of molecular biologic assays has allowed the diagnosis of CTCL at an early stage in many cases. In fact, molecular biologic analysis of TCR gene rearrangements suggests that CTCL may contain a dominant monoclonal tumor cell population from the time of its earliest clinically recognizable lesions, such as the cutaneous patches once termed large plaque parapsoriasis and now generally regarded as early CTCL. Furthermore, available data indicate that, at least in some cases, tumor cells are distributed widely among cutaneous and extracutaneous tissues at a time long before this involvement can be appreciated morphologically. It is apparent that, in addition to their value in the early diagnosis and staging of cutaneous lymphomas, these molecular biologic assays are valuable in monitoring the response to therapy, detecting early relapse, and improving understanding of the compartmentalization and trafficking of tumor cells. In order to reap the full clinical benefit from this new information, however, it is important to perform prospective long-term studies designed to determine the clinical significance of molecular biologic data. In addition, the complexity of cutaneous lymphoproliferative disorders dictates that molecular biologic clonality data should never be interpreted in a vacuum. In skin disease, dominant clonality does not always equate with clinical malignancy. The proper diagnosis of CTCL and other cutaneous lymphoproliferative diseases requires the thoughtful integration of molecular biologic data with the clinicopathologic and immunophenotypic

  4. An unusual enteropathy-associated T-cell lymphoma with MYC translocation arising in a Japanese patient: A case report

    Institute of Scientific and Technical Information of China (English)

    Kenji Okumura; Masahiko Ikebe; Tatsuro Shimokama; Morishige Takeshita; Nao Kinjo; Keishi Sugimachi; Hidefumi Higashi

    2012-01-01

    Enteropathy-associated T-cell lymphoma (EATL) is a rare peripheral T-cell lymphoma classified into 2 types,with or without celiac disease,based on histology.Type 2 EATL is less commonly associated with celiac disease,in which cells are characterized by being monomorphic and small-to medium-sized.Cells are characterized by CD8 and CD56 expression and c-MYC oncogene locus gain.We present an atypical case of type 2 EATL in the jejunum,with human T-lymphotropic virus-1 that was CD4-CD8+ CD56-CD30-CD25-TIA-1+ and granzyme B+ on immunohistological staining.It also displayed translocation of chromosome 8p24 (c-MYC),as determined by fluorescent in situ hybridization.Mucosal spreading and intraepithelial invasion by lymphoma with villous atrophy were detected adjacent to the mucosal layer.The lymphoma may be derived from intraepithelial CD8+ T cells,similar to celiac disease.

  5. Pseudocarcinomatous hyperplasia mimicking squamous cell carcinoma in a case of CD56-positive cytotoxic T-cell lymphoma.

    Science.gov (United States)

    Ginsberg, David; Hill, Hilary; Wilson, Barbara; Plaza, Jose A; Schieke, Stefan M

    2015-03-01

    We present the case of an 84-year-old patient with a cutaneous CD56 positive cytotoxic T-cell lymphoma associated with substantial pseudocarcinomatous hyperplasia mimicking squamous cell carcinoma (SCC). The patient presented with a 7-month history of several progressive, ulcerated plaques on his right forearm. An initial biopsy showed changes consistent with a diagnosis of SCC for which the patient underwent surgical treatment. Several months later, the patient developed recurrent ulcerated plaques on the right forearm of which several biopsies were performed. The biopsies repeatedly showed marked pseudocarcinomatous hyperplasia resembling SCC. Deeper punch biopsies, however, showed a dense superficial and deep infiltrate of markedly atypical lymphocytes. Immunohistochemical analysis revealed strong positive staining for CD3, CD8, CD56 with negative stains for CD30 and Epstein-Barr virus-encoded small non-polyadenylated RNAs (EBER). Staining for beta F1 and gamma-delta T-cell receptor (γδ TCR) were both negative. This constellation was most consistent with a diagnosis of cutaneous peripheral T-cell lymphoma, unspecified in association with marked pseudocarcinomatous hyperplasia. Our case adds cutaneous peripheral T-cell lymphoma, unspecified to the list of conditions associated with pseudocarcinomatous hyperplasia (PCH) and illustrates once again the potential pitfalls of distinguishing marked pseudocarcinomatous hyperplasia from SCC.

  6. Accurate detection of the tumor clone in peripheral T-cell lymphoma biopsies by flow cytometric analysis of TCR-Vβ repertoire.

    Science.gov (United States)

    Salameire, Dimitri; Solly, Françoise; Fabre, Blandine; Lefebvre, Christine; Chauvet, Martine; Gressin, Rémy; Corront, Bernadette; Ciapa, Agnès; Pernollet, Martine; Plumas, Joël; Macintyre, Elizabeth; Callanan, Mary B; Leroux, Dominique; Jacob, Marie-Christine

    2012-09-01

    Multiparametric flow cytometry has proven to be a powerful method for detection and immunophenotypic characterization of clonal subsets, particularly in lymphoproliferative disorders of the B-cell lineage. Although in theory promising, this approach has not been comparably fulfilled in mature T-cell malignancies. Specifically, the T-cell receptor-Vβ repertoire analysis in blood can provide strong evidence of clonality, particularly when a single expanded Vß family is detected. The purpose of this study was to determine the relevance of this approach when applied to biopsies, at the site of tumor involvement. To this end, 30 peripheral T-cell lymphoma and 94 control biopsies were prospectively studied. Vβ expansions were commonly detected within CD4+ or CD8+ T cells (97% of peripheral T-cell lymphoma and 54% of non-peripheral T-cell lymphoma cases); thus, not differentiating malignant from reactive processes. Interestingly, we demonstrated that using a standardized evaluation, the detection of a high Vβ expansion was closely associated with diagnosis of peripheral T-cell lymphoma, with remarkable specificity (98%) and sensitivity (90%). This approach also identified eight cases of peripheral T-cell lymphoma that were not detectable by other forms of immunophenotyping. Moreover, focusing Vβ expression analysis to T-cell subsets with aberrant immunophenotypes, we demonstrated that the T-cell clone might be heterogeneous with regard to surface CD7 or CD10 expression (4/11 cases), providing indication on 'phenotypic plasticity'. Finally, among the wide variety of Vβ families, the occurrence of a Vβ17 expansion in five cases was striking. To our knowledge, this is the first report demonstrating the power of T-cell receptor-Vβ repertoire analysis by flow cytometry in biopsies as a basis for peripheral T-cell lymphoma diagnosis and precise T-cell clone identification and characterization.

  7. Efficacy and tolerability of currently available therapies for the mycosis fungoides and Sezary syndrome variants of cutaneous T-cell lymphoma.

    Science.gov (United States)

    Whittaker, Sean J; Foss, Francine M

    2007-04-01

    Primary cutaneous T-cell lymphomas are a heterogenous group of non-Hodgkin lymphomas. The characteristic clinicopathologic and immunophenotypic features and prognoses of the various cutaneous lymphomas have been recently described by the World Health Organization and European Organization for Research and Treatment of Cancer. Cutaneous T-cell lymphoma variants include mycosis fungoides and Sezary syndrome, which are generally associated, respectively, with indolent and aggressive clinical courses and are the subject of this review. Currently utilized treatments for cutaneous T-cell lymphoma include skin-directed therapies (topical agents such as corticosteroids, mechlorethamine, carmustine, and retinoids, phototherapy, superficial radiotherapy, and total skin electron beam therapy), systemic therapies (photophoresis, retinoids, denileukin diftitox, interferons, and chemotherapy), and stem cell transplantation (autologous and allogeneic). This review will describe recent advances in our understanding of the biology (immunologic, cytogenetic, and genetic) of cutaneous T-cell lymphomas and discuss the efficacy and tolerability of the current therapeutic options for cutaneous T-cell lymphomas. Disease progression in over 20% of patients with early stages of disease and the current lack of a definitive treatment which produces durable responses in advanced stages of disease indicates a critical unmet need in CTCL. New insights into the molecular and immunologic changes associated with cutaneous T-cell lymphomas should ultimately lead to the identification of novel therapeutic targets and the development of improved therapeutic options for patients with these malignancies.

  8. Role of Synchrotron infra red microspectroscopy in studying epidermotropism of cutaneous T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    El Bedewi, A.; El Anany, G; El Mofty, M

    2010-01-01

    The molecular mechanisms of epidermotropism in mycosis fungoides (MF) are not well understood to date. The aim of this study was to differentiate between epidermal and dermal lymphocytes within the skin of MF patients. This study was done on 10 MF patients with a mean age of 50 years diagnosed clinically in the Department of Dermatology, Cairo University, Egypt. A 6 mm biopsy was taken from each patient in order to confirm the diagnosis. Skin biopsies were cut, put on low e-slides and then stained with H&E. Further examination with Synchrotron infrared (IR) microspectroscopy was done in National Synchrotron Light Source - Brookhaven National Laboratory, New York, USA. Immunophenotyping using antibodies CD3, CD4, CD8, CD20 and CD30 was also done. Statistical analysis was done by Student's t-test and cluster analysis. Both epidermal and dermal lymphocytes were clustered separately. Also, Amide I and RNA and DNA within the lymphocytes were significantly different between the epidermis and the dermis. The biochemical analysis of protein, RNA and DNA with Synchrotron IR microspectroscopy is a promising tool for studying epidermotropism in cutaneous T-cell lymphoma.

  9. Matrix Metalloproteinase-2 Promoter Genotype as a Marker of Cutaneous T-Cell Lymphoma Early Stage

    Directory of Open Access Journals (Sweden)

    Anna Vasku

    2010-01-01

    Full Text Available The aim of the study was to investigate the DNA polymorphic genotype in MMP-2 promoter gene as a potential candidate region for the development of the cutaneous T-cell lymphoma (CTCL and/or its progression. A total of 89 Czech patients with CTCL (including 23 patients with large plaque parapsoriasis were compared to 198 controls of similar age and sex distribution, without personal or family history of chronic skin diseases and without personal history of malignancy. The three selected polymorphisms in the promoter of MMP-2 gene (−1575G/A, −1306C/T, and −790T/G were determined using the PCR-based methodology with RFLP. In our cohort, the associated GGCCTT MMP-2 promoter genotype was highly significantly more frequent in CTCL-Ia stage patients compared to patients with parapsoriasis, the tests having high sensitivity and specificity (78%, 83%, resp.. To conclude, use of associated MMP-2 promoter genotype as a DNA marker might make it possible to distinguish between the patients with parapsoriasis and those with CTCL stage Ia, which could substantially improve possibilities of clinical diagnostics, therapy design, and prognosis of this serious condition in the early stages.

  10. Matrix metalloproteinase-2 promoter genotype as a marker of cutaneous T-cell lymphoma early stage.

    Science.gov (United States)

    Vasku, Anna; Vasku, Julie Bienertova; Necas, Miroslav; Vasku, Vladimir

    2010-01-01

    The aim of the study was to investigate the DNA polymorphic genotype in MMP-2 promoter gene as a potential candidate region for the development of the cutaneous T-cell lymphoma (CTCL) and/or its progression. A total of 89 Czech patients with CTCL (including 23 patients with large plaque parapsoriasis) were compared to 198 controls of similar age and sex distribution, without personal or family history of chronic skin diseases and without personal history of malignancy. The three selected polymorphisms in the promoter of MMP-2 gene (-1575G/A, -1306C/T, and -790T/G) were determined using the PCR-based methodology with RFLP. In our cohort, the associated GGCCTT MMP-2 promoter genotype was highly significantly more frequent in CTCL-Ia stage patients compared to patients with parapsoriasis, the tests having high sensitivity and specificity (78%, 83%, resp.). To conclude, use of associated MMP-2 promoter genotype as a DNA marker might make it possible to distinguish between the patients with parapsoriasis and those with CTCL stage Ia, which could substantially improve possibilities of clinical diagnostics, therapy design, and prognosis of this serious condition in the early stages.

  11. Chemotherapeutic treatment is associated with Notch1 induction in cutaneous T-cell lymphoma.

    Science.gov (United States)

    Kamstrup, Maria R; Biskup, Edyta; Manfè, Valentina; Savorani, Cecilia; Liszewski, Walter; Wirèn, Johan; Specht, Lena; Gniadecki, Robert

    2017-01-01

    The Notch pathway is important for survival of cutaneous T-cell lymphoma (CTCL) cells. We investigated the effect of chemotherapy (doxorubicin, etoposide, and gemcitabine) and radiation modalities on Notch signaling in CTCL cell lines. Chemotherapy induced Notch1 expression at the mRNA and protein level in MyLa2000 and Hut78. Upregulation of well-established Notch targets supported the functional activity of Notch1. Transfection of Notch1 siRNA into MyLa2000 cells was not able to suppress the effects of chemotherapy on Notch1 activation significantly. Notch1 knockdown in combination with doxorubicin, etoposide, or gemcitabine compared to chemotherapy alone decreased cell viability by 12, 20, and 26%, respectively (p < 0.05). Additionally, X-rays (in MyLa2000 but not SeAx) and psoralen plus UVA (PUVA) (in MyLa2000, Hut78, and SeAx) increased the expression of Notch1 family members. Our results indicate that CTCL cells activate the Notch pathway in vitro in response to chemotherapy and radiation modalities as a possible protective mechanism.

  12. Sequential chemoradiotherapy for stage I/II nasal natural killer/T cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Young Joo [Ulsan University Hospital, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Ahn, Yong Chan; Kim, Won Seog; Ko, Young Hyeh [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    Authors would report the results of sequential CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisone) and involved field radiotherapy (IFRT) for early stage nasal natural killer/T-cell lymphoma (NKTCL). Fourteen among 17 patients, who were registered at the Samsung Medical Center tumor registry with stage I and II nasal NKTCL from March 1995 to December 1999 received this treatment protocol. Three to four cycles of CHOP chemotherapy were given at 3 weeks' interval, which was followed by local IFRT including the known tumor extent and the adjacent draining lymphatics. Favorable responses after chemotherapy (before IFRT) were achievable only in seven patients (5 CR's + 2 PR's: 50%), while seven patients showed disease progression. There were six patients with local failures, two with distant relapses, and none with regional lymphatic failure. The actuarial overall survival and progression-free survival at 3 years were 50.0% and 42.9%. All the failures and deaths occurred within 13 months of the treatment start. The factors that correlated with the improved survival were the absence of 'B' symptoms, the favorable response to chemotherapy and overall treatment, and the low risk by international prognostic index on univariate analyses. Compared with the historic treatment results by IFRT either alone or followed by chemotherapy, the current trial failed to demonstrate advantages with respect to the failure pattern and survival. Development of new treatment strategy in combining IFRT and chemotherapy is required for improving outcomes.

  13. Hepatosplenic gamma-delta T-cell lymphoma as a late-onset posttransplant lymphoproliferative disorder in renal transplant recipients.

    Science.gov (United States)

    Wu, H; Wasik, M A; Przybylski, G; Finan, J; Haynes, B; Moore, H; Leonard, D G; Montone, K T; Naji, A; Nowell, P C; Kamoun, M; Tomaszewski, J E; Salhany, K E

    2000-04-01

    We report 2 cases of renal transplant recipients in whom hepatosplenic gamma-delta T-cell lymphoma (gamma-delta HSTCL) developed 5 and 10 years after transplantation. Both patients had marked hepatosplenomegaly, B symptoms (weight loss, fever, and night sweats), and abnormal peripheral blood findings, including anemia in both, thrombocytopenia and leukoerythroblastic changes in 1, and leukocytosis in the other. Markedly atypical lymphoid infiltrate of intermediate to large cells was observed in the spleen, liver, and bone marrow. The malignant cells showed typical immunophenotype of gamma-delta T cells (CD2+, CD3+, CD4-, CD8-, CD7+, gamma-delta T-cell receptor-positive, and alpha-beta T-cell receptor-negative) with clonal T-cell receptor gene rearrangement and were of the V-delta-1 subset. In addition, the cells contained a cytolytic granule-associated protein, TIA-1, and Fas ligand, indicating cytotoxic T-cell differentiation. The malignant T cells in both cases were of host tissue origin. Both cases were negative for Epstein-Barr virus genome using Southern blot analysis. The patients did not respond to reduction of immunosuppression. Despite initial response to chemotherapy, both patients died within 6 months of diagnosis. Our findings indicate that gamma-delta HSTCL can occur as a late complication in transplant recipients.

  14. Nodular lymphocyte predominant hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma--endpoints of a spectrum of one disease?

    Directory of Open Access Journals (Sweden)

    Sylvia Hartmann

    Full Text Available In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL, T cell/histiocyte rich large B cell lymphoma (THRLBCL is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL with considerable histopathologic overlap compared to THRLBCL. Especially THRLBCL-like NLPHL, a diffuse form of NLPHL, often presents a histopathologic pattern similar to THRLBCL, suggesting a close relationship between both lymphoma entities. To corroborate this hypothesis, we performed gene expression profiling of microdissected tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. In unsupervised analyses, the lymphomas did not cluster according to their entity. Moreover, even in supervised analyses, very few consistently differentially expressed transcripts were found, and for these genes the extent of differential expression was only moderate. Hence, there are no clear and consistent differences in the gene expression of the tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. Based on the gene expression studies, we identified BAT3/BAG6, HIGD1A, and FAT10/UBD as immunohistochemical markers expressed in the tumor cells of all three lymphomas. Characterization of the tumor microenvironment for infiltrating T cells and histiocytes revealed significant differences in the cellular composition between typical NLPHL and THRLBCL cases. However, THRLBCL-like NLPHL presented a histopathologic pattern more related to THRLBCL than NLPHL. In conclusion, NLPHL and THRLBCL may represent a spectrum of the same disease. The different clinical behavior of these lymphomas may be strongly influenced by differences in the lymphoma microenvironment, possibly related to the immune status of the patient at the timepoint of diagnosis.

  15. Differential effects of interleukin-2 and interleukin-15 versus interleukin-21 on CD4+ cutaneous T-cell lymphoma cells

    DEFF Research Database (Denmark)

    Marzec, Michal; Halasa, Krzysztof; Kasprzycka, Monika

    2008-01-01

    In this study, we compared the effects of interleukin-2 (IL-2), IL-15, and IL-21 on gene expression, activation of cell signaling pathways, and functional properties of cells derived from CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 modulated, in a CTCL cell line, the expres......In this study, we compared the effects of interleukin-2 (IL-2), IL-15, and IL-21 on gene expression, activation of cell signaling pathways, and functional properties of cells derived from CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 modulated, in a CTCL cell line...... of transcription 5, phosphoinositide 3-kinase/Akt, and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase/ERK signaling pathways in the cell lines and mitogen-primed native cells. In contrast, IL-21 selectively activated signal transducers and activators of transcription 3. Whereas all...

  16. Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels.

    Science.gov (United States)

    Kochenderfer, James N; Somerville, Robert P T; Lu, Tangying; Shi, Victoria; Bot, Adrian; Rossi, John; Xue, Allen; Goff, Stephanie L; Yang, James C; Sherry, Richard M; Klebanoff, Christopher A; Kammula, Udai S; Sherman, Marika; Perez, Arianne; Yuan, Constance M; Feldman, Tatyana; Friedberg, Jonathan W; Roschewski, Mark J; Feldman, Steven A; McIntyre, Lori; Toomey, Mary Ann; Rosenberg, Steven A

    2017-03-14

    Purpose T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 (CAR-19) have potent activity against acute lymphoblastic leukemia, but fewer results supporting treatment of lymphoma with CAR-19 T cells have been published. Patients with lymphoma that is chemotherapy refractory or relapsed after autologous stem-cell transplantation have a grim prognosis, and new treatments for these patients are clearly needed. Chemotherapy administered before adoptive T-cell transfer has been shown to enhance the antimalignancy activity of adoptively transferred T cells. Patients and Methods We treated 22 patients with advanced-stage lymphoma in a clinical trial of CAR-19 T cells preceded by low-dose chemotherapy. Nineteen patients had diffuse large B-cell lymphoma, two patients had follicular lymphoma, and one patient had mantle cell lymphoma. Patients received a single dose of CAR-19 T cells 2 days after a low-dose chemotherapy conditioning regimen of cyclophosphamide plus fludarabine. Results The overall remission rate was 73% with 55% complete remissions and 18% partial remissions. Eleven of 12 complete remissions are ongoing. Fifty-five percent of patients had grade 3 or 4 neurologic toxicities that completely resolved. The low-dose chemotherapy conditioning regimen depleted blood lymphocytes and increased serum interleukin-15 (IL-15). Patients who achieved a remission had a median peak blood CAR(+) cell level of 98/μL and those who did not achieve a remission had a median peak blood CAR(+) cell level of 15/μL ( P = .027). High serum IL-15 levels were associated with high peak blood CAR(+) cell levels ( P = .001) and remissions of lymphoma ( P < .001). Conclusion CAR-19 T cells preceded by low-dose chemotherapy induced remission of advanced-stage lymphoma, and high serum IL-15 levels were associated with the effectiveness of this treatment regimen. CAR-19 T cells will likely become an important treatment for patients with relapsed lymphoma.

  17. Computer-assisted quantification of CD3+ T cells in follicular lymphoma.

    Science.gov (United States)

    Abas, Fazly S; Shana'ah, Arwa; Christian, Beth; Hasserjian, Robert; Louissaint, Abner; Pennell, Michael; Sahiner, Berkman; Chen, Weijie; Niazi, Muhammad Khalid Khan; Lozanski, Gerard; Gurcan, Metin

    2017-01-22

    The advance of high resolution digital scans of pathology slides allowed development of computer based image analysis algorithms that may help pathologists in IHC stains quantification. While very promising, these methods require further refinement before they are implemented in routine clinical setting. Particularly critical is to evaluate algorithm performance in a setting similar to current clinical practice. In this article, we present a pilot study that evaluates the use of a computerized cell quantification method in the clinical estimation of CD3 positive (CD3+) T cells in follicular lymphoma (FL). Our goal is to demonstrate the degree to which computerized quantification is comparable to the practice of estimation by a panel of expert pathologists. The computerized quantification method uses entropy based histogram thresholding to separate brown (CD3+) and blue (CD3-) regions after a color space transformation. A panel of four board-certified hematopathologists evaluated a database of 20 FL images using two different reading methods: visual estimation and manual marking of each CD3+ cell in the images. These image data and the readings provided a reference standard and the range of variability among readers. Sensitivity and specificity measures of the computer's segmentation of CD3+ and CD- T cell are recorded. For all four pathologists, mean sensitivity and specificity measures are 90.97 and 88.38%, respectively. The computerized quantification method agrees more with the manual cell marking as compared to the visual estimations. Statistical comparison between the computerized quantification method and the pathologist readings demonstrated good agreement with correlation coefficient values of 0.81 and 0.96 in terms of Lin's concordance correlation and Spearman's correlation coefficient, respectively. These values are higher than most of those calculated among the pathologists. In the future, the computerized quantification method may be used to investigate

  18. Analysis of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-reactive CD8(+) T cell responses in children with NPM-ALK(+) anaplastic large cell lymphoma.

    Science.gov (United States)

    K Singh, V; Werner, S; Hackstein, H; Lennerz, V; Reiter, A; Wölfel, T; Damm-Welk, C; Woessmann, W

    2016-10-01

    Cellular immune responses against the oncoantigen anaplastic lymphoma kinase (ALK) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) have been detected using peptide-based approaches in individuals preselected for human leucocyte antigen (HLA)-A*02:01. In this study, we aimed to evaluate nucleophosmin (NPM)-ALK-specific CD8(+) T cell responses in ALCL patients ensuring endogenous peptide processing of ALK antigens and avoiding HLA preselection. We also examined the HLA class I restriction of ALK-specific CD8(+) T cells. Autologous dendritic cells (DCs) transfected with in-vitro-transcribed RNA (IVT-RNA) encoding NPM-ALK were used as antigen-presenting cells for T cell stimulation. Responder T lymphocytes were tested in interferon-gamma enzyme-linked immunospot (ELISPOT) assays with NPM-ALK-transfected autologous DCs as well as CV-1 in Origin with SV40 genes (COS-7) cells co-transfected with genes encoding the patients' HLA class I alleles and with NPM-ALK encoding cDNA to verify responses and define the HLA restrictions of specific T cell responses. NPM-ALK-specific CD8(+) T cell responses were detected in three of five ALK-positive ALCL patients tested between 1 and 13 years after diagnosis. The three patients had also maintained anti-ALK antibody responses. No reactivity was detected in samples from five healthy donors. The NPM-ALK-specific CD8(+) T cell responses were restricted by HLA-C-alleles (C*06:02 and C*12:02) in all three cases. This approach allowed for the detection of NPM-ALK-reactive T cells, irrespective of the individual HLA status, up to 9 years after ALCL diagnosis.

  19. Analysis of human T-cell lymphotropic virus in CD25+ anaplastic large cell lymphoma in children.

    Science.gov (United States)

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

    2009-07-01

    Anaplastic large cell lymphoma (ALCL) is recognized as 2 distinct diseases: anaplastic lymphoma kinase (ALK)+ ALCL and ALK- ALCL. ALK+ ALCL occurs in younger patients and has a better prognosis. Human T-cell lymphotropic virus (HTLV-1) is linked to the development of adult T-cell leukemia/lymphoma (ATLL), which frequently expresses CD25. CD25 is significantly expressed in childhood ALCL. In Brazil, HTLV-1 infection is endemic, and vertical transmission is responsible for spread to children. Of HTLV-1 carriers, 90% or more remain asymptomatic. Some cases of adult HTLV-1-related lymphomas have characteristics of ALCL but are considered CD30+ ATLL subtypes. No similar cases have been described in children. We analyzed 33 cases of pediatric ALCL, CD25+ and CD25-, for proviral HTLV-1 DNA. All cases corresponded to the common histologic ALCL type and were CD30+ in virtually all neoplastic cells. ALK expression was observed in 31 (94%) of 33 cases; CD25 was positive in 27 (82%), including 1 ALK- ALCL case. There was a strong positive correlation between ALK and CD25 expression. None of the cases showed proviral HTLV-1 DNA. ALCL in children has no relationship with HTLV-1; the frequent CD25 expression must be explained by a mechanism different from that in ATLL.

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

    Science.gov (United States)

    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.

  1. Clinicoradiological changes of brain NK/T cell lymphoma manifesting pure akinesia: a case report

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    Shimokawa Reiko

    2011-11-01

    Full Text Available Abstract Background Pure akinesia (PA is a distinct form of parkinsonism characterized by freezing phenomena. Little is known about brain tumor-associated PA. We highlight the clinicoradiological changes in a patient with PA and central nervous system (CNS metastases of natural killer/T-cell lymphoma (NKTL. Case presentation A 68-year-old man with stage IVB extranodal NKTL developed a gait disturbance. Neurological examination of his gait revealed freezing, start hesitation, short step, forward flexion posture, festination and postural instability. Mild facial hypomimia and micrographia were observed. There was no rigidity or tremor in any of the four extremities. Brain magnetic resonance imaging (MRI displayed T2-hyperintense lesions in the dorsal brainstem, cerebellum and periventricular white matter. Diffusion-weighted imaging (DWI and the apparent diffusion coefficient (ADC revealed hyperintensity in these regions. Cerebrospinal fluid cytology revealed CD56-positive cells on immunohistochemical staining. The patient's neurological deficits did not respond to L-dopa treatment and intrathecal administration of methotrexate (MTX. Two weeks later, he displayed confusion and generalized convulsions. T2-hyperintense lesions spread to the basal ganglia and the infratentorial regions. Gadolinium enhancement was observed in the cerebellum and frontal subcortex. DWI and the ADC revealed diffusion-restricted lesions in the middle cerebellar peduncles, left internal capsules and cerebral white matter. MTX pulse therapy and intrathecal administration of cytosine arabinoside and MTX were performed. Two months later, his ambulatory state was normalized. Brain MRI also revealed marked alleviation of the infratentorial and supratentorial lesions. Conclusions The clinicoradiological profile of our patient suggested that dorsal ponto-mesencephalic lesions could contribute to the pathogenesis of PA. Physicians should pay more attention to striking CNS seeding

  2. Pyoderma gangrenosum preceding the onset of extranodal natural killer/T-cell lymphoma

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    Yang, Ting-Hua; Hu, Chung-Hong; Tsai, Hsiou-Hsin

    2016-01-01

    Abstract Introduction: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that may be associated with systemic diseases. The association of PG with lymphoid malignancies has rarely been reported. Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare but aggressive entity with a poor prognosis. Here, we report the case of a patient who had idiopathic PG refractory to systemic steroids and subsequently developed ENKTL. Case report: A 70-year-old man presented with a 2-month history of intermittent fever and multifocal painful papules, plaques, and ulcerations on his extremities. The histological and culture results of the lesions were consistent with those of PG. A thorough work-up was performed and did not demonstrate any underlying systemic diseases including malignancy. The PG lesions were refractory to systemic steroid therapy. An enlarging nodule was observed over his right infraorbital area 4 months after the onset of the skin eruptions. The nodule was later biopsied and diagnosed as ENKTL by using histopathological and immunohistochemical studies. Fludeoxyglucose positron emission tomography/computed tomography revealed multiple intense fludeoxyglucose-avid masses in the bones and lungs, suggesting multiorgan metastases. The patient rejected chemotherapy and died 4 weeks after the diagnosis. Conclusion: The present case indicates that in any patient with idiopathic PG refractory to conventional therapy, the presence of any underlying disease or malignancy must be thoroughly evaluated. The present case serves as a reminder that when assessing patients with PG, clinicians should increase their awareness regarding the delayed association with malignancy, even in the absence of a concomitant systemic disease at presentation. Furthermore, the prompt evaluation of any suspicious lesions in the context of PG for the possibility of a malignant nature can improve the prognosis, particularly in cases of aggressive malignancy. Understanding the cutaneous

  3. Clonal structure of rapid-onset MDV-driven CD4+ lymphomas and responding CD8+ T cells.

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    William N Mwangi

    2011-05-01

    Full Text Available Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans. With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both "public" and "private" CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus

  4. Diagnosis of cutaneous T-cell lymphoma detecting T-cell receptor gamma chain gene monoclonality by denaturing gradient gel electrophoresis.

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    Lapière, K; Dhaene, K; Matthieu, L; Hübner, R; Lambert, J; Van Marck, E

    1999-04-01

    Cutaneous T-cell lymphomas represent a group of malignant lymphoproliferative disorders characterised by the occurrence of a monoclonal population of T-lymphocytes. Diagnosis of early stages of this disease is a difficult challenge for both the dermatologist and the dermatopathologist. With the aid of the polymerase chain reaction it is possible to amplify specific regions of the T-cell receptor gamma gene. The amplification products can then be separated by denaturing gradient gel electrophoresis in order to detect a monoclonal population of T-lymphocytes in the infiltrate. We studied 4 patients with the clinicopathologic diagnosis of mycosis fungoides and 2 patients diagnosed as large plaque parapsoriasis. A monoclonal population was detected in 3 of the 4 mycosis fungoides cases and in 1 of the patients with large plaque parapsoriasis. This indicates that our analysis can help us establishing a diagnosis, and it can also help us to identify patients with a possible early stage of the disease, which clinically or histologically is not yet recognised as such.

  5. Peripheral T-cell lymphoma presenting as an ischemic stroke in a 23-year-old woman: a case report and review of the literature

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    Fragou Mariantina

    2009-10-01

    Full Text Available Abstract Introduction Peripheral T-cell lymphoma of the unspecified variant is a highly aggressive subtype of T-cell non-Hodgkin's lymphoma. This is the first reported case of this type of lymphoma presenting as an ischemic stroke in a woman. Case presentation A previously healthy 23-year-old woman presented with fever and hemiplegia. She was subsequently intubated after scoring 7 out of 15 at the Glasgow Coma Scale. Brain computed tomography scans of the patient depicted a massive sylvian infarction while an abdominal computed tomography scan revealed multiple enlarged abdominal lymph nodes and a retroperitoneal mass adjacent to the left psoas muscle. A diagnostic work up for inherited thrombophilia yielded negative results. Blood and cerebrospinal fluid cultures for infectious agents also gave negative results. A biopsy of the retroperitoneal mass guided by computed tomography was inconclusive. A biopsy of an enlarged inguinal lymph node of the patient, combined with an immunophenotypic analysis, revealed an unspecified variant of peripheral T-cell lymphoma. The patient underwent chemotherapy but developed multiple organ failure. She died 26 days after she was admitted to our intensive care unit. Conclusion Peripheral T-cell lymphoma of the unspecified variant is a highly aggressive subtype of peripheral T-cell lymphomas. The latter exhibit no consistent immunophenotypic, genetic, or clinical features. Clinicians should be aware of atypical clinical presentations of the above lymphomas such as ischemic stroke.

  6. Regulatory T cells in dogs with multicentric lymphoma: peripheral blood quantification at diagnosis and after initial stage chemotherapy

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    T.D. Munhoz

    2016-02-01

    Full Text Available Lymphoma is the most common hematopoietic malignancy in dogs and one of the most frequent among all neoplastic diseases in this species. It can occur in several anatomical locations with distinct histological and immunophenotypes. Depending on the host immune response towards the tumor, prognosis information could be collected. Because its well established immunosuppressant, antitumor activity, the function of regulatory T cells (Tregs in canine neoplasias has been investigated. In this study, we sought to quantify, using flow cytometry, the Tregs subpopulation in peripheral blood of healthy dogs (10 and in those diagnosed with type-B (14 and type-T (8 multicentric lymphoma before (at diagnosis and after the first cycle (5-week of 19-week Madison-Wisconsin (MW protocol of chemotherapy. Our results indicated that dogs with lymphoma showed higher percentage of Tregs (18,84±2,56 when compared to healthy dogs (4,70±0,50 (P0,05. There was no difference in Tregs percentage between B-type (17,45±2,77 and T-type (21,27±5,27 lymphoma (P>0,05. With this, we conclude that canine lymphoma increases Tregs in the peripheral blood and the MW protocol of chemotherapy reduces this cell subpopulation to control values.

  7. Contrast-enhanced fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography in mediastinal T-cell lymphoma with superior vena cava syndrome.

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    Santhosh, Sampath; Gorla, Arun Kumar Reddy; Bhattacharya, Anish; Varma, Subhash Chander; Mittal, Bhagwant Rai

    2016-01-01

    Positron emission tomography-computed tomography (PET/CT) is a routine investigation for the staging of lymphomas. Contrast-enhanced computed tomography is mandatory whenever parenchymal lesions, especially in the liver and spleen are suspected. We report a rare case of primary mediastinal T-cell lymphoma evaluated with contrast-enhanced PET/CT that showed features of superior vena cava syndrome.

  8. Intracellular TCR-signaling pathway: novel markers for lymphoma diagnosis and potential therapeutic targets.

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    Agostinelli, Claudio; Rizvi, Hasan; Paterson, Jennifer; Shende, Vishvesh; Akarca, Ayse U; Agostini, Elena; Fuligni, Fabio; Righi, Simona; Spagnolo, Sebastiano; Piccaluga, Pier Paolo; Clark, Edward A; Pileri, Stefano A; Marafioti, Teresa

    2014-10-01

    Despite the immunologic functions of T-cell receptor signaling molecules being extensively investigated, their potential as immunohistochemical markers has been poorly explored. With this background, we evaluated the expression of 5 intracellular proteins-GADS, DOK2, SKAP55, ITK, and PKCα-involved in T-cell receptor signaling in normal and neoplastic hematologic tissue samples, using antibodies raised against fixation-resistant epitopes of the 5 molecules. All 5 antibodies were associated with normal T-cell differentiation. GADS, DOK2, SKAP55, and ITK turned out to be T-cell lineage-specific markers in the setting of lymphoid and myeloid precursor neoplasms but showed differential expression in peripheral T-cell lymphoma (PTCL) subtypes, being detected in PTCL/not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma but negative in anaplastic large cell lymphoma (ALCL). Peripheral B-cell lymphomas were consistently negative for ITK, with occasional cases showing expression of DOK2 and SKAP55, and a proportion (47%) of hairy cell leukemias were GADS. Notably, PKCα highlighted a defective antigen in both PTCL/NOS (6%) and angioimmunoblastic T-cell lymphoma (10%), mostly negative in ALCL, and was aberrantly expressed in classical Hodgkin lymphoma (65%), Burkitt lymphoma (48%), and plasma cell myeloma (48%). In conclusion, all five molecules evaluated play a role in T-cell differentiation in normal and neoplastic tissues. They can be applied confidently to routine sections contributing primarily to assignment of T-lineage differentiation in the setting of hematopoietic precursor neoplasms (GADS/DOK2/SKAP55/ITK) and for the differential diagnosis between ALCL and PTCL/NOS (GADS/DOK2/SKAP55/ITK) or classical Hodgkin lymphoma (PKCα). Finally, association with specific tumor subtypes may have therapeutic potential.

  9. Usefulness of F-18 FDG PET/CT in subcutaneous panniculitis-like T cell lymphoma: disease extent and treatment response evaluation

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    Kim, Jin-Suk; Jeong, Young Jin; Sohn, Myung-Hee; Jeong, Hwan-Jeong; Lim, Seok Tae; KIM, Dong Wook; Kwak, Jae-Yong; Yim, Chang-Yeol

    2012-01-01

    Background. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cutaneous lymphomas, accounting for less than 1% of cases of non-Hodgkin’s lymphoma. Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron-emission tomography/computed tomography (PET/CT) findings of SPTCL before and after treatment were rarely reported. Case report. We report a case of SPTCL in which F-18 FDG PET/CT showed increased FDG accumulations in numerous subcutaneous nodules without extracutaneous disea...

  10. Subcutaneous panniculitis-like T-cell lymphoma with macrophage activation syndrome treated by cyclosporine and prednisolone

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    Dinesh P Asati

    2016-01-01

    Full Text Available Subcutaneous panniculitis-like T-cell lymphoma (SPTCL; α/β T-cell subtype is a distinct variantof cutaneous T-cell lymphomas, which presents as inflammatory subcutaneous nodules. A 17-year-old male presented with recurrent fever with concomitant facial swelling, pedal edema, hepatosplenomegaly, and mildly tender subcutaneous plaques in generalized distribution along with patches of scarring alopecia on scalp. There were features of macrophage activation syndrome in the form of hemophagocytosis in the bone marrow, pancytopenia, high serum lactate dehydrogenase levels, low fibrinogen clotting activity, prolonged activated prothrombine time (aPTT, increased serum ferritin, hypoalbuminemia, and hypertriglyceridemia. Histopathology showed lobular panniculitis-like infiltration by atypical lymphocytes rimming the adipocytes. Immunohistochemistry revealed positive CD3 and CD8 markers, whereas CD4, CD56, and CD20 were negative, consistent with the diagnosis of α/β type of SPTCL. Treatment with oral prednisolone (1mg/kg/day and cyclosporine (2mg/kg/day; 100 mg led to rapid subsidence of fever, plaques, and abnormal hematological parameters within a few weeks.

  11. Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas.

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    Tsuyama, Naoko; Ennishi, Daisuke; Yokoyama, Masahiro; Baba, Satoko; Asaka, Reimi; Mishima, Yuko; Terui, Yasuhito; Hatake, Kiyohiko; Takeuchi, Kengo

    2017-03-23

    Expression of T-cell markers, generally investigated for immunophenotyping of T-cell lymphomas, is also observed in several types of B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We previously reported that CD5 expression in DLBCL is an inferior prognostic factor in the era of rituximab. However, data regarding the frequencies, histological relevance, and prognostic importance of T-cell markers other than CD5 are currently unavailable. In the present study, we comprehensively evaluated the expression of T-cell markers (CD2, CD3, CD4, CD5, CD7, and CD8) in 501 B-cell lymphomas, including 225 DLBCLs, by flow cytometry and subsequent immunohistochemistry. T-cell markers other than CD5, such as CD2, CD4, CD7, and CD8, were expressed in 27 (5%) patients, and notably, all of these cases were classified as large B-cell lymphoma subtypes: 25 DLBCLs and 2 intravascular large B-cell lymphomas. CD5 and other T-cell markers were expressed in 15% (31/225) and 10% (25/225) of DLBCL cases, respectively. Five of them co-expressed CD5 and other T-cell markers. Retrospectively analyzing the prognostic relevance of T-cell markers in 169 patients with primary DLBCL treated with rituximab-based chemotherapy, we showed that only CD5 was a strong predictor of poor survival. This study provides information about the occurrence of T-cell markers other than CD5 in B-cell lymphomas, their frequent histological subtypes, and their prognostic significance in DLBCL. CD5 was reconfirmed as a negative prognostic marker in DLBCL patients receiving rituximab-inclusive chemotherapy, whereas T-cell markers other than CD5 were found to have no impact on clinicopathological and survival analyses.

  12. New drugs for aggressive B-cell and T-cell lymphomas.

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    Murawski, Niels; Pfreundschuh, Michael

    2010-11-01

    Over the past decade an unprecedented number of new drugs for lymphomas have been developed. Most of these new drugs target molecules or pathways that are important for the growth and proliferation of lymphomas. The introduction of the B-lymphoma specific monoclonal anti-CD20 antibody, rituximab, has improved the prognosis of patients with B-cell lymphomas more than any other drug in the past 50 years; today less than half of the patients with aggressive B-cell lymphomas die of their disease than in the pre-rituximab era. Many new drugs are now available for clinical testing in addition to new CD20 antibodies and antibodies directed against other surface molecules specifically or preferentially expressed on the lymphoma-cell surface. A prerequisite for the development of these drugs was the recognition of aberrant cell-signal transduction involved in lymphoma pathogenesis and progression. New therapeutic targets include receptor tyrosine and cyclin-dependent kinases, histone deacetylases, and molecules involved in the regulation of apoptosis. The definition of the role of these new drugs alone or in combination with established chemotherapy regimens in adequately designed prospective trials represents one of the major challenges in clinical lymphoma research.

  13. CD13-positive anaplastic large cell lymphoma of T-cell origin--a diagnostic and histogenetic problem.

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    Popnikolov, N K; Payne, D A; Hudnall, S D; Hawkins, H K; Kumar, M; Norris, B A; Elghetany, M T

    2000-12-01

    The expression of myelomonocytic-associated antigens in anaplastic large cell lymphomas (ALCLs), particularly those presenting in extranodal sites, can make their distinction from extramedullary myeloid cell tumors (EMCTs) or histiocytic tumors problematic. Yet, this distinction is clinically significant because of its therapeutic and prognostic implications. Herein, we describe a case of extranodal anaplastic lymphoma kinase-positive CD30-positive ALCL of T-cell origin in a 12-year-old boy, which was initially called an EMCT because of the expression of CD13 and HLA-DR detected by flow cytometry and the absence of other T-cell-related surface markers. However, the detection of cytoplasmic CD3 by flow cytometry prompted further studies. The tumor was composed of large cells with abundant slightly eosinophilic vacuolated cytoplasm and ovoid or reniform nuclei with a few small nucleoli. Using immunohistochemistry, the tumor was positive for CD45, CD30, CD45RO, and CD43 with a strong cytoplasmic and nuclear anaplastic lymphoma kinase stain. The tumor cells showed a T-cell clonal genotype. Electron microscopy revealed no ultrastructural features of myelomonocytic or histiocytic origin. The patient responded well to the chemotherapy and was in complete remission for 10 months at the time of submission of this manuscript. Review of the literature showed inconsistencies regarding the diagnosis, nomenclature, and, therefore, treatment and prognosis of these tumors. In addition, the CD13 expression in ALCL raises some histogenetic questions and may indicate origin from a pluripotent stem cell, misprogramming during malignant transformation, or a microenvironmental effect on lymphoid cell expression of surface antigens. Therefore, ALCL should be considered in the differential diagnosis of EMCTs or histiocytic tumors, particularly when surface marker lineage assignment is ambiguous.

  14. Transformation of Sézary syndrome into CD30+ anaplastic large T-cell lymphoma after alemtuzumab therapy with evidence of clonal unity.

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    Nevet, Mariela Judith; Zuckerman, Tsila; Sahar, Dvora; Bergman, Reuven

    2015-01-01

    Alemtuzumab is a humanized mouse antibody targeting the CD52 cell surface, which has been effective in patients with advanced stage mycosis fungoides (MF) including erythrodermic MF and Sézary syndrome. There are a few descriptions of large cell transformation after its administration. A young patient with an acute onset of Sézary syndrome treated initially unsuccessfully with fludarabine and cyclophosphamide and later on successfully with alemtuzumab has been described. Three weeks after the beginning of therapy, however, she developed transformed T-cell lymphoma indistinguishable from CD30 anaplastic large-cell lymphoma. After bone marrow transplantation, the transformed CD30 cutaneous T-cell lymphoma recurred as a transformed CD30 plaque MF. All 3 types of lesions showed the same T-cell receptor clonal gene rearrangement, which supports the notion that Sézary syndrome, CD30 anaplastic large-cell lymphoma, and MF are interrelated.

  15. The ALK inhibitor ASP3026 eradicates NPM-ALK⁺ T-cell anaplastic large-cell lymphoma in vitro and in a systemic xenograft lymphoma model.

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    George, Suraj Konnath; Vishwamitra, Deeksha; Manshouri, Roxsan; Shi, Ping; Amin, Hesham M

    2014-07-30

    NPM-ALK⁺ T-cell anaplastic large-cell lymphoma (ALCL) is an aggressive type of cancer. Standard treatment of NPM-ALK⁺ ALCL is CHOP polychemotherapy. Although patients initially respond favorably to CHOP, resistance, relapse, and death frequently occur. Recently, selective targeting of ALK has emerged as an alternative therapeutic strategy. ASP3026 is a second-generation ALK inhibitor that can overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK⁺ solid tumors. However, NPM-ALK⁺ ALCL patients are not included in these trials. We studied the effects of ASP3026 on NPM-ALK⁺ ALCL cell lines in vitro and on systemic lymphoma growth in vivo. ASP3026 decreased the viability, proliferation, and colony formation, as well as induced apoptotic cell death of NPM-ALK⁺ ALCL cells. In addition, ASP3026 significantly reduced the proliferation of 293T cells transfected with NPM-ALK mutants that are resistant to crizotinib and downregulated tyrosine phosphorylation of these mutants. Moreover, ASP3026 abrogated systemic NPM-ALK⁺ ALCL growth in mice. Importantly, the survival of ASP3026-treated mice was superior to that of control and CHOP-treated mice. Our data suggest that ASP3026 is an effective treatment for NPM-ALK⁺ ALCL, and support the enrollment of patients with this lymphoma in the ongoing clinical trials.

  16. Study of regulatory T-cells in patients with gastric malt lymphoma: influence on treatment response and outcome.

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    Mar García

    Full Text Available PURPOSE: FOXP3+ regulatory T cells (Treg play an essential role in modulating host responses to tumors and infections. The role of these cells in the pathogenesis of MALT lymphomas remains unknown. The aims of the study were to quantify the number of infiltrating FOXP3+ and CD3+ cells in patients with gastric MALT lymphoma at diagnosis and to study kinetics of these cells and CD20+ tumor cells after treatment and during long-term follow-up. METHODS: FOXP3+, CD3+ and CD20+ cells were analyzed by immunohistochemistry and the number of cells was quantified using a micrometric ocular. Samples of 35 patients with gastric MALT lymphoma at diagnosis and after treatment were included. Diagnostic samples were compared to 19 cases of chronic gastritis and diffuse large B-cell lymphoma (DLBCL of the stomach. RESULTS: The median number of FOXP3+ infiltrating cells was higher (27 cells/cm(2 in gastric MALT patients than in DLBCL (10 cells; p = 0.162 but similar to chronic gastritis (20 cells; p = 0.605. No characteristic or specific distribution pattern of infiltrating FOXP3+ cells was found. Gastric MALT lymphoma patients responding to bacterial eradication therapy had higher number of FOXP3+ cells at study entry. Kinetics of both infiltrating FOXP3+ cells and tumor CD20+ cells were strongly dependent on the treatment administered. DISCUSSION: Gastric MALT lymphomas have a number of Treg cells more similar to chronic gastritis than to DLBCL. Patients with higher number of tumor infiltrating FOXP3+ cells at study entry seem to have better response to antibiotics. Kinetics of Treg and tumor cells are influenced by type of treatment.

  17. Bifocal Presentation of Primary Testicular Extranasal NK/T-Cell Lymphoma: A Case Report and Review of the Literature

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    Ali Naboush

    2013-01-01

    Full Text Available Introduction. Testicular lymphoma is an aggressive disease with a very poor prognosis. Nasal-type natural killer/T-cell lymphoma (NKTCL-N in particular is very uncommon and has a rapidly progressive, fatal course. Case Report. We report a case of primary NKTCL-N of the testis in a 38-years-old Middle Eastern man. The patient had a history of primary right testicular tumor diagnosed at an outside institution as a seminoma and treated with orchiectomy followed by chemo/radiation. On admission, the patient had an enormous nasal granuloma with blood workup showing pancytopenia and elevated liver function tests due to active hepatitis B infection. CT scan of the sinuses showed a very large soft tissue mass, and PET scan showed splenomegaly with multiple lymph node masses in the pelvis and the chest areas. Bone marrow and nasal tumor biopsies as well as review of the slides from the initial orchiectomy were all in favor of NKTCL-N lymphoma. The patient was treated with CHOD based combination chemotherapy and responded dramatically to the first two cycles but passed away from fulminant hepatitis B infection. Conclusion. Despite all known treatments of NKTCL-N lymphoma of the testes, this disease has a very poor prognosis and invariably follows an aggressive clinical course.

  18. Evaluation of the Reactive T-Cell Infiltrate in Uveitis and Intraocular Lymphoma with Flow Cytometry of Vitreous Fluid (An American Ophthalmological Society Thesis)

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    Davis, Janet L.; Ruiz, Philip; Shah, Milan; Mandelcorn, Efrem D.

    2012-01-01

    Purpose: To describe the reactive T-cell infiltrate in uveitis and intraocular lymphoma using flow cytometry of clinical intraocular specimens acquired during diagnostic pars plana vitrectomy. Methods: This was a retrospective review of diagnostic vitreous specimens (1992–2011) obtained at a university-based, tertiary care center. Seventy-eight patients with uveitis or lymphoma undergoing pars plana vitrectomy were selected for intraocular testing based on clinical diagnostic uncertainty. Pars plana vitrectomy with flow cytometry, gene rearrangement studies, and cytology was performed. Results: T-cell infiltrates were found in all diagnostic categories with limited power to discriminate between uveitis and T-lymphocyte reactive infiltrates in response to intraocular lymphoma. Statistically significant differences by two-sample test of means between group means were found between 35 uveitis and 35 B-cell lymphoma cases for T-cell markers CD2, 3, 4, 5, and 7, but not for CD8. The CD4:CD8 ratio had a higher mean value in the uveitis group (P=.0113), and 8 T-cell lymphomas had a statistically greater number of CD3+ lymphocytes compared to uveitis (P=.0199) by two-sample test of means. Likelihood ratios were highest for CD2, CD5, CD7, CD4:CD8 ratio, CD20, and CD22. Conclusions: Discrimination between uveitis and lymphoma based on cell identification by flow cytometry was limited because of the prevalence of T lymphocytes in all diagnostic categories, emphasizing the importance of a reactive T-cell infiltrate in B-cell lymphomas, which may impede diagnosis. Flow cytometry may allow identification of more cases of T-cell lymphoma than reported when it is combined with gene rearrangement and cytology. PMID:23818738

  19. Circulating and Tumor-Infiltrating Foxp3+ Regulatory T Cell Subset in Chinese Patients with Extranodal NK/T Cell Lymphoma

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    Rou-Jun Peng, Zhou-Feng Huang, Yi-Lan Zhang, Zhong-Yu Yuan, Yi Xia, Wen-Qi Jiang, Yi-Xin Zeng, Jiang Li

    2011-01-01

    Full Text Available Foxp3+ regulatory T lymphocytes (Tregs usually act as an immune suppressor and correlate with poorer survival in malignancies. This study aims to investigate the distribution and characterization of Foxp3+ subset in peripheral blood mononuclear cells (PBMCs and tumor tissues from extranodal NK/T cell lymphoma (ENKTL. Our study showed the percentage of Foxp3+ subset from PBMC was significantly higher than that of healthy individuals (P<0.001. The Foxp3+ subset from PBMCs expressed CD45RO, CTLA4, GITR, CCR7, and had an IL-10highIFNγ+TGFβ+IL-2lowIL-17low cytokine secreting phenotype. Interestingly, the existence of EBV antigen-specific CD8+Foxp3+ Tregs was discovered in ENKTL. Furthermore, the high density of Foxp3+ TILs was associated with improved progression-free survival (PFS in ENKTL patients (P<0.05. Collectively, our study implicates that EBV antigens could induce antigen-specific CD8+Foxp3+ Tregs in ENKTL, and Foxp3+ TILs is an independent factor for PFS in ENKTL.

  20. PHENYTOIN-ASSOCIATED LYMPHOADENOPATHY MIMICKING A PERIPHERAL T-CELL LYMPHOMA

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    Mark E. Johns

    2010-09-01

    Full Text Available We report a case of phenytoin-induced pseudolymphoma in a 28-year-old male with a history of autism and seizure disorder.  The patient presented with bilateral cervical lymphadenopathy that was shown to be moderately to markedly FDG-avid on a whole body PET/CT scan.  Flow cytometry analysis of peripheral blood and bone marrow mononuclear cells detected identical T cell population with aberrant immunophenotype.  Additionally, a TCR beta gene was found to be clonally rearranged in both peripheral blood and bone marrow supporting a clonal origin of atypical T cells. However, no such clonal population of T-cells could be detected in a pathologic specimen obtained from an excisional biopsy of one of the patient’s cervical lymph nodes. After discontinuing the patient’s phenytoin, his lymphadenopathy has nearly completely resolved and circulation clonal T cell population disappeared with 12 months of follow-up.

  1. Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: active principles from Physalis pruinosa and structure-activity relationships with withanolides.

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    Nakano, Daisuke; Ishitsuka, Kenji; Hatsuse, Takahiro; Tsuchihashi, Ryota; Okawa, Masafumi; Okabe, Hikaru; Tamura, Kazuo; Kinjo, Junei

    2011-07-01

    Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I (HTLV-1). Clinical manifestations of ATL range from smoldering to chronic, lymphoma and acute subtypes. Patients with acute and lymphoma-type ATL require therapeutic intervention. Conventional chemotherapeutic regimens used against other malignant lymphoma have been administered to ATL patients, but the therapeutic outcomes of acute and lymphoma-type ATL remain very poor. In this study, 214 extracts from 162 plants belonging to 65 families were screened for the purpose of elucidating the anti-proliferative effect against HTLV-1-infected T-cell lines. Extracts from aerial parts of Physalis pruinosa showed potent inhibitory effect. We isolated five withanolides from the extracts by activity-guided fractionation and examined the structure-activity relationships. The presence of a 5β,6β-epoxy function is suggested to be essential for the activity, and the most active principle showed selective toxicity to HTLV-1-infected T-cell lines.

  2. Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II.

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    Weici Zhang

    Full Text Available Hepatosplenic T cell lymphoma (HSTCL is a distinct and lethal subtype of peripheral T cell lymphoma with an aggressive course and poor outcome despite multiagent chemotherapy. Contradictory literature, an unknown etiology, and poor response to treatment highlight the need to define the malignant process and identify molecular targets with potential for successful therapeutic interventions. Herein, we report that mice homozygously expressing a dominant negative TGFβRII (dnTGFβRII under the control of the CD4 promoter spontaneously develop lymphoma-like T cell infiltration involving both spleen and liver. Splenomegaly, hepatomegaly and liver dysfunction were observed in homozygous dnTGFβRII mice between 10 weeks and 10 months of age associated with a predominant infiltration of CD4(-CD8(-TCRβ(+NK1.1(+ or CD8(+TCRβ(+NK1.1(- T cell subsets. Notch 1 and c-Myc expression at the mRNA levels were significantly increased and positively correlated with the cell number of lymphoid infiltrates in the liver of dnTGFβRII homozygous compared to hemizygous mice. Further, 2×10(4 isolated lymphoma-like cells transplant disease by adoptive cell transfers. Collectively, our data demonstrate that increased copy number of dnTGFβRII is critical for development of lymphoma-like T cell infiltration.

  3. Quantitative PCR for HTLV-1 provirus in adult T-cell leukemia/lymphoma using paraffin tumor sections.

    Science.gov (United States)

    Kato, Junki; Masaki, Ayako; Fujii, Keiichiro; Takino, Hisashi; Murase, Takayuki; Yonekura, Kentaro; Utsunomiya, Atae; Ishida, Takashi; Iida, Shinsuke; Inagaki, Hiroshi

    2016-11-01

    Detection of HTLV-1 provirus using paraffin tumor sections may assist the diagnosis of adult T-cell leukemia/lymphoma (ATLL). For the detection, non-quantitative PCR assay has been reported, but its usefulness and limitations remain unclear. To our knowledge, quantitative PCR assay using paraffin tumor sections has not been reported. Using paraffin sections from ATLLs and non-ATLL T-cell lymphomas, we first performed non-quantitative PCR for HTLV-1 provirus. Next, we determined tumor ratios and carried out quantitative PCR to obtain provirus copy numbers. The results were analyzed with a simple regression model and a novel criterion, cut-off using 95 % rejection limits. Our quantitative PCR assay showed an excellent association between tumor ratios and the copy numbers (r = 0.89, P PCR assay should be interpreted very carefully and that our quantitative PCR assay is useful to estimate the status of HTLV-1 involvement in the tumor cases. In conclusion, our quantitative PCR assay using paraffin tumor sections may be useful for the screening of ATLL cases, especially in HTLV-1 non-endemic areas where easy access to serological testing for HTLV-1 infection is limited.

  4. Phase II study of gemcitabine and bexarotene (GEMBEX) in the treatment of cutaneous T-cell lymphoma

    Science.gov (United States)

    Illidge, T; Chan, C; Counsell, N; Morris, S; Scarisbrick, J; Gilson, D; Popova, B; Patrick, P; Smith, P; Whittaker, S; Cowan, R

    2013-01-01

    Background: Both gemcitabine and bexarotene are established single agents for the treatment of cutaneous T-cell lymphoma (CTCL). We investigated the feasibility and efficacy of combining these drugs in a single-arm phase II study. Methods: Cutaneous T-cell lymphoma patients who had failed standard skin-directed therapy and at least one prior systemic therapy were given four cycles of gemcitabine and concurrent bexarotene for 12 weeks. Responders were continued on bexarotene maintenance until disease progression or unacceptable toxicity. Results: The median age was 65 years, stage IB (n=5), stage IIA (n=2), stage IIB (n=8), stage III (n=8) and stage IVA (n=12), 17 patients were erythrodermic, 17 patients were B1, and 10 patients were both erythrodermic and B1. Thirty (86%) patients completed four cycles of gemcitabine. In all, 80.0% of patients demonstrated a reduction in modified Severity-Weighted Assessment Tool (mSWAT) score although the objective disease response rate at 12 weeks was 31% (partial response (PR) 31%) and at 24 weeks 14% (PR 14%, stable disease (SD) 23%, progressive disease (PD) 54%, not evaluable 9%). Median progression-free survival was 5.3 months and median overall survival was 21.2 months. Conclusion: The overall response rate of the combination did not reach the specified target to proceed further and is lower than that previously reported for gemcitabine as a single agent. PMID:24136145

  5. The histone deacetylase inhibitor romidepsin synergizes with lenalidomide and enhances tumor cell death in T-cell lymphoma cell lines

    Science.gov (United States)

    Cosenza, Maria; Civallero, Monica; Fiorcari, Stefania; Pozzi, Samantha; Marcheselli, Luigi; Bari, Alessia; Ferri, Paola; Sacchi, Stefano

    2016-01-01

    ABSTRACT We investigated the cytotoxic interactions of romidepsin, a histone deacetylase inhibitor, and lenalidomide, an immunomodulatory agent, in a T-cell lymphoma preclinical model. Hut-78 and Karpas-299 cells were treated with romidepsin and lenalidomide alone and in combination. The interaction between romidepsin and lenalidomide was evaluated by the Chou–Talalay method, and cell viability and clonogenicity were also evaluated. Apoptosis, reactive oxygen species (ROS) levels, and cell cycle distribution were determined by flow cytometry. ER stress, caspase activation, and the AKT, MAPK/ERK, and STAT-3 pathways were analyzed by Western blot. Combination treatment with romidepsin and lenalidomide had a synergistic effect in Hut-78 cells and an additive effect in Karpas-299 cells at 24 hours and did not decrease the viability of normal peripheral blood mononuclear cells. This drug combination induced apoptosis, increased ROS production, and activated caspase-8, −9, −3 and PARP. Apoptosis was associated with increased hallmarks of ER stress and activation of UPR sensors and was mediated by dephosphorylation of the AKT, MAPK/ERK, and STAT3 pathways.The combination of romidepsin and lenalidomide shows promise as a possible treatment for T-cell lymphoma. This work provides a basis for further studies. PMID:27657380

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

    Directory of Open Access Journals (Sweden)

    Jorge Hurtado-Cordovi

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2011-01-01

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

  8. T-cell population of primary and secondary cutaneous B-cell lymphomas does not express the cutaneous lymphocyte-associated antigen (CLA).

    Science.gov (United States)

    Marti, R M; Hausmann, G; Estrach, T; Cid, M C; Palou, J; Herrero, C; Mascaro, J M

    1997-05-01

    Primary cutaneous B-cell lymphomas (CBCL) are a group of malignant lymphomas with apparently distinct clinicopathological and immunophenotypical features. As in other B-cell lymphomas, the accompanying benign cell population in CBCL includes a variable number of T lymphocytes whose role is not well understood. In the present study we characterized the immunophenotype of these T cells and compared it with that of the reactive T-cell population in specific skin involvement by noncutaneous B-cell malignancies. Our results indicated that most T cells in both primary and secondary B-cell lymphomas were CLA+ memory/effector helper T cells which differed from the currently known CLA+ memory/effector helper T lymphocytes of the skin-associated lymphoid tissue (SALT) system. However, the endothelial CLA ligand, E-selectin, was expressed on dermal vessels. These results suggest that a B cell environment and/or a lack of epidermal involvement promote(s) the recruitment into the skin of a different, apparently less specific, subset of memory helper T cells from those seen in T-cell-mediated dermatoses.

  9. Cutaneous epitheliotropic T-cell lymphoma in the cat: a review of the literature and five new cases.

    Science.gov (United States)

    Fontaine, Jacques; Heimann, Marianne; Day, Michael J

    2011-10-01

    Cutaneous epitheliotropic T-cell lymphoma (CETL) is characterized by cutaneous infiltration of neoplastic T lymphocytes with a specific tropism for the epidermis and adnexal epithelium. This disease is reported very rarely in the cat. Clinical data were collected from an informal discussion with veterinary dermatologists through the Vetdermlist (vetderm@lists.ncsu.edu). In parallel, case archives of two European diagnostic histopathology laboratories (Institut de Pathologie et Génétique/Bio.be Gosselies, Belgium and the School of Veterinary Sciences, University of Bristol, UK) were reviewed. Fifteen cases with a good clinical description were selected, and five sets of skin biopsies were available for review. Cutaneous epitheliotropic T-cell lymphoma generally affects older cats with no apparent sex or breed predisposition. Solitary or multiple lesions were reported without predilection for any particular location. The lesions consisted of erythematous plaques or patches, scaly alopecic patches and nonhealing ulcers or nodules, which sometimes mimicked an eosinophilic plaque. Pruritus was rarely reported. No lesions affecting the oral mucosa were observed. Clinical diagnosis of CETL is more challenging in cats than in dogs. Final diagnosis must be based on histopathological examination of skin biopsy samples. The characteristic lesions of feline CETL are similar to those reported in the dog, but involvement of the adnexal glands was not observed in this series (n=5). The neoplastic T cells were generally small to medium in size. The survival time of cats with CETL seems to be more variable than that of affected dogs. Too few cases have been evaluated to permit clear recommendations to be made with respect to treatment.

  10. Expression of miR-155 and miR-126 in situ in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kopp, Katharina L; Ralfkiaer, Ulrik; Nielsen, Boye S;

    2013-01-01

    Recently, miR-155 has been implicated in cutaneous T-cell lymphoma (CTCL). Thus, elevated levels of miR-155 were observed in skin lesions from CTCL patients as judged from qPCR and micro-array analysis and aberrant, high miR-155 expression was associated with severe disease. Moreover, miR-155...... promoted proliferation of malignant T cells in vitro. Little is, however, known about which cell types express miR-155 in vivo in CTCL skin lesions. Here, we study miR-155 expression using in situ hybridization (ISH) with a miR-155 probe, a negative control (scrambled), and a miR-126 probe as a positive...... control in nine patients with mycosis fungoides, the most frequent subtype of CTCL. We provide evidence that both malignant and non-malignant T cells stain weakly to moderately positive with the miR-155 probe, but generally negative with the miR-126 and negative control probes. Reversely, endothelial...

  11. Hepatosplenic gamma/delta T-cell lymphoma: a report of two cases in immunocompromised patients, associated with isochromosome 7q.

    Science.gov (United States)

    François, A; Lesesve, J F; Stamatoullas, A; Comoz, F; Lenormand, B; Etienne, I; Mendel, I; Hémet, J; Bastard, C; Tilly, H

    1997-07-01

    Two cases of peripheral T-cell lymphoma, characterized by hepatosplenic presentation and gamma/delta T-cell receptor phenotype on malignant cells, are reported. Little is known about the chromosomal changes in these peculiar lymphomas. We report the cytogenetic analysis of these two patients. Isochromosome 7q and trisomy 8 were observed. These abnormalities were reported previously in five cases of gamma/delta T-cell lymphoma. These two patients had lymphomatous infiltration of the spleen, liver, bone marrow, and (in one case) lymph nodes. These abnormalities occurred in immunocompromised patients (i.e., immunosuppressive therapy for kidney transplantation and chemotherapy for Hodgkin's disease), without Epstein-Barr virus infection stigmata in tumor cells.

  12. A Case Report of Primary Nasal Natural Killer (NK)/T-Cell Lymphoma in an African American Patient Presenting with Hemophagocytic Syndrome

    Science.gov (United States)

    Tan, Bowei; Abdelmalek, Cherif; O’Donnell, James E.; Toltaku, Thomas; Chaudhry, Rashid; Wang, Jen C.; Gotlieb, Vladimir

    2017-01-01

    Patient: Male, 55 Final Diagnosis: Primary NK-T cell lymphoma • nasal type Symptoms: Fever • nasal bleeding • nasal mass • weight loss Medication: — Clinical Procedure: Chemotherapy×2 cycles • radiation therap Specialty: Oncology Objective: Rare disease Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL) is generally an aggressive and rare non-Hodgkin lymphoma. It is most common in East Asians, Native Americans, and South Americans, but is rarely reported in blacks. Case Report: A 55-year-old African American male born in Grenada presented with a left nostril mass with facial swelling and biopsy subsequently confirmed a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKTCL). Immunochemistry was positive for CD2, cytoplasmic CD3, CD7, CD 43, CD 56, granzyme B, and TIA-1. In situ hybridization was positive for Epstein-Barr virus encoded ribonucleic acid (EBERs). Bone marrow aspiration did not show lymphoma involvement. The patient had progressive neutropenia upon presentation, with further investigations showing hepatomegaly, hyperferritinemia, and hemophagocytosis in the bone marrow. We reached a diagnosis of hemophagocytic syndrome. He was treated with a high-dose combination chemotherapy and radiation therapy; the neutropenia improved significantly with steroids as treatment for immune activation in the setting of hemophagocytic syndrome. Conclusions: To the best of our knowledge, this is the only second report of extranodal NK/T-cell lymphoma, nasal type in a black patient, and it raises the awareness of early recognition of rare manifestations of NK/T-cell lymphoma such as hemophagocytic syndrome. PMID:28193996

  13. Prognostic significance of tumor burden in the blood of patients with erythrodermic primary cutaneous T-cell lymphoma.

    Science.gov (United States)

    Scarisbrick, J J; Whittaker, S; Evans, A V; Fraser-Andrews, E A; Child, F J; Dean, A; Russell-Jones, R

    2001-02-01

    Erythrodermic cutaneous T-cell lymphoma (CTCL) includes patients with erythrodermic mycosis fungoides who may or may not exhibit blood involvement and Sézary syndrome and in whom hematological involvement is, by definition, present at diagnosis. These patients were stratified into 5 hematologic stages (H0-H4) by measuring blood tumor burden, and these data were correlated with survival. The study identified 57 patients: 3 had no evidence of hematologic involvement (H0), 8 had a peripheral blood T-cell clone detected by polymerase chain reaction (PCR) analysis of the T-cell receptor gene and less than 5% Sézary cells on peripheral blood smear (H1), and 14 had either a T-cell clone detected by Southern blot analysis or PCR positivity with more than 5% circulating Sézary cells (H2). Twenty-four patients had absolute Sézary counts of more than 1 x 10(9) cells per liter (H3), and 8 patients had counts in excess of 10 x 10(9) cells per liter (H4). The disease-specific death rate was higher with increasing hematologic stage, after correcting for age at diagnosis. A univariate analysis of 30 patients with defined lymph node stage found hematologic stage (P =.045) and lymph node stage (P =.013) but not age (P =.136) to be poor prognostic indicators of survival. Multivariate analysis identified only lymph node stage to be prognostically important, although likelihood ratio tests indicated that hematologic stage provides additional information (P =.035). Increasing tumor burden in blood and lymph nodes of patients with erythrodermic CTCL was associated with a worse prognosis. The data imply that a hematologic staging system could complement existing tumor-node-metastasis staging criteria in erythrodermic CTCL.

  14. [Neuropathy in angioimmunoblastic lymphadenopathy (author's transl)].

    Science.gov (United States)

    Brunet, P; Binet, J L; de Saxce, H; Gray, F; De Baecque, C; Raphael, M; Lyon-Caen, O

    1981-01-01

    Four cases of angioimmunoblastic lymphadenopathy associated to peripheral neuropathy are described. The neuropathy was mixed, sensory and motor, more or less extensive, always asymetrical. In two cases, the clinical symptomatology and the clinical course were very peculiar, characterized by sensory disorders of a precise topography, circumscribed and sometimes suspended and by a relapsing and remitting course. In the third case, the neurological signs were acute and rapidly extensive with mandatory respiratory assistance. In this case, death occurred after a few weeks and the exact diagnosis was only attained at post-mortem examination. In the fourth case the neuropathy was very painful but the course was slow. In all four cases marked and extensive pain was present prior to the neurological disorders. Electrophysiological abnormalities were a constant feature with a marked slowing down of nerve conduction velocity. CSF was normal at the beginning in one case but was otherwise markedly pathological with an increased number of cells due to a large number of lymphocytes ranging from 6 to 40 cells while protein ranged from 60 to 160 mg per 100 ml. Nerve and muscle biopsies were non specific, i.e. neurogenous muscular atrophy and demyelination, except in case n. 4 where specific angioimmunoblastic lymphadenopathy infiltrates were present both in nerve and muscle. In cases 1 and 3 a non specific lymphohistiocytic infiltrate was present in spinal roots and meninges. Corticotherapy was used and efficient in two cases. These data are compared with a review of the literature. Since 1976, 7 cases of angioimmunoblastic lymphadenopathy associated to peripheral neuropathy have been reported. Clinical, electrophysiological and biological features are similar. Only one case underwent a post mortem examination of the central nervous system: a non specific lymphocytic infiltration in the spinal roots and meninges was mentioned. The role of the dysproteinemia associated with the AIL

  15. Uveitis and Myositis as Immune Complications in Chemorefractory NK/T-Cell Nasal-Type Lymphoma Successfully Treated with Allogeneic Stem-Cell Transplant

    Directory of Open Access Journals (Sweden)

    Maria José Gómez-Crespo

    2016-01-01

    Full Text Available NK/T-cell lymphomas are a group of clonal proliferations of NK- or, rarely, T-cell types and have peculiar clinicopathologic features. Most common site of involvement is the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate. Association of autoimmune paraneoplastic disorders with NK/T-cell lymphomas is not well studied. Our patient was diagnosed with NK/T-cell lymphoma stage IV with skin involvement and treated frontline with CHOEP regimen. While he was under treatment, two immune complications presented: anterior uveitis of autoimmune origin refractory to steroids and myositis in lower limbs muscles. Autologous transplantation was rejected due to confirmed early relapse after first-line treatment, and the patient received second-line treatment according to the SMILE scheme, reaching complete response after four cycles. The patient underwent allogeneic transplantation and at the time of manuscript preparation is alive despite multiple complications. The disease should be suspected in patients with rhinitis or recurrent sinusitis, and early biopsy is recommended for all patients to avoid a delay in diagnosis. Our patient also presented symptoms of disease progression after first-line treatment, representing a paraneoplastic process, a very rare phenomenon in T-type lymphomas. This case is novel for the appearance of an inflammatory myositis, a histologically verified paraneoplastic phenomenon that responded to treatment for lymphoma.

  16. Uveitis and Myositis as Immune Complications in Chemorefractory NK/T-Cell Nasal-Type Lymphoma Successfully Treated with Allogeneic Stem-Cell Transplant

    Science.gov (United States)

    Gómez-Crespo, Maria José; López-Lorenzo, Jose Luis; Villaescusa, Teresa; Rodríguez-Pinilla, María; Fortes, José; Serrano, Cristina; Machan, Salma; Llamas, Pilar; Córdoba, Raúl

    2016-01-01

    NK/T-cell lymphomas are a group of clonal proliferations of NK- or, rarely, T-cell types and have peculiar clinicopathologic features. Most common site of involvement is the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate). Association of autoimmune paraneoplastic disorders with NK/T-cell lymphomas is not well studied. Our patient was diagnosed with NK/T-cell lymphoma stage IV with skin involvement and treated frontline with CHOEP regimen. While he was under treatment, two immune complications presented: anterior uveitis of autoimmune origin refractory to steroids and myositis in lower limbs muscles. Autologous transplantation was rejected due to confirmed early relapse after first-line treatment, and the patient received second-line treatment according to the SMILE scheme, reaching complete response after four cycles. The patient underwent allogeneic transplantation and at the time of manuscript preparation is alive despite multiple complications. The disease should be suspected in patients with rhinitis or recurrent sinusitis, and early biopsy is recommended for all patients to avoid a delay in diagnosis. Our patient also presented symptoms of disease progression after first-line treatment, representing a paraneoplastic process, a very rare phenomenon in T-type lymphomas. This case is novel for the appearance of an inflammatory myositis, a histologically verified paraneoplastic phenomenon that responded to treatment for lymphoma.

  17. Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing

    DEFF Research Database (Denmark)

    Nagasawa, T; Zhang, Q; Raghunath, P N

    2006-01-01

    To understand better T-cell lymphomagenesis, we examined promoter CpG methylation and mRNA expression of closely related genes encoding p16, p15, and p14 tumor suppressor genes in cultured malignant T-cells that were derived from cutaneous, adult type, and anaplastic lymphoma kinase (ALK......)-expressing T-cell lymphomas. p16 gene was epigenetically silenced in all but one of the 10 malignant T-cell lines examined, p15 gene silenced in roughly half of the lines, and p14 was the least frequently affected. Extensive methylation of the p16 promoter was seen in six out of 10 cutaneous T-cell lymphoma...... patient samples and corresponded with lack of p16 protein expression in the cases examined. Treatment of cultured T-cells with the DNA methyltransferase inhibitor, 5-aza-2-deoxy-cytidine, resulted in reversal of the p16 gene silencing. However, expression of p16 protein was delayed in relationship to p16...

  18. Total-skin electron irradiation for cutaneous T-cell lymphoma: The Northern Israel Oncology Center experience

    Energy Technology Data Exchange (ETDEWEB)

    Kuten, A.; Stein, M.; Mandelzweig, Y.; Tatcher, M.; Yaacov, G.; Epelbaum, R.; Rosenblatt, E. (Northern Israel Oncology Center, Haifa (Israel). Radiotherapy Unit)

    1991-07-01

    Total skin electron irradiation (TSEI) is effective and frequently used in the treatment of cutaneous T-cell lymphoma. A treatment technique has been developed at our center, using the Philips SL 75/10 linear accelerator. In our method, the patient is irradiated in a recumbent position by five pairs of uncollimated electron beams at a source to skin distance of 150 cm. This method provides a practical solution to clinical requirements with respect to uniformity of electron dose and low X-ray contamination. Its implementation does not require special equipment or modification of the linear accelerator. 19 of 23 patients (83%) with mycosis fungoides, treated by this method, achieved complete regression of their cutaneous lesions. (orig.).

  19. Total skin electron beam and total nodal irradiation for treatment of patients with cutaneous T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Micaily, B.; Vonderheid, E.C.; Brady, L.W.; Andrews, C.

    1985-06-01

    Sixteen patients with advanced cutaneous T-cell lymphoma (CTCL) with or without lymph node involvement, but without evidence of extranodal manifestations, were treated with a combination of total skin electron beam therapy (TSEB) and total nodal irradiation (TNI). Fourteen (87%) patients achieved a complete response (CR) lasting from 1 to 84+ months (median, 8+ months) from the completion of treatment. The best results occurred in 6 patients with pretumorous intracutaneous CTCL (Stages IB and IIA) where the CR has lasted in all patients from 8 to 84+ months (median about 27+ months). Radiotherapy was well tolerated with the major toxicity being bone marrow suppression. The authors conclude that combined TSEB and TNI is a relatively safe and effective treatment for patients with CTCL prior to the development of lymph node involvement. Long-term follow-up is needed to assess the curative potential of this treatment.

  20. Monitoring Pc 4 photodynamic therapy in clinical trials of cutaneous T-cell lymphoma using noninvasive spectroscopy.

    Science.gov (United States)

    Lee, Tammy K; Baron, Elma D; Foster, Thomas H

    2008-01-01

    Silicon phthalocyanine Pc 4 photodynamic therapy (Pc 4-PDT) has emerged as a potentially effective treatment for cutaneous T-cell lymphoma (CTCL). Noninvasive reflectance and fluorescence spectroscopy before, during, and after PDT may provide useful dose metrics and enable therapy to be tailored to individual lesions. We present the design and implementation of a portable bedside spectroscopy system for initial clinical trials of Pc 4-PDT of CTCL. Reflectance and fluorescence spectra were obtained from an early stage CTCL patient throughout the course of the PDT treatment. Preliminary patient data show a significant effect of Pc 4 on the tissue absorption, modest Pc 4 photobleaching, and heterogeneity of Pc 4 within and between the lesions.

  1. Romidepsin Used as Monotherapy in Sequence with Allogeneic Stem Cell Transplant in a Patient with Peripheral T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Nicholas Finn

    2014-01-01

    Full Text Available Despite advances in the field, a clear treatment algorithm for most peripheral T-cell lymphoma (PTCL subtypes remains to be defined. Generating reliable randomized data for this type of pathology remains a challenge because of the relative rarity of the disease and the heterogeneity of subtypes. Newer agents, such as the class-I selective histone deacetylase inhibitor romidepsin, have demonstrated efficacy and manageable toxicity in the relapsed and refractory setting. Whether novel agents should be used in conjunction with more conventional cytotoxic therapies or in sequence with a transplant strategy is unknown at this time. Here we report the successful use of romidepsin monotherapy as a bridge to allogeneic stem cell transplantation in a patient who had previously relapsed after several lines of conventional cytotoxic therapy for PTCL. Romidepsin provided the patient with sufficient disease control to proceed to transplantation while remaining in complete remission.

  2. STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kopp, Katharina L; Ralfkiaer, Ulrik; Gjerdrum, Lise Mette R

    2013-01-01

    show that malignant T cells constitutively express high levels of miR-155 and its host gene BIC (B cell integration cluster). Using ChIP-seq, we identify BIC as a target of transcription factor STAT5, which is aberrantly activated in malignant T cells and induced by IL-2/IL-15 in non-malignant T cells....... Incubation with JAK inhibitor or siRNA-mediated knockdown of STAT5 decreases BIC/miR-155 expression, whereas IL-2 and IL-15 increase their expression in cell lines and primary cells. In contrast, knockdown of STAT3 has no effect, and BIC is not a transcriptional target of STAT3, indicating that regulation...... of BIC/miR-155 expression by STAT5 is highly specific. Malignant proliferation is significantly inhibited by an antisense-miR-155 as well as by knockdown of STAT5 and BIC.   In conclusion, we provide the first evidence that STAT5 drives expression of oncogenic BIC/miR-155 in cancer. Moreover, our data...

  3. The Use of Synchrotron Infrared Microspectroscopy in the Assessment of Cutaneous T-cell Lymphoma vs. Pityriasis lichenoides Chronica

    Energy Technology Data Exchange (ETDEWEB)

    El Bedewi, A.; El Anany, G; El Mofty, M; Kretlow, A; Park, S; Miller, L

    2010-01-01

    The diagnosis of cutaneous lymphomas remains a challenge for both the clinician and dermatopathologist. To differentiate between frank malignant and premalignant lymphocytes within the skin. This study was performed on 20 patients with a mean age of 50 years. They were divided into two groups: mycosis fungoides (MF) (stage IA, IB and IIA) and pityriasis lichenoides chronica (PLC). Immunophenotyping using antibodies CD3, CD4, CD8, CD20 and CD30 was performed. Synchrotron Fourier transform infrared microspectroscopy (S-FTIRM) was performed on cell nuclei to assess chemical differences between MF and PLC cases as a potential complementary screening tool. Dermal spectra of both MF and PLC were compared using principal components analysis (PCA) of the S-FTIRM data. All PLC spectra was clustered together. However, the MF spectra formed two clusters, one that grouped with the PLC and the other grouped separately. Moreover, protein and nucleic acids showed highly significant differences between MF (IIA and IB), MF (IA) and PLC. The malignant transformation within lymphocytes was identifiable through the spectroscopic analysis of protein, RNA and DNA with S-FTIRM, making it a promising tool for classifying the progression of cutaneous T-cell lymphoma.

  4. THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

    Science.gov (United States)

    Cayrol, Florencia; Praditsuktavorn, Pannee; Fernando, Tharu M.; Kwiatkowski, Nicholas; Marullo, Rosella; Calvo-Vidal, M. Nieves; Phillip, Jude; Pera, Benet; Yang, Shao Ning; Takpradit, Kaipol; Roman, Lidia; Gaudiano, Marcello; Crescenzo, Ramona; Ruan, Jia; Inghirami, Giorgio; Zhang, Tinghu; Cremaschi, Graciela; Gray, Nathanael S.; Cerchietti, Leandro

    2017-01-01

    Peripheral T-cell lymphomas (PTCL) are aggressive diseases with poor response to chemotherapy and dismal survival. Identification of effective strategies to target PTCL biology represents an urgent need. Here we report that PTCL are sensitive to transcription-targeting drugs, and, in particular, to THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7). The STAT-signalling pathway is highly vulnerable to THZ1 even in PTCL cells that carry the activating STAT3 mutation Y640F. In mutant cells, CDK7 inhibition decreases STAT3 chromatin binding and expression of highly transcribed target genes like MYC, PIM1, MCL1, CD30, IL2RA, CDC25A and IL4R. In surviving cells, THZ1 decreases the expression of STAT-regulated anti-apoptotic BH3 family members MCL1 and BCL-XL sensitizing PTCL cells to BH3 mimetic drugs. Accordingly, the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. PMID:28134252

  5. SOLITARY T-CELL HEPATIC LYMPHOMA WITH LARGE GRANULAR LYMPHOCYTE MORPHOLOGY IN A CAPTIVE CHEETAH (ACINONYX JUBATUS).

    Science.gov (United States)

    Lindemann, Dana M; Carpenter, James W; Almes, Kelli M; Schumacher, Loni; Ryseff, Julia K; Hallman, Mackenzie

    2015-06-01

    A 13-yr-old male cheetah (Acinonyx jubatus) presented for an acute history of lateral recumbency and anorexia. Upon physical examination under general anesthesia, severe icterus was noted. A serum biochemical profile confirmed markedly elevated total bilirubin and alanine transaminase. Based on ultrasound-guided liver aspirates and cytology, a presumptive diagnosis of large granular lymphocyte hepatic lymphoma was reached. Abdominal and thoracic radiographs did not assist in reaching an antemortem diagnosis. Postmortem examination and histopathology provided a definitive diagnosis of hepatic lymphoma with acute massive hepatocelluar necrosis and hemorrhage, as well as concurrent lesions of gastric ulcers, ulcerative and sclerosing enteritis, myocardial hypertrophy, and splenic myelolipomas. Immunohistochemistry of the liver yielded CD-3 positive and CD-20 negative results, confirming lymphocytes of a T-cell lineage. Due to concern for possible retrovirus-associated disease, enzyme-linked immunosorbent assays for feline leukemia virus and feline immunodeficiency virus were performed retrospectively on a banked serum sample and yielded negative results, thus diminishing concern for the male conspecific housed in the same exhibit.

  6. Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type.

    Science.gov (United States)

    Lee, Seungbok; Park, Ha Young; Kang, So Young; Kim, Seok Jin; Hwang, Jinha; Lee, Seungho; Kwak, Soo Heon; Park, Kyong Soo; Yoo, Hae Yong; Kim, Won Seog; Kim, Jong-Il; Ko, Young Hyeh

    2015-07-10

    Extranodal NK/T-cell lymphoma nasal type (ENKL) is a rare type of non-Hodgkin lymphoma that more frequently occurs in East Asia and Latin America. Even though its molecular background has been discussed in the last few years, the current knowledge does not explain the disease pathogenesis in most cases of ENKL. Here, we performed multiple types of next-generation sequencing on 34 ENKL samples, including whole-exome sequencing (9 cancer tissues and 4 cancer cell lines), targeted sequencing (21 cancer tissues), and RNA sequencing (3 cancer tissues and 4 cancer cell lines). Mutations were found most frequently in 3 genes, STAT3, BCOR, and MLL2 (which were present in 9, 7, and 6 cancer samples, respectively), whereas there were only 2 cases of JAK3 mutation. In total, JAK/STAT pathway- and histone modification-related genes accounted for 55.9% and 38.2% of cancer samples, respectively, and their involvement in ENKL pathogenesis was also supported by gene expression analysis. In addition, we provided 177 genes upregulated only in cancer tissues, which appear to be linked with angiocentric and angiodestructive growth of ENKL. In this study, we propose several novel driver genes of ENKL, and show that these genes and their functional groups may be future therapeutic targets of this disease.

  7. Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma.

    Science.gov (United States)

    Kim, Youn H; Duvic, Madeleine; Obitz, Erik; Gniadecki, Robert; Iversen, Lars; Osterborg, Anders; Whittaker, Sean; Illidge, Timothy M; Schwarz, Thomas; Kaufmann, Roland; Cooper, Kevin; Knudsen, Kim M; Lisby, Steen; Baadsgaard, Ole; Knox, Susan J

    2007-06-01

    The efficacy and safety of zanolimumab in patients with refractory cutaneous T-cell lymphoma (CTCL) have been assessed in two phase 2, multicenter, prospective, open-label, uncontrolled clinical studies. Patients with treatment refractory CD4(+) CTCL (mycosis fungoides [MF], n = 38; Sézary syndrome [SS], n = 9) received 17 weekly infusions of zanolimumab (early-stage patients, 280 and 560 mg; advanced-stage patients, 280 and 980 mg). The primary end point was objective response (OR) as assessed by composite assessment of index lesion disease activity score. Secondary end points included physician's global assessment (PGA), time to response, response duration, and time to progression. ORs were recorded for patients in both CTCL types (MF, 13 ORs; SS, 2 ORs). In the high-dose groups (560 and 980 mg dose groups), a response rate of 56% was obtained with a median response of 81 weeks. Adverse events reported most frequently included low-grade infections and eczematous dermatitis. Zanolimumab showed marked clinical efficacy in the treatment of patients with refractory MF, with early onset of response, high response rate, and durable responses. The treatment was well tolerated with no dose-related toxicity other than the targeted depletion of peripheral T cells. A pivotal study has been initiated based on these findings.

  8. Blood eosinophilia: A poor prognostic factor for primary cutaneous T cell lymphomas? A cohort of 72 cases

    Directory of Open Access Journals (Sweden)

    Kelati Awatef

    2016-04-01

    Full Text Available Introduction: Blood eosinophilia (BE is described as a poor prognosis marker for some T cell malignancies. Objective: to detect the presence and the prognostic significance of BE in patients with cutaneous T cell lymphoma (CTL. Methods: This was a retro prospective study of 72 patients with CTL. Patients with other factors that may increase BE were excluded. Results: We had 14 cases of BE, 10 cases were in the erythrodermic stage of the disease and 6 in the tumoral stage and we had 4 cases of death. The BE was associated with deterioration of the general condition (p=0.001; depilation of the body (p=0.04, erythroderma (p=0.008, scalp and nails involvement (p=0.000, high rate of lactate Dehydrogenase (LDH (p=0.000 and beta 2 microglobulin (B2M, (p=0.000, the histological type of Mycosis fungoides (MF with positive Immunohistochemistry for CD4 (p=0.014 and CD3(0.05. Conclusions: BE was significantly related to MF, to advanced stages of the disease, to pejorative clinical signs and to elevated rate of LDH and B2M which are poor prognostic factors of MF with four cases of death, which prove that BE is also a poor Prognostic factor of MF.

  9. Mutational Analysis of Extranodal NK/T-Cell Lymphoma Using Targeted Sequencing with a Comprehensive Cancer Panel

    Science.gov (United States)

    Choi, Seungkyu; Go, Jai Hyang; Kim, Eun Kyung; Lee, Hojung; Lee, Won Mi; Cho, Chun-Sung

    2016-01-01

    Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future. PMID:27729836

  10. γ-Tocotrienol induces apoptosis in human T cell lymphoma through activation of both intrinsic and extrinsic pathways.

    Science.gov (United States)

    Wilankar, Chandan; Khan, Nazir M; Checker, Rahul; Sharma, Deepak; Patwardhan, Raghavendra; Gota, Vikram; Sandur, Santosh Kumar; Devasagayam, T P A

    2011-01-01

    Tocotrienols are members of vitamin E family and possess broad biological activities including antioxidant, anti-inflammatory and antitumor effects. In the present study, we examine the potential of α-tocotrienol (AT) and γ-tocotrienol (GT) in inhibiting the proliferation of human T cell lymphoma Jurkat cells and elucidate the pathways involved in anti tumor effects of GT. GT but not AT inhibited proliferation and induced apoptosis in Jurkat cells in a dose dependent manner. GT treatment resulted in elevated mitochondrial ROS production, activation of JNK and suppression of ERK and p38 MAPK. GT also induced calcium release, loss of mitochondrial membrane potential and cytochrome c release from the mitochondria. These changes were accompanied by increase in Bax expression with a concomitant decrease in Bcl-xl expression suggesting activation of mitochondrial apoptotic pathway. GT induced increase in mitochondrial ROS was abrogated by catalase. Besides, GT also up-regulated surface expression of Fas and FasL on Jurkat cells. Further, caspase activation and PARP degradation were also seen in cells treated with GT. Inhibitors of caspase-8 and caspase-9 significantly abrogated GT mediated apoptosis. In contrast GT was not toxic to normal human peripheral blood mononuclear cells suggesting differential cytotoxicity towards normal lymphocytes and transformed lymphoma cells. Cellular uptake studies with tocotrienols showed higher intracellular accumulation of GT as compared to AT which may be responsible for its better antitumor activity. Our results show antitumor effects of GT in human lymphoma cells via increased mitochondrial ROS generation and activation of both intrinsic and extrinsic apoptotic pathways.

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

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2015-01-01

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

  12. Epstein-Barr virus-positive nodal peripheral T cell lymphomas: clinicopathologic and gene expression profiling study.

    Science.gov (United States)

    Ha, Sang Yun; Sung, Jiyeon; Ju, Hyunjung; Karube, Kennosuke; Kim, Soek Jin; Kim, Won Seog; Seto, Masao; Ko, Young-Hyeh

    2013-07-01

    Epstein-Barr virus-positive peripheral T cell lymphoma, not otherwise specified (EBV+ PTCL-NOS), in which virtually all neoplastic T cells harbor EBV, is a very rare disease with poor prognosis. To analyze the clinicopathologic characteristics and gene expression profile, we retrospectively collected six cases of EBV+ PTCL-NOS with no known primary immunodeficiency. The patients were 5 men and 1 woman, their age ranging from 48 years to 88 years (median 61.5 years). Lymphadenopathy was the most common presentation. Four patients had underlying disease, including HBV carrier, HCV infection, diabetes mellitus, and prostate cancer. All patients showed fatal clinical course in spite of chemotherapy. Histopathologically, monotonous infiltration of atypical lymphocytes of small to medium size was shown in four patients and medium to large tumor cells in two patients. Five patients showed CD4-/CD8+/bF-1+ phenotype with TIA-1 expression. In gene expression analysis using mRNA microarray, genes differentially expressed in EBV+ PTCL-NOS compared to normal reactive lymph nodes included 1515 genes (Mann-Whitney U-test pgenes involved in B cell differentiation or activation were mostly down-regulated, and T cell activation was mostly suppressed by down-regulation of activation genes and up-regulation of regulatory genes. Genes associated with cytotoxic activity were mostly up-regulated. Based on its peculiar clinical, histopathologic, and gene expression findings in EBV+ PTCL-NOS, we suggest EBV+ PTCL-NOS as a distinct disease entity from PTCL-NOS. In this study, the finding that most significantly enriched the functional term was immune response, suggesting a specific relation between EBV infection and alteration of immune response in the patients with EBV+ PTCL-NOS.

  13. HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma-A Tale of Two Proteins: Tax and HBZ.

    Science.gov (United States)

    Giam, Chou-Zen; Semmes, Oliver John

    2016-06-16

    HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10-20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%-5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling-the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)-to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided.

  14. miR-122 regulates p53/Akt signalling and the chemotherapy-induced apoptosis in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Manfè, Valentina; Biskup, Edyta; Rosbjerg, Anne;

    2012-01-01

    Advanced cutaneous T-cell lymphoma (CTCL) is resistant to chemotherapy and presents a major area of medical need. In view of the known role of microRNAs (miRNAs) in the regulation of cellular signalling, we aimed to identify the functionally important miRNA species, which regulate apoptosis in CT...

  15. Ultrafractionated radiotherapy for murine DDL1 T cell lymphomas in nude mice; Ultrafraktionierte Strahlentherapie bei murinen DDL1 T-Zell-Lymphomen in Nacktmaeusen

    Energy Technology Data Exchange (ETDEWEB)

    Prager, J.; Krause, M.; Hessel, F.; Zips, D.; Petersen, C. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Technische Univ. Dresden (Germany); Wohlfarth, J.; Baumann, M. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Technische Univ. Dresden (Germany)]|[Experimentelles Zentrum, Medizinische Fakultaet Carl Gustav Carus, Technische Univ. Dresden (Germany); Haase, M. [Medizinische Fakultaet Carl Gustav Carus, Technische Univ. Dresden (Germany). Inst. fuer Pathologie

    2004-07-01

    The present study was dedicated to the DDL1 T cell lymphoma tumour model. There have been no in vivo studies on this model to date. [German] Als Tumormodell wurde in der vorliegenden Arbeit das murine T-Zell-Lymphom DDL1 untersucht, ueber das keine in-vitro-Untersuchungen vorliegen. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Jeffrey Carson

    2012-01-01

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

  17. Characterization of the T-cell receptor gamma chain gene rearrangements as an adjunct tool in the diagnosis of T-cell lymphomas in the gastrointestinal tract of cats.

    Science.gov (United States)

    Gress, Verena; Wolfesberger, Birgitt; Fuchs-Baumgartinger, Andrea; Nedorost, Nora; Saalmüller, Armin; Schwendenwein, Ilse; Rütgen, Barbara C; Hammer, Sabine E

    2016-08-01

    Feline alimentary lymphoma is the most common hematopoietic neoplasia in cats. It affects mainly the small intestines and is most frequently of T-cell origin. Evaluation of a fine needle aspirate is often the first step in the diagnostic work-up. Differentiation between a resident mature lymphocyte population as encountered in inflammatory bowel disease and small cell lymphoma cannot be achieved by cytology alone. Even full thickness biopsies evaluated by histopathology can be inconclusive. These cases warrant the application of complementary tools like PCR-based T-cell receptor (TCR) clonality testing for confirmation. The aim of this study was to optimize the DNA extraction protocol for formalin fixed and paraffin embedded tissues (FFPE) and to establish a heteroduplex analysis to enhance resolution of the PCR fragments of the T-cell receptor gamma (TCRG) V-J gene. The new protocols resulted in improved quantity and quality of the extracted DNA. Heteroduplex analysis of the samples improved the resolution of the electrophoresis results so that rules for interpretation of the different patterns could be established. Application of this improved setup detected clonal rearrangements in at least one TCRG primer reaction in 31 of 36 of our feline intestinal lymphoma samples after DNA quality testing.

  18. Type I enteropathy-associated T-cell lymphoma in the colon of a 29-year-old patient and a brief literature review

    Directory of Open Access Journals (Sweden)

    Zhang JC

    2016-02-01

    Full Text Available Jiu-Cong Zhang, Yong Wang, Xiu-Feng Wang, Fang-Xin Zhang Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, People’s Republic of China Abstract: Enteropathy-associated T-cell lymphoma (EATL is a rare gastrointestinal non-Hodgkin’s lymphoma, originating from intraepithelial T-lymphocyte, which is specifically associated with celiac disease. EATL most commonly presents in the sixth and seventh decades of life. We report a unique case of type I EATL in the colon with liver metastasis, which was presented with nonspecific radiological findings and at a very young age (29 years old compared with previously published data. We suggest that EATL should be regarded as part of differential diagnosis in any patient presenting with abdominal pain, diarrhea, weight loss, and malabsorption because delay in treatment can result in an irreversible clinical outcome. Keywords: enteropathy-associated T-cell lymphoma, colon, ulcer, liver metastasis

  19. cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas

    DEFF Research Database (Denmark)

    Manfè, Valentina; Biskup, Edyta; Willumsgaard, Ayalah;

    2013-01-01

    improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc...... and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where...

  20. T-cell-rich large B-cell lymphoma. A study of 30 cases, supporting its histologic heterogeneity and lack of clinical distinctiveness.

    Science.gov (United States)

    Krishnan, J; Wallberg, K; Frizzera, G

    1994-05-01

    To determine whether correlations existed between morphologic and immunophenotypic findings and clinical characteristics, 30 cases of T-cell-rich large B-cell lymphomas (TBL) were evaluated by histopathology, immunostaining, and polymerase chain reaction on paraffin-embedded material. All were characterized by a polymorphic cell composition, including a variable mixture of small and large lymphoid cells and reactive cell. Most cases (87%) fitted into one of three main histologic types of non-Hodgkin's lymphoma (diffuse, mixed cell; diffuse, large cell; follicular and diffuse, mixed cell), and one group of eight cases had the prototypic features described by Ramsay et al. (17). All cases showed a component of large CD20(L26)+ MB2+ B cells in a predominant back-ground of reactive T cells (> 50% of the total lymphoid forms). Clonality was demonstrated by light chain restriction in 67% of cases and by rearrangement of the immunoglobulin heavy chain gene and bcl-2 gene in 64% and 28% of cases, respectively. The patients were predominantly men (70%), ages 18-83 years (median of 62.5), and were initially seen predominantly with nodal disease (and extranodal involvement in 20%) at advanced stages (III-IV: 77%). Treatment was mostly aggressive chemotherapy, and the outcomes were favorable (84% alive and well). These features are not distinctive as compared with those of typical large-cell lymphoma, nor did subgroups within the series (prototypic cases versus others; cases with less [ 70%] T-cell infiltration) significantly differ in clinical presentation or outcome. Thus, this study confirms that TBL, while useful as a diagnostic variant to be distinguished from both peripheral T-cell lymphoma and Hodgkin's disease, is a heterogeneous assortment of diverse histopathologic categories rather than a clinicopathologic entity. The term "T-cell rich" might, however, be usefully retained as a morphologic specification to be added to recognized histologic categories of lymphoma.

  1. [Aggressive NK/T cell leukemia/lymphoma associated with EBV].

    Science.gov (United States)

    Sousa, Jamira; Cabezuelo, Lourdes; Almeida, Sérgio; Filipe, Carlos; Simão, Adélia; Carvalho, Armando; Nascimento Costa, J

    2011-12-01

    The authors describe an unusual case of a young man presenting with fever, asthenia, anorexia and jaundice, associated to hepatosplenomegaly, evolving rapidly to multiorganic failure. Final diagnosis revealed an aggressive NK cell leukemia/lymphoma associated to the Epstein-Barr virus (EBV). The diagnosis, suggested clinically and after bone marrow immunophenotyping, was confirmed by morphologic and immunohistochemical findings on the post-mortem hepatic and splenic biopsy .The tumor cells were positive for CD3 and cytotoxic molecules, TIA, granzyme B and perforin. The herein reported case is a rare clinical entity, only recently recognized and with a difficult early diagnosis. We emphasize the necessity to exclude a Natural Killer cell malignancy in cases with identical characteristics.

  2. B-cell-rich T-cell lymphoma associated with Epstein-Barr virus-reactivation and T-cell suppression following antithymocyte globulin therapy in a patient with severe aplastic anemia

    Directory of Open Access Journals (Sweden)

    Nobuyoshi Hanaoka

    2015-09-01

    Full Text Available B-cell lymphoproliferative disorder (B-LPD is generally characterized by the proliferation of Epstein-Barr virus (EBV-infected B lymphocytes. We here report the development of EBV-negative B-LPD associated with EBV-reactivation following antithymocyte globulin (ATG therapy in a patient with aplastic anemia. The molecular autopsy study showed the sparse EBV-infected clonal T cells could be critically involved in the pathogenesis of EBV-negative oligoclonal B-LPD through cytokine amplification and escape from T-cell surveillances attributable to ATG-based immunosuppressive therapy, leading to an extremely rare B-cell-rich T-cell lymphoma. This report helps in elucidating the complex pathophysiology of intractable B-LPD refractory to rituximab.

  3. Imaging of cutaneous T cell lymphoma (CTCL) with In-111-T101 monoclonal antibody

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    Carrasquillo, J.A.; Bunn, P.A.; Keenan, A.M.; Reynolds, J.C.; Schroff, R.W.; Foon, K.A.; Ming-Hsu, S.; Gazdar, A.F.; Mulshine, J.M.; Perentesis, P.

    1985-05-01

    T101 is a murine monoclonal antibody (MoAb), IgC2a, directed against a cell surface pan T-cell antigen present in high concentration in CTCL cells. In-111 labelling was performed with a modification of the Krejcarek method (Hybritech, Inc.). I mg of DTPA conjugated T101 was labeled with 5 mCi, with a mean incorporation of 95%. Immunoreactivity was preserved, mean 88%. In vivo, less than 3.6% of the injected dose was on circulating transferrin. 11 patients (pts) received 2-6h intravenous infusion of 1 mg (5 pts), 10 mg (3 pts), 50 mg (3 pts) of In-111 T101. By 24h all pts showed avid uptake in pathologically or clinically involved nodes and erythroderma including several previously unsuspected nodal regions. Skin plaques were not visualized. In addition, there was localization in liver, spleen and bone marrow. Concentration of In-111 in biopsied nodes was 0.01, 0.02 and 0.03% of the injected dose per gram. Control studies with In-111Cl/sub 3/ or a nonspecific MoAb, 9.2.27, did not concentrate in nodes or skin disease. No dose dependent differences in tumor localization was seen although blood clearance was prolonged for doses less than or equal to 10 mgs of T101. All pts receiving less than or equal to 10 mgs developed transient itching, urticaria and chills. 1 of 8 pts tested had an antimouse immune response. Modulation of the antigen from circulating T-cells, skin and nodes was seen. This study shows the feasibility of imaging CTCL pts with In-111 T101 and suggest a potential for radioimmunotherapy.

  4. Changes in Foxp3-Positive Regulatory T Cell Number in the Intestine of Dogs With Idiopathic Inflammatory Bowel Disease and Intestinal Lymphoma.

    Science.gov (United States)

    Maeda, S; Ohno, K; Fujiwara-Igarashi, A; Uchida, K; Tsujimoto, H

    2016-01-01

    Although regulatory T cells (Tregs) play an integral role in immunologic tolerance and the maintenance of intestinal homeostasis, their involvement in canine gastrointestinal diseases, including idiopathic inflammatory bowel disease (IBD) and intestinal lymphoma, remains unclear. Here we show altered numbers of forkhead box P3 (Foxp3)-positive Tregs in the intestine of dogs with IBD and intestinal lymphoma. IBD was diagnosed in 48 dogs; small cell intestinal lymphoma was diagnosed in 46 dogs; large cell intestinal lymphoma was diagnosed in 30 dogs; and 25 healthy beagles were used as normal controls. Foxp3-positive Tregs in the duodenal mucosa were examined by immunohistochemistry and immunofluorescence. Duodenal expression of interleukin-10 mRNA was quantified by real-time reverse transcription polymerase chain reaction. The number of Foxp3-positive lamina propria cells and the expression of interleukin-10 mRNA were significantly lower in dogs with IBD than in healthy dogs and dogs with intestinal lymphoma. The number of Foxp3-positive intraepithelial cells was higher in dogs with small cell intestinal lymphoma. Some large cell intestinal lymphoma cases had high numbers of Foxp3-positive cells, but the increase was not statistically significant. Double-labeling immunofluorescence showed that CD3-positive granzyme B-negative helper T cells expressed Foxp3. In small cell intestinal lymphoma cases, the overall survival of dogs with a high Treg density was significantly worse than that of dogs with a normal Treg density. These results suggest that a change in the number of Foxp3-positive Tregs contributes to the pathogenesis of canine IBD and intestinal lymphoma by disrupting mucosal tolerance and suppressing antitumor immunity, respectively.

  5. [Analyses of the rearrangement of T-cell receptor- and immunoglobulin genes in the diagnosis of lymphoproliferative disorders].

    Science.gov (United States)

    Griesser, D H

    1995-01-01

    Rearrangements are developmentally regulated genetic recombinations in T and B cells which generate functional T cell receptor (TcR) and immunoglobulin genes, respectively. Different variable, sometimes diversity, and joining gene segments which are discontinuously spread out within their chromosomal location in germline configuration, are randomly assembled in individual lymphocytes. These rearrangements can be detected by Southern Blot analysis if more than 5% of a total lymphocyte population in a biopsy specimen carries the same clonal rearrangement. We analyzed DNA from 324 snap-frozen biopsy specimens from lympho-proliferative disorders. None of the 20 reactive lesions and four malignant myelomonocytic tumors had a clonal antigen receptor gene rearrangement. All 117 malignant B cell lymphomas of different subtypes and 95 of 97 malignant T cell lymphomas showed a clonal gene rearrangement. Only two angioimmunoblastic lymphadenopathy(AILD)-type T cell lymphomas did not have immune receptor gene rearrangements. They were morphologically indistinguishable from the other 47 T/AILD lymphomas with clonal rearrangement patterns. In most cases TcR beta and immunoglobulin heavy chain (IgH) gene probes were sufficient for lineage assignment of the clonal T or B lymphocyte population. In 18% of B lymphomas, however, a cross-lineage rearrangement of TcR beta genes, and in 20% of the T cell lymphomas a clonal IgH gene rearrangement was detected. After exclusion of centrocytic, large cell anaplastic lymphomas (LCAL) of B-type, and T/AILD lymphomas which are overrepresented in our study, only 10% of the remaining 147 T and B cell lymphomas had aberrant rearrangements. TcR rearrangements other than those of the beta chain genes were extremely rare in B cell lymphomas, as were Ig kappa rearrangements in T lymphomas. Only two T/AILD lymphomas had IgH and Ig kappa rearrangement in addition to their clonal T cell receptor gene rearrangements. Both samples likely contain a clonal B

  6. Regulation of T-plastin expression by promoter hypomethylation in primary cutaneous T-cell lymphoma.

    Science.gov (United States)

    Jones, Christine L; Ferreira, Silvia; McKenzie, Robert C T; Tosi, Isabella; Caesar, Jacqueline A; Bagot, Martine; Whittaker, Sean J; Mitchell, Tracey J

    2012-08-01

    T-plastin (PLS3) is an actin-bundling protein normally expressed in epithelial cells but absent in cells of hematopoietic origin. Aberrant PLS3 expression has been demonstrated in lymphocytes from Sézary syndrome (SS) patients and has been proposed as a biomarker for SS; however, the mechanism underlying dysregulation of PLS3 has not been determined. In this study, PLS3 mRNA expression was demonstrated in 21/35 (60%) SS patients and in 3/8 (38%) mycosis fungoides patients, all of whom had clonal blood involvement. No evidence for PLS3 mutations within coding or promoter regions was found, but significant hypomethylation of CpG dinucleotides 95-99 within the PLS3 CpG island was observed and this was restricted to the PLS3+ population. A polyclonal antibody specific to PLS3 was raised to examine coexpression of PLS3 with a panel of T-cell differentiation markers. All PLS3+ cells were CD3+CD4+ and CD26-, suggesting that loss of CD26 is consistently associated with gain of PLS3, whereas all other markers were distributed heterogeneously. However, a patient-specific TCR copy number assay also demonstrated heterogeneity in PLS3 expression in tumor cell populations. Importantly, our findings demonstrate PLS3 expression in the majority of SS patients and provide insight into the molecular regulation of PLS3 expression in CTCL.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    expression is 50% lower in CTCL cell lines (MyLa2000, SeAx and Hut-78) than in normal T-cells. USP2 is expressed in neoplastic cells in early, plaque-stage mycosis fungoides (MF) and is downregulated in advanced tumor stages. Upon treatment with psoralen with UVA (PUVA) or a p53 activator, nutlin3a, USP2...... expression is significantly increased in MyLa2000 (p53wt/wt), but not in SeAx (p53mut) or Hut-78 (p53-/-). USP2 knockdown decreases MyLa2000 cell viability after PUVA by 50% but not Hut-78, suggesting that the function of USP2 in CTCL cells is p53-dependent. Furthermore, USP2 knockdown results in a decreased...... Mdm2 expression and upregulation of p53. Taken together, our findings suggest that USP2 stabilizes Mdm2 which antagonizes pro-apoptotic activity of p53 and possibly contributes to therapeutic resistance in CTCL....

  8. CEOP/IVE/GDP Compared With CEOP as the First-line Therapy for Newly Diagnosed Adult Patients With PTCL

    Science.gov (United States)

    2016-04-18

    Peripheral T-Cell Lymphoma; Angioimmunoblastic T Cell Lymphoma; ALK-negative Anaplastic Large Cell Lymphoma; Enteropathy Associated T Cell Lymphoma; Subcutaneous Panniculitis Like T Cell Lymphoma; Acute Adult T-Cell Leukemia/Lymphoma

  9. MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma.

    Science.gov (United States)

    Sandoval, Juan; Díaz-Lagares, Angel; Salgado, Rocío; Servitje, Octavio; Climent, Fina; Ortiz-Romero, Pablo L; Pérez-Ferriols, Amparo; Garcia-Muret, Maria P; Estrach, Teresa; Garcia, Mar; Nonell, Lara; Esteller, Manel; Pujol, Ramon M; Espinet, Blanca; Gallardo, Fernando

    2015-04-01

    MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID. A 40 microRNA signature was found in MFt including upregulated onco-microRNAs (miR-146a, miR-142-3p/5p, miR-21, miR-181a/b, and miR-155) and downregulated tumor-suppressor microRNAs (miR-200ab/429 cluster, miR-10b, miR-193b, miR-141/200c, and miR-23b/27b). Regarding CD30+ cALCL, 39 differentially expressed microRNAs were identified. Particularly, overexpression of miR-155, miR-21, or miR-142-3p/5p and downregulation of the miR-141/200c clusters were observed. DNA methylation in microRNA gene promoters, as expression regulatory mechanism for deregulated microRNAs, was analyzed using Infinium 450K array and approximately one-third of the differentially expressed microRNAs showed significant DNA methylation differences. Two different microRNA methylation signatures for MFt and CD30+ cALCL were found. Correlation analysis showed an inverse relationship for microRNA promoter methylation and microRNA expression. These results reveal a subgroup-specific epigenetically regulated microRNA signatures for MFt and CD30+ cALCL patients.

  10. Epstein-Barr virus infection and development of T-cell lymphoma%EB病毒感染与T细胞淋巴瘤的发生

    Institute of Scientific and Technical Information of China (English)

    谢晓利; 甘润良

    2009-01-01

    Epstein-Barr virus (EBV) is a kind of DNA tumor virus. Previous Studies on the tumorigenic mechanism of EBV mainly focus on human B lymphocyte. Now there are evidences that EBV exists in human T-cell lymphoma. Exploration in recent years show that EBV could infect T lymphocyte and likely play an important role in the pathogenesis of T-cell lymphoma. Investigation of molecular biological effect of LMP1 in T cell will be helpful for us to understand the approach and mode of EBV infecting T lymphocyte as well as the mechanism of T-cell lymphoma development.%EB病毒(EBV)是一种DNA肿瘤病毒,以往有关EBV致瘤机制的研究主要集中在B淋巴细胞.日前检测发现人类T细胞淋巴瘤也存在EBV感染.近年来研究表明EBV感染可转化T淋巴细胞,EBV可能在T细胞淋巴瘤的发生中起重要作用.观察LMP1在T细胞中的分子生物效应,有助于了解T淋巴细胞中EBV的感染途径、感染方式以及T细胞淋巴瘤的发生机制.

  11. Human T-lymphotropic virus 1 (HTLV-1)-associated lichenoid dermatitis induced by CD8+ T cells in HTLV-1 carrier, HTLV-1-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia/lymphoma.

    Science.gov (United States)

    Tokura, Yoshiki; Ito, Taisuke; Kawakami, Chika; Sugita, Kazunari; Kasuya, Akira; Tatsuno, Kazuki; Sawada, Yu; Nakamura, Motonobu; Shimauchi, Takatoshi

    2015-10-01

    Human T-lymphotropic virus type 1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and carrier. ATLL is a mature CD4+ CD25+ CCR4+ T-cell neoplasm, and approximately half of patients have direct skin involvement manifesting patch, plaque, tumor, multiple papules, erythroderma and purpura. However, there exist secondary eruptions without tumor cell infiltration in patients with ATLL or HAM/TSP and carriers of HTLV-1. To clarify the presence of reactive skin eruptions in HTLV-1-infected individuals, we reviewed our patients with HTLV-1-associated diseases. In 2002-2012, we saw 50 ATLL or HAM/TSP patients and HTLV-1 carriers presenting with skin lesions. We retrospectively selected cases that histologically showed lichenoid tissue reactions with predominant infiltration of CD8+ T cells, but not CD4+ tumor cells. The cases included erythroderma (HTLV-1 carrier), lichen planus (HTLV-1 carrier), alopecia areata (HAM/TSP), chronic actinic dermatitis (HTLV-1 carrier to acute ATLL conversion) and discoid lupus erythematosus (smoldering ATLL). They were graft-versus-host disease-like, major secondary lesions and seen in HTLV-1 carriers and patients with HAM/TSP and smoldering ATLL. We coin the term HTLV-1-associated lichenoid dermatitis (HALD) to encompass the conditions. HALD may occur in association with the elevated immunity toward HTLV-1-infected CD4+ T cells, thus sharing the pathogenetic role of cytotoxic T cells with HAM/TSP.

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

    Science.gov (United States)

    2014-11-04

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

  13. NK/T细胞淋巴瘤细胞凋亡和细胞增殖特征及意义%The significance and features of apoptosis and proliferation of NK/T cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Dabin Wang; Meng Ming; Junhua Liu; Jianhua Yi; Dianding Zou

    2011-01-01

    Objective:The aim was to study the features and clinical significance of cell apoptosis and proliferation of NK/T cell lymphoma. Methods:TdT-mediated dUTP nick end labeling and immunohistochemical Streptavidin-peroxidase method were used to study cell apoptosis and the expression of proliferation cell nuclear antigen in 25 NK/T cell lymphoma and 10reactive lymphoid tissues. Results:Apoptotic index (AI) and proliferative index (PI) averaged (1.92% ± 0.86%) and (41.48%± 5.10%) respectively in the 25 NK/T cell lymphomas and (6.70% ± 1.89%) and (20.10% ± 2.77%) in the 10 reactive lymphoid tissues. Compared with reactive lymphoid tissues, AI was significantly reduced in NK/T cell lymphoma (t = 10.80, P < 0.01)while PI significantly increased (t = 12.39, P < 0.01). In addition, in NK/T cell lymphoma, AI and PI were positively related (r = 0.69, P < 0.01). Conclusion:In NK/T cell lymphoma, cell apoptosis is reduced while cell proliferation increased. The imbalance between cell apoptosis and cell proliferation is closely related to the development and progression of NK/T cell lymphoma.

  14. [Molecular abnormalities in lymphomas].

    Science.gov (United States)

    Delsol, G

    2010-11-01

    . Gene profiling analysis shows that the expression of several genes is deregulated including PDGFRA (platelet-derived growth factor receptor) gene, encoding a receptor with tyrosine kinase activity. In angio-immunoblastic T-cell lymphomas molecular abnormalities are found in follicular helper T-cell (TFH) that express some distinctive markers such as CD10, PD-1, CXCR5 and the CXCL13 chemokine. ALK-positive anaplastic large cell lymphoma is a paradigme of T-cell lymphoma since it is associated with an X-ALK oncogenic fusion protein due to a translocation involving ALK gene at 2p23. ALK tyrosine kinase activates downstream pathways (Stat3/5b, Src kinases, PLCγ, PI3 kinase) implicated in lymphomagenesis, proliferation and protection against apoptosis. Specific ALK inhibitors are currently in clinical evaluation. Lastly several lymphomas are associated with infectious agents that play a direct (EB virus, HTLV1) or indirect role (e.g. Helicobacter pylori in MALT lymphoma) in lymphomagenesis.

  15. Palliative Local Radiotherapy in the Treatment of Tumor-stage Cutaneous T-cell Lymphoma/Mycosis Fungoides

    Institute of Scientific and Technical Information of China (English)

    Chen-chen Xu; Tao Zhang; Tao Wang; Jie Liu; Yue-hua Liu

    2014-01-01

    Objective To determine the efficacy of palliative radiotherapy in treating tumor-stage cutaneous T-cell lymphoma/mycosis fungoides (MF). Methods From January 2008 to January 2013, a total of 11 patients with tumor-stage MF were treated with local radiation therapy in Peking Union Medical College Hospital. The median age of these patients was 53.36±14.45 years. Female-male ratio was 1:1.2. The average course of disease was 10.82±3.37 years. All the patients were treated with local electronic beam irradiation with a total median dosage of 48.55±9.51 (40-74) Gy in an average of 24.55±5.57 (20-40) fractions, 5 fractions per week. Results The median follow-up time was 55.27±29.3 (13-103) months. No severe acute or chronic side effects of irradiation were observed. Complete clinical response (CR) rate of the radiated sites was 54.5%(6/11), partial response (PR) rate was 36.4%(4/11), and the overall response rate (CR+PR) was 90.9%. One patient showed no response. Conclusion Local radiotherapy with psolaren plus ultraviolet A and/or interferon maintaining treatment is an effective palliative therapy in the treatment of tumor-stage MF patients.

  16. LMP1 and LMP2A are potential prognostic markers of extranodal NK/T-cell lymphoma, nasal type (ENKTL

    Directory of Open Access Journals (Sweden)

    Mao Yuan

    2012-12-01

    Full Text Available Abstract Background Latent membrane protein (LMP 1 and LMP2A encoded by Epstein-Barr virus (EBV are associated with the development of malignancies, but their expression in extranodal NK/T-cell lymphoma, nasal type (ENKTL and the relationship with clinical characteristics of this disease remain poorly understood. In the present study, we examined the expression of LMP1 and LMP2A in ENKTL, and investigated the correlations between LMP1 and LMP2A expression with clinicopathological characteristics of ENKTL patients. Methods Paraffin sections of surgically removed samples from 16 ENKTL patients were analyzed by immunohistochemistry and the related clinicopathological data were collected and analyzed. Results Elevated expression (immunohistochemistry score ≥ 4 of LMP1 and LMP2A was detected in the tumor cells of ENKTL. High LMP1 expression was associated with positive B symptoms (p = 0.012, while high LMP2A expression was related to gender (p = 0.029. The expression of both LMP1 and LMP2A showed significant correlations with patients’ overall survival (p = 0.049, p = 0.036. Conclusion LMP1 and LMP2A may be prognostic indicators of survival in patients with ENKTL. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2443352538545899

  17. Therapeutic Efficacy of L-asparaginase in the Treatment of Refractory Midfacial Peripheral T-Cell Non-Hodgkin's Lymphoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To improve the efficacy of refractory midfacial peripheral T-cell non-Hodgkin's lymphoma (MPTC-NHL) with L-asparaginase (L-ASP) based salvage chemotherapy. Methods: 21 patients with refractory MPTC-NHL were analyzed. 11patients (L-ASP group) received L-asparaginase based salvage chemotherapy consisting of L-asparaginase, vincristine and dexame-thosone. 10 patients (control group) received salvage combination chemotherapy without L-asparaginase. Results: Complete remission rates were 45.6% for L-ASP group and 0.0% for control group (p<0.05). Overall response rates (CR+PR) were 63.6% for L-ASP group and 10.0% for control group, respectively (p<0.05). 2-year survival rates were 45.5% for L-ASP group and 0.0% for control group (p<0.05). The major adverse effects of L-ASP were leukopenia, elevation of serum bilirubin and hyperglycemia. Conclusion: The preliminary clinical study shows that the L-ASP based salvage chemotherapy may improve the response rate and 2-year survival rate of the patients with refractory MPTC-NHL. It is necessary to continue the study further.

  18. Effects of microRNA-21 on the biological functions of T-cell acute lymphoblastic lymphoma/leukemia

    Science.gov (United States)

    Shi, Cunzhen; Zhang, Xudong; Li, Xin; Zhang, Lei; Li, Ling; Sun, Zhenchang; Fu, Xiaorui; Wu, Jingjing; Chang, Yu; Li, Wencai; Chen, Qingjiang; Zhang, Mingzhi

    2016-01-01

    Previous studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is significantly upregulated in tumor tissue. However, its association with T-cell acute lymphoblastic lymphoma/leukemia (T-ALL) remains poorly understood. The aim of the present study was to investigate the effects of miR-21 on T-ALL cells by constructing Jurkat cells infected with recombinant adenovirus adv-miR-21 or adv-anti-miR-21. In addition, the target gene of miR-21 was identified by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that miR-21 expression in Jurkat cells was markedly upregulated. Furthermore, upregulating miR-21 expression in Jurkat cells promoted cell proliferation and invasion and decreased the apoptosis rate. By contrast, knockdown of miR-21 in Jurkat cells suppressed proliferation and invasion and increased the apoptosis rate. Furthermore, the results indicated that signal transducer and activator of transcription (STAT) 3 was targeted by miR-21, and that miR-21 inhibited STAT3 expression at the protein level rather than at the messenger RNA level. In conclusion, targeting the inhibition of miR-21 may be a novel therapeutic strategy for patients with T-ALL. PMID:27895788

  19. Association between genetic variations in tumor necrosis factor receptor genes and survival of patients with T-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Kan Zhai; Jiang Chang; Chen Wu; Ning Lu; Li-Ming Huang; Tong-Wen Zhang; Dian-Ke Yu; Wen Tan; Dong-Xin Lin

    2012-01-01

    The prognosis of T-cell lymphoma (TCL) has been shown to be associated with the clinical characteristics of patients.However,there is little knowledge of whether genetic variations also affect the prognosis of TCL.This study investigated the associations between single nucleotide polymorphisms (SNPs) in tumor necrosis factor receptor superfamily (TNFRSF) genes and the survival of patients with TCL.A total of 38tag SNPs in 18 TNFRSF genes were genotyped using Sequenom platform in 150 patients with TCL.Kaplan-Meier survival estimates were plotted and significance was assessed using log-rank tests.Cox proportional hazard models were used to analyze each of these 38 SNPs with adjustment for covariates that might influence patient survival,including sex and international prognostic Index score.Hazard ratios (HRs) and their 95% confidence intervals (Cls) were calculated.Among the 38 SNPs tested,3 were significantly associated with the survival of patients with TCL.These SNPs were located at LTβR (rs3759333C>T) and TNFRSF17 (rs2017662C >T and rs2071336C>T).The 5-year survival rates were significantly different among patients carrying different genotypes and the HRs for death between the different genotypes ranged from 0.45 to 2.46.These findings suggest that the SNPs in TNFRSF genes might be important determinants for the survival of TCL patients.

  20. Analysis of the efficacy and safety of a combined gemcitabine, oxaliplatin and pegaspargase regimen for NK/T-cell lymphoma

    Science.gov (United States)

    Xia, Zhong-jun; Huang, Hui-qiang; Jiang, Wen-qi; Lu, Yue

    2016-01-01

    Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive neoplasm with a poor outcome. Novel L-asparaginase-based treatment regimens, such as GELOX (gemcitabine, oxaliplatin, and L-asparaginase) and P-gemox (gemcitabine, oxaliplatin, and pegaspargase), have shown promising results against stage IE/IIE ENKTL. To define the general applicability of P-gemox, in a retrospective analysis we examined the efficacy and safety of P-gemox in a cohort of 117 patients with newly diagnosed or relapsed/refractory ENKTL. Treatment included 2 to 8 cycles of P-gemox: intravenous gemcitabine (1250 mg/m2) and oxaliplatin (85 mg/m2) and intramuscular pegaspargase (2500 IU/m2) on day 1 and repeated every 2 weeks, or intravenous gemcitabine (1000 mg/m2) on days 1 and 8 and intravenous oxaliplatin (130 mg/m2) and intramuscular pegaspargase (2500 IU/m2) on day 1 and repeated every 3 weeks. Upon completion of treatment, the overall response rate was 88.8%, and responses were similar for newly diagnosed and relapsed/refractory patients. After a median follow-up of 17 months, the 3-year overall and progression-free survival rates were 72.7% and 57.8%, respectively. Multivariate analysis showed that CR after treatment was the most significant factor affecting survival. P-gemox thus appears to be an effective and well-tolerated treatment for patients with ENKTL. PMID:27072578

  1. Ex Vivo γ-Retroviral Gene Therapy of Dogs with X-linked Severe Combined Immunodeficiency and the Development of a Thymic T Cell Lymphoma

    Science.gov (United States)

    Kennedy, Douglas R.; Hartnett, Brian J.; Kennedy, Jeffrey S.; Vernau, William; Moore, Peter F.; O’Malley, Thomas; Burkly, Linda C.; Henthorn, Paula S.; Felsburg, Peter J.

    2011-01-01

    We have previously shown that in vivo γ-retroviral gene therapy of dogs with X-linked severe combined immunodeficiency (XSCID) results in sustained T cell reconstitution and sustained marking in myeloid and B cells for up to 4 years with no evidence of any serious adverse effects. The purpose of this study was to determine whether ex vivo γ-retroviral gene therapy of XSCID dogs results in a similar outcome. Eight of 12 XSCID dogs treated with an average of dose of 5.8 × 106 transduced CD34+ cells/kg successfully engrafted producing normal numbers of gene-corrected CD45RA+ (naïve) T cells. However, this was followed by a steady decrease in CD45RA+ T cells, T cell diversity, and thymic output as measured by T cell receptor excision circles (TRECs) resulting in a T cell lymphopenia. None of the dogs survived past 11 months post treatment. At necropsy, few gene-corrected thymocytes were observed correlating with the TREC levels and one of the dogs was diagnosed with a thymic T cell lymphoma that was attributed to the gene therapy. This study highlights the outcome differences between the ex vivo and in vivo approach to γ-retroviral gene therapy and is the first to document a serious adverse event following gene therapy in a canine model of a human genetic disease. PMID:21536334

  2. Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells.

    Science.gov (United States)

    Turtle, Cameron J; Hanafi, Laïla-Aïcha; Berger, Carolina; Hudecek, Michael; Pender, Barbara; Robinson, Emily; Hawkins, Reed; Chaney, Colette; Cherian, Sindhu; Chen, Xueyan; Soma, Lorinda; Wood, Brent; Li, Daniel; Heimfeld, Shelly; Riddell, Stanley R; Maloney, David G

    2016-09-07

    CD19-specific chimeric antigen receptor (CAR)-modified T cells have antitumor activity in B cell malignancies, but factors that affect toxicity and efficacy have been difficult to define because of differences in lymphodepletion and heterogeneity of CAR-T cells administered to individual patients. We conducted a clinical trial in which CD19 CAR-T cells were manufactured from defined T cell subsets and administered in a 1:1 CD4(+)/CD8(+) ratio of CAR-T cells to 32 adults with relapsed and/or refractory B cell non-Hodgkin's lymphoma after cyclophosphamide (Cy)-based lymphodepletion chemotherapy with or without fludarabine (Flu). Patients who received Cy/Flu lymphodepletion had increased CAR-T cell expansion and persistence, and higher response rates [50% complete remission (CR), 72% overall response rate (ORR)] than patients who received Cy-based lymphodepletion without Flu (8% CR, 50% ORR). The CR rate in patients treated with Cy/Flu at the maximally tolerated dose was 64% (82% ORR; n = 11). Cy/Flu minimized the effects of an immune response to the murine single-chain variable fragment component of the CAR, which limited CAR-T cell expansion and clinical efficacy in patients who received Cy-based lymphodepletion without Flu. Severe cytokine release syndrome (sCRS) and grade ≥3 neurotoxicity were observed in 13 and 28% of all patients, respectively. Serum biomarkers, one day after CAR-T cell infusion, correlated with subsequent sCRS and neurotoxicity. Immunotherapy with CD19 CAR-T cells in a defined CD4(+)/CD8(+) ratio allowed identification of correlative factors for CAR-T cell expansion, persistence, and toxicity, and facilitated optimization of lymphodepletion that improved disease response and overall and progression-free survival.

  3. Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients

    DEFF Research Database (Denmark)

    Bagdonaite, Ieva; Wandall, Hans H; Litvinov, Ivan V

    2015-01-01

    CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22∆N), which lacks the N-terminal domain as demonstrated by exon...... biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22∆N (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells...

  4. The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sunaoshi, Masaaki [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Blyth, Benjamin J. [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Morioka, Takamitsu [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kaminishi, Mutsumi [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shang, Yi [Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Shimada, Yoshiya [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Tachibana, Akira [Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); and others

    2015-09-15

    Highlights: • T-cell lymphoma incidence, latency and weight did not change with age at exposure. • Lymphomas had frequent loss of heterozygosity on chromosomes 4, 11 and 19. • These lesions targeted the Cdkn2a, Ikaros and Pten tumor suppressor genes. • Age at exposure may influence which tumor suppressor genes are lost in each tumor. • The mechanisms of tumor suppressor gene loss were different at each locus. - Abstract: Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age-at-exposure and their underlying mechanisms remain unclear. We assessed genome-wide DNA copy number and mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). Although T-cell lymphoma incidence was similar, loss of heterozygosity at Cdkn2a on chromosome 4 and at Ikaros on chromosome 11 was more frequent in the two older groups, while loss at the Pten locus on chromosome 19 was more frequent in the infant-irradiated group. Cdkn2a and Ikaros mutation/loss was a common feature of the young adult-irradiation group, with Ikaros frequently (50%) incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik12, which lacks two DNA binding zinc-finger domains). Conversely, Pten mutations were more frequent after early irradiation (60%) than after young adult-irradiation (30%). Homozygous Pten mutations occurred without DNA copy number change after irradiation starting in infancy, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Our findings demonstrate that while deletions on chromosomes 4 and 11 affecting Cdkn2

  5. Advance in treatment of the peripheral T-cell and natural killer/T-cell lymphoma%外周T/NK细胞淋巴瘤治疗的进展

    Institute of Scientific and Technical Information of China (English)

    朱军

    2010-01-01

    外周T细胞淋巴瘤(PTCL)是一组异质性非常明显的淋巴瘤,起源于成熟T淋巴细胞,对传统化疗反应不佳,大部分患者预后差.对复发难治患者的治疗选择尚未达成共识.目前正在进行一些新的临床试验,探讨一些新的治疗方法和药物,如第一次缓解后采用自体干细胞移植进行巩固治疗的前瞻性临床研究,以及denileukin diftitox或者CD_(52)单抗(alemtuzumab)等靶向治疗药物与化疗的联合等.文章对外周T/NK细胞淋巴瘤的流行病学、预后因子和目前的治疗进行了探讨.%Peripheral T-cell lymphomas(PTCL)are a heterogeneous group of neoplasms,which originate from mature T-cells,with poor response to conventional chemotherapy and associated,in most cases,with a dismal prognosis.There has been no consensus on the best treatment strategy for patients with relapsed/refractory disease.Attempts to adapt treatment regiments commonly used for B-cell iymphomas to PTCL have yielded disappointing results.A number of trials have been conducted to explore novel approaches,including prospective trials of consolidation therapy after first remission with autologous stem cell transplantation and the addition of agents such as denileukin diftitox or alemtuzumab to chemotherapy.This review aims to describe the epidemiology as well as the prognosis and current therapeutic strategies of the peripheral T-cell and natural killer/T-cell lymphoma.

  6. Microarray analysis of gene expression by microdissected epidermis and dermis in mycosis fungoides and adult T-cell leukemia/lymphoma.

    Science.gov (United States)

    Hashikawa, Keiko; Yasumoto, Shinichiro; Nakashima, Kazutaka; Arakawa, Fumiko; Kiyasu, Junichi; Kimura, Yoshizo; Saruta, Hiroshi; Nakama, Takekuni; Yasuda, Kaori; Tashiro, Kosuke; Kuhara, Satoru; Hashimoto, Takashi; Ohshima, Koichi

    2014-09-01

    The characteristic histopathological feature of mycosis fungoides (MF) and adult T-cell leukemia/lymphoma (ATLL) is epidermotropism. To identify the mechanism for epidermotropism of lymphoma cells, total RNAs were obtained from skin biopsies of epidermis and dermis of MF and ATLL patients by means of laser capture microdissection, and used for subsequent complementary DNA (cDNA) microarray experiments. This procedure has made it possible for us to observe and evaluate the regional environment of MF and ATLL. Hierarchical cluster analysis revealed that the cDNAs could be clearly differentiated into MF and ATLL. CCL27 was expressed in the dermis generated from keratinocytes, CCR4/CCR6/CCR7/CCR10/cutaneous lymphocyte-associated antigen (CLA) lymphoma cells in the dermis, and CCL21 in the extracellular matrix (stroma). Lymphotoxin (LT) β and CCL21 expression was significantly higher and that of CCR10 relatively for MF, while CCR4 and CLA expression was relatively higher for ATLL. In the epithelium, keratinocytes expressed CCL20/CCL27, and lymphoma cells CCR4/CCR6/CCR10, while CCR4, CCR6, CCL20 and CCL27 expression was relatively higher for ATLL than MF. The dermis of MF, but not that of ATLL, showed correlation between CCR7 and CCL21. These findings support the suggestion that chemokines and chemokine receptors are involved in the pathogenesis of MF and ATLL, indicate that cutaneous homing seems to be different for MF and ATLL, and point to the possibility that cutaneous T-cell lymphomas originate in regulatory T cells, especially in the case of ATLL.

  7. Acute liver failure due to natural killer-like T-cell leukemia/lymphoma: A case report and review of the Literature

    Institute of Scientific and Technical Information of China (English)

    Evan S Dellon; Shannon R Morris; Wozhan Tang; Cherie H Dunphy; Mark W Russo

    2006-01-01

    Acute liver failure (ALF) is a medical emergency requiring immediate evaluation for liver transplantation. We describe an unusual case of a patient who presented with ascites, jaundice, and encephalopathy and was found to have ALF due to natural killer (NK)-like T cell leukemia/lymphoma. The key immunophenotype was CD2+, CD3+, CD7+, CD56+. This diagnosis, which was based on findings in the peripheral blood and ascitic fluid, was confirmed with liver biopsy, and was a contraindication to liver transplantation. A review of the literature shows that hematologic malignancies are an uncommon cause of fulminant hepatic failure, and that NK-like T-cell leukemia/lymphoma is a relatively recently recognized entity which is characteristically CD3+ and CD56+. This case demonstrates that liver biopsy is essential in diagnosing unusual causes of acute liver failure, and that infiltration of the liver with NK-like T-cell lymphoma/leukemia can cause acute liver failure.

  8. Disrupted p53 function as predictor of treatment failure and poor prognosis in B- and T-cell non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Gerdes, A M; Skjødt, K;

    1999-01-01

    Mutation of the p53 gene has been associated with treatment failure and poor outcome in various malignancies. It has been suggested that immunohistochemical analysis of p53 and p21Waf1, a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemical...... screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin's lymphomas (NHLs). On the basis of p53 gene mutation status and immunohistochemically detected p53 and p21Waf1 expression in 34 lymphomas, we established an immunophenotype (delta p53......) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry and was correlated with clinical parameters. Delta p53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis...

  9. Usefulness of F-18 FDG PET/CT in subcutaneous panniculitis-like T cell lymphoma: disease extent and treatment response evaluation.

    Science.gov (United States)

    Kim, Jin-Suk; Jeong, Young Jin; Sohn, Myung-Hee; Jeong, Hwan-Jeong; Lim, Seok Tae; Kim, Dong Wook; Kwak, Jae-Yong; Yim, Chang-Yeol

    2012-12-01

    BACKGROUND.: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cutaneous lymphomas, accounting for less than 1% of cases of non-Hodgkin's lymphoma. Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron-emission tomography/computed tomography (PET/CT) findings of SPTCL before and after treatment were rarely reported. CASE REPORT.: We report a case of SPTCL in which F-18 FDG PET/CT showed increased FDG accumulations in numerous subcutaneous nodules without extracutaneous disease. Contrast-enhanced CT during F-18 FDG PET/CT showed multiple minimally enhancing nodules with an infiltrative pattern in the subcutaneous layer throughout the body. Follow-up F-18 FDG PET/CT after three cycles of CHOP chemotherapy showed a complete metabolic remission of the lesions. CONCLUSIONS.: F-18 FDG PET/CT is suggested to be useful in assessing the disease activity, extent and treatment response in SPTCL.

  10. cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Valentina Manfè

    Full Text Available Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed cMyc and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. Overexpression of cMyc repressed miR-125b-5p transcription and sensitized lymphoma cells to bortezomib. The central role of miR-125b-5p was further confirmed in a mouse model of T-cell lymphoma, where xenotransplantation of human CTCL cells overexpressing miR-125b-5p resulted in enhanced tumor growth and a shorter median survival. Our findings describe a novel mechanism through which miR-125b-5p not only regulates tumor growth in vivo, but also increases cellular resistance to proteasome inhibitors via modulation of MAD4.

  11. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2010-08-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Promyelocytic Leukemia (M3); Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; De Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-Cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent

  12. C7a, a Biphosphinic Cyclopalladated Compound, Efficiently Controls the Development of a Patient-Derived Xenograft Model of Adult T Cell Leukemia/Lymphoma

    Directory of Open Access Journals (Sweden)

    Carlos R. Figueiredo

    2011-07-01

    Full Text Available Adult T-cell leukemia/lymphoma (ATLL is a highly aggressive disease that occurs in individuals infected with the human T lymphotropic virus type 1 (HTLV-1. Patients with aggressive ATLL have a poor prognosis because the leukemic cells are resistant to conventional chemotherapy. We have investigated the therapeutic efficacy of a biphosphinic cyclopalladated complex {Pd2 [S(−C2, N-dmpa]2 (μ-dppeCl2}, termed C7a, in a patient-derived xenograft model of ATLL, and investigated the mechanism of C7a action in HTLV-1-positive and negative transformed T cell lines in vitro. In vivo survival studies in immunocompromised mice inoculated with human RV-ATL cells and intraperitoneally treated with C7a led to significantly increased survival of the treated mice. We investigated the mechanism of C7a activity in vitro and found that it induced mitochondrial release of cytochrome c, caspase activation, nuclear condensation and DNA degradation. These results suggest that C7a triggers apoptotic cell death in both HTLV-1 infected and uninfected human transformed T-cell lines. Significantly, C7a was not cytotoxic to peripheral blood mononuclear cells (PBMC from healthy donors and HTLV-1-infected individuals. C7a inhibited more than 60% of the ex vivo spontaneous proliferation of PBMC from HTLV-1-infected individuals. These results support a potential therapeutic role for C7a in both ATLL and HTLV-1-negative T-cell lymphomas.

  13. Outcome of Patients Treated With a Single-Fraction Dose of Palliative Radiation for Cutaneous T-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Tarita O.; Agrawal, Priya [Department of Radiation Oncology, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Guitart, Joan [Department of Dermatology, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Rosen, Steven T. [Division of Hematology/Oncology, Department of Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Rademaker, Alfred W. [Department of Preventive Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Querfeld, Christiane [Department of Medicine/Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Hayes, John P. [Department of Radiation Oncology, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Kuzel, Timothy M. [Division of Hematology/Oncology, Department of Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Mittal, Bharat B., E-mail: bmittal@nmh.org [Department of Radiation Oncology, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States)

    2013-03-01

    Purpose: Cutaneous T-cell lymphoma (CTCL) is a radiosensitive tumor. Presently, treatment with radiation is given in multiple fractions. The current literature lacks data that support single-fraction treatment for CTCL. This retrospective review assesses the clinical response in patients treated with a single fraction of radiation. Methods and Materials: This study reviewed the records of 58 patients with CTCL, primarily mycosis fungoides, treated with a single fraction of palliative radiation therapy (RT) between October 1991 and January 2011. Patient and tumor characteristics were reviewed. Response rates were compared using Fisher's exact test and multiple logistic regressions. Survival rates were determined using the Kaplan-Meier method. Cost-effectiveness analysis was performed to assess the cost of a single vs a multifractionated treatment regimen. Results: Two hundred seventy individual lesions were treated, with the majority (97%) treated with ≥700 cGy; mean follow-up was 41.3 months (range, 3-180 months). Response rate by lesion was assessed, with a complete response (CR) in 255 (94.4%) lesions, a partial response in 10 (3.7%) lesions, a partial response converted to a CR after a second treatment in 4 (1.5%) lesions, and no response in 1 (0.4%) lesion. The CR in lower extremity lesions was lower than in other sites (P=.0016). Lesions treated with photons had lower CR than those treated with electrons (P=.017). Patients with lesions exhibiting large cell transformation and tumor morphology had lower CR (P=.04 and P=.035, respectively). Immunophenotype did not impact response rate (P=.23). Overall survival was significantly lower for patients with Sézary syndrome (P=.0003) and erythroderma (P<.0001). The cost of multifractionated radiation was >200% higher than that for single-fraction radiation. Conclusions: A single fraction of 700 cGy-800 cGy provides excellent palliation for CTCL lesions and is cost effective and convenient for the patient.

  14. Clinical experience with a single field rotational total skin electron irradiation technique for cutaneous T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, C.R.; Shenouda, G.; Vuong, T.; Souhami, L.; Pla, M.; Podgorsak, E.B.; Pla, C. (McGill University, Montreal (Canada). Division of Radiation Oncology, Department of Oncology); Suissa, S. (McGill University, Montreal (Canada). Department of Epidemiology and Biostatics)

    1992-07-01

    Between October 1981 and December 1989, 44 patients with CTCL (cutaneous T-cell lymphoma) were treated with a single-field RTSEI (rotational total skin electron irradiation) technique developed in McGill University Radiation Oncology Department. Only 11/44 patients received no prior treatment (25%). Advanced (T[sub 3] or T[sub 4]) disease had 75% (33/44). Complete response was seen in 32/44 (73%) of patients (91% T[sub 2], 71% T[sub 3] and 58% T[sub 4]), only 27% (3/11) of patients with T[sub 2] and 14% (3/21) with T[sub 3] disease remain in continuous complete remission in the skin, after median intervals of 58 and 35 moths, resp. Median cause-specific survival for whole group is 43 months and survival at 5 years is 38%. Survival was much better for patients with T[sub 2] disease than for patients with T[sub 3] disease (relative risk 4.3; 95% CI 1.4-13.2) and patients with T[sub 4] disease (relative risk 3.1; 95% CI 0.8-12.1). The RTSEI technique used at McGill has depth-dose characteristics and photon contamination similar to other commonly used TSEI techniques. It is relatively simple and provides a homogenous dose distribution over entire skin surface in short treatment time. Results of treatment are similar to those obtained with other techniques. For T[sub 2] disease, TSEI is an effective treatment modality with a possibility of long-term tumor control. For more advanced disease, more aggressive treatment, which may include TSI, is necessary. (author). 27 refs.; 7 figs.; 3 tab.

  15. Myelopoietic efficacy of orlistat in murine hosts bearing T cell lymphoma: implication in macrophage differentiation and activation.

    Science.gov (United States)

    Kant, Shiva; Kumar, Ajay; Singh, Sukh Mahendra

    2013-01-01

    Orlistat, an inhibitor of fatty acid synthase (FASN), acts as an antitumor agent by blocking de novo fatty acid synthesis of tumor cells. Although, myelopoiesis also depends on de novo fatty acid synthesis, the effect of orlistat on differentiation of macrophages, which play a central role in host's antitumor defence, remains unexplored in a tumor-bearing host. Therefore, the present investigation was undertaken to examine the effect of orlistat administration on macrophage differentiation in a T cell lymphoma bearing host. Administration of orlistat (240 mg/kg/day/mice) to tumor-bearing mice resulted in a decline of tumor load accompanied by an augmentation of bone marrow cellularity and survival of bone marrow cells (BMC). The expression of apoptosis regulatory caspase-3, Bax and Bcl2 was modulated in the BMC of orlistat-administered tumor-bearing mice. Orlistat administration also resulted in an increase in serum level of IFN-γ along with decreased TGF-β and IL-10. BMC of orlistat-administered tumor-bearing mice showed augmented differentiation into macrophages accompanied by enhanced expression of macrophage colony stimulating factor (M-CSF) and its receptor (M-CSFR). The macrophages differentiated from BMC of orlistat-administered mice showed characteristic features of M1 macrophage phenotype confirmed by expression of CD11c, TLR-2, generation of reactive oxygen species, phagocytosis, tumor cell cytotoxicity, production of IL-1,TNF-α and nitric oxide. These novel findings indicate that orlistat could be useful to support myelopoesis in a tumor-bearing host.

  16. Treating Cutaneous T-cell Lymphoma with Highly Irregular Surfaces with Photon Irradiation Using Rice as Tissue Compensator

    Directory of Open Access Journals (Sweden)

    Lonika eMajithia

    2015-02-01

    Full Text Available Purpose: Cutaneous T-cell lymphoma (CTCL is known to have an excellent response to radiotherapy, an important treatment modality for this disease. In patients with extremity and digit involvement, the irregular surface and depth variations create difficulty in delivering a homogenous dose using electrons. We sought to evaluate photon irradiation with rice packing as tissue equivalence and determine clinical tolerance and response. Materials and Methods: Three consecutive CTCL patients with extensive lower extremity involvement including the digits were treated using external beam photon therapy with rice packing for tissue compensation. The entire foot was treated to 30-40 Gy in 2-3 Gy per fraction using 6 MV photons prescribed to the mid-plane of an indexed box filled with rice in which the foot was placed. Optically stimulated luminescence dosimeter (OSLD was used for dose measurement to determine the dose deposition to the skin surface. Treatment tolerance and response were monitored with clinical evaluation. Results: All patients tolerated the treatment without treatment breaks. Toxicities included grade 3 erythema and desquamation with resolution within 4 weeks. No late toxicities were observed. All four treated sites had partial response (PR by the end of the treatment course. All patients reported improved functionality after treatment, with less pain, drainage, or swelling. No local recurrence has been observed in these patients with a median follow-up time of 14 months. Conclusion: Tissue compensation with rice packing offers a convenient, inexpensive and reproducible method for the treatment of CTCL with highly irregular surfaces.

  17. Total Skin Electron Therapy for Cutaneous T-Cell Lymphoma Using a Modern Dual-Field Rotational Technique

    Energy Technology Data Exchange (ETDEWEB)

    Heumann, Thatcher R. [Emory University School of Medicine, Emory University, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute (WCI), Emory University, Atlanta, Georgia (United States); Parker, Sareeta [Department of Dermatology, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Biostatistics Shared Core Resource at WCI, Emory University, Atlanta, Georgia (United States); Dhabbaan, Anees [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute (WCI), Emory University, Atlanta, Georgia (United States); Goodman, Michael [Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia (United States); Lechowicz, Mary Jo; Flowers, Christopher R. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Department of Hematology and Oncology, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K., E-mail: drkhurram2000@gmail.com [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute (WCI), Emory University, Atlanta, Georgia (United States)

    2015-05-01

    Purpose: To report our experience with rotational total skin electron irradiation (RTSEI) in cutaneous T-cell lymphoma (CTCL), and to examine response by disease stage and race. Methods and Materials: We reviewed our outcomes for 68 CTCL patients who received RTSEI (≥30 Gy) from 2000 to 2013. Primary outcomes were complete clinical response (CCR), recurrence-free survival (RFS), and overall survival (OS). Using log–rank tests and Cox proportional hazards, OS and RFS were compared across tumor stages at time of RTSEI with further racial subgroup analysis. Results: Median age at diagnosis and at time of radiation was 52 and 56 years, respectively. Median follow-up was 5.1 years, 49% were African American, and 49% were female. At time of treatment, 18, 37, and 13 patients were T stage 2, 3, and 4, respectively. At 6 weeks after RTSEI, overall CCR was 82% (88%, 83%, and 69% for T2, T3, and T4, respectively). Median RFS was 11 months for all patients and 14, 10, and 12 months for stage T2, T3, and T4, respectively. Tumor stage was not associated with RFS or CCR. Maintenance therapy after RTSEI was associated with improved RFS in both crude and multivariable analysis, controlling for T stage. Median OS was 76 months (91 and 59 months for T3 and T4, respectively). With the exception of improved OS in African Americans compared with whites at stage T2, race was not associated with CCR, RFS, or OS. Conclusions: These results represent the largest RTSEI clinical outcomes study in the modern era using a dual-field rotational technique. Our observed response rates match or improve upon the standard set by previous outcome studies using conventional TSEI techniques, despite a large percentage of advanced CTCL lesions in our cohort. We found that clinical response after RTSEI did not seem to be affected by T stage or race.

  18. Genome-based identification of cancer genes by proviral tagging in mouse retrovirus-induced T-cell lymphomas.

    Science.gov (United States)

    Kim, Rachel; Trubetskoy, Alla; Suzuki, Takeshi; Jenkins, Nancy A; Copeland, Neal G; Lenz, Jack

    2003-02-01

    The identification of tumor-inducing genes is a driving force for elucidating the molecular mechanisms underlying cancer. Many retroviruses induce tumors by insertion of viral DNA adjacent to cellular oncogenes, resulting in altered expression and/or structure of the encoded proteins. The availability of the mouse genome sequence now allows analysis of retroviral common integration sites in murine tumors to be used as a genetic screen for identification of large numbers of candidate cancer genes. By positioning the sequences of inverse PCR-amplified, virus-host junction fragments within the mouse genome, 19 target genes were identified in T-cell lymphomas induced by the retrovirus SL3-3. The candidate cancer genes included transcription factors (Fos, Gfi1, Lef1, Myb, Myc, Runx3, and Sox3), all three D cyclins, Ras signaling pathway components (Rras2/TC21 and Rasgrp1), and Cmkbr7/CCR7. The most frequent target was Rras2. Insertions as far as 57 kb away from the transcribed portion were associated with substantially increased transcription of Rras2, and no coding sequence mutations, including those typically involved in Ras activation, were detected. These studies demonstrate the power of genome-based analysis of retroviral insertion sites for cancer gene discovery, identify several new genes worth examining for a role in human cancer, and implicate the pathways in which those genes act in lymphomagenesis. They also provide strong genetic evidence that overexpression of unmutated Rras2 contributes to tumorigenesis, thus suggesting that it may also do so if it is inappropriately expressed in human tumors.

  19. IGF-IR tyrosine kinase interacts with NPM-ALK oncogene to induce survival of T-cell ALK+ anaplastic large-cell lymphoma cells.

    Science.gov (United States)

    Shi, Ping; Lai, Raymond; Lin, Quan; Iqbal, Abid S; Young, Leah C; Kwak, Larry W; Ford, Richard J; Amin, Hesham M

    2009-07-01

    Type I insulin-like growth factor receptor (IGF-IR) tyrosine kinase plays important roles in the pathogenesis of several malignancies. Although it promotes the growth of stimulated hematopoietic cells, a direct role of IGF-IR in malignant lymphoma has not been identified. Anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma (ALK(+) ALCL) is a unique type of T-cell lymphoma. Approximately 85% of ALK(+) ALCL cases harbor the translocation t(2;5)(p23;q35), which generates the chimeric oncogene NPM-ALK. In the present study, we explored a possible role of IGF-IR in ALK(+) ALCL. Our results demonstrate that IGF-IR and IGF-I are widely expressed in ALK(+) ALCL cell lines and primary tumors. Importantly, we identified novel reciprocal functional interactions between IGF-IR and NPM-ALK. Antagonism of IGF-IR decreased the viability, induced apoptosis and cell-cycle arrest, and decreased proliferation and colony formation of ALK(+) ALCL cell lines. These effects could be explained by alterations of cell survival regulatory proteins downstream of IGF-IR signaling. Our findings improve current understanding of the biology of IGF-IR and NPM-ALK and have significant therapeutic implications as they identify IGF-IR signaling as a potential therapeutic target in ALK(+) ALCL and possibly other types of malignant lymphoma.

  20. Primary Uterine Peripheral T-cell Lymphoma: A Case Report of MRI and 18F-FDG PET/CT Findings.

    Science.gov (United States)

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

    2016-04-01

    Primary uterine non-Hodgkin's lymphoma is extremely rare accounting for 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.

  1. 滤泡变型外周T细胞淋巴瘤临床病理学及遗传学分析%Follicular variant of peripheral T-cell lymphoma: a clinicopathologic and genetic study of 2 cases

    Institute of Scientific and Technical Information of China (English)

    詹鹤琴; 朱雄增; 李小秋; 周晓燕

    2011-01-01

    Objective To observe the clinicopathologic and genetic features of follicular variant of peripheral T-cell lymphoma (FV-PTCL), with particular attention to the relationship of this type of lymphoma with angioimmunoblastic T-cell lymphoma (AIIL). Methods The clinical data, hemstoxylin and eosin-stained sections of lymph node biopsies from 2 FV-PTCL cases were reviewed.Immunohistochemical phenotyping and detection of EBV-encoded RNAs (EBER) through in situ hybridization (ISH) were performed. The EnVision two-step method was used for all antibodies except CXCL13 (by using three-step streptavidin immunoperoxidase method). Analysis of clonality and ITK/SYK gene rearrangement was conducted using PCR and RT-PCR assays, respectively. Results Clinically, the two patients presented with superficial lymphadenopathy similarly. Histologically, case 1 showed a follicular/nodular lymphoid proliferation without marked germinal centers. The neoplastic cells comprised mainly medium sized cells with abundant, sometimes clear cytoplasms. Similar histologic findings were seen in case 2 in addition to a concurrent component mimicking typical AITL noticed. Of both cases, the neoplastic cells showed positive reactivity to CD3, CD4, CD10, PD1, and CXCL13. Positive hybridization signals for EBER were only seen in case 2, and double stains demonstrated that those EBV-positive cells were mostly the reactive transformed B-cells. Monoclonal T-cell proliferation was proved by the rearranged TCR gene detection in both cases. Neither of the current cases expressed ITK/SYK fusion transcripts. Conclusion FV-PTCL shows the similar or overlapped morphological and immunophenotypic features to those of AITL,possibly suggesting the presence of a potential relationship between these two types of lymphomas.%目的 观察滤泡变型外周T细胞淋巴瘤的临床病理特征和遗传学改变,探讨其与血管免疫母细胞性T细胞淋巴瘤的关系.方法 对2例滤泡变型外周T细胞淋巴瘤进

  2. Human T cell leukemia/lymphoma virus type I infection of a CD4+ proliferative/cytotoxic T cell clone progresses in at least two distinct phases based on changes in function and phenotype of the infected cells.

    Science.gov (United States)

    Yssel, H; de Waal Malefyt, R; Duc Dodon, M D; Blanchard, D; Gazzolo, L; de Vries, J E; Spits, H

    1989-04-01

    The effect of human T cell leukemia/lymphoma virus type I (HTLV-I) infection on the function and the phenotype of a human proliferating/cytotoxic T cell clone, specific for tetanus toxin, was investigated. During the period after infection, two distinct phases were observed, based on growth properties, phenotype, and functional activity of the infected cells. Phase I HTLV-I infected cells (0 to about 150 days after infection) proliferated in an IL-2-dependent way, but without the requirement for repetitive antigenic stimulation. No differences in expression of the CD2, CD3, CD4, Tp103, and CD28 Ag between these cells and the parental cells could be demonstrated, with the exception of the expression of IL-R p55 and HLA-DR Ag, which were constitutively expressed on the phase I cells. The phase I HTLV-I-infected cells, as well as the parental 827 cells reacted with a mAb specific for an epitope on the variable part of the TCR beta-chain, indicating that the TCR was not altered after HTLV-I infection. Like the parental clone, the phase I cells proliferated in response to tetanus toxin, but the tetanus toxin-specific response of the phase I cells did not require the presence of APC. Results of experiments, in which the levels of intracellular Ca2+ were measured, indicated that HTLV-I cells can acquire the capability to process Ag and present that to themselves. Phase I HTLV-I-infected T cells had lost their cytotoxic activity which was likely to be due to an effect on the lytic machinery rather than on Ag recognition by the TCR, inasmuch as it was found that phase I HTLV-I-infected T cells did no longer contain N-alpha-benzyloxy-L-lysine thiobenzylester-serine esterase activity. Furthermore, it was found that phase I HTLV-I-infected T cells had a diminished capacity to form conjugates with target cells. From a period of about 200 days after HTLV-I infection, phase II cells emerged that proliferated strongly in the absence of IL-2 and that had lost all functional

  3. An unusual case of posttransplant peritoneal primary effusion lymphoma with T-cell phenotype in a HIV-negative female, not associated with HHV-8.

    Science.gov (United States)

    Venizelos, Ioannis; Tamiolakis, Demetrio; Lambropoulou, Maria; Nikolaidou, Sylva; Bolioti, Sophia; Papadopoulos, Hlias; Papadopoulos, Nikolas

    2005-01-01

    Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin's lymphoma (WHO classification) that mainly develops in HIV infected males, more frequently in homosexuals and advanced stages of the disease (total CD4+ lymphocyte count below 100-200/microL). Occasionally, it appears in other immunodepressive states (such as solid organs transplant period) and even, although very rarely, in immunocompetent patients. From a pathogenetic point of view, PEL has been related to Kaposi's sarcoma associated herpes virus (also named human herpesvirus 8, HHV-8), an etiological factor of Kaposi's sarcoma. The relative infrequency of this disease, the absence of wide casuistics allowing a better characterization, and its unfavorable outcome support the need of a deeper knowledge. We present here the clinical-biological findings of a patient, HIV seronegative, who was diagnosed with peritoneal PEL of T-cell origin, and not HHV-8-associated, five years after renal transplantation.

  4. Global Patterns of Methylation in Sézary Syndrome Provide Insight into the Role of Epigenetics in Cutaneous T-Cell Lymphoma.

    Science.gov (United States)

    Whittaker, Sean

    2016-09-01

    van Doorn et al. have defined the DNA methylomes of Sézary cells based on a genome-wide methylation analysis using the Illumina 450K array platform (Illumina, San Diego, CA). Their results show aberrant DNA methylation patterns in CD4-enriched T cells from peripheral blood samples, patterns that are distinct from those of patients with inflammatory erythroderma and from healthy volunteers. Whereas 7.8% of 473,921 5'-cytosine-phosphate-guanine-3' (CpG) sites were hypomethylated, 3.2% showed marked enrichment and selection for hypermethylated CpG sites within the proximal region of gene promoters, including some genes that have previously been shown to be hypermethylated in cutaneous T-cell lymphomas (CTCLs), using standard bisulfite modification techniques.

  5. Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides--cutaneous T-cell lymphoma: clinical implications.

    Science.gov (United States)

    Alcántara-Hernández, M; Torres-Zárate, C; Pérez-Montesinos, G; Jurado-Santacruz, F; Domínguez-Gómez, M A; Peniche-Castellanos, A; Ferat-Osorio, E; Neri, N; Nambo, M J; Alvarado-Cabrero, I; Moreno-Lafont, M; Huerta-Yepez, S; Bonifaz, L C

    2014-05-01

    Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4(+) T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4(+) T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4(+) T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4(+) T cells. In addition, we found a decrease in the percentage of FoxP3(+) cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3(+) T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.

  6. Azidothymidine Sensitizes Primary Effusion Lymphoma Cells to Kaposi Sarcoma-Associated Herpesvirus-Specific CD4+ T Cell Control and Inhibits vIRF3 Function

    Science.gov (United States)

    Stürzl, Michael; Sabbah, Shereen

    2016-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use. PELs co-cultured with KSHV-specific CD4+ T cells in the absence of AZT showed no control of PEL outgrowth. However in the presence of AZT PEL outgrowth was controlled in an MHC-restricted manner. To investigate how AZT sensitizes PELs to immune control we first examined BJAB cells transduced with individual KSHV-latent genes for their ability to resist apoptosis mediated by stimuli delivered through Fas and TRAIL receptors. This showed that in addition to the previously described vFLIP protein, expression of vIRF3 also inhibited apoptosis delivered by these stimuli. Importantly vIRF3 mediated protection from these apoptotic stimuli was inhibited in the presence of AZT as was a second vIRF3 associated phenotype, the downregulation of surface MHC class II. Although both vFLIP and vIRF3 are expressed in PELs, we propose that inhibiting vIRF3 function with AZT may be sufficient to restore T cell control of these tumor cells. PMID:27893813

  7. Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-Cell lymphomas suggesting impaired cell cycle control in disease pathogenesis.

    Science.gov (United States)

    Mao, Xin; Orchard, Guy; Vonderheid, Eric C; Nowell, Peter C; Bagot, Martine; Bensussan, Armand; Russell-Jones, Robin; Young, Bryan D; Whittaker, Sean J

    2006-06-01

    Upregulation of cyclin D1/B-cell leukemia/lymphoma 1 (CCND1/BCL1) is present in most mantle cell lymphomas with the t(11;14)(q13;q32) translocation. However, little is known about the abnormalities of CCND1 and its regulator RB1 in primary cutaneous T-cell lymphomas (CTCL). We analyzed CCND and RB status in CTCL using fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and Affymetrix expression microarray. FISH revealed loss of CCND1/BCL1 in five of nine Sézary syndrome (SS) cases but gain in two cases, and RB1 loss in four of seven SS cases. IHC showed absent CCND1/BCL1 expression in 18 of 30 SS, 10 of 23 mycosis fungoides (MF), and three of 10 primary cutaneous CD30+ anaplastic large-cell lymphoma (C-ALCL). Increased CCND1/BCL1 expression was seen in nine MF, seven C-ALCL, and six SS cases. Absent RB1 expression was detected in 8 of 12 MF and 7 of 9 SS cases, and raised RB1 expression in 7 of 8 C-ALCL. Affymetrix revealed increased gene expression of CCND2 in four of eight CTCL cases, CCND3 in three cases, and CDKN2C in two cases with a normal expression of CCND1 and RB1. These findings suggest heterogeneous abnormalities of CCND and RB in CTCL, in which dysregulated CCND and RB1 may lead to impaired cell cycle control.

  8. Macrophages in T cell/histiocyte rich large B cell lymphoma strongly express metal-binding proteins and show a bi-activated phenotype.

    Science.gov (United States)

    Hartmann, Sylvia; Tousseyn, Thomas; Döring, Claudia; Flüchter, Patricia; Hackstein, Holger; Herreman, An; Ponzoni, Maurilio; de Wolf-Peeters, Chris; Facchetti, Fabio; Gascoyne, Randy D; Küppers, Ralf; Steidl, Christian; Hansmann, Martin-Leo

    2013-12-01

    Abundant macrophage infiltration in tumors often correlates with a poor prognosis. T cell/histiocyte rich large B cell lymphoma (THRLBCL) is a distinct aggressive B cell lymphoma entity showing a high macrophage content. To further elucidate the role of tumor-associated macrophages in THRLBCL, we performed gene expression profiling of microdissected histiocyte subsets of THRLBCL, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), Piringer lymphadenitis, sarcoidosis, nonspecific lymphadenitis and monocytes from peripheral blood. In a supervised principal component analysis, histiocytes from THRLBCL were most closely related to epithelioid cells from NLPHL, with both types of cells expressing genes related to proinflammatory and regulatory macrophage activity. Moreover, histiocytes from THRLBCL strongly expressed metal-binding proteins like MT2A, by which histiocytes of THRLBCL can be distinguished from the other histiocyte subsets investigated. Interestingly, the validation at the protein level showed a strong expression of TXN, CXCL9, MT2A and SOD2 not only in macrophages of THRLBCL but also in the tumor cells of NLPHL and classical Hodgkin lymphoma (cHL). Overall, the present findings indicate that macrophages in the microenvironment of THRLBCL have acquired a distinct gene expression pattern that is characterized by a mixed M1/M2 phenotype and a strong expression of several metal binding proteins. The microenvironments in NLPHL and THRLBCL appear to have a similar influence on the macrophage phenotype. The high expression of metal binding proteins in histiocytes of THRLBCL may be diagnostically useful, but a potential pathophysiological role remains to be identified.

  9. HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4⁺ T-cell lymphocytes

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Boué, François;

    2011-01-01

    The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4⁺ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1-infected...... lost 98 CD4 cells (95% CI, -159 to -36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P HIV-1 replication on cART may harbor HL....

  10. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part I. Diagnosis: clinical and histopathologic features and new molecular and biologic markers.

    Science.gov (United States)

    Jawed, Sarah I; Myskowski, Patricia L; Horwitz, Steven; Moskowitz, Alison; Querfeld, Christiane

    2014-02-01

    Mycosis fungoides (MF) and Sézary syndrome (SS) comprise approximately 53% of cutaneous lymphomas. Both MF and SS may clinically and histologically mimic benign skin conditions, posing a diagnostic challenge to the dermatologist. Precise clinicopathologic correlation is necessary to support a diagnosis, especially in the early stages of disease. In addition to the identification of histopathologic criteria, ancillary studies, including the identification of CD4(+) T cells with aberrant immunophenotypes and T-cell receptor gene rearrangements within skin lesions and peripheral blood are used to support the diagnosis. Recent studies evaluating the pathogenesis of MF have found that the skin microenvironment, including immune cells, such as dendritic cells and reactive cytotoxic and regulatory T cells, plays a crucial supporting role in MF. The skin-homing ability of malignant T cells is the result of chemokines, cytokines, adhesion molecules, and defective apoptosis, and is believed to play a role in disease pathogenesis and progression. In addition, recent studies have also suggested that MF and SS arise from distinct memory T cell subsets and advanced/erythrodermic MF and SS may be distinguished by identification of certain molecules, including Programmed-Death-1.

  11. Increased percentage of CD8 CD28– suppressor lymphocytes in peripheral blood and skin infiltrates correlates with advanced disease in patients with cutaneous T-cell lymphomas

    Directory of Open Access Journals (Sweden)

    Donata Urbaniak-Kujda

    2009-07-01

    Full Text Available Introduction: T cells with the CD8 CD28– phenotype are CD8 lymphocytes with regulatory function. Their increased numbers were observed in infections, autoimmune and neoplastic diseases, and in elderly healthy individuals. CD8 CD28– lymphocyte levels in patients with cutaneous T-cell lymphoma (CTCL has not yet been described. The aim of the study was to determine their levels in these patients’ peripheral blood and cutaneous infiltrates and their relation to the clinical stage of disease.Material/Methods: Forty-one untreated patients, 26 males and 15 females, with CTCL were enrolled in the study. CD8 CD28– lymphocyte levels were determined by flow cytometry in peripheral blood and by immunochemistry in skin infiltrates.Results: The percentage of CD8 CD28– lymphocytes in the peripheral blood of the patients was significantly higher than in the controls. Patients with advanced disease displayed a higher percentage of CD8 CD28– lymphocytes in the peripheral blood and skin than did the individuals with early stages of the disease. Moreover, positive correlations between CD8 CD28– lymphocyte level in peripheral blood and age, clinical stage, and the levels in the skin infiltrates was revealed. Additionally, the percentage of CD8 CD28– T cells in the skin infiltrates correlated positively with age and clinical stage of the disease.Conclusions: These data suggest that CD8 CD28– lymphocytes play an important role in the development of immunotolerance in the progression of cutaneous T-cell lymphoma.

  12. Features of intestinal T-cell lymphomas in Chinese population without evidence of celiac disease and their close association with Epstein-Barr virus infection

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wen-yan; LI Gan-di; LIU Wei-ping; OUYANG Qin; REN Xing-chang; LI Feng-yuan; XU Huan

    2005-01-01

    Background Intestinal T-cell lymphoma (ITCL) is a heterogeneous lymphoid neoplastic group with variable clinical and pathological features. ITCL in oriental countries is different from enteropathy-type intestinal T-cell lymphoma (ETCL) in relation to celiac disease and Epstein-Barr virus (EBV). The objective of this study was to investigate the clinicopathological features, immunophenotype, expression of cytotoxic molecule (TIA-1), T-cell receptor (TCR)-γ gene rearrangement, and Epstein-Barr virus (EBV) latent infection in primary ITCL without celiac disease in Chinese.Methods The clinical data of 42 patients were analyzed, and the patients were followed up. Compared with human reactive lymphoid tissues, in situ hybridization for EBER1/2, polymerase chain reaction for TCR-γ gene rearrangement, and immunohistochemical staining for immunophenotypes, TIA-1 and EBV latent membrane proteins (LMP-1) were investigated. Survival curves of different clinicopathological features, immuno-phenotypes, expression of LMP1, TCR-γ gene rearrangement and therapy were analyzed.Results Three fourths of the patients suffered from ITCL in China were men with a peak age incidence in the 4th decade. Common presenting features included fever and hemotochezia. The prognosis was poor with a median survival of 3.0 months. The lesions were mostly localized in the ileocecum and colon. About 38/42 (90.5%) patients demonstrated pleomorphic medium-sized on large cells. Histological features of celiac disease were rarely seen. All 42 patients with ITCL revealed CD45RO positive. Neoplastic cells partially expressed T-cell differentiated antigens (CD3ε, CD4, CD8) and NK cell associated antigen (CD56). The positive frequency of CD3ε, CD4, CD8 and CD56 was 28/42 (66.7%), 7/42 (16.7%), 10/42 (23.8%) and 12/42 (28.6%) respectively. Thirty-nine cells (92.9%) expressed TIA-1, but none expressed CD20 and CD68. More than half of the patients (64.3%, 64.3% and 59.5%) revealed TCR-γ gene rearrangement by

  13. Genotypic analysis of cutaneous T-cell lymphoma: a comparative study of Southern blot analysis with polymerase chain reaction amplification of the T-cell receptor-gamma gene.

    Science.gov (United States)

    Curcó, N; Servitje, O; Llucià, M; Bertran, J; Limón, A; Carmona, M; Romagosa, V; Peyrí, J

    1997-11-01

    The diagnosis of early cutaneous T-cell lymphoma (CTCL) is a difficult point in dermatology. Recently, Southern blot analysis (SBA) and polymerase chain reaction (PCR) have been used to detect clonality in initial lesions in which clinical and histological findings are unspecific. Forty-one samples from 25 patients with CTCL were investigated for the presence of T-cell receptor-gamma gene rearrangement using a nested PCR technique and analysed by polyacrylamide gel electrophoresis (PAGE). Conventional SBA was also performed on 28 samples from 20 of these patients. In addition, 20 samples corresponding to patients with large plaque parapsoriasis (LPP), cutaneous B-cell lymphoma (CBCL) and eczema were analysed by PCR in the same way as were the CTCL specimens. Most of the CTCL specimens (81%) showed clonality on PCR analysis. Among patients with mycosis fungoides, 71% of initial patch lesions and 100% of plaques and tumours showed clonal disease. Clonality could be detected in three of four histologically negative post-treatment lesions. Clonal rearrangement was detected in one of three patients with LPP and in three of 10 patients with CBCL. None of the samples corresponding to patients with eczema showed positive results. SBA was significantly less sensitive than PCR in detecting clonality in CTCL patients (42% among early disease and 60% among advanced cases). The results indicate that this PCR/PAGE technique is a reliable and useful method for the detection of clonality in early skin lesions of CTCL patients and probably in the identification of silent extracutaneous involvement.

  14. Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Ji-Young [Department of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 150-950 (Korea, Republic of); Cha, Eun Suk; Lee, Jee Eun [Department of Radiology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of); Sung, Sun Hee [Department of Pathology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of)

    2013-07-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.

  15. Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical, Hematompoietic Progenitor-Cell Transplant

    Science.gov (United States)

    2011-05-01

    determine whether the persistence of adoptively transferred T cells directly correlated with tumor size for individual mice. This was accomplished by plotting...to the SB11 transposase gene ( size f830 bp) was detected in T cells that were electroporated with the SB transposon and transposase and had undergone...unrelated adult volunteers after con- sent on an Institutional Review Board–approved protocol) were cocultured in culture medium (RPMI containing peni

  16. The antihistamines clemastine and desloratadine inhibit STAT3 and c-Myc activities and induce apoptosis in cutaneous T-cell lymphoma cell lines.

    Science.gov (United States)

    Döbbeling, Udo; Waeckerle-Men, Ying; Zabel, Franziska; Graf, Nicole; Kündig, Thomas M; Johansen, Pål

    2013-02-01

    Mycosis fungoides and its leukaemic counterpart Sézary syndrome are the most frequent cutaneous T-cell lymphomas (CTCL), and there is no cure for these diseases. We evaluated the effect of clinically approved antihistamines on the growth of CTCL cell lines. CTCL cell lines as well as blood lymphocytes from patients with Sézary syndrome were cultured with antihistamines, and the cell were analysed for proliferation, apoptosis and expression of programmed death molecules and transcription factors. The two antihistamines clemastine and desloratadine, currently used for symptom alleviation in allergy, induced potent reduction of the activities of the constitutively active transcription factors c-Myc, STAT3, STAT5a and STAT5b in mycosis fungoides and Sézary syndrome cell lines. This inhibition was followed by apoptosis and cell death, especially in the Sézary syndrome-derived cell line Hut78 that also showed increased expression of the programmed death-1 (PD-1) after clemastine treatment. In lymphocytes isolated from Sézary syndrome patients, the CD4-positive fraction underwent apoptosis after clemastine treatment, while CD4-negative lymphocytes were little affected. Because both c-Myc and STAT transcription factors are highly expressed in proliferating tumours, their inhibition by clemastine, desloratadine and other inhibitors could complement established chemotherapies not only for cutaneous T-cell lymphomas but perhaps also other cancers.

  17. Development of a novel nitro-derivative of noscapine for the potential treatment of drug-resistant ovarian cancer and T-cell lymphoma.

    Science.gov (United States)

    Aneja, Ritu; Vangapandu, Surya N; Lopus, Manu; Chandra, Ramesh; Panda, Dulal; Joshi, Harish C

    2006-06-01

    We have shown previously that an antitussive plant alkaloid, noscapine, binds tubulin, displays anticancer activity, and has a safe pharmacological profile in humans. Structure-function analyses pointed to a proton at position-9 of the isoquinoline ring that can be modified without compromising tubulin binding activity. Thus, many noscapine analogs with different functional moieties at position-9 were synthesized. Those analogs that kill human cancer cells resistant to other antimicrotubule agents, vincas and taxanes, were screened. Here, we present one such analog, 9-nitro-noscapine (9-nitro-nos), which binds tubulin and induces apoptosis selectively in tumor cells (ovarian and T-cell lymphoma) resistant to paclitaxel, vinblastine, and teniposide. 9-Nitro-nos treatment at doses as high as 100 microM did not affect the cell cycle profile of normal human fibroblasts. This selectivity of 9-nitro-nos for cancer cells represents a unique edge over the other available antimitotics. 9-Nitro-nos perturbs the progression of cell cycle by mitotic arrest, followed by apoptotic cell death associated with increased caspase-3 activation and appearance of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. Thus, we conclude that 9-nitro-nos has great potential to be a novel therapeutic agent for ovarian and T-cell lymphoma cancers, even those that have become drug-resistant to currently available chemotherapeutic drugs.

  18. Concurrent Epstein-Barr virus associated NK/T cell lymphoma after immunosuppressive therapy for aplastic anemia: report of a case and review of literature.

    Science.gov (United States)

    Yin, Guangli; Ni, Ying; Xiao, Zhengrui; He, Guangsheng; Miao, Kourong

    2015-01-01

    Aplastic anemia (AA) patients with prolonged immunosuppression have a risk of development of lymphoproliferative disorders (LPDs), especially combined with Epstein-Barr virus (EBV) infection. However, development of nature killer/T (NK/T) cell lymphoma, in a nontransplantation setting, has not been documented for AA patients with immunosuppressive therapy (IST). Herein, we described a middle-aged man, Han ethnic, who presented with swelled parotid gland after a long history of IST for AA. Fever, night sweating, weight loss had not been found. Increased heterotypic lymphocytes had been detected in the left side of parotid gland demonstrated as cCD3(+), CD56(+), GranB(+), TIA-1(+), MUM-1(+), KI-67 (50%-75%)(++), Bcl-6(-), MPO(-) by immunohistochemistry, and in-situ hybridization (ISH) indicated EBER positive. Chromosome analysis by R banding method revealed 46, XY [20]. NK/T cell lymphoma concurrent with aplastic anemia was diagnosed and a mild chemotherapy regimen including vincristine, prednisone, L-asparaginase was administered. The parotid mass was gradually regressed after the first cycle of chemotherapy. The patient discharged from the hospital voluntarily and lost the follow-up.

  19. Helical Irradiation of the Total Skin with Dose Painting to Replace Total Skin Electron Beam Therapy for Therapy-Refractory Cutaneous CD4+ T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Chen-Hsi Hsieh

    2013-01-01

    Full Text Available A 36-year-old woman was diagnosed with a therapy-refractory cutaneous CD4+ T-cell lymphoma, T3N0M0B0, and stage IIB. Helical irradiation of the total skin (HITS and dose painting techniques, with 30 Gy in 40 fractions interrupted at 20 fractions with one week resting, 4 times per week were prescribed. The diving suit was dressed whole body to increase the superficial dose and using central core complete block (CCCB technique for reducing the internal organ dose. The mean doses of critical organs of head, chest, and abdomen were 2.1 to 29.9 Gy, 2.9 to 8.1 Gy, and 3.6 to 15.7 Gy, respectively. The mean dose of lesions was 84.0 cGy. The dosage of left side pretreated area was decreased 57%. The tumor regressed progressively without further noduloplaques. During the HITS procedure, most toxicity was grade I except leukocytopenia with grade 3. No epitheliolysis, phlyctenules, tumor lysis syndrome, fever, vomiting, dyspnea, edema of the extremities, or diarrhea occurred during the treatment. HITS with dose painting techniques provides precise dosage delivery with impressive results, sparing critical organs, and offering limited transient and chronic sequelae for previously locally irradiated, therapy-refractory cutaneous T-cell lymphoma.

  20. Development of a modified prognostic index of patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: a possible risk-adapted management strategies including allogeneic transplantation.

    Science.gov (United States)

    Fuji, Shigeo; Yamaguchi, Takuhiro; Inoue, Yoshitaka; Utsunomiya, Atae; Moriuchi, Yukiyoshi; Uchimaru, Kaoru; Owatari, Satsuki; Miyagi, Takashi; Taguchi, Jun; Choi, Ilseung; Otsuka, Eiichi; Nakachi, Sawako; Yamamoto, Hisashi; Kurosawa, Saiko; Tobinai, Kensei; Fukuda, Takahiro

    2017-03-24

    Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma to construct a new large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor level (> 5,000 U/mL), high adjusted calcium level (≥ 12 mg/dL), and high C-reactive protein level (≥ 2.5 mg/dL) were independent adverse prognostic factors using the training set. We used these five variables to divide patients into three risk groups. In the validation set, medial overall survival was 626 days, 322 days, and 197 days for the low-, intermediate-, and high-risk groups, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a new promising risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy.

  1. [Application of digital pathology tools. An unusual case of non-Hodgkin lymphoma].

    Science.gov (United States)

    Meyer, A-S K; Dallenbach, F E; Lienert, G; Möller, P; Lennerz, J K

    2012-11-01

    Currently, lymphoma diagnosis is based on a combination of morphology, immunophenotyping, and molecular testing. Using the example of an unusual case of malignant non-Hodgkin lymphoma, we show that improved visualization using digital pathology contributes to the convergence of these complementary diagnostic modalities. A 45-year-old woman presented with skin rash and cervical lymphadenopathy. Histological workup of an excised lymph node showed loss of normal architecture with diffuse infiltration and increased mitotic activity. Immunohistochemistry for CD3/CD5 showed atypical arrangement and infiltration of a T-cell population that dominated over regionally dense, MUM1-positive plasmacellular infiltrates. Expanded CD21/CD23-positive meshworks of follicular dendritic cells were present within and between regressed follicles and the T-cell infiltrate; staining for CD56 and cyclin-D1 was negative. Quantification of Ki-67 staining within the T-, B- and plasmacellular compartments was achieved by digital image conversion, overlay and subsequent quantification algorithms that revealed proliferation within more than 60% of T-cells, over 50% of plasma cells and only 20% of B-cells. Clonality analysis by PCR revealed monoclonal rearrangement for both T-cell receptor gamma chains and immunoglobulin heavy chains. Taken together, we present an unusual combination of an angioimmunoblastic T-cell lymphoma (AITL) and simultaneous plasmacellular lymphoma. This report demonstrates how application of modern tools of digital pathology can visually integrate unusual morphological and molecular findings.

  2. Improved polymerase chain reaction-based method to detect early-stage epitheliotropic T-cell lymphoma (mycosis fungoides) in formalin-fixed, paraffin-embedded skin biopsy specimens of the dog.

    Science.gov (United States)

    Chaubert, Pascal; Baur Chaubert, Audrey S; Sattler, Ursula; Forster, Ursula; Bornand, Valérie; Suter, Maja; Welle, Monika

    2010-01-01

    In the dog, early-stage epitheliotropic T-cell lymphoma (ETCL) can clinically and histologically mimic a large range of inflammatory dermatoses and often progresses rapidly to a more aggressive tumor stage. Early diagnosis of ETCL is essential to proceed with a specific oncologic therapy that is favorable for the prognosis. In the present study, an improved method for the detection of T-cell receptor gamma (TCRgamma) rearrangement was developed by designing a new set of consensus primers to amplify the different forms of rearranged canine TCRgamma gene sequences by polymerase chain reaction. The amplicons were analyzed by conventional polyacrylamide gel electrophoresis, which requires minimal specific equipment and may be performed in almost every pathology laboratory at low costs. The method proved to be highly specific and sensitive to detect early ETCL in formalin-fixed, paraffin-embedded biopsy specimens, providing an efficient tool for veterinary pathologists to distinguish early neoplastic from reactive cutaneous T-cell infiltrates (tumor-specific marker) or to discriminate T-cell lymphoma from B-cell lymphomas or nonlymphoid neoplasms (T-cell lineage marker). By direct sequencing analysis of amplified TCRgamma gene sequences, ETCL was found to rearrange exclusively the joining (J) 4 region, which suggests specific biology for primary cutaneous T-cell lymphomas. Also, a novel (seventh) functional J region in the TCRgamma gene, localized approximately 2.3 kb upstream of J5, was identified.

  3. Adult T-cell leukemia/lymphoma: report of two cases Leucemia/linfoma de células T do adulto: relato de dois casos

    Directory of Open Access Journals (Sweden)

    Ricardo Aparecido Olivo

    2008-06-01

    Full Text Available Adult T-cell leukemia/lymphoma is a lymphoproliferative disorder of mature T lymphocytes associated with infection with human T-cell lymphotrophic virus type I (HTLV-I. Adult T-cell leukemia/lymphoma is characterized by clinical and laboratory polymorphism that allows it to be classified into four distinct subgroups: smoldering, chronic, acute and lymphomatous types. We present here two cases of adult T-cell leukemia/lymphoma, respectively in the acute and lymphomatous forms of the disease. Case 1 was a 35-year-old woman who presented abdominal distension accompanied by hepatosplenomegaly, adenomegaly, skin lesions, positivity for anti-HTLV-I antibodies and leukocytosis with the presence of flower cells. Case 2 was a 38-year-old man who was admitted with generalized lymphadenomegaly, positivity for anti-HTLV-I antibodies, hypercalcemia and osteolytic lesions. In this paper, we correlate the clinical-laboratory findings of these two cases with data in the literature.A leucemia/linfoma de células T do adulto é um distúrbio linfoproliferativo de linfócitos T maduros associado à infecção pelo vírus linfotrópico de células T humanas tipo I (HTLV-I. A leucemia/linfoma de células T do adulto tem polimorfismo clínico e laboratorial, que a classifica em quatro subgrupos distintos entre si: smoldering, crônica, aguda e linfomatosa. Apresentamos neste artigo, dois casos de leucemia/linfoma de células T do adulto, respectivamente, nas formas aguda e linfomatosa da doença. O caso 1: uma paciente de 35 anos apresentava distensão abdominal com hepato-esplenomegalia, adenomegalia, lesões cutâneas, anticorpos anti-HTLV-I positivo e leucocitose com presença de flower cell. O caso 2: homem de 38 anos, internado com linfadenomegalia generalizada, anticorpos anti-HTLV-I positivo, hipercalcemia e lesões osteolíticas. Neste artigo correlacionamos os achados clínicos e laboratoriais destes dois casos com dados da literatura.

  4. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

    Science.gov (United States)

    Pinheiro, Dammy; Chang, Yu-Mei; Bryant, Hannah; Szladovits, Balazs; Dalessandri, Tim; Davison, Lucy J; Yallop, Elizabeth; Mills, Emily; Leo, Chiara; Lara, Ana; Stell, Anneliese; Polton, Gerry; Garden, Oliver A

    2014-01-01

    The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

  5. Enhanced T cell lymphoma in NOD.Stat5b transgenic mice is caused by hyperactivation of Stat5b in CD8+ thymocytes.

    Directory of Open Access Journals (Sweden)

    Bo Chen

    Full Text Available Activation of signal transducers and activators of transcription (STAT proteins may be critical to their oncogenic functions as demonstrated by the development of B-cell lymphoma/leukemia in transgenic (TG mice overexpressing a constitutively activated form of Stat5b. However, low incidence of CD8(+ T cell lymphoma was observed in B6 transgenic mice overexpressing a wild-type Stat5b (B6.Stat5b(Tg despite of undetectable Stat5b phosphorylation and the rate of lymphomagenesis was markedly enhanced by immunization or the introduction of TCR transgenes [1]. Here, we report that the wild-type Stat5b transgene leads to the acceleration and high incidence (74% of CD8(+ T cell lymphoblastic lymphomas in the non-obese-diabetic (NOD background. In contrast to the B6.Stat5b(Tg mice, Stat5b in transgenic NOD (NOD.Stat5b(Tg mice is selectively and progressively phosphorylated in CD8(+ thymocytes. Stat5 phosphorylation also leads to up-regulation of many genes putatively relevant to tumorigenesis. Treatment of NOD.Stat5b(Tg mice with cancer chemopreventive agents Apigenin and Xanthohumol efficiently blocked lymphomagenesis through reduction of Stat5 phosphorylation and genes up-regulated in the NOD.Stat5b(Tg mice. These results suggest that NOD genetic background is critical to the Stat5b-mediated lymphomagenesis through regulation of Stat5 hyperactivation. NOD.Stat5b(Tg mouse is an excellent model for studying the molecular mechanisms underlying lymphomagenesis and testing novel chemoprevention strategies.

  6. A TLR7 agonist enhances the antitumor efficacy of obinutuzumab in murine lymphoma models via NK cells and CD4 T cells.

    Science.gov (United States)

    Cheadle, E J; Lipowska-Bhalla, G; Dovedi, S J; Fagnano, E; Klein, C; Honeychurch, J; Illidge, T M

    2017-01-03

    Anti-CD20 monoclonal antibodies (mAb) such as rituximab have been proven to be highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-CLL. We hypothesized that immune stimulation through Toll-like receptor 7 (TLR7) agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term antitumor immune responses. Here we demonstrate, in syngeneic human CD20 (hCD20)-expressing models of lymphoma, that systemic administration of a TLR7 agonist (R848) increases responses when administered in combination with obinutuzumab and protects against disease recurrence. Depletion studies demonstrate that primary antitumor activity is dependent on both NK cells and CD4(+) T cells but not on CD8(+) T cells. However, both CD4(+) and CD8(+) T cells appear necessary for the generation of protective immunological memory. Importantly, increased tumor-free survival post obinutuzumab and R848 combination therapy was seen in hCD20 transgenic mice, which express hCD20 on normal B cells. These findings provide a rationale for clinical testing of obinutuzumab in combination with systemically administered TLR7 agonists to further improve outcome.Leukemia advance online publication, 3 January 2017; doi:10.1038/leu.2016.352.

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

    Science.gov (United States)

    2017-01-27

    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

  8. Occurrence of nodular lymphocyte-predominant hodgkin lymphoma in hermansky-pudlak type 2 syndrome is associated to natural killer and natural killer T cell defects.

    Directory of Open Access Journals (Sweden)

    Luisa Lorenzi

    Full Text Available Hermansky Pudlak type 2 syndrome (HPS2 is a rare autosomal recessive primary immune deficiency caused by mutations on β3A gene (AP3B1 gene. The defect results in the impairment of the adaptor protein 3 (AP-3 complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56(brightCD16(- Natural Killer (NK cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-γ production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.

  9. Regression of the tumor after withdrawal of cyclosporine in relapsed extranodal natural killer/T cell lymphoma following allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kako, Shinichi; Izutsu, Koji; Oshima, Kumi; Sato, Hiroyuki; Kanda, Yoshinobu; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2007-10-01

    The prognosis of patients with advanced-stage extranodal natural killer/T cell lymphoma, nasal type (ENKL) has been generally poor, and several anecdotal reports have suggested the role of allogeneic hematopoietic stem cell transplantation (HSCT). A potential advantage of allogeneic HSCT may be the graft-versus-lymphoma (GVL) effect. The susceptibility to the GVL effect, however, has been shown to vary according to histologic subtypes, and it has been hardly documented yet whether ENKL is susceptible to the GVL effect. Here we report a patient with advanced-stage ENKL who underwent allogeneic HSCT from an HLA one-allele mismatched related donor, whose clinical course after HSCT suggested the potent GVL effect against ENKL. A 43-year-old female underwent allogeneic HSCT for advanced-stage, chemorefractory ENKL, and achieved complete response. In 4 months after the transplantation, however, the ENKL relapsed in multiple sites. These lesions markedly responded to the discontinuation of immunosuppressive agents and disappeared. Except for a temporal exacerbation of bronchiolitis obliterans organizing pneumonia, she has been free from disease for more than a year without other treatments against lymphoma. The clinical course of the current patient suggests the potent GVL effect against ENKL. Allogeneic HSCT, including that with reduced-intensity regimens, is a promising treatment option for high-risk ENKL.

  10. Immunomodulatory Effects of Hemagglutinin- (HA- Modified A20 B-Cell Lymphoma Expanded as a Brain Tumor on Adoptively Transferred HA-Specific CD4+ T Cells

    Directory of Open Access Journals (Sweden)

    Valentin P. Shichkin

    2014-01-01

    Full Text Available Previously, the mouse A20 B-cell lymphoma engineered to express hemagglutinin (HA antigen (A20HA was used as a systemic tumor model. In this work, we used the A20HA cells as a brain tumor. HA-specific CD4+ T cells were transferred intravenously in a tail vein 5 days after A20HA intracranial inoculation and analyzed on days 2, 9, and 16 after the adoptive transfer by different methods. The transferred cells demonstrated state of activation as early as day 2 after the adoptive transfer and most the of viable HA-specific cells became anergic on day 16. Additionally, symptoms of systemic immunosuppression were observed in mice with massive brain tumors at a late stage of the brain tumor progression (days 20–24 after the A20HA inoculation. Despite that, a deal of HA-specific CD4+ T cells kept the functional activity even at the late stage of A20HA tumor growth. The activated HA-specific CD4+ T cells were found also in the brain of brain-tumor-bearing mice. These cells were still responding to reactivation with HA-peptide in vitro. Our data support an idea about sufficient role of both the tumor-specific and -nonspecific mechanisms inducing immunosuppression in cancer patients.

  11. HLA Class II Defects in Burkitt Lymphoma: Bryostatin-1-Induced 17 kDa Protein Restores CD4+ T-Cell Recognition

    Directory of Open Access Journals (Sweden)

    Azim Hossain

    2011-01-01

    Full Text Available While the defects in HLA class I-mediated Ag presentation by Burkitt lymphoma (BL have been well documented, CD4+ T-cells are also poorly stimulated by HLA class II Ag presentation, and the reasons underlying this defect(s have not yet been fully resolved. Here, we show that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. The observed defect was not associated with low levels of BL-expressed costimulatory molecules, as addition of external co-stimulation failed to result in BL-mediated CD4+ T-cell activation. We further demonstrate that BL cells express the components of the class II pathway, and the defect was not caused by faulty Ag/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Treatment of BL with broystatin-1, a potent modulator of protein kinase C, led to significant improvement of functional class II Ag presentation in BL. The restoration of immune recognition appeared to be linked with an increased expression of a 17 kDa peptidylprolyl-like protein. These results demonstrate the presence of a specific defect in HLA class II-mediated Ag presentation in BL and reveal that treatment with bryostatin-1 could lead to enhanced immunogenicity.

  12. The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.

    Science.gov (United States)

    Jones, K; Wockner, L; Brennan, R M; Keane, C; Chattopadhyay, P K; Roederer, M; Price, D A; Cole, D K; Hassan, B; Beck, K; Gottlieb, D; Ritchie, D S; Seymour, J F; Vari, F; Crooks, P; Burrows, S R; Gandhi, M K

    2016-02-01

    In 40% of cases of classical Hodgkin lymphoma (cHL), Epstein-Barr virus (EBV) latency-II antigens [EBV nuclear antigen 1 (EBNA1)/latent membrane protein (LMP)1/LMP2A] are present (EBV(+) cHL) in the malignant cells and antigen presentation is intact. Previous studies have shown consistently that HLA-A*02 is protective in EBV(+) cHL, yet its role in disease pathogenesis is unknown. To explore the basis for this observation, gene expression was assessed in 33 cHL nodes. Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL. To ascertain the impact of HLA class I on EBV latency antigen-specific immunodominance, we used a stepwise functional T cell approach. In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients. Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines. In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02. Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens. Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.

  13. Human cord blood lymphocytes. Ultrastructural and immunologic surface marker characteristics: a comparison with B- and T-cell lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Hamburg, A.; Brynes, R.K.; Reese, C.; Golomb, H.M.

    1976-01-01

    The ultrastructural and surface marker characteristics of human cord blood lymphocytes were studied. These properties were compared with those in cells of patients in the leukemic phase of both malignant lymphoma, poorly differentiated lymphocytic type, and mycosis fungoides. Nuclear folding in cord blood lymphocytes was similar to that seen in lymphocytes of patients with malignant lymphoma, poorly differentiated lymphocytic type and mycosis fungoides. Surface marker characteristics of cord blood lymphocytes included increased percentages of surface IgD on cells bearing surface immunoglobulins and decreased percentages of E-rosette-forming cells. The hypothesis that both malignant lymphoma, poorly differentiated lymphocytic type and mycosis fungoides represent an arrest in the normal lymphocyte maturation sequence is discussed.

  14. 外周T细胞淋巴瘤的治疗新策略%New therapeutic strategy for peripheral T-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    王华庆; 钱正子; 张会来; 宋拯

    2009-01-01

    外周T细胞淋巴瘤(peripheral T-cell lymphonla,PTCL)是亚洲国家发病率较高的非霍奇金淋巴瘤.T细胞淋巴瘤各亚型具有明显的异质性,疗效和预后截然不同.目前尚没有标准的治疗方案.传统的治疗多采用CHOP或CHOP样方案,但疗效欠佳.第二、三代剂量强度方案(m-BACOD、ProMACE-CytaBOM及MACOP-B方案)与CHOP方案比较,并未显示出生存优势.新的治疗研究包括细胞毒性药物吉西他滨,无论是作为一线治疗还是针对复发和难治的PTCL患者都显示出了良好的疗效,有望成为治疗PTCL,患者的新策略.阿仑单抗在PTCL的治疗中取得良好的效果.Zanohmumab单抗在复发和难治PTCL Ⅱ期临床试验中疗效突出.地尼白介素、新型抗叶酸药Pralatrexate、蛋白酶体抑制剂硼替佐米及抗血管生成药物贝伐单抗在Ⅱ、Ⅲ期临床试验中显示了颇有前景的疗效.自体干细胞移植可作为具有高危因素的PTCL患者缓解后的巩固治疗.%The incidence rate is high in Asia country, accounting for 15 %-20 % of Non-Hodgkin lymphoma. Every phynotype has different heterogeneity, therapeutic effect and prognosis are also different. There is no standard rigemen for T cell lymphoma at present. CHOP like regimen is commonly used. But therapeutic effect is not as good as we expected. Clinical research shows that dose and intensity regimen, such as m-BACOD,ProMACE-CytaBOM, MACOP-B, do not exhibit survival advantage compared with CHOP regimen. New treatment includes cytotoxic drug, such as gemcitabine. As first line therapy for T cell lymphoma or as salvage therapy for refractory or relapsed T cell lymphoma, the therapeutic effect is good. Gemcitabine based regimen is new for PTCL. Alemtuzumab is a humanized CD52 mono-clonal antibody and is expected as good effect on PTCL therapy. Zanolimumab is a humanized mono-clonal antibody which targets CD4 antigen on T cell. Phase Ⅱclinical research has also got good effect. Denileukin

  15. Research progress of T cell lymphoma: reports from 2014 international conference on T cell lymphoma in clinical treatment%T细胞淋巴瘤研究新进展:2014年国际T细胞淋巴瘤临床治疗大会报道

    Institute of Scientific and Technical Information of China (English)

    马军; 朱军; 石远凯; 姜文奇; 黄慧强; 邱林

    2014-01-01

    The treatment status and progress in T cell lymphoma including epigenetic involved mutations that control DNA and histone methylation were reported and intensively discussed in 2014 international T cell lymphoma forum.According to the theory,treatment with HDAC inhibitor belinostat and romidepsin for peripheral T cell lymphoma (PTCL) can achieve 29 %-38 % overall response rate (ORR) and 13.6 months median relief time.NK/T cell lymphoma in southeast asia is a common malignant lymphoma,15 %-28 % of the NHL accounted in China and Japan for,which is significantly higher than that in the European and American countries,mainly related to EB virus widespread infection.L-asparaginase enzymes,such as SMILE and AspMetDex,can make the early cases with more than 70 % long-term survival rate,advanced cases with 40 % response rate.Some new drugs,such as pralatrexate,combined with romidepsin can be used in PTCL cases to improve the complete remission rate.%2014年国际T细胞淋巴瘤临床大会主要报告了T细胞淋巴瘤的治疗状况及进展,其中包括靶向表观遗传学在T细胞淋巴瘤中的应用.有研究发现在外周T细胞淋巴瘤(PTCL)中控制DNA和组蛋白甲基化的基因存在突变.根据这一研究结果应用组蛋白去乙酰化酶(HDAC)抑制剂belinostat和romidepsin可使PTCL获得29% ~ 38%的总反应率,中位缓解时间为13.6个月.NK/T细胞淋巴瘤是东南亚国家常见的恶性淋巴瘤,在中国和日本占非霍奇金淋巴瘤的15%~ 28%,明显高于欧美国家,主要与亚洲人群EB病毒感染率高有关.应用含左旋门冬酰胺酶的方案如SMILE和AspMetDex方案,可使早期病例长期生存率超过70%,晚期病例可达到近40%.对于PTCL可以将新药如普拉曲沙、罗咪酯肽等联合应用,从而提高完全缓解率.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    patients, approximately half were eligible for multiagent chemotherapy with or without consolidating SCT. Both IPI and PIT are useful prognostic indices in all 'primary nodal' PTCL entities. The prognostic value of ALK protein expression in anaplastic large cell lymphoma is significantly downsized when...

  17. Relapsed/refractory paediatric T cell lymphoblastic leukaemia and lymphoma. | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available IA. A.3.2Name or abbreviated title of the trial where available NK cells in leukemia / lymphoma Células NK en leucemia...a de rescate en pacientes con leucemia aguda linfoblástica/linfoma linfoblástico (LLT) en recaída o refracta...HIV serology 1. Pacientes de edad comprendida entre 0 y 21 años diagnosticados de leucemia aguda linfoblásti

  18. Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T-Cells Secreting an Engineered Tumor-Specific Immunotoxin

    Science.gov (United States)

    2010-06-01

    5% CO2. The level of proliferation was then assessed using an ATP assay (CellTiter-Glo G7570; Promega, Madison, WI). Phenotyping. Cell-surface...trypan blue or an ATP assay (Promega). Cytotoxicity assay. T cell cytotoxic activity was evaluated in a flow cytometry based assay. Target cells...ml PMA and 1µM ionomycin. Cells were collected and lysed, and the lysate analyzed for bioluminescent signal. This revealed that the promoter induced

  19. Coinfection by Strongyloides stercoralis in blood donors infected with human T-cell leukemia/lymphoma virus type 1 in São Paulo city, Brazil

    Directory of Open Access Journals (Sweden)

    Pedro P Chieffi

    2000-10-01

    Full Text Available The frequency of coinfection with Strongyloides stercoralis and human T-cell leukemia/lymphoma virus type 1 (HTML-1 was determined in 91 blood donors examined at the blood bank of a large hospital in São Paulo city, Brazil. As control group 61 individuals, not infected by HTLV-1, were submitted to the same techniques for the diagnosis of S. stercoralis infection. In HTLV-1 infected patients the frequency of S. stercoralis infection was 12.1%; on the other hand, the control group showed a frequency significantly lower of S. stercoralis infection (1.6%, suggesting that HTLV-1 patients shoud be considered as a high risk group for strongyloidiasis in São Paulo city.

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

    Science.gov (United States)

    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

  1. A genomic and expression study of AP-1 in primary cutaneous T-cell lymphoma: evidence for dysregulated expression of JUNB and JUND in MF and SS.

    Science.gov (United States)

    Mao, Xin; Orchard, Guy; Mitchell, Tracey J; Oyama, Noritaka; Russell-Jones, Robin; Vermeer, Maarten H; Willemze, Rein; van Doorn, Remko; Tensen, Cornelis P; Young, Bryan D; Whittaker, Sean J

    2008-10-01

    Activator protein 1 (AP-1) consists of a group of transcription factors including the JUN and FOS family proteins with diverse biological functions. This study assessed the genomic and expression status of the AP-1 transcription factors in primary cutaneous T-cell lymphoma (CTCL) by using immunohistochemistry (IHC), Affymetrix expression microarray, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH). IHC showed JUNB protein expression in tumor cells from 17 of 33 cases of Sezary syndrome (SS) and JUND protein expression in 16 of 23 mycosis fungoides cases. There was no correlation between JUNB and CD30 expression. However, 7 of 12 JUNB-positive SS cases expressed both phosphorylated and total extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK) proteins. Expression microarray showed over threefold increased expression of JUNB in three of six SS patients and similar findings were also noted after re-analysis of previously published data. Real-time RT-PCR confirmed the overexpression of JUNB in four SS cases and of JUND in three of four cases. FISH showed increased JUNB copy number in four of seven SS cases. These findings suggest that deregulation of AP-1 expression in CTCL is the result of aberrant expression of JUNB and possible JUND resulting from genomic amplification and constitutive activation of ERK1/2 MAPK in this type of lymphoma.

  2. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography evaluation of subcutaneous panniculitis-like T cell lymphoma and treatment response

    Science.gov (United States)

    Gorodetskiy, Vadim R; Mukhortova, Olga V; Aslanidis, Irakli P; Klapper, Wolfram; Probatova, Natalya A

    2016-01-01

    Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare variant of non-Hodgkin’s lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone (commonly known as “GEM-P”) as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intra-abdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy. PMID:27672640

  3. CHO(E)P-14 followed by alemtuzumab consolidation in untreated peripheral T cell lymphomas: final analysis of a prospective phase II trial.

    Science.gov (United States)

    Binder, C; Ziepert, M; Pfreundschuh, M; Dührsen, U; Eimermacher, H; Aldaoud, A; Rosenwald, A; Loeffler, M; Schmitz, N; Truemper, L

    2013-11-01

    The rate of long-term remissions after treatment of peripheral T cell lymphomas (PTCL) with standard CHOP-like protocols is unsatisfactory. A prospective multicenter phase II trial was initiated in untreated patients with PTCL of all International Prognostic Index-risk groups, evaluating alemtuzumab consolidation in patients with complete or good partial remission after CHO(E)P-14 induction. Twenty-nine (70.7 %) of the 41 enrolled patients received alemtuzumab consolidation (133 mg in total). The main grades 3-4 toxicities during alemtuzumab therapy were infections and neutropenia with one potentially treatment-related death. Complete responses were seen in 58.5 %, partial responses in 2.4 % and 29.3 % had progressive disease. After a median observation time of 46 months, 19 patients have died, 16 of them due to lymphoma and/or salvage therapy complications. Event-free and overall survival at 3 years in the whole intent to treat population are 32.3 and 62.5 %, respectively, and 42.4 and 75.1 % in the patients who received alemtuzumab. In conclusion, application of a short course of alemtuzumab after CHO(E)P-14 induction is feasible although complicated by severe infections. A current phase III trial, applying alemtuzumab as part of the initial chemotherapy protocol to avoid early progression, will further clarify its significance for the therapeutic outcome.

  4. The first-line treatment regimens of peripheral T-cell lymphomas%外周T细胞淋巴瘤的一线治疗

    Institute of Scientific and Technical Information of China (English)

    周世勇; 吴少华

    2013-01-01

    Peripheral T-cell lymphomas (PTCLs) are a kind of non-Hodgkin's lymphoma (NHL),which arise from heterogeneous mature T-lymphocyte and include a variety of different subtypes.Compared with B-cell lymphoma,PTCLs are characterized by a lower incidence,resistance to conventional chemotherapy,widespread dissemination,a higher recurrence rate and unfavorable prognosis.At present,the standard first-line treatment regimens have not yet been developed for PTCLs.Though,there are many studies and trials about new drugs and novel intensive regimens,which improve the clinical curative effects and prognosis of PTCL patients significantly.In this paper,the progress of first-line treatment regimens of patients with different PTCL subtypes was reviewed.%外周T细胞淋巴瘤(PTCL)是非霍奇金淋巴瘤的一种类型,起源于异质性的成熟T细胞,包括多种不同亚型.与B细胞淋巴瘤相比,PTCL发病率较低、对传统化疗方案不敏感、病情迁延、易复发、预后较差.目前该病的标准一线治疗尚处于探索阶段,很多新药的研发正在进行,新强化方案的尝试也已展开,从很大程度上提高了PTCL患者的临床疗效及预后.文章着重对目前PTCL不同亚型一线治疗方案的研究进展进行介绍.

  5. T cell activation. II. Activation of human T lymphoma cells by cross-linking of their MHC class I antigens

    DEFF Research Database (Denmark)

    Dissing, S; Geisler, C; Rubin, B;

    1990-01-01

    The present work demonstrates that antibody-induced cross-linking of MHC class I antigens on Jurkat T lymphoma cells leads to a rise in intracellular calcium (Cai2+) and, in the presence of phorbol ester (PMA), to IL-2 production and IL-2 receptor expression. The rise in Cai2+ exhibited a profile...... very different from that obtained after anti-CD3 antibody-induced activation suggesting that activation signals are transduced differently after binding of anti-CD3 antibody and class I cross-linking, respectively. However, when Cai2+ was examined in individual Jurkat cells by means of a digital image...

  6. miR-122 regulates p53/Akt signalling and the chemotherapy-induced apoptosis in cutaneous T-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Valentina Manfè

    Full Text Available Advanced cutaneous T-cell lymphoma (CTCL is resistant to chemotherapy and presents a major area of medical need. In view of the known role of microRNAs (miRNAs in the regulation of cellular signalling, we aimed to identify the functionally important miRNA species, which regulate apoptosis in CTCL. Using a recently established model in which apoptosis of CTCL cell lines is induced by Notch-1 inhibition by γ-secretase inhibitors (GSIs, we found that miR-122 was significantly increased in the apoptotic cells. miR-122 up-regulation was not specific for GSI-1 but was also seen during apoptosis induced by chemotherapies including doxorubicin and proteasome blockers (bortezomib, MG132. miR-122 was not expressed in quiescent T-cells, but was detectable in CTCL: in lesional skin in mycosis fungoides and in Sézary cells purified from peripheral blood. In situ hybridization results showed that miR-122 was expressed in the malignant T-cell infiltrate and increased in the advanced stage mycosis fungoides. Surprisingly, miR-122 overexpression decreased the sensitivity to the chemotherapy-induced apoptosis via a signaling circuit involving the activation of Akt and inhibition of p53. We have also shown that induction of miR-122 occurred via p53 and that p53 post-transcriptionally up-regulated miR-122. miR-122 is thus an amplifier of the antiapoptotic Akt/p53 circuit and it is conceivable that a pharmacological intervention in this pathway may provide basis for novel therapies for CTCL.

  7. miR-122 Regulates p53/Akt Signalling and the Chemotherapy-Induced Apoptosis in Cutaneous T-Cell Lymphoma

    Science.gov (United States)

    Manfè, Valentina; Biskup, Edyta; Rosbjerg, Anne; Kamstrup, Maria; Skov, Anne Guldhammer; Lerche, Catharina Margrethe; Lauenborg, Britt Thyssing; Ødum, Niels; Gniadecki, Robert

    2012-01-01

    Advanced cutaneous T-cell lymphoma (CTCL) is resistant to chemotherapy and presents a major area of medical need. In view of the known role of microRNAs (miRNAs) in the regulation of cellular signalling, we aimed to identify the functionally important miRNA species, which regulate apoptosis in CTCL. Using a recently established model in which apoptosis of CTCL cell lines is induced by Notch-1 inhibition by γ-secretase inhibitors (GSIs), we found that miR-122 was significantly increased in the apoptotic cells. miR-122 up-regulation was not specific for GSI-1 but was also seen during apoptosis induced by chemotherapies including doxorubicin and proteasome blockers (bortezomib, MG132). miR-122 was not expressed in quiescent T-cells, but was detectable in CTCL: in lesional skin in mycosis fungoides and in Sézary cells purified from peripheral blood. In situ hybridization results showed that miR-122 was expressed in the malignant T-cell infiltrate and increased in the advanced stage mycosis fungoides. Surprisingly, miR-122 overexpression decreased the sensitivity to the chemotherapy-induced apoptosis via a signaling circuit involving the activation of Akt and inhibition of p53. We have also shown that induction of miR-122 occurred via p53 and that p53 post-transcriptionally up-regulated miR-122. miR-122 is thus an amplifier of the antiapoptotic Akt/p53 circuit and it is conceivable that a pharmacological intervention in this pathway may provide basis for novel therapies for CTCL. PMID:22235305

  8. Increased Levels of Plasma Epstein Barr Virus DNA Identify a Poor-Risk Subset of Patients With Advanced Stage Cutaneous T-Cell Lymphoma

    Science.gov (United States)

    Haverkos, Bradley M.; Gru, Alejandro A.; Geyer, Susan M.; Bingman, Anissa K.; Hemminger, Jessica A.; Mishra, Anjali; Wong, Henry K.; Pancholi, Preeti; Freud, Aharon G.; Caligiuri, Michael A.; Baiocchi, Robert A.; Porcu, Pierluigi

    2016-01-01

    Discovering prognostic factors that simultaneously describe tumor characteristics and improve risk stratification is a priority in cutaneous T-cell lymphoma (CTCL). More than a third of advanced stage CTCL patients in this cohort had detectable cell free plasma Epstein–Barr virus (EBV)-DNA (pEBVd) using quantitative real-time polymerase chain reaction. An increased level of pEBVd was highly concordant with EBV (ie, Epstein–Barr virus RNAs) in tumor tissue and was associated with inferior survival. Introduction Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein–Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. Patients and Methods Patients (n = 46; 2006–2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed. Results Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd+) than pEBVd− patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd+ and 22 of 29 pEBVd− patients; 12 of 14 (85.7%) pEBVd+ patients were EBER+ versus 0 of 22 pEBVd− patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd+ patients, but was not significant (10 of 14 pEBVd+ vs. 10 of 23 pEBVd−; P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd+ vs. 27 of 29 pEBVd−). pEBVd detection was associated with

  9. Potential role of enzastaurin in the treatment of patients with relapsed or refractory advanced cutaneous T-cell lymphomas: a review

    Directory of Open Access Journals (Sweden)

    Katz DA

    2012-06-01

    Full Text Available Deborah A Katz, Janet MD Plate, Sunita Nathan, Lydia UshaDivision of Hematology and Oncology, Rush University Medical Center, Chicago, IL, USAAbstract: Cutaneous T-cell lymphomas (CTCLs are rare extranodal non-Hodgkin lymphomas characterized by neoplastic T-lymphocyte accumulation in the skin. The two most common types of CTCLs are mycosis fungoides and the leukemic variant, Sézary syndrome. Prognosis of CTCLs depends on the stage, with a poor prognosis in advanced-stage disease. A number of agents have recently been developed for the treatment of CTCLs: chemotherapeutic agents such as pralatrexate, interferon-alpha, retinoids such as bexarotene, monoclonal antibodies such as alemtuzumab, and histone deacetylase inhibitors such as vorinostat and romidepsin. Nevertheless, there is no cure for CTCLs except for allogeneic stem cell transplant. A promising new drug is enzastaurin. Enzastaurin is a novel serine/threonine kinase inhibitor that binds to protein kinase C-β (PKC-β and inhibits the phosphoinositide-3 kinase (PI3K/AKT/phosphatase and tensin homolog (PTEN signaling pathway. Enzastaurin induces apoptosis and inhibits angiogenesis; it was also shown to suppress growth of CTCL cell lines in vitro. Given its low toxicity, enzastaurin has been tested against both solid tumors and hematologic malignancies. This article is focused on the potential role of enzastaurin in the treatment of CTCLs. A phase II multicenter trial evaluated enzastaurin monotherapy in patients with CTCLs. However, the results from this study were disappointing, demonstrating that enzastaurin had only modest clinical activity. Hence, enzastaurin is not currently developed for treating CTCLs. Potential strategies to improve enzastaurin efficacy against CTCLs are discussed: validation of enzastaurin targets such as PKC-β expression in CTCL lesions and or/blood; measurement of serum vascular endothelial growth factor levels; dose optimization; combining enzastaurin with

  10. Exosomes Isolated from Ascites of T-Cell Lymphoma-Bearing Mice Expressing Surface CD24 and HSP-90 Induce a Tumor-Specific Immune Response

    Science.gov (United States)

    Menay, Florencia; Herschlik, Leticia; De Toro, Julieta; Cocozza, Federico; Tsacalian, Rodrigo; Gravisaco, María José; Di Sciullo, María Paula; Vendrell, Alejandrina; Waldner, Claudia I.; Mongini, Claudia

    2017-01-01

    Extracellular vesicles (EVs), including endosome-derived nanovesicles (exosomes), are involved in cell–cell communication. Through transfer of their molecular contents, extracellular nanovesicles can alter the function of recipient cells. Due to these characteristics, EVs have shown potential as a new alternative for cancer immunotherapy. Tumor exosomes isolated from malignant ascites can activate dendritic cells, thereby priming the immune system to recognize and kill cancer cells. However, a suppressive role on tumor immune response has also been reported, suggesting that the neoplastic stage of carcinogenesis and the microenvironment where tumor cells grow may influence the amount of EVs released by the cell. This neoplastic stage and microenvironment may also impact EVs’ components such as proteins and miRNA, determining their biological behavior. Most T-cell lymphomas have an aggressive clinical course and poor prognosis. Consequently, complementary alternative therapies are needed to improve the survival rates achieved with conventional treatments. In this work, we have characterized EVs isolated from ascites of mice bearing a very aggressive murine T-cell lymphoma and have studied their immunogenic properties. Small EVs were isolated by differential centrifugation, ultrafiltration, and ultracentrifugation at 100,000 × g on a sucrose cushion. The EVs were defined as exosomes by their morphology and size analyzed by electron microscopy, their floating density on a sucrose gradient, as well as their expression of endosome marker proteins ALIX, TSG-101; the tetraspanins CD63, CD9, and CD81. In addition, they contain tumor antigens, the marker for malignancy CD24, the heat shock protein HSP-70, and an unusual surface expression of HSP-90 was demonstrated. The administration of EVs isolated from ascites (EVs A) into naïve-syngeneic mice induced both humoral and cellular immune responses that allowed the rejection of subsequent tumor challenges. However

  11. Multicentric T-cell lymphoma associated with feline leukemia virus infection in a captive namibian cheetah (Acinonyx jubatus).

    Science.gov (United States)

    Marker, Laurie; Munson, Linda; Basson, Peter A; Quackenbush, Sandra

    2003-07-01

    This case report describes a multicentric lymphoma in a 4 yr old female wildborn captive cheetah (Acinonyx jubatus) in Namibia after being housed in an enclosure adjacent to a feline leukemia virus (FeLV) infected cheetah that had previously been in contact with domestic cats. The year prior to the onset of clinical signs, the wild-born cheetah was FeLV antigen negative. The cheetah subsequently developed lymphoma, was found to be infected with FeLV, and then rapidly deteriorated and died. At necropsy, the liver, spleen, lymph nodes, and multiple other organs were extensively infiltrated with neoplastic T-lymphocytes. Feline leukemia virus DNA was identified in neoplastic lymphocytes from multiple organs by polymerase chain reaction and Southern blot analysis. Although the outcome of infection in this cheetah resembles that of FeLV infections in domestic cats, the transmission across an enclosure fence was unusual and may indicate a heightened susceptibility to infection in cheetahs. Caution should be exercised in holding and translocating cheetahs where contact could be made with FeLV-infected domestic, feral, or wild felids.

  12. Cytotoxic natural killer/T-cell lymphomas of the lymph nodes%淋巴结细胞毒性自然杀伤/T细胞淋巴瘤

    Institute of Scientific and Technical Information of China (English)

    林涛; 刘卫平; 李甘地; 李俸媛; 袁菊

    2001-01-01

    Objective  To investigate the clinicopathologic features of cytotoxi c natural killer (NK)/T-cell lymphomas of the lymph nodes. Methods  Clinicopatho logic observations and follow up on 5 cases of cytotoxic NK/T-cell lymphomas of the lymph nodes, immunohistochemical staining for CD45RO,CD8,CD56,CD30,CD20,TIA -1 and in situ hybridization for EBER1/2 were performed. Results  (1) The clinico pathologic features of cytotoxic NK-T-cell lymphomas of the lymph nodes were s um marized; (2) The tumor cells were positive for CD45RO in 4 of the 5 cases, in wh ich 3 cases were also positive for CD56. One case was of null cell type. The tum or cells were positive for TIA-1 and EBER1/2 in all 5 cases. Conclusions  The clin icopathological features and special immunophenotypes of cytotoxic NK/T-cell ly m phomas of the lymph nodes were present in all 5 cases. Clinically, this entity t ends to be an aggressive process with poor prognosis.%目的探讨淋巴结细胞毒性自然杀伤(NK/T)细胞淋巴瘤的临床病理学特征。方法对5例淋巴结细胞毒性NK/T细胞淋巴瘤作临床病理观察及随访、用LSAB法做免疫表型分析(CD45RO、CD 8、CD56、CD30、CD20、TIA-1)及EBER1/2原位杂交检测。结果淋巴结细胞毒性NK/T细胞淋巴瘤的病理组织学特点为:(1)淋巴结结构明显破坏并被瘤细胞所取代; (2) 瘤细胞呈多形性;(3)多数肿瘤细胞表达淋巴细胞分化抗原。5例中CD45RO阳性的有4例,其中3例瘤细胞同时呈CD56阳性;1例为无标记细胞性;所有病例的TIA-1和EBER均为阳性。结论淋巴结细胞毒性NK/T细胞淋巴瘤有特征性的形态改变和免疫表型,提示肿瘤进展及预后不良。

  13. Development of ultra-super sensitive immunohistochemistry and its application to the etiological study of adult T-cell leukemia/lymphoma.

    Science.gov (United States)

    Hasui, Kazuhisa; Wang, Jia; Tanaka, Yuetsu; Izumo, Shuji; Eizuru, Yoshito; Matsuyama, Takami

    2012-04-26

    Antigen retrieval (AR) and ultra-super sensitive immunohistochemistry (ultra-IHC) have been established for application to archival human pathology specimens. The original ultra-IHC was the ImmunoMax method or the catalyzed signal amplification system (ImmunoMax/CSA method), comprising the streptavidin-biotin complex (sABC) method and catalyzed reporter deposition (CARD) reaction with visualization of its deposition. By introducing procedures to diminish non-specific staining in the original ultra-IHC method, we developed the modified ImmunoMax/CSA method with AR heating sections in an AR solution (heating-AR). The heating-AR and modified ImmunoMax/CSA method visualized expression of the predominantly simple present form of HTLV-1 proviral DNA pX region p40Tax protein (Tax) in adult T-cell leukemia/lymphoma (ATLL) cells in archival pathology specimens in approximately 75% of cases. The simple present form of Tax detected exhibited a close relation with ATLL cell proliferation. We also established a new simplified CSA (nsCSA) system by replacing the sABC method with the secondary antibody- and horse radish peroxidase-labeled polymer reagent method, introducing the pretreatments blocking non-specific binding of secondary antibody reagent, and diminishing the diffusion of deposition in the CARD reaction. Combined with AR treating sections with proteinase K solution (enzymatic-AR), the nsCSA system visualized granular immunostaining of the complex present form of Tax in a small number of ATLL cells in most cases, presenting the possibility of etiological pathological diagnosis of ATLL and suggesting that the complex present form of Tax-positive ATLL cells were young cells derived from ATLL stem cells. The heating-AR and ultra-IHC detected physiological expression of the p53 protein and its probable phosphorylation by Tax in peripheral blood mononuclear cells of peripheral blood tissue specimens from HTLV-1 carriers, as well as physiological and pathological expression

  14. Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

    Science.gov (United States)

    Günther, Claudia; Zimmermann, Nick; Berndt, Nicole; Großer, Marianne; Stein, Annette; Koch, Andre; Meurer, Michael

    2011-01-01

    Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma (CTCL), which can deteriorate from patch stage to dermal-based tumors and systemic involvement in years. The interaction of chemokines in the skin with CTCL cells might have implications for the pathogenesis of the disease. In this study, we show by PCR analysis and immunofluorescence staining that the chemokine CCL18 is present in skin biopsy specimens of patients with MF and its precursor form parapsoriasis en plaque but not in healthy tissue. In addition, the serum levels of CCL18 were increased threefold in MF patients compared with those in healthy controls. In skin, CCL18 was specifically expressed by CD163+ CD209+ macrophages at the invasive margin of the tumor and not expressed by mature CD208+ dendritic cells in the center of the tumor. The chemokine CCL17 was, by contrast, ubiquitously expressed. Furthermore, CCL18 promoted the chemotaxis but not the proliferation of CTCL cells. CCL18 inhibited proliferation of tumor cells and abolished the CXCL12-induced growth of a CTCL cell line. These data link the increased expression of CCL18 with CTCL and suggest an immunomodulatory effect of the chemokine in the pathogenesis of CTCL. PMID:21741937

  15. The treatment of 45 patients with cutaneous T-cell lymphoma with low doses of interferon-alpha 2a and etretinate.

    Science.gov (United States)

    Dréno, B; Claudy, A; Meynadier, J; Verret, J L; Souteyrand, P; Ortonne, J P; Kalis, B; Godefroy, W Y; Beerblock, K; Thill, L

    1991-11-01

    Forty-five patients with cutaneous T-cell lymphomas (CTCL), 32 with mycosis fungoides (MF) and 13 with Sézary syndrome (SS), were treated with interferon-alpha 2a (IFN-alpha 2a) (6-9 x 10(6) IU daily) for 3 months. Those responding to treatment were then treated with interferon-alpha alone (6-9 x 10(6) IU three times weekly), and non-responders received a combination of etretinate (0.5 mg/kg/day) and IFN-alpha 2a in similar concentrations. After 12 months of treatment, 28/45 patients (62.2%) were in complete or partial (greater than 50%) remission. Of these, 17 (60.7%) were receiving IFN-alpha alone and 11 the combined interferon-retinoid therapy. Of the patients with MF stage I and II, 20/25 were responders (12 receiving IFN-alpha alone and eight on combined therapy), whereas only 8/20 with stage IV or SS responded to treatment (five receiving IFN-alpha 2a alone and three combined therapy). These results suggest that the association of etretinate with low-dose recombinant IFN-alpha 2a is an effective means of treating epidermotropic CTCL, particularly in the early stages.

  16. Post-treatment plasma EBV-DNA positivity predicts early relapse and poor prognosis for patients with extranodal NK/T cell lymphoma in the era of asparaginase.

    Science.gov (United States)

    Wang, Liang; Wang, Hua; Wang, Jing-hua; Xia, Zhong-jun; Lu, Yue; Huang, Hui-qiang; Jiang, Wen-qi; Zhang, Yu-jing

    2015-10-06

    Circulating Epstein-Barr virus (EBV) DNA is a biomarker of EBV-associated malignancies. Its prognostic value in early stage NK/T-cell lymphoma (NKTCL) in the era of asparaginase was investigated. 68 patients were treated with a median of 4 cycles of asparaginase-based chemotherapy followed by a median of 54.6 Gy (range 50-60 Gy) radiation. The amount of EBV-DNA was prospectively measured in both pretreatment and post-treatment plasma samples by real-time quantitative PCR. At the end of treatment, complete response (CR) rate was 79.4%, and overall response rate (ORR) was 88.2%. Patients with negative pretreatment EBV-DNA had a higher CR rate (96.0% vs. 69.8%, p = 0.023). The 3-year progression-free survival (PFS) rate and overall survival (OS) rate was 71% and 83%, respectively. In multivariate survival analysis, post-treatment EBV-DNA positivity and treatment response (non-CR) were prognostic factors for both worse PFS and OS (p EBV-DNA positivity correlated with inferior PFS and OS (both p EBV-DNA, negative post-treatment EBV-DNA correlated with better PFS and OS (both p EBV-DNA positivity can predict early relapse and poor prognosis for patients with early stage NKTCL in the era of asparaginase, and may be used as an indicator of minimal residual disease.

  17. Efficacy and tolerance of pegaspargase, gemcitabine and oxaliplatin with sandwiched radiotherapy in the treatment of newly-diagnosed extranodal nature killer (NK)/T cell lymphoma.

    Science.gov (United States)

    Jing, Xiao-Mei; Zhang, Zhi-Hui; Wu, Ping; Zhang, Shi-Chuan; Ren, Yuan-Rong; Xiong, Zhu-Juan; Wei, Wen; Luo, Lei; Li, Li

    2016-08-01

    Extranodal nature killer (NK)/T cell lymphoma (ENKL), nasal type, is a highly aggressive and heterogeneous disease. Here we report a retrospective study of 38 newly-diagnosed ENKL patients treated with pegaspargase, gemcitabine, oxaliplatin (P-Gemox) and sandwiched radiotherapy in our department during 2012-2016. A median of 4 (range, 2-6) (total=141) cycles of P-Gemox were administered. Interim restaging after at least 2 cycles showed complete remission (CR) rate of 23.68%, partial remission (PR) rate of 63.16%, giving an overall response rate (ORR) of 86.84%. On treatment completion, the ORR became 92.1% (CR=86.84%, PR=5.26%). Only one patient experienced disease progression during therapy. Multivariate analysis showed gender was a significant independent factor impacting on CR. Hematologic toxicity was common yet nonhematologic toxicity was mild, both of them can be well controlled by supportive treatments and only one treatment-related death was observed. At a median follow-up of 15.5 months, 4 patients (10.53%) experienced disease progression and died of disease. 1-year progression-free survival (PFS) rate and 1-year overall survival (OS) rate for the whole cohort were 86.7% and 86.6%. The P-Gemox regimen with sandwiched radiotherapy may be a promising option in the treatment of newly-diagnosed ENKL due to its high efficacy yet low toxicity.

  18. HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4⁺ T-cell lymphocytes

    DEFF Research Database (Denmark)

    Bohlius, Julia; Schmidlin, Kurt; Boué, François;

    2011-01-01

    The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4¿ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1-infected...... patients (median age, 36 years; 70% male; median CD4 cell count, 234 cells/µL) from 16 European cohorts were observed during 159 133 person-years; 78 patients developed HL. The incidence was 49.0 (95% confidence interval [CI], 39.3-61.2) per 100,000 person-years, and similar on cART and not on cART (P...... = .96). The risk of HL declined as the most recent (time-updated) CD4 count increased: the adjusted hazard ratio comparing more than 350 with less than 50 cells/µL was 0.27 (95% CI, 0.08-0.86). Sixty-one HL cases diagnosed on cART were matched to 1652 controls: during the year before diagnosis, cases...

  19. Synergistic effect of EMF-BEMER-type pulsed weak electromagnetic field and HPMA-bound doxorubicin on mouse EL4 T-cell lymphoma.

    Science.gov (United States)

    Říhová, Blanka; Etrych, Tomáš; Šírová, Milada; Tomala, Jakub; Ulbrich, Karel; Kovář, Marek

    2011-12-01

    We have investigated the effects of low-frequency pulsed electromagnetic field (LF-EMF) produced by BEMER device on experimental mouse T-cell lymphoma EL4 growing on conventional and/or athymic (nude) mice. Exposure to EMF-BEMER slowed down the growth of tumor mass and prolonged the survival of experimental animals. The effect was more pronounced in immuno-compromised nude mice compared to conventional ones. Acceleration of tumor growth was never observed. No measurable levels of Hsp 70 or increased levels of specific anti-EL4 antibodies were detected in the serum taken from experimental mice before and at different intervals during the experiment, i.e. before solid tumor appeared, at the time of its aggressive growth, and at the terminal stage of the disease. A significant synergizing antitumor effect was seen when EL4 tumor-bearing mice were simultaneously exposed to EMF-BEMER and treated with suboptimal dose of synthetic HPMA copolymer-based doxorubicin, DOX(HYD)-HPMA. Such a combination may be especially useful for heavily treated patients suffering from advanced tumor and requiring additional aggressive chemotherapy which, however, at that time could represent almost life-threatening way of medication.

  20. Clinicopathologic and molecular features of 122 Brazilian cases of nodal and extranodal NK/T-cell lymphoma, nasal type, with EBV subtyping analysis.

    Science.gov (United States)

    Gualco, Gabriela; Domeny-Duarte, Pollyanna; Chioato, Lucimara; Barber, Glen; Natkunam, Yasodha; Bacchi, Carlos E

    2011-08-01

    Extranodal natural killer/T-cell lymphoma, nasal type (NK/TCL) is more prevalent in Asia and in some areas of South and Central America, but it is rarely seen in the United States and Europe. In this study, a series of 122 cases of NK/TCL from Brazil was analyzed with respect to clinicopathologic features. Clinical characteristics and geographic distribution were evaluated in 97 cases of nasal/nasopharyngeal region and 23 cases in extranasal sites including 6 nodal cases. Clinical staging and follow-up information was available in a subset of 21 patients. All cases harbored Epstein-Barr virus (EBV), 95% and 85% expressed cytoplasmic CD3 and CD56, respectively, and all cases were positive for at least 1 marker for cytotoxic granules. The global distribution of EBV subtypes showed predominance of strain subtype A, 89%, and subtype B, 11%. No dual infections were detected. TCR-γ TCR-gene rearrangement was observed in 7 cases; all of them extranodal. Three of TCR-γ(+) cases showed EBV subtype A. Two TCR-γ(+)/CD56(+) cases showed EBV subtype B. Geographic distribution of NK/TCL showed higher frequency in the southeast and northeast regions of Brazil. Striking differences among geographic regions were seen with the vast majority of EBV subtype B (86%) occurring in the south and southeast regions.

  1. Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial.

    Science.gov (United States)

    Uyttebroeck, Anne; Suciu, Stefan; Laureys, Geneviève; Robert, Alain; Pacquement, Hélène; Ferster, Alina; Marguerite, Geneviève; Mazingue, Françoise; Renard, Marleen; Lutz, Patrick; Rialland, Xavier; Mechinaud, Françoise; Cavé, Hélène; Baila, Liliana; Bertrand, Yves

    2008-04-01

    From June 1989 through to November 1998, 121 children with newly diagnosed T-cell lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted by the Children's Leukaemia Group. The therapy regimen was based on a Berlin-Frankfurt-Munster protocol, for a total duration of 24 months. Cranial irradiation, prophylactic cranial and local, was omitted, even for patients with central nervous involvement at diagnosis. In total, 119 patients were evaluable. The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at 6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year after complete remission (range 0.2-5.9 years). Only two (1.8%) patients had an isolated central nervous system relapse. For patients with complete response (n=16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14% (P<0.001) for patients with no response (n=7). Overall survival rate at 6 years was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy regimen without irradiation leads to a high cure and survival rate in childhood T-LBL without an increased CNS recurrence. This suggests that prophylactic cranial irradiation can safely be omitted. Response to the prephase appeared to be a strong prognostic factor for EFS.

  2. Hyper-CVAD chemotherapy or autologous stem cell transplantation in patients with peripheral T cell lymphomas:a single centre report

    Institute of Scientific and Technical Information of China (English)

    XU Yang; WU Xiao-jin; WANG Ying; JIN Zheng-ming; SUN Ai-ning; WU De-pei

    2012-01-01

    Background Peripheral T-cell lymphoma(PTCL)is generally characterized by poor prognosis after conventional chemotherapy.The place for high-dose chemotherapy and autologous stem cell transplantation(ASCT)in these patients is still not clear.In this study,we presented the outcomes of PTCL patients followed these treatments in our centre.Methods We retrospectively analyzed the outcomes of 39 patients with PTCL received the two treatments between 1999 and 2010.Results The 3-year overall survival(OS)of 61.9% and 3-year progression free survival(PFS)of 35.7% were observed in the 39 patient.Twenty-one patients received Hyper-CVAD chemotherapy with 3-year OS of 46.2% and 3-year PFS of 27.9%.Eighteen patients received ASCT with 3-year OS of 70.3% and 3-year PFS of 44.2%.Further analysis revealed that patients with elevated lactate dehydrogenase,at least 2 international prognostic index(IPI)points,and extranodal involvement had a poorer outcome compared with the control group.Conclusion These findings might suggest that Hyper-CVAD chemotherapy and ASCT could offer a durable survival benefit for patients with aggressive PTCL.

  3. Human T Lymphotropic Virus Type I (HTLV-I Oncogenesis: Molecular Aspects of Virus and Host Interactions in Pathogenesis of Adult T cell Leukemia/Lymphoma (ATL

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    Sanaz Ahmadi Ghezeldasht

    2013-03-01

    Full Text Available     The study of tumor viruses paves the way for understanding the mechanisms of virus pathogenesis, including those involved in establishing infection and dissemination in the host tumor affecting immune-compromised patients. The processes ranging from viral infection to progressing malignancy are slow and usually insufficient for establishment of transformed cells that develop cancer in only a minority of infected subjects. Therefore, viral infection is usually not the only cause of cancer, and further environmental and host factors, may be implicated. HTLV-I, in particular, is considered as an oncovirus cause of lymphoproliferative disease such as adult T cell leukemia/lymphoma (ATL and disturbs the immune responses which results in HTLV-I associated meylopathy/tropical spastic parapresis (HAM/TSP. HTLV-I infection causes ATL in a small proportion of infected subjects (2-5% following a prolonged incubation period (15-30 years despite a strong adaptive immune response against the virus.   Overall, these conditions offer a prospect to study the molecular basis of tumorgenicity in mammalian cells. In this review, the oncogencity of HTLV-I is being considered as an oncovirus in context of ATL.    

  4. Lobular panniculitic infiltrates with overlapping histopathologic features of lupus panniculitis (lupus profundus) and subcutaneous T-cell lymphoma: a conceptual and practical dilemma.

    Science.gov (United States)

    Bosisio, Francesca; Boi, Sebastiana; Caputo, Valentina; Chiarelli, Concetta; Oliver, Fergus; Ricci, Roberto; Cerroni, Lorenzo

    2015-02-01

    Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is characterized by panniculitic infiltrates that may be difficult to distinguish from inflammatory disorders, particularly lupus erythematosus profundus (LEP). We report on 11 patients (M:F=5:6; median age: 49 y; range: 20 to 75 y) presenting with lobular panniculitic infiltrates showing histopathologic features of both SPTCL and LEP in different parts of the same biopsy specimen. The areas showing aspects of SPTCL revealed dense infiltrates of small and medium-sized, atypical α/β T-cytotoxic lymphocytes with focal rimming of the adipocytes and high proliferation. In other areas the infiltrate was composed of nodules of B lymphocytes arranged characteristically at the periphery of the fat lobules and in the septa and showing a low proliferation rate. CD123-positive plasmocytoid dendritic cells arranged in small clusters could be observed in 3 cases. Our observation raises an important question concerning the relationship between SPTCL and LEP. A simple chance overlap of 2 unrelated pathologies seems unlikely, as we could observe these unusual features in 11 cases, much more than mere chance would justify. Three other hypotheses may explain the features observed in our patients: (1) these are examples of SPTCL with focal histologic features mimicking those of LEP; (2) these are examples of LEP with focal atypical histologic features mimicking those of SPTCL; (3) SPTCL and LEP may represent 2 ends of a spectrum, a hypothesis that may be supported by the frequent association of the 2 diseases.

  5. 鼻腔NK/T细胞淋巴瘤的影像学诊断%Diagnosis of Primary Nasal Cavity NK/T Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    张宽; 彭通略

    2011-01-01

    目的 探讨鼻腔NK/T细胞淋巴瘤的CT及MRI表现特征.材料和方法 回顾性分析21例经病理证实的鼻腔NK/T细胞淋巴瘤患者的CT和MRI影像学资料及临床资料.结果 本组21例中单侧7例,双侧14例,依据病变范围将本病分为局限型和弥漫型两种类型.局限型13例,主要位于鼻腔内,其中鼻腔前部11例,鼻腔后部2例;骨质改变不明显,浸润鼻旁或面部皮下组织9例,弥漫型8例,肿瘤范围广泛并向鼻腔周围结构浸润扩展,其中累及鼻旁窦7例,侵入眼眶1例、颞下窝2例,延伸至鼻咽、口咽部并累及咽旁间隙6例,骨质破坏7例,颈部淋巴结受累1例.CT显示肿瘤呈软组织密度充填鼻腔并沿鼻黏膜蔓延,增强后轻到中度不均匀强化.MRI T1WI肿瘤呈等信号,信号强度类似或稍低于肌肉;T2WI呈不均匀稍高信号,信号强度高于肌肉,但低于鼻黏膜,增强后轻到中度不均匀强化.结论 鼻腔NK/T细胞型淋巴瘤影像学表现有一定特征,CT、MRI检查可提示诊断,有利于确定病变范围及临床分期.%Purpose To characterize CT and MRI features of primary nasal cavity NK/T cell non-Hodgkin's lymphoma. Materials and Methods CT or/and MRI findings of 21 cases with nasal cavity NK/T cell lymphoma verified by pathologically were analyzed retrospectively. Results Of all 21 cases, 7 were involved in unilateral nasal cavity, 14 were involved in bilateral nasal cavity. Nasal cavity NK/T cell lymphoma was divided into localized type and diffuse type according to the range of lesion. A total of 13 cases were localized type, mainly located in the nasal cavity, 11 of them located in front of the nasal cavity, 2 located in posterior nasal cavity, bone mass showed no obvious change, 9 were involved in paranasal or facial subcutaneous tissue. A total of 8 cases were diffuse type, the lesion was involved extensively and infiltrated to the adjacent structures of nasal cavity, 7 cases among them involved the paranasal

  6. The Mus cervicolor MuLV isolate M813 is highly fusogenic and induces a T-cell lymphoma associated with large multinucleated cells.

    Science.gov (United States)

    Prassolov, V; Ivanov, D; Hein, S; Rutter, G; Münk, C; Löhler, J; Stocking, C

    2001-11-10

    M813 is a type-C murine leukemia virus (MuLV) isolated from the Asian rodent Mus cervicolor. We have recently demonstrated that M813 defines a distinct MuLV receptor interference group. Here we show that M813 rapidly induces fusion of MuLV-expressing fibroblasts from "without," with syncytia being observed within 1 h after exposure to virus. Infection of fibroblasts with MuLV from all tested receptor-interference groups imparts susceptibility to M813-induced fusion, provided the cells also express the M813 receptor. Syncytium induction is also observed in vivo; mice infected with M813 develop a peripheral T-cell lymphoma, which is associated with large multinucleated cells of macrophage origin. A recombinant Moloney MuLV/M813 chimeric virus demonstrated that syncytium induction is a function of the Env SU protein. We postulate that the highly fusogenic property of M813 is attributable to either its unique receptor usage or sequences in the proline-rich domain of the Env protein.

  7. Rate of primary refractory disease in B and T-cell non-Hodgkin's lymphoma: correlation with long-term survival.

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    Corrado Tarella

    Full Text Available BACKGROUND: Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL. This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients. METHODS: Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%, intensive therapy with autograft (16.9%, or other therapies (19.9%. Among B-cell NHL, 1,356 (47.8% received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months. RESULTS: Overall, 690 (22.2% patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001. Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001. Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001. CONCLUSION: Chemosensitivity to primary

  8. Seroprevalence and correlates of human T-cell lymphoma/leukemia virus type 1 antibodies among pregnant women at the University of Nigeria Teaching Hospital, Enugu, Nigeria

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    Okoye AE

    2014-09-01

    Full Text Available Augustine Ejike Okoye,1 Obike Godswill Ibegbulam,2 Robinson Chukwudi Onoh,3 Paul Olisaemeka Ezeonu,3 Ngozi I Ugwu,1 Lucky Osaheni Lawani,3 Chukwudi Simon Anigbo,2 Charles E Nonyelu21Department of Haematology and Immunology, Federal Teaching Hospital, Abakaliki, 2Department of Haematology and Immunology, University of Nigeria Teaching Hospital (UNTH, Ituku-Ozalla, 3Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, NigeriaBackground: Human T-cell lymphoma/leukemia virus (HTLV-1 is a retrovirus transmitted vertically from mother to child parenterally and sexually by infected lymphocytes.Objective: The objective of this study was to determine the seroprevalence of HTLV-1 antibodies and associated risk factors for HTLV-1 infection among pregnant women in University of Nigeria Teaching Hospital, Enugu, southeast Nigeria.Materials and methods: A cross-sectional study was carried out from July to October 2010. Two hundred pregnant women were recruited consecutively from the antenatal clinic. Five milliliters of blood was collected from each of the participants into a plain sterile bottle and allowed to clot. The serum obtained was stored at -20°C until required for analysis. The serum samples were then analyzed for antibodies to HTLV-1 using a one-step incubation double-antigen sandwich enzyme-linked immunosorbent assay kit. Participants' demographic characteristics and degree of exposure to the risk factors associated with HTLV-1 infection were captured using a questionnaire. Statistical analysis of results was done using SPSS version 17.Results: The average age of the pregnant women was 28.94 years (standard deviation 4.17. The age-group with the highest representation was those between the ages of 26 and 30 years. Thirty-six percent of the population was above 30 years old. The result of the tests showed that only one respondent, a 31-year-old pregnant woman tested positive for HTLV-1 antibodies. Therefore, the

  9. The Genetic Deletion of 6q21 and PRDM1 and Clinical Implications in Extranodal NK/T Cell Lymphoma, Nasal Type

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    Li Liang

    2015-01-01

    Full Text Available 6q21 genetic deletion has been frequently detected in extranodal NK/T cell lymphoma, nasal type (EN-NK/T-NT, and PRDM1 is considered as candidate gene. However, direct detection of PRDM1 deletion has not been well documented. We investigated genetic alterations of 6q21 and PRDM1 in 43 cases of EN-NK/T-NT and cell lines by FISH. PRDM1 expression was evaluated by immunohistochemistry and Western blot. The correlation between genetic alteration and PRDM1 expression and the significance in clinic-pathologic were analyzed. Heterozygous deletion of 6q21 and/or PRDM1 was observed in 24 of 43 cases (55.81% of EN-NK/T-NT including 16 cases (37.21% for 6q21 deletion and 19 cases (44.19% for PRDM1 deletion. Similarly, heterozygous codeletion of 6q21 and PRDM1 was identified in NK92 and NKL cells. The heterozygous deletion of 6q21 and/or PRDM1 was correlated with PRDM1 expression. However, genetic deletion of 6q21 and/or PRDM1 was not correlated with clinicopathological features of EN-NK/T-NT, while PRDM1 expression showed positive effect on the outcome of patients as those as disease site, B symptom, and clinical stage. Thus, heterozygous deletion of 6q21 and/or PRDM1 was frequently detected in EN-NK/T-NT and correlated with downregulation of PRDM1. But the prognostic role of genetic deletion needs to be further evaluated in larger cohort.

  10. Concurrent IMRT and weekly cisplatin followed by GDP chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell lymphoma.

    Science.gov (United States)

    Ke, Q-H; Zhou, S-Q; Du, W; Liang, G; Lei, Y; Luo, F

    2014-01-01

    On the basis of the benefits of frontline radiation in early-stage, extranodal natural killer (NK)/T-cell lymphoma (ENKTL), we conducted the trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of gemcitabine, dexamethasone and cisplatin (GDP). Thirty-two patients with newly diagnosed, stage IE to IIE, nasal ENKTL received CCRT (that is, all patients received intensity-modulated radiotherapy 56 Gy and cisplatin 30 mg/m(2) weekly, 3-5 weeks). Three cycles of GDP (gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4 and cisplatin 75 mg/m(2) i.v. on day 1 (GDP), every 21 days as an outpatient were scheduled after CCRT. All patients completed CCRT, which resulted in 100% response that included 24 complete responses (CRs) and eight partial responses. The CR rate after CCRT was 75.0% (that is, 24 of 32 responses). Twenty-eight of the 32 patients completed the planned three cycles of GDP, whereas four patients did not because they withdrew (n = 1) or because they had an infection (n = 3). The overall response rate and the CR rate were 90.6% (that is, 29 of 32 responses) and 84.4% (that is, 27 of 32 responses), respectively. Only two patient experienced grade 3 toxicity during CCRT (nausea), whereas 13 of the 30 patients experienced grade 4 neutropenia. The estimated 3-year overall survival and progression-free rates were 87.50% and 84.38%, respectively. In conclusion, CCRT followed by GDP chemotherapy can be a feasible and effective treatment strategy for stage IE to IIE nasal ENKTL.

  11. Linfoma subcutâneo de células T paniculite-símile Subcutaneous panniculitis-like T-cell lymphoma

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    Renato Soriani Paschoal

    2009-08-01

    Full Text Available Linfoma subcutâneo de células T paniculite-símile foi recentemente reconhecido como entidade clínico-patológica. Paciente do sexo feminino, 17 anos, relatou nodosidades eritêmato-violáceas e depressões nos membros e abdome há três anos e discreta perda ponderal, sem outros sintomas gerais. Adenomegalia, visceromegalias e infiltração da medula óssea estavam ausentes, e a histopatologia da pele mostrou densa infiltração de linfócitos atípicos CD3/CD8 no subcutâneo. A quimioterapia interrompeu o surgimento de novas lesões com remissão das pré-existentes no seguimento de oito meses. Aspectos imunofenotípicos e moleculares são relevantes para elucidação diagnóstica e avaliação do prognóstico.Subcutaneous panniculitis-like T-cell lymphoma is extremely rare and has recently been recognized as a clinicopathological entity. Young female, 17 years old, has complained of subcutaneous nodules and plaques in the limbs and abdomen for three years, accompanied of mild weight loss without other constitutional symptoms. Nodal, visceral and bone marrow involvement was absent, and subcutaneous CD3/CD8 atypical lymphocyte infiltration was observed in the skin sample. Chemotherapy interrupted the onset of new lesions and led to remission in the 8-month follow-up. Immunophenotypic and molecular aspects were relevant to the diagnosis and as prognosis makers.

  12. Loss of heterozygosity on 10q and microsatellite instability in advanced stages of primary cutaneous T-cell lymphoma and possible association with homozygous deletion of PTEN.

    Science.gov (United States)

    Scarisbrick, J J; Woolford, A J; Russell-Jones, R; Whittaker, S J

    2000-05-01

    Previous cytogenetic studies of primary cutaneous T-cell lymphoma (CTCL) were based on limited numbers of patients and seldom showed consistent nonrandom chromosomal abnormalities. In this study, 54 tumor DNA samples from patients with CTCL were analyzed for loss of heterozygosity on 10q. Allelic loss was identified in 10 samples, all of which were from the 44 patients with mycosis fungoides (10/44 patients; 23%). Of the patients with allelic loss, 3 were among the 29 patients with early-stage myosis fungoides (T(1) or T(2)) (3/29 patients; 10%), whereas the other 7 were among the 15 patients with advanced cutaneous disease (T(3) or T(4)) (7/15 patients; 47%). The overlapping region of deletion was between 10q23 and 10q24. In addition, microsatellite instability (MSI) was present in 13 of the 54 samples (24%), 12 from patients with mycosis fungoides and 1 from a patient with Sezary syndrome. There was also an association between MSI and disease progression in patients with mycosis fungoides, with 6 of 15 (40%) patients with MSI having advanced cutaneous disease and only 6 of 29 (21%) having early-stage disease. Samples with allelic loss on 10q were analyzed for abnormalities of the tumor suppressor gene PTEN (10q23.3). No tumor-specific mutations were detected, but homozygous deletion was found in 2 patients. Thus, we found loss of heterozygosity on 10q and MSI in advanced cutaneous stages of mycosis fungoides. These findings indicate that a tumor suppressor gene or genes in this region may be associated with disease progression. Furthermore, abnormalities of PTEN may be important in the pathogenesis of mycosis fungoides, but our data imply that this gene is rarely inactivated by small deletions or point mutations. (Blood. 2000;95:2937-2942)

  13. Low-Dose (10-Gy) Total Skin Electron Beam Therapy for Cutaneous T-Cell Lymphoma: An Open Clinical Study and Pooled Data Analysis

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    Kamstrup, Maria R., E-mail: mkam0004@bbh.regionh.dk [Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen (Denmark); Gniadecki, Robert [Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen (Denmark); Iversen, Lars [Department of Dermatology, Aarhus University Hospital, Aarhus (Denmark); Skov, Lone [Department of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen (Denmark); Petersen, Peter Meidahl [Department of Oncology and Hematology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Loft, Annika [Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Specht, Lena [Department of Oncology and Hematology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark)

    2015-05-01

    Purpose: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. Methods and Materials: In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. Results: The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Conclusions: Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT.

  14. miR-223 regulates cell growth and targets proto-oncogenes in mycosis fungoides/cutaneous T-cell lymphoma.

    Science.gov (United States)

    McGirt, Laura Y; Adams, Clare M; Baerenwald, Devin A; Zwerner, Jeffrey P; Zic, John A; Eischen, Christine M

    2014-04-01

    The pathogenesis of the cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF), is unclear. MicroRNA (miRNA) are small noncoding RNAs that target mRNA leading to reduced mRNA translation. Recently, specific miRNA were shown to be altered in CTCL. We detected significantly reduced expression of miR-223 in early-stage MF skin, and further decreased levels of miR-223 in advanced-stage disease. CTCL peripheral blood mononuclear cells and cell lines also had reduced miR-223 as compared with controls. Elevated expression of miR-223 in these cell lines reduced cell growth and clonogenic potential, whereas inhibition of miR-223 increased cell numbers. Investigations into putative miR-223 targets with oncogenic function, including E2F1 and MEF2C, and the predicted miR-223 target, TOX, revealed that all three were targeted by miR-223 in CTCL. E2F1, MEF2C, and TOX proteins were decreased with miR-223 overexpression, whereas miR-223 inhibition led to increased protein levels in CTCL. In addition, we showed that the 3'-UTR of TOX mRNA was a genuine target of miR-223. Therefore, reduced levels of miR-223 in MF/CTCL lead to increased expression of E2F1, MEF2C, and TOX, which likely contributes to the development and/or progression of CTCL. Thus, miR-223 and its targets may be useful for the development of new therapeutics for MF/CTCL.

  15. Clinicopathological analysis of cutaneous natural killer/T cell lymphoma: 36 case report%36例皮肤天然杀伤细胞/T细胞淋巴瘤临床病理学研究

    Institute of Scientific and Technical Information of China (English)

    徐教生; 谷从友; 安方; 高子芬; 李敏; 黄欣; 张永红; 周春菊; 薛学敏; 段泽君; 孙琳; 刘翠苓

    2011-01-01

    目的 探讨皮肤天然杀伤细胞(NK)/T细胞淋巴瘤临床病理学特点、与EB病毒的关系及预后。方法 收集2000—2010年北京大学医学部病理学系确诊为皮肤NK/T细胞淋巴瘤36例,分为原发与继发两组,分别观察临床病理学特点及与EB病毒的关系,并进行随访。结果 36例皮肤NK/T细胞淋巴瘤中,原发13例,继发20例,未能明确原发或继发3例。原发性与继发性皮肤NK/T细胞淋巴瘤均以男性好发,但两组男女性别比差异无统计学意义(P>0.05)。与原发者相比,继发者发病年龄早(中位年龄,43.5比54岁,P< 0.05)、且临床上出现B症状(包括发热、盗汗或体质量下降)及多发皮损改变的频率较高(P值分别为<0.05和<0.01)。EB病毒在原发和继发病例中的检出率类似,分别为92.3%和85%。36例皮肤NK/T细胞淋巴瘤中位生存期为8个月,其中继发性皮肤NK/T细胞淋巴瘤中位生存期为6个月,明显短于原发者(18个月,x2= 6.074,P<0.05)。结论 皮肤NK/T细胞淋巴瘤是一组与EB病毒密切相关、临床侵袭性强的肿瘤。但原发者较继发者发病年龄晚、预后较好。%Objective To investigate the clinicopathological features and prognosis of natural killer (NK)/T cell lymphoma and to analyze its relationship with Epstein-barr virus (EBV). Methods Totally, 36 cases of cutaneous NK/T cell lymphoma were collected from 2000 to 2010 at the Department of Pathology, Peking University Health Science Center, and classified into primary and secondary groups according to whether there is evidence of extracutaneous involvement within 6 months after diagnosis. Clinicopathological features were analyzed and Epstein-barr virus (EBV) was detected. Results Of these 36 cases, 13 (36.1%) were classified as primary cutaneous NK/T cell lymphoma, 20 (55.6%) as secondary, and 3 (8.3%) remained unclassified because of the lack of clinical data. Males were more likely

  16. Is an increase in CD4/CD8 T-cell ratio in lymph node fine needle aspiration helpful for diagnosing Hodgkin lymphoma? A study of 85 lymph node FNAs with increased CD4/CD8 ratio

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    Hernandez Osvaldo

    2005-01-01

    Full Text Available Abstract Background An elevated CD4/CD8 T-cell ratio on flow cytometry (FCM analysis has been reported in the literature to be associated with Hodgkin lymphoma (HL. The purpose of our study was to determine the diagnostic significance of an elevated CD4/CD8 ratio in lymph node fine needle aspiration (FNA specimens. Design Between 1996 and 2002, out of 837 lymph node FNAs submitted for flow cytometry analysis, 85 cases showed an elevated CD4/CD8 ratio, defined as greater than or equal to 4, without definitive evidence of a lymphoproliferative disorder. The cytologic diagnoses of these 85 cases were grouped into four categories: reactive, atypical, Hodgkin lymphoma (HL, and non-Hodgkin lymphoma (NHL. Histologic follow-up was available in 17/85 (20% of the cases. Results 5 of the 64 cases in which FCM and cytology did not reveal evidence of a lymphoproliferative disease had tissue follow-up because of persistent lymphadenopathy and high clinical suspicion. 3/5 (60% confirmed the diagnosis of reactive lymphadenopathy. The two remaining cases (40% were positive for lymphoma (1HL, 1NHL. 8/15 cases called atypical on cytology had histologic follow-up. 7/8 (87.5% cases were positive for lymphoma (3HL, 4NHL. 3/4 cases called HL on cytology had tissue follow-up and all 3 (100% confirmed the diagnosis of HL. One case diagnosed as NHL on cytology was found to be a diffuse large B-cell lymphoma. In summary, out of 17 cases with histologic follow-up 4/17 (24% were reactive with CD4/CD8 T-cell ratio of 4.1–29, 7/17 (41% were HLs with CD4/CD8 T-cell ratio of 5.3 – 11, and 6/17 (35% were NHLs with CD4/CD8 T-cell ratio of 4.2 – 14. Conclusion An elevated CD4/CD8 ratio on FCM is a nonspecific finding which may be seen in both reactive and lymphoproliferative disorders. The cytomorphologic features of the smear are more relevant than the sole flow cytometric finding of an elevated CD4/CD8 ratio.

  17. 早期鼻腔NK/T细胞淋巴瘤放疗模式的研究现状%Current study status of radiotherapy modality on early stage nasal NK/T cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    韩宝林

    2012-01-01

    鼻腔NK/T细胞淋巴瘤属于结外非霍奇金淋巴瘤的一种少见特殊类型,目前研究已经确立了放疗在其治疗中的地位和作用,但对于具体的放疗模式,如适宜的放疗靶区、放疗剂量以及颈部预防照射等问题仍存在着较大的争议.多数研究表明扩大野放疗和较高的放疗剂量是取得较好放疗疗效的关键;局限期病例多不主张颈部预防照射,但对于病变范围广泛者仍有较大争论.%Nasal NK/T cell lymphoma is a rare and distinct type of extranodal Non-Hodgkin' s lymphoma. Current study has proved that Radiotherapy is the most effective treatment method in the early stage nasal NK/T cell lymphoma, but there is no universal standard for concrete radiotherapy modality, such as the radiation target, the radiation dose and preventive neck radiation. Most studies have proved that radiotherapy of extended field and higher dose achieved good effect in early stage nasal NK/T cell lymphoma.And the studies also do not suggested preventive neck radiation in local stage patients, but it need further study in the extensive stage patients.

  18. Increased T-cell responses to Epstein-Barr virus with high viral load in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.

    Science.gov (United States)

    Morishima, Satoko; Nakamura, Shigeo; Yamamoto, Kazuhito; Miyauchi, Hidemasa; Kagami, Yoshitoyo; Kinoshita, Tomohiro; Onoda, Hiroshi; Yatabe, Yasushi; Ito, Masafumi; Miyamura, Kouichi; Nagai, Hirokazu; Moritani, Suzuko; Sugiura, Isamu; Tsushita, Keitaro; Mihara, Hidetsugu; Ohbayashi, Kaneyuki; Iba, Sachiko; Emi, Nobuhiko; Okamoto, Masataka; Iwata, Seiko; Kimura, Hiroshi; Kuzushima, Kiyotaka; Morishima, Yasuo

    2015-04-01

    The immunological status of patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) without obvious immunodeficiency has not been elucidated. A multicenter prospective study was conducted to assess pretreatment T-cell responses to EBV, EBV-DNA load and anti-EBV antibody in these patients. The proliferative and interferon (IFN)-γ-producing capacity of T-cells in response to autologous B-lymphoblastoid cell lines was determined using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay. Frequencies of EBV-specific CD4+ T-cells in patients with EBV+ DLBCL (n = 13) were significantly higher than in healthy controls (HCs) (n = 16) after both ex vivo and in vitro stimulation. Frequencies of EBV-specific CD8+ T-cells in patients with EBV+ DLBCL tended to be higher than in HCs after in vitro stimulation. Patients with EBV+ DLBCL also showed increased immunoglobulin G (IgG) responses to lytic EBV-encoded antigens. Pretreatment plasma EBV-DNA level was significantly higher in patients with EBV+ DLBCL than in patients with EBV- DLBCL or HCs. In conclusion, EBV-specific T-cells showed increased reactivity, accompanied by higher levels of plasma virus DNA in patients with EBV+ DLBCL.

  19. Genetic aberration of PTEN in peripheral T cell lymphoma, not otherwise specified%非特指外周T细胞淋巴瘤中PTEN的改变

    Institute of Scientific and Technical Information of China (English)

    朱文娟; 张建中

    2012-01-01

    目的 观察非特指外周T细胞淋巴瘤(peripheral T cell lymphoma,not otherwise specified,PTCL-NOS)中抑癌基因(phosphatase and tensin homolog deleted on chromosome ten,PTEN)的改变情况,探讨其与肿瘤生物学行为的关系,为阐明PTCL-NOS的发生、发展机制提供科学依据.方法应用间期双色荧光原位杂交(fluorescence in situ hybridization,FISH)技术检测36例PTCL-NOS石蜡包埋组织中PTEN基因的改变情况,分析其改变与各临床参数的关系.结果 36例PTCL-NOS中8例出现PTEN杂合性缺失(loss of heterozygosity,LOH);Kaplan-Meier生存分析显示该基因异常组较正常组生存期明显缩短(P0.05).结论 PTCL-NOS存在的抑癌基因PTEN杂合性缺失,在PTCL-NOS发生、发展中可能起重要作用,是评估该肿瘤预后的重要指标.%Purpose To investigate the genetic changes of tumor suppressor gene PTEN in PTCL-NOS, and to explore its relationship with the development of PTCL-NOS and other clinicopathological parameters. Methods Thirty-six cases of PTCL-NOS were studied by fluorescence in-situ hybridization ( FISH ) using interphase dual-colour probes. The probes were generated from BAC clones RP11 - 380G5 corresponding to PTEN gene. Correlation of the genetic changes with patients prognosis and other clinical parameters was analyzed. Results Loss of heterozygosity ( LOH ) of PTEN presented in 8/36 cases; Kaplan-Meier survival analysis indicated there was a trend that the group with PTEN gene change had a poorer prognosis than the group without PTEN gene change ( P 0. 05 ). Conclusion A significant percentage of PTCL-NOS carry the genetic alteration of PTEN that may play an important role in the pathogenesis of PTCL-NOS and the e-valuation of the patient' s prognosis.

  20. Processos linfoproliferativos da pele: parte 2 - linfomas cutâneos de células T e de células NK Processos linfoproliferativos da pele: part 2 - cutaneous T-cell and NK-cell lymphomas

    Directory of Open Access Journals (Sweden)

    José Antonio Sanches Jr

    2006-02-01

    currently classified and subdivided based on their clinical behavior, according to a consensus reached between the World Health Organization and the European Organization for Research and Treatment of Cancer. The cutaneous NKT/cell lymphomas of indolent clinical behavior comprise the classical mycosis fungoides, folliculotropic mycosis fungoides, pagetoid reticulosis, granulomatous slack skin, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, subcutaneous panniculitis-like T-cell lymphoma and primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma. The aggressive clinical behavior cutaneous NKT/cell lymphomas include Sézary syndrome, extranodal NK/T-cell lymphoma, nasal type, primary cutaneous aggressive epidermotropic CD8+T-cell lymphoma, cutaneous gamma-delta T-cell lymphoma and primary cutaneous peripheral T-cell lymphoma, unspecified. The adult T-cell leukemia lymphoma and CD4+ CD56+ hematodermic neoplasm are considered systemic lymphomas but are addressed in this article for their initial cutaneous manifestations in a significant number of patients. The diagnosis of these processes is based on histological examination complemented by phenotypic analysis of neoplastic cells, which is essential for classification. The recommended staging is based on type and extension of cutaneous involvement, clinical conditions and histological examination of lymph nodes and organs. Hematological assessment is fundamental to characterize Sézary syndrome. The recommended therapies include exclusively cutaneous treatment, biological response modifiers and systemic chemotherapy.

  1. Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kakinuma, Shizuko, E-mail: skakinum@nirs.go.jp [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Amasaki, Yoshiko; Takada, Mayumi; Yamauchi, Kazumi; Sudo, Satomi; Shang, Yi [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Doi, Kazutaka; Yoshinaga, Shinji [Regulatory Sciences Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shimada, Yoshiya [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2012-09-01

    Ionizing radiation is a well-known carcinogen, but its potency may be influenced by other environmental carcinogens, which is of practical importance in the assessment of risk. Data are scarce, however, on the combined effect of radiation with other environmental carcinogens and the underlying mechanisms involved. We studied the mode and mechanism of the carcinogenic effect of radiation in combination with N-ethyl-N-nitrosourea (ENU) using doses approximately equal to the corresponding thresholds. B6C3F1 mice exposed to fractionated X-irradiation (Kaplan's method) followed by ENU developed T-cell lymphomas in a dose-dependent manner. Radiation doses above an apparent threshold acted synergistically with ENU to promote lymphoma development, whereas radiation doses below that threshold antagonized lymphoma development. Ikaros, which regulates the commitment and differentiation of lymphoid lineage cells, is a critical tumor suppressor gene frequently altered in both human and mouse lymphomas and shows distinct mutation spectra between X-ray- and ENU-induced lymphomas. In the synergistically induced lymphomas, we observed a low frequency of LOH and an inordinate increase of Ikaros base substitutions characteristic of ENU-indcued point mutations, G:C to A:T at non-CpG, A:T to G:C, G:C to T:A and A:T to T:A. This suggests that radiation doses above an apparent threshold activate the ENU mutagenic pathway. This is the first report on the carcinogenic mechanism elicited by combined exposure to carcinogens below and above threshold doses based on the mutation spectrum of the causative gene. These findings constitute a basis for assessing human cancer risk following exposure to multiple carcinogens.

  2. A stable aberrant immunophenotype characterizes nearly all cases of cutaneous T-cell lymphoma in blood and can be used to monitor response to therapy

    Directory of Open Access Journals (Sweden)

    Duvic Madeleine

    2002-12-01

    Full Text Available Abstract Background Abnormal variations in the expression level of some commonly expressed T-cell antigens are a feature of many T-cell malignancies. Methods We sought to assess the frequency of such abnormal antigen expression by flow cytometry in peripheral blood (PB samples from patients with mycosis fungoides (MF and Sézary syndrome (SS. We correlated presence of morphologically identifiable tumor cells on PB smear with the frequency of abnormalities in the level of expression of CD3, CD4, CD7, CD8 and CD26. We also examined the degree of stability of these abnormal findings in tumor cells over the course of disease. The flow cytometric findings in 100 PB samples from 44 patients, including 38 who had multiple sequential PB samples (2–8 samples each, were assessed. Results Abnormalities were seen in the expression level of one or more T-cell markers in 41 cases (93% including CD3 in 34% of patients, CD4 in 54%, CD26 in 86% and CD 45 in 40% (10 cases tested. In all but 2 cases, the abnormal T-cell immunophenotype remained similar over the course of treatment and correlated with the relative numbers of tumor cells counted on PB smear. Conclusions Using a standard T-cell panel, stable phenotypically aberrant T-cell populations representing the tumor are detected in the vast majority of involved PB samples in MF/SS and can be used to monitor response to therapy.

  3. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

    Science.gov (United States)

    Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

    1999-12-01

    Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

  4. Sint1, a common integration site in SL3-3-induced T-cell lymphomas, harbors a putative proto-oncogene with homology to the septin gene family

    DEFF Research Database (Denmark)

    Sørensen, A B; Lund, Anders Henrik; Ethelberg, S;

    2000-01-01

    The murine retrovirus SL3-3 is a potent inducer of T-cell lymphomas when inoculated into susceptible newborn mice. Previously, DNAs from twenty SL3-3-induced tumors were screened by PCR for provirus integration sites. Two out of 20 tumors demonstrated clonal provirus insertion into a common region....... This region has now been isolated and characterized. The region, named SL3-3 integration site 1 (Sint1), maps to the distal end of mouse chromosome 11, corresponding to human chromosome 17q25, and may be identical to a mouse mammary tumor virus integration site in a T-cell lymphoma, Pad3. Two overlapping...... genomic lambda clones spanning about 35 kb were isolated and used as a starting point for a search for genes in the neighborhood of the virus integration sites. A genomic fragment was used as a hybridization probe to isolate a 3-kb cDNA clone, the expression of which was upregulated in one of two tumors...

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

    Science.gov (United States)

    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

  6. Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells.

    Science.gov (United States)

    Pinz, K; Liu, H; Golightly, M; Jares, A; Lan, F; Zieve, G W; Hagag, N; Schuster, M; Firor, A E; Jiang, X; Ma, Y

    2016-03-01

    Peripheral T-cell lymphomas (PTCLs) are aggressive lymphomas with no effective upfront standard treatment and ineffective options in relapsed disease, resulting in poorer clinical outcomes as compared with B-cell lymphomas. The adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) is a promising new approach for treatment of hematological malignancies. However, preclinical reports of targeting T-cell lymphoma with CARs are almost non-existent. Here we have designed a CAR, CD4CAR, which redirects the antigen specificity of CD8+ cytotoxic T cells to CD4-expressing cells. CD4CAR T cells derived from human peripheral blood mononuclear cells and cord blood effectively redirected T-cell specificity against CD4+ cells in vitro. CD4CAR T cells efficiently eliminated a CD4+ leukemic cell line and primary CD4+ PTCL patient samples in co-culture assays. Notably, CD4CAR T cells maintained a central memory stem cell-like phenotype (CD8+CD45RO+CD62L+) under standard culture conditions. Furthermore, in aggressive orthotropic T-cell lymphoma models, CD4CAR T cells efficiently suppressed the growth of lymphoma cells while also significantly prolonging mouse survival. Combined, these studies demonstrate that CD4CAR-expressing CD8+ T cells are efficacious in ablating malignant CD4+ populations, with potential use as a bridge to transplant or stand-alone therapy for the treatment of PTCLs.

  7. Among diffuse large B-cell lymphomas, T-cell-rich/histiocyte-rich BCL and CD30+anaplastic B-cell subtypes exhibit distinct clinical features

    NARCIS (Netherlands)

    Maes, B; Anastasopoulou, A; Kluin-Nelemans, JC; Teodorovic, [No Value; Achten, R; Carbone, A; De Wolf-Peeters, C

    2001-01-01

    Background: The EORTC clinical trial 20901, activated in 1990, was designed to treat non-Hodgkin's lymphomas (NHL) of intermediate/high-grade malignancy according to the Working Formulation. Established in 1994, the R.E.A.L. Classification on NHL has now replaced all former classifications. Patients

  8. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

    DEFF Research Database (Denmark)

    Sibbesen, Nina A; Kopp, Katharina L; Litvinov, Ivan V;

    2015-01-01

    of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence...

  9. Lymphoma of the eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik H; Heegaard, Steffen

    2017-01-01

    Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B-cell lymph......Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B...... chemotherapy with or without adjuvant treatment is the treatment of choice for high-grade or disseminated lymphomas. The majority of subtypes, especially low-grade subtypes, have a good prognosis with few recurrences or progression. Some subtypes, including mycosis fungoides, have a poorer prognosis...

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

    Science.gov (United States)

    2016-12-15

    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

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

    Science.gov (United States)

    2017-01-26

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

  12. Malignant lymphoma of the conjunctiva

    DEFF Research Database (Denmark)

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

    2015-01-01

    Conjunctival lymphomas constitute 25% of all ocular adnexal lymphomas. The majority are B-cell non-Hodgkin lymphomas (NHLs) (98%), whereas conjunctival T-cell NHLs are rare (2%). The most frequent subtype of conjunctival B-cell lymphoma is extranodal marginal zone lymphoma (EMZL; 81%), followed b...

  13. Inhibition of ALK enzymatic activity in T-cell lymphoma cells induces apoptosis and suppresses proliferation and STAT3 phosphorylation independently of Jak3

    DEFF Research Database (Denmark)

    Marzec, Michal; Kasprzycka, Monika; Ptasznik, Andrzej;

    2005-01-01

    Aberrant expression of the ALK tyrosine kinase as a chimeric protein with nucleophosmin (NPM) and other partners plays a key role in malignant cell transformation of T-lymphocytes and other cells. Here we report that two small-molecule, structurally related, quinazoline-type compounds, WHI-131...... and WHI-154, directly inhibit enzymatic activity of NPM/ALK as demonstrated by in vitro kinase assays using a synthetic tyrosine-rich oligopeptide and the kinase itself as the substrates. The inhibition of NPM/ALK activity resulted in malignant T cells in suppression of their growth, induction...... of apoptosis and inhibition of tyrosine phosphorylation of STAT3, the key effector of the NPM/ALK-induced oncogenesis. We also show that the STAT3 tyrosine phosphorylation is mediated in the malignant T cells by NPM/ALK independently of Jak3 kinase as evidenced by the presence of STAT3 phosphorylation...

  14. Toxoplasma gondii myelitis in a patient with adult T-cell leukemia-lymphoma Mielite por Toxoplasma gondii em um paciente com leucemia-linfoma de células T do adulto

    Directory of Open Access Journals (Sweden)

    ELVES MACIEL

    2000-12-01

    Full Text Available Adult T cell leukemia-lymphoma (ATL caused by HTLV-I may be associated with severe immunosupression and several opportunistic infections. Toxoplasmic encephalitis is a common central nervous system opportunistic infection in severely immunosupressed patients, however spinal cord involvement by this parasite is rare. In this paper, we report a case of toxoplasmic myelitis in a patient with ATL.Leucemia de células T do adulto (ATL, causada pelo HTLV-I, pode estar associada com imunossupressão severa e muitas infecções oportunistas. Encefalite por toxoplasmose é uma infecção oportunista do sistema nervoso central em pacientes imunossuprimidos, no entanto o envolvimento da medula espinal por este parasita é raro. Neste artigo, apresentamos um caso de mielite em um paciente com ATL.

  15. SMILE方案治疗复发难治NK/T细胞淋巴瘤的初步临床报告%Preliminary outcomes of patients with relapsed or refractory NK/T-cell lymphoma treated by SMILE regimen

    Institute of Scientific and Technical Information of China (English)

    周颖; 蔡清清; 林旭滨; 高岩; 卜庆; 王潇潇; 黄慧强

    2009-01-01

    目的 探索SMILE方案治疗NK/T细胞淋巴瘤的疗效和不良反应.方法 2006年11月至2008年2月,5例初治和5例复发NK/T细胞淋巴瘤患者接受SMILE方案(甲氨蝶呤、异环磷酰胺、左旋门冬酰胺酶、依托泊苷等)化疗.1例患者进一步接受了自体外周血造血干细胞支持下的超大剂量化疗,2例患者进一步接受局部放疗.结果 10例患者中有8例可以评价疗效,总有效率50%(4/8),无完全缓解.其中初治和复发患者有效率均为50%.主要不良反应为骨髓抑制及氨基转移酶升高,其中Ⅲ~Ⅳ度粒细胞减少占65%,发热性粒细胞减少占25%,Ⅲ度氨基转移酶升高占10%,其他不良反应少见,无治疗相关死亡.26.1%患者由于严重的不良反应中止治疗.结论 SMILE治疗复发耐药的NK/T细胞淋巴瘤有一定疗效,但不良反应明显,目前尚不能作为复发难治NK/T细胞淋巴瘤的标准一线方案.%Objective To evaluate the efficacy and toxicity of SMILE regimen for NK/T-cell lymphoma. Methods From November 2006 to February 2008, 5 patients with relapsed and 5 with first treatment NK/T-cell lymphoma were involved in this study. These patients were treated with SMILE regimen including methotrexate, isofosfamide, L-asparaginase and etoposide.1 patient were treated with autolognus hematopoietic stem cell transplantation (AHSCT), and 2 patients received local regional radiation following SMILE. Results Among 10 patients, 8 were eligible to response evaluation. The overall response rate for whole group was 50 %(4/8) without complete remission. The overall response rate for both previously untreated and relapsed patients were 50 %(2/4). Major toxicity were bone marrow supression and transient transaminase elevation, the incidence of grade Ⅲ -Ⅳ neutroponia was 65 %, and febrile neutropenia was 25 %, Grade Ⅲ transaminase elevation was 10 %. Other toxicities were mild, no treatment-related mortality occurred. 26.1% cycles discontinued due to

  16. 13-methyltetradecanoic acid exhibits anti-tumor activity on T-cell lymphomas in vitro and in vivo by down-regulating p-AKT and activating caspase-3.

    Directory of Open Access Journals (Sweden)

    Qingqing Cai

    Full Text Available 13-Methyltetradecanoic acid (13-MTD, a saturated branched-chain fatty acid purified from soy fermentation products, induces apoptosis in human cancer cells. We investigated the inhibitory effects and mechanism of action of 13-MTD on T-cell non-Hodgkin's lymphoma (T-NHL cell lines both in vitro and in vivo. Growth inhibition in response to 13-MTD was evaluated by the cell counting kit-8 (CCK-8 assay in three T-NHL cell lines (Jurkat, Hut78, EL4 cells. Flow cytometry analyses were used to monitor the cell cycle and apoptosis. Proteins involved in 13-MTD-induced apoptosis were examined in Jurkat cells by western blotting. We found that 13-MTD inhibited proliferation and induced the apoptosis of T-NHL cell lines. 13-MTD treatment also induced a concentration-dependent arrest of Jurkat cells in the G1-phase. During 13-MTD-induced apoptosis in Jurkat cells, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP, a caspase enzymolysis product were detected after incubation for 2 h, and increased after extending the incubation time. However, there was no change in the expression of Bcl-2 or c-myc proteins. The appearance of apoptotic Jurkat cells was accompanied by the inhibition of AKT and nuclear factor-kappa B (NF-κB phosphorylation. In addition, 13-MTD could also effectively inhibit the growth of T-NHL tumors in vivo in a xenograft model. The tumor inhibition rate in the experimental group was 40%. These data indicate that 13-MTD inhibits proliferation and induces apoptosis through the down-regulation of AKT phosphorylation followed by caspase activation, which may provide a new approach for treating T-cell lymphomas.

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

    Science.gov (United States)

    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

  18. T-Cell Project: an international, longitudinal, observational study of patients with aggressive peripheral T-cell lymphoma Projeto de célula-T: estudo internacional, longitudinal de pacientes com linfoma de célula-T periférica agressivo

    Directory of Open Access Journals (Sweden)

    Massimo Federico

    2009-08-01

    Full Text Available Peripheral T-cell lymphomas (PTCLs comprise a heterogeneous group of neoplasms that are derived from post-thymic lymphoid cells at different stages of differentiation and with different morphological patterns, phenotypes, and clinical presentations. PTCLs are highly diverse, reflecting the diverse cells from which they can originate and are currently sub-classified using World Health Organization (WHO 2008 criteria. Peripheral T-Cell Lymphomas account for 5%-10% of all lymphoproliferative disorders in the Western hemisphere, with an overall incidence of 0.5-2 per 100,000 individuals per year, and have a striking epidemiological distribution, with higher incidence in Asia. The clinical features of PTCL are extremely heterogeneous. PTCLs express even more clinical diversity than B-cell non-Hodgkin's lymphomas, and there is a close, though not absolute, relationship between some unusual clinical features and certain histological subtypes.Linfomas T periféricos (PTCLs compreendem um grupo heterogêneo de neoplasias que derivam das células linfoides pós-tímicas nos diversos estágios de maturação, com diversos padrões histológicos, fenotípicos, e clínicos. PTCLs são muito diversos entre si e refletem diversas células das quais foram originadas e são atualmente subclassificadas, usando-se a classificação da Organização Mundial da Saúde (OMS 2008, apresentada neste texto na tabela 1. PTCLs compreendem 5%-10% de todas as doenças linfoproliferativas no mundo ocidental, com uma incidência global de 0.5 a 2 a cada 100.000 pessoas por ano e têm uma distribuição epidemiológica diversa com maior incidência na Ásia. Os achados clínicos dos PTCLs são muito heterogêneos. PTCLs expressam muito maior variação de apresentações clínicas do que os linfomas B, e há uma íntima, mas não absoluta, relação entre algum achado clínico não usual e certos subtipos histológicos. O autor faz aqui uma revisão do assunto altamente

  19. Utility of baseline, interim and end-of-treatment 18F-FDG PET/CT in extranodal natural killer/T-cell lymphoma patients treated with L-asparaginase/pegaspargase

    Science.gov (United States)

    Chang, Yu; Fu, Xiaorui; Sun, Zhenchang; Xie, Xinli; Wang, Ruihua; Li, Zhaoming; Zhang, Xudong; Sheng, Guangyao; Zhang, Mingzhi

    2017-01-01

    Positron emission tomography-computed tomography (PET/CT) is widely used for initial staging and monitoring treatment responses in Hodgkin and diffuse large B-cell lymphoma. However, its prognostic value in extranodal natural killer (NK)/T-cell lymphoma (ENKL) remains unclear. Here, we conducted a retrospective study to determine the impact of PET/CT in ENKL. Fifty-two patients newly diagnosed with ENKL were enrolled. Baseline maximum standardized uptake values (SUVmax), whole-body metabolic tumor volume (WBMTV) and whole-body total lesion glycolysis (WBTLG) were recorded. Additionally, interim PET/CT (I-PET) and end-of-treatment PET/CT (E-PET) results were scored using a 5-point scale. Patients were divided into groups using baseline parameter cut-off values; significant differences were found in overall survival (OS) and progression-free survival (PFS) between the high and low WBMTV and WBTLG groups and in OS between the two SUVmax groups. Positive I-PET and E-PET results predicted inferior PFS and OS. A multivariate analysis showed that baseline WBTLG, I-PET and E-PET results were associated with PFS and OS, and baseline SUVmax was an independent predictor of OS. Thus, baseline WBTLG, I-PET and E-PET results are good predictors of PFS and OS in ENKL patients who received L-asparaginase/pegaspargase in their first-line treatment, and baseline SUVmax is a valuable tool for assessing OS. PMID:28117395

  20. Clinical reversible myelopathy in T-cell lymphoblastic lymphoma treated with nelarabine and radiotherapy: report of a case and review of literature of an increasing complication.

    Science.gov (United States)

    Tisi, Maria Chiara; Ausoni, Giuseppe; Vita, Maria Gabriella; Tartaglione, Tommaso; Balducci, Mario; Laurenti, Luca; Chiusolo, Patrizia; Hohaus, Stefan; Sica, Simona

    2015-01-01

    Eleven cases of neurological defects in T-ALL patients treated with nelarabine have been described in the last 4 years, seven of these after stem cell transplantation (SCT) for T Lymphoblastic Lymphoma (T-LBL). Most of these patients had an unfavorable outcome or irreversible neurological damage. We now report the case of a 41-year-old woman suffering from T-LBL who presented with severe, but reversible myelopathy after receiving nelarabine-based treatment and mediastinal radiotherapy, and we provide a review of the literature on the topic.

  1. ClinicaI Reversible Myelopathy in T-Cell Lymphoblastic Lymphoma Treated with Nelarabine and Radiotherapy: Report of a Case and Review of Literature of an Increasing Complication

    Directory of Open Access Journals (Sweden)

    Maria Chiara Tisi

    2015-02-01

    Full Text Available To date, eleven cases of irreversible neurological defects in T- ALL patients treated with nelarabine have been described in the last 4 years, seven of these after stem cell transplantation (SCT for T Lymphoblastic Lymphoma (T-LBL. Most of patients had an unfavorable outcome or irreversible damage. We report the case of a 41-year-old woman suffering from T-LBL who presented severe but reversible myelopathy after nelarabine based treatment and mediastinum radiotherapy, and we perform a review of literature.

  2. Non Hodgkin T cell lymphoma: an atypical clinical presentation Linfoma não Hodgkin de células T citotóxico: uma apresentação clínica atípica

    Directory of Open Access Journals (Sweden)

    Paula Maio

    2013-04-01

    Full Text Available Cytotoxic lymphomas comprise a spectrum of peripheral T-cell lymphomas that can have a initial or late cutaneous presentation. We describe a 46-year-old man from Cape Verde, with a dermatosis involving his face and trunk, consisting of monomorphic papules with a smooth surface and both motor and sensory polyneuropathy.The hypothesis of leprosy was supported by the clinical and initial hystopathological findings and the patient was referred to our hospital with suspected Hansen's disease. In the new skin and lymph node biopsies a lymphocyte population was identified whose immunohystochemistry study allowed the diagnosis of T-cell lymphoma with expression of cytotoxic markers. The patient was started on chemotherapy with initial remission of the skin lesions but, subsequently, progression of systemic disease.Os linfomas citotóxicos compreendem um espectro de linfomas de células T periféricos e linfomas Natural Killer que podem ter expressão cutânea primária ou secundária. Descrevemos o caso de um homem com 46 anos de idade, natural de Cabo Verde,com dermatose envolvendo a face e tronco constituída por pápulas monomorfas superfície lisa e polineuropatia sensitivo motora.A hipótese de Hanseníase foi colocada suportada por achados histopatológicos sugestivos sendo o doente referenciado à consulta de Doença de Hansen do nosso hospital. Em biopsia de pele e de gânglio identificou-se proliferação linfocitária cujo estudo imunohistoquímico permitiu o diagnóstico de linfoma T com expressão de marcadores citotóxicos. Iniciou quimioterapia verificando-se inicialmente remissão parcial das lesões cutâneas mas posteriormente a progressão da doença sistémica.

  3. 结外NK/T细胞淋巴瘤,鼻型的诊断与治疗进展%Diagnosis and treatment of extranodal NK/T-cell lymphoma, nasal type

    Institute of Scientific and Technical Information of China (English)

    冯帆; 李志铭

    2016-01-01

    Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) is an uncommon subtype of non-Hodgkin's lymphoma, which is aggressive and has poor prognosis. ENKL occurs predominantly in the nasal cavity and less frequently in the skin and in the gastrointestinal tract. The pathology of this disease is characterized by vascular invasion and destruction. ENKL is strongly associated with the Epstein–Barr virus, which aids in the diagnosis of ENKL. The characteristic markers on the surface of an NK/T cell and the spe-cific genetic variations are also useful in the diagnosis. At present, the treatment of ENKL is still under discussion. Although radiothera-py combined with chemotherapy on patients with early-stage ENKL and L-ASP-based chemotherapy and hematopoietic stem cell trans-plant on patients with advance-stage ENKL have achieved favorable effects, further studies are still necessary to develop the principles and methods of a standardized treatment.%结外NK/T细胞淋巴瘤,鼻型(extranodal natural killer/T-cell lymphoma,nasal type,ENKL)是非霍奇金淋巴瘤(non-hodgkin lymphoma,NHL)的一种少见亚型,其侵袭性强且预后较差。ENKL主要发生于鼻腔,其次是皮肤、胃肠道等。该病以血管的侵犯和组织破坏为主要病理学表现。ENKL与EBV的感染密切相关,EBV水平对其辅助诊断有重要的意义。NK/T细胞表面的特征性标志物和特异性遗传学改变也可以帮助诊断该病。目前对于ENKL的治疗尚在讨论中,虽然对早期患者采用放疗±化疗联合治疗,以及对中晚期患者采用以左旋门冬酰胺酶为基础的化疗和造血干细胞移植得到了一定疗效,但仍需进一步的研究探索以形成规范的治疗原则。

  4. Hormone and thalidomide may be effective in the treatment of adult mediastinal T-cell lymphoblastic lymphoma: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Hongyang Wu

    2013-06-01

    Full Text Available A case of a 53-year-old man with adult T-lymphoblastic lymphoma (T-LBL in mediastinum who survived more than 33 months in our hospital was reported. LBL was more common in schoolage and teenage boys than adults. The reported patient manifested progressive dyspnea. Chest CT scanning showed a huge irregular soft tissue shadow in anterior mediastinum which extended into posterior mediastinum and left chest wall. The tumor was 20 cm×15 cm×15 cm in size in left upper mediastinum and its boundaries with pericardium and left lower lung were unclear. The diagnosis of T-lymphoblastic lymphoma was confirmed by immunohistochemical staining. After surgery, he received five chemotherapy courses including Gem, CTX and VCR and biological therapies with IL-2 and IFN-α2b. About 16 months later, he complained of diplopia in the left eye without any evidence of recurrence. Blood examination which showed leukemoid reaction twice returned to normal after dehydration, hormone and thalidomide treatments. Finally, his condition became worse and died of pulmonary infection 33 months after first medical service. In summary, T-LBL is a rare disease which may result in poor prognosis even if the patient has received immediate chemotherapy. Hormone and thalidomide can be applied to treat adult T-LBL.

  5. Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens.

    Science.gov (United States)

    Nakano, Daisuke; Ishitsuka, Kenji; Matsuda, Narumi; Kouguchi, Ai; Tsuchihashi, Ryota; Okawa, Masafumi; Okabe, Hikaru; Tamura, Kazuo; Kinjo, Junei

    2017-01-01

    During the course of our studies towards the identification of promising chemotherapeutic candidates from plants against two human T-cell lymphotropic virus type I-infected T-cell lines (MT-1 and MT-2), we screened 17 extracts from 9 rutaceous plants against MT-1 and MT-2 cells. The extracts from the aerial parts and roots of Boenninghausenia japonica, as well as the leaves and roots of Ruta graveolens showed potent antiproliferative effects. After activity-guided fractionation, we isolated 44 compounds from two rutaceous plants, including three new compounds (1-3), which were classified into 26 coumarin analogs (13 coumarins, 8 furanocoumarins, 4 dihydrofuranocoumarins and one dihydropyranocoumarin), 15 alkaloid analogs (7 quinolone alkaloids, 4 acridone alkaloids, 3 furanoquinoline alkaloids and one tetrahydroacridone alkaloid) and 3 flavonoid glycosides. Structure-activity relationship studies were also evaluated. The coumarin compounds (2, 3 and 7-9) bearing a 3-dimethylallyl moiety showed potent activity. Similarly, of all the furanocoumarins evaluated in the current study, compound 17 bearing a 3-dimethylallyl group also showed potent activity. A dihydrofuranocoumarin (27) bearing a 3-dimethylallyl moiety showed the most potent activity. Following 27, compound 28 showed potent activity. These results therefore suggested that the presence of a 3-dimethylallyl moiety was important to the antiproliferative activity of these coumarin analogs.

  6. Reactivation of Latent Infection of Human Herpesvirus 8 in BC-3 Cells from Primary Effusion Lymphoma by Recombinant CytokinesSimilar to that Produced by HIV-1-infected T Cells

    Institute of Scientific and Technical Information of China (English)

    卢春; 曾怡; 黄丽

    2003-01-01

    Objective:To study and confirm that recombinant cytokines similar to those produced by HIV-1 infected T cells induced lytic cycle replication of human pervirus 8(HHV-8) in BC-3 cells,another cell line from primary effusion lymphoma(PEL).Methods:The persistent stimulation of BC-3 was conducted by several cytokines known to be produced by HIV-1-infected T cells and important in grouth and proliferation of Kaposi's sarcoma(KS) cells in vitro,such as the inter feron-γ(IFN-γ),the hepatocyte grouth factor /scatter factor (HGF/SF),the Oncostain M(OSM),and the tumor necrosis factor-α(TNF-α)which is not produced by HIV-1-infeted T cells.Treated and antrented BC-3 cells were collected at the 3rd and 7th day of persistent stimulation,respeclively.Immunohistochemical(IHC) staining. Northern blot,quantitative PCR(real-time PCR) and electron microscopy(EM) were carried out to detect the expression of immumogenic protein ORF59,messenger RNA(mRNA) of minor capsid protein ORF26,and the presence of viral particles of HHV-8 from treated and untreated BC-3 cells.Results:It showed that IFN-γ,HGF/SF/OSM,and TNF-α were found to induce an increase in mRNA expression of ORF26 when added individually to BC-3 cells.Particularly,ORF26 expression stimulated with IFN-γ and TNF-α respectively,increased 6.1 and 2.5-fold(from,real-time PCR results) at the 7th day when compared with untreated BC-3 cells.Meanwhile ,about 20% of IFN-γ stimulated BC-3 cells expressed ORF59 at the 7th day as compared with 1.5% of untreated BC-3 cells when IHC staining was employed.In addition,viral particles of HHV-8 were readily idelified in BC-3 cells stimulated with IFN-γ at the 7th day with EM analysis.Conclusion:TNF-α and recombinant cytokines being similar to those produced by HIV-1 infected T Cells could really induce HHV-8 lytic cycle replication in BC-3 cells,another cell line of PEL.

  7. 原发鼻腔NK/T细胞淋巴瘤影响预后的因素分析%Prognostic factors of nasal NK/T-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    马芹; 张会来; 刘霞; 周世勇; 钱正子; 翟琼莉; 付凯; 王华庆

    2013-01-01

    目的 分析鼻腔NK/T细胞淋巴瘤患者的临床特征及血液学指标,探讨影响预后的因素.方法 回顾性分析天津医科大学附属肿瘤医院80例鼻腔NK/T细胞淋巴瘤患者的临床特征及血液学指标,采用Kaplan-Meier法进行生存分析,Cox模型进行多因素分析.结果 80例患者经过治疗后,33例患者达到完全缓解,5年总生存率和无进展生存率分别为52.5%和32.5%.单因素分析显示,美国东部肿瘤协作组评分(Eastern Cooperative Oncology Group performance status,ECOGPS)、Ann Arbor分期、腔外受累、国际预后指数(international prognostic index,IPI)评分、首次治疗是否达完全缓解、治疗模式(单纯化疗与放化疗联合)、血清乳酸脱氢酶(LDH)和β2-微球蛋白和球蛋白水平、外周血白细胞计数与鼻腔NK/T细胞淋巴瘤患者的预后相关(P值均<0.05).多因素分析显示,首次治疗是否达完全缓解、LDH、腔外受累是影响鼻腔NK/T细胞淋巴瘤预后的独立危险因素(x2值分别为17.109、15.695和13.503,P值均<0.01).结论 首次治疗是否达完全缓解、LDH、腔外受累可作为鼻腔NK/T细胞淋巴瘤临床预后的参考指标.%Objective To investigate the prognostic predictors of nasal NK/T cell lymphoma.Methods Records of 80 patients with nasal NK/T cell lymphoma were analyzed retrospectively.The correlation between clinical and haematological factors and prognosis was analyzed with univariate and multivariate analysis.Results After treatment,33 of 80 patients achieved complete response,the 5-year overall survival and progression free survival were 52.5% and 32.5%,respectively.In univariate analysis,Eastern Cooperative Oncology Group performance status,Ann Arbor stage,local tumor invasion out of the nasal cavity,international prognostic index,complete response rate to the primary treatment,treatment model,lactate dehydrogenase (LDH),β2-microglobulin level,globulin and white blood cell were found to

  8. Apoptosis Induction and Gene Expression Profile Alterations of Cutaneous T-Cell Lymphoma Cells following Their Exposure to Bortezomib and Methotrexate

    Science.gov (United States)

    Kontsioti, Frieda; Konsta, Eugene; Vikentiou, Miriam; Spathis, Aris; Papageorgiou, Sotiris; Vasilatou, Diamantina; Gkontopoulos, Konstantinos; Mpazani, Efthimia; Karakitsos, Petros; Rigopoulos, Dimitrios; Dimitriadis, George

    2017-01-01

    Mycosis fungoides (MF) and its leukemic variant Sézary syndrome (SS) comprise the majority of CTCL, a heterogenous group of non-Hodgkins lymphomas involving the skin. The CTCL’s resistance to chemotherapy and the lack of full understanding of their pathogenesis request further investigation. With the view of a more targeted therapy, we evaluated in vitro the effectiveness of bortezomib and methotrexate, as well as their combination in CTCL cell lines, regarding apoptosis induction. Our data are of clinical value and indicate that the bortezomib/methotrexate combinational therapy has an inferior impact on the apoptosis of CTCL compared to monotherapy, with bortezomib presenting as the most efficient treatment option for SS and methotrexate for MF. Using PCR arrays technology, we also investigated the alterations in the expression profile of genes related to DNA repair pathways in CTCL cell lines after treatment with bortezomib or methotrexate. We found that both agents, but mostly bortezomib, significantly deregulate a large number of genes in SS and MF cell lines, suggesting another pathway through which these agents could induce apoptosis in CTCL. Finally, we show that SS and MF respond differently to treatment, verifying their distinct nature and further emphasizing the need for discrete treatment approaches. PMID:28107479

  9. Primary site and regional lymph node involvement are independent prognostic factors for early-stage extranodal nasal-type natural killer/T cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    ShaoQing Niu; YuJing Zhang; Yong Yang; YiYang Li; Ge Wen; Liang Wang; ZhiMing Li; HanYu Wang; LuLu Zhang; YunFei Xia

    2016-01-01

    Background: Nasal‑type extranodal natural killer/T‑cell lymphoma (ENKTCL) originates primarily in the nasal cavity or extra‑nasal sites within the upper aerodigestive tract. However, it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement. The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early‑stage nasal‑type ENKTCL. Methods: To develop a nomogram, we reviewed the clinical data of 215 consecutively diagnosed patients with early‑stage nasal‑type ENKTCL who were treated in Sun Yat‑sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C‑index) and calibration curve. Results: The 5‑year overall survival (OS) and progression‑free survival (PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra‑nasal ENKTCL (OS: 68.2% vs. 46.0%, P = 0.030; PFS: 53.4% vs. 26.6%, P = 0.010).The 5‑year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage IIE ENKTCL (OS: 66.3% vs. 59.2%, P = 0.003; PFS: 51.4% vs. 40.3%, P = 0.009). Multivariate analysisshowed that age >60 years, ECOG performance status score nasal primary site, and regional lymph node involvement were significantly associated with lower 5‑year OS rate;≥2, elevated lactate dehydrogenase (LDH) level, extra‑age >60 years, elevated LDH level, extra‑nasal primary site, and regional lymph node involvement were significantly associated with lower 5‑year PFS rate. The nomogram included the primary site and regional lymph node involve‑ment based on multivariate analysis. The

  10. Seroprevalence of human T-cell lymphoma/leukemia virus type-1 (HTLV-1 antibodies among blood donors at Enugu, Nigeria

    Directory of Open Access Journals (Sweden)

    Okoye AE

    2015-01-01

    Full Text Available Augustine Ejike Okoye,1 Obike Godswill Ibegbulam,2 Robinson Chukwudi Onoh,3 Ngozi Immaculata Ugwu,1 Chukwudi Simon Anigbo,2 Charles Emeka Nonyelu2 1Department of Haematology and Immunology, Federal Teaching Hospital Abakaliki, Ebonyi State, Nigeria; 2Department of Haematology and Immunology, University of Nigeria Teaching Hospital (UNTH Ituku-Ozalla, Enugu State, Nigeria; 3Department of Obstetrics and Gynaecology, Federal Teaching Hospital Abakaliki, Ebonyi State, Nigeria Background: Human T-cell lymphotrophic/leukemia virus (HTLV-1 is a retrovirus implicated in transfusion-transmitted infection. Objective: The objective of this study was to determine the seroprevalence of HTLV-1 antibodies among blood donors at the University of Nigeria Teaching Hospital, Enugu, Eastern Nigeria. Methods: A cross-sectional study was carried out on consented participants over 4 months. A total of 300 blood donors were recruited consecutively from the blood bank. The serum of the collected 5 mL of blood obtained from each participant was stored at -20°C until required for analysis. The serum samples were then analyzed for antibodies to HTLV-1 using a one-step incubation double-antigen sandwich ELISA (enzyme-linked immunosorbent assay kit. Participants' demographic characteristics and degree of exposure to the risk factors associated with HTLV-1 infection were captured using a questionnaire. Statistical analysis of results was done using SPSS version 17. Results: Of the 300 blood donors, 288 (96% were male, while 12 (4% were female. The average age of the blood donors was 26.85±8.52 years. The age group with the highest representation among the blood donors were those aged between 21 and 25 years. Only 22.3% of the blood donors were above 30 years. None of the 300 screened blood donors tested positive to HTLV-1 antibodies. Hence, the seroprevalence of HTLV-1 infection among blood donors was 0%. Of the blood donors, 5% had history of previous sexually transmitted

  11. Staging and prognosis of epidermotropic cutaneous T- cell lymphoma%第一讲向表皮性皮肤T细胞淋巴瘤的分期和预后

    Institute of Scientific and Technical Information of China (English)

    邱丙森

    2002-01-01

    @@ 向表皮性皮肤T细胞淋巴瘤(epidermotropic cutaneous T-cell lymphomas,ECTCL)系恶性辅助T细胞疾病,常开始于皮肤而后累及骨髓、血中淋巴细胞、淋巴结和内脏器官[1],包括具有独特和重叠临床表现的蕈样肉芽肿(mycosis fungoides,MF)和Sézary综合征(Sézary's syndrome,SS).近应用聚合酶链反应扩增T-细胞受体γ链基因重排,证明MF在早期即示克隆性T细胞成分系统性侵犯[2],SS患者血中恶性T细胞成分明显扩增[3].ECTCL的分期与预后有关.兹阐述ECTCL的分期和预后如下:

  12. GDP (Gemcitabine, Dexamethasone, and Cisplatin) Is Highly Effective and Well-Tolerated for Newly Diagnosed Stage IV and Relapsed/Refractory Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.

    Science.gov (United States)

    Wang, Jing-Jing; Dong, Mei; He, Xiao-Hui; Li, Ye-Xiong; Wang, Wei-Hu; Liu, Peng; Yang, Jian-Liang; Gui, Lin; Zhang, Chang-Gong; Yang, Sheng; Zhou, Sheng-Yu; Shi, Yuan-Kai

    2016-02-01

    This study was conducted to evaluate the effectiveness and tolerance of GDP (gemcitabine, dexamethasone, and cisplatin) regimen in patients with newly diagnosed stage IV and relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKTL).The study enrolled 41 ENKTL patients who received GDP regimen at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2008 and January 2015.The disease status was newly diagnosed stage IV in 15 patients and relapsed/refractory in 26 patients. The median number of cycles of chemotherapy per patient was 6 (range, 2-8 cycles). The overall response rate and complete-remission rate were 83.0% (34/41) and 41.5% (17/41), respectively. After a median follow-up of 16.2 months, 1-year progression-free survival rate and 1-year overall survival rate for the whole cohort were 54.5% and 72.7%. Grade 3 to 4 adverse events included neutropenia (34.1%), thrombocytopenia (19.5%), and anemia (14.6%).Our study has suggested high efficacy and low toxicity profile of GDP regimen in patients with newly diagnosed stage IV and relapsed/refractory ENKTL.

  13. Detecting EB virus to determine curative effect in extranodal natu-ral killer/T-cell lymphoma%结外NK/T细胞淋巴瘤检测EB病毒与疗效关系的研究

    Institute of Scientific and Technical Information of China (English)

    刘文硕; 南飞飞; 贾思思; 李素彩; 张明智; 张蕾

    2015-01-01

    目的:探讨血浆中EB病毒阳性在评价结外NK/T细胞淋巴瘤近期疗效和远期疗效中的临床意义。方法:收集2011年1月至2014年4月郑州大学第一附属医院经病理及免疫组化确诊为结外NK/T细胞淋巴瘤的患者109例,应用qRT-PCR方法检测其血浆中EBV-DNA拷贝数,比较EBV阴性和EBV阳性患者对治疗疗效与预后的差异。结果:109例结外NK/T细胞淋巴瘤患者,53例阳性患者中有34例(64.2%)为晚期(Ⅲ~Ⅳ期),56例阴性患者中22例(39.3%)为晚期(Ⅲ~Ⅳ期),EBV阳性组中伴有B症状33例(62.3%),阴性组患者21例(37.5%),EBV阴性患者与EBV阳性患者在分期及B症状方面均具有统计学意义(P<0.05)。34例(60.7%)EBV阴性结外NK/T细胞淋巴瘤患者达到客观缓解率,显著高于EBV阳性患者的客观缓解率(22例,41.5%)(P<0.05)。EBV阴性组与EBV阳性组相比,其2年无进展生存期更高(P<0.05)。结论:检测结外NK/T细胞淋巴瘤患者血浆中EB病毒对评价其近期疗效及2年无进展生存期具有重要的临床意义。%Objective:To investigate the clinical significance of detecting Epstein Barr virus (EBV) infection in evaluating recent curative and long-term effects in patients with extranodal natural killer (NK)/T-cell lymphoma. Methods:The EBV-DNA copies in the plasma of 109 patients, who were pathologically and immunohistochemically diagnosed with extranodal natural killer/T-cell lymphoma in the First Affiliated Hospital of Zhengzhou University between January 2011 and April 2014, were monitored via quantitative re-al-time polymerase chain reaction. Subsequently, the difference in recent curative and long-term effects between EBV positive and EBV negative patients was compared. Results:Among the 109 patients with extranodal NK/T-cell lymphoma, 34 (64.2%) cases of EBV posi-tive patients were at the advanced stage (Ⅲ~Ⅳ stages), and 22 (39.3%) cases of EBV

  14. Adult T-cell leukemia-lymphoma in a patient with HTLV-I/II associated myelopathy Leucemia - linfoma de células T do adulto em um paciente com mielopatia associada a HTLV-I/II

    Directory of Open Access Journals (Sweden)

    Virgínia Freitas

    1997-06-01

    Full Text Available Chronic myelopathy associated with T-lymphotropic virus type I (HAM has been described as an endemic disease in several areas of the world, meanwhile there are few papers describing the association between HAM and adult T cell leukemia-lymphoma. We report the case of a man that, after four years of progressive spastic paraparesis and neurogenic bladder, developed a clinical picture of a lymphoproliferative disorder characterized by dermal and systemic envolvement, mimicking mycosis fungoides/Sézary syndrome.Apesar da infecção pelo HTLV-I ser endêmica em várias regiões do mundo, poucos são os relatos da associação entre leucemia-linfoma de células T do adulto (ATLL e encefalomieloneuropatia pelo HTLV-I. No presente artigo é descrito um paciente que no curso do comprometimento neurológico pelo HTLV-I desenvolveu quadro de leucemia com infiltração de tecido dérmico semelhante ao encontrado na micose fungóide/síndrome de Sézary.

  15. The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: a consensus statement update from the UK Photopheresis Society.

    Science.gov (United States)

    Alfred, Arun; Taylor, Peter C; Dignan, Fiona; El-Ghariani, Khaled; Griffin, James; Gennery, Andrew R; Bonney, Denise; Das-Gupta, Emma; Lawson, Sarah; Malladi, Ram K; Douglas, Kenneth W; Maher, Tracey; Guest, Julie; Hartlett, Laura; Fisher, Andrew J; Child, Fiona; Scarisbrick, Julia J

    2017-02-21

    Extracorporeal photopheresis (ECP) has been used for over 35 years in the treatment of erythrodermic cutaneous T-cell lymphoma (CTCL) and over 20 years for chronic and acute graft-versus-host disease (GvHD) and solid organ transplant rejection. ECP for CTCL and GvHD is available at specialised centres across the UK. The lack of prospective randomised trials in ECP led to the development of UK Consensus Statements for patient selection, treatment schedules, monitoring protocols and patient assessment criteria for ECP. The recent literature has been reviewed and considered when writing this update. Most notably, the national transition from the UVAR XTS(®) machine to the new CELLEX machine for ECP with dual access and a shorter treatment time has led to relevant changes in these schedules. This consensus statement updates the previous statement from 2007 on the treatment of CTCL and GvHD with ECP using evidence based medicine and best medical practise and includes guidelines for both children and adults.

  16. Clinicopathologic features of intestinal natural killer/T-cell lymphoma%肠道自然杀伤细胞/T细胞淋巴瘤的临床病理分析

    Institute of Scientific and Technical Information of China (English)

    周军; 余波; 何燕; 吴波; 张新华; 周晓军; 石群立

    2013-01-01

    目的 探讨肠道自然杀伤细胞(NK)/T细胞淋巴瘤的临床病理特点、诊断和鉴别诊断.方法 收集14例原发于肠道的NK/T细胞淋巴瘤的临床资料,对其形态学、免疫组织化学标记(EnVision法)情况进行观察分析并随访患者,结合相关文献进行讨论.结果 14例肠道NK/T细胞淋巴瘤男女之比为9∶5,中位年龄45岁.发生部位包括小肠6例、结肠6例、小肠和结肠同时受累2例.临床症状主要表现为腹部占位性病变或腹痛等消化道症状,可伴发热、消瘦等消耗性疾病的共同特点,严重者可并发肠穿孔或急性腹膜炎.组织学示异型的肿瘤细胞弥漫浸润肠壁全层,细胞中等大小或多形,炎性改变背景明显,常伴有围血管破坏和凝固性坏死形成.免疫表型:瘤细胞CD3ε、CD43、CD56、粒酶B、穿孔素均阳性,CD20、CD79α、髓过氧化物酶均阴性,Ki-67呈高表达.原位杂交EB病毒编码的小RNA均为核阳性.8例获得随访(0.5~36个月),其中5例在20个月内死亡.结论 肠道原发的NK/T细胞淋巴瘤是少见的结外NK/T细胞淋巴瘤,恶性度高,但因临床症状不具备特征性易导致误诊.它的正确诊断需结合临床表现和相关病史,依据病理学形态特点及免疫指标综合判断.%Objective To study the clinicopathologic features,diagnosis and differential diagnosis of intestinal natural killer (NK)/T-cell lymphoma.Methods The clinical features,histopathology,immunohistochemical findings and follow-up data of 14 cases of intestinal NK/T-cell lymphoma were retrospectively reviewed.Results The male-to-female ratio was 9∶ 5.The medium age of patients was 45 years.The sites of involvement included small intestine (6 cases),colon (6 cases) or both (2 cases).The main clinical manifestations were an abdominal mass,other gastrointestinal symptoms such as abdominal pain,as well as systemic symptoms such as fever and cachexia.Intestinal perforation complicated by acute

  17. Cholecalciferol in Improving Survival in Patients With Newly Diagnosed Cancer With Vitamin D Insufficiency

    Science.gov (United States)

    2016-12-20

    Aggressive Non-Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Diffuse Large B-Cell Lymphoma; Enteropathy-Associated T-Cell Lymphoma; Hepatosplenic T-Cell Lymphoma; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Nasal Type Extranodal NK/T-Cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Primary Cutaneous Anaplastic Large Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Small Lymphocytic Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma

  18. Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells.

    Science.gov (United States)

    Hiwarkar, Prashant; Qasim, Waseem; Ricciardelli, Ida; Gilmour, Kimberly; Quezada, Sergio; Saudemont, Aurore; Amrolia, Persis; Veys, Paul

    2015-12-24

    Unrelated cord blood transplantation (CBT) without in vivo T-cell depletion is increasingly used to treat high-risk hematologic malignancies. Following T-replete CBT, naïve CB T cells undergo rapid peripheral expansion with memory-effector differentiation. Emerging data suggest that unrelated CBT, particularly in the context of HLA mismatch and a T-replete graft, may reduce leukemic relapse. To study the role of CB T cells in mediating graft-versus-tumor responses and dissect the underlying immune mechanisms for this, we compared the ability of HLA-mismatched CB and adult peripheral blood (PB) T cells to eliminate Epstein-Barr virus (EBV)-driven human B-cell lymphoma in a xenogeneic NOD/SCID/IL2rg(null) mouse model. CB T cells mediated enhanced tumor rejection compared with equal numbers of PB T cells, leading to improved survival in the CB group (P cells that were autologous vs allogeneic to the lymphoma demonstrated that this antitumor effect was mediated by alloreactive rather than EBV-specific T cells. Analysis of tumor-infiltrating lymphocytes demonstrated that CB T cells mediated this enhanced antitumor effect by rapid infiltration of the tumor with CCR7(+)CD8(+) T cells and prompt induction of cytotoxic CD8(+) and CD4(+) T-helper (Th1) T cells in the tumor microenvironment. In contrast, in the PB group, this antilymphoma effect is impaired because of delayed tumoral infiltration of PB T cells and a relative bias toward suppressive Th2 and T-regulatory cells. Our data suggest that, despite being naturally programmed toward tolerance, reconstituting T cells after unrelated T-replete CBT may provide superior Tc1-Th1 antitumor effects against high-risk hematologic malignancies.

  19. Clinicopathologic analysis of five cases of cutaneous intravascular natural killer/T-cell lymphoma%皮肤血管内NK/T细胞淋巴瘤五例分析

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective To improve the understanding of cutaneous intravascular natural killer/T-cell lymphoma (CIVNKTC). Methods Clinical data on five cases of CIVNKTC were collected. The histopathological feature, treatment and prognosis of CIVNKTC were retrospectively analyzed and discussed. Results Of the 5 patients, 1 was male and 4 were female. The age of onset ranged from 38 to 83 years (average, 56.2 years). All the patients presented with multiple plaques and nodules as the primary symptoms. Histopathological examination revealed vasodilatation in the dermis and subcutaneous tissue, as well as atypical lymphoid cells with large hyperchromatic nuclei containing 1-2 small nucleoli in dilated veins. Immunohistochemical studies of tumor cells showed positive staining for CD3ε, cytotoxic proteins (including T cell-restricted intracellular antigen-1, granzyme B and perforin)and Epstein-Barr virus(EBV)-encoded microRNA, but negative staining for cytokeratin, CD20, CD79a, CD4 and CD8. Furthermore, the tumor cells stained positive for CD56 in two patients. Among the 5 patients, only 2 received chemotherapy and the remaining received no treatment. During a 24-month follow-up, 4 patients died, and only 1 survived with the tumor. Conclusion CIVNKTC is a rare extranodal Hodgkin′s lymphoma with distinct histologic manifestations and immunophenotypes, rapid and aggressive clinical course, and poor prognosis.%目的:提高对皮肤血管内NK/T细胞淋巴瘤(CIVNKTC)的认识。方法回顾分析5例CIVNKTC的临床资料、组织病理学、治疗及预后,并进行讨论。结果5例患者中男1例,女4例,发病年龄38~83岁(平均56.2岁),均以多发皮肤斑块或结节为初发表现。组织病理显示:真皮及皮下组织内可见血管扩张,扩张的血管内可见异形淋巴样细胞,细胞核大,可见1~2个小核仁。肿瘤细胞表达CD3ε,细胞毒蛋白(T细胞限制性细胞内抗原-1,粒酶B和穿孔素)和EB病毒编

  20. A comparison of volumetric modulated arc therapy and sliding-window intensity-modulated radiotherapy in the treatment of Stage I-II nasal natural killer/T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xianfeng [Department of Radiation Oncology, Chongqing Cancer Institute, Chongqing (China); Yang, Yong [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Jin, Fu; He, Yanan; Zhong, Mingsong; Luo, Huanli; Qiu, Da; Li, Chao; Yang, Han; He, Guanglei [Department of Radiation Oncology, Chongqing Cancer Institute, Chongqing (China); Wang, Ying, E-mail: zjajf@126.com [Department of Radiation Oncology, Chongqing Cancer Institute, Chongqing (China)

    2016-04-01

    This article is aimed to compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for Stage I-II nasal natural killer/T-cell lymphoma (NNKTL). Ten patients with Stage I-II NNKTL treated with IMRT were replanned with VMAT (2 arcs). The prescribed dose of the planning target volume (PTV) was 50 Gy in 25 fractions. The VMAT plans with the Anisotropic Analytical Algorithm (Version 8.6.15) were based on an Eclipse treatment planning system; the monitor units (MUs) and treatment time (T) were scored to measure the expected treatment efficiency. All the 10 patients under the study were subject to comparisons regarding the quality of target coverage, the efficiency of delivery, and the exposure of normal adjacent organs at risk (OARs). The study shows that VMAT was associated with a better conformal index (CI) and homogeneity index (HI) (both p < 0.05) but slightly higher dose to OARs than IMRT. The MUs with VMAT (650.80 ± 24.59) were fewer than with IMRT (1300.10 ± 57.12) (relative reduction of 49.94%, p = 0.00) when using 2-Gy dose fractions. The treatment time with VMAT (3.20 ± 0.02 minutes) was shorter than with IMRT (7.38 ± 0.18 minutes) (relative reduction of 56.64%, p = 0.00). We found that VMAT and IMRT both provide satisfactory target dosimetric coverage and OARs sparing clinically. Likely to deliver a bit higher dose to OARs, VMAT in comparison with IMRT, is still a better choice for treatment of patients with Stage I-II NNKTL, thanks to better dose distribution, fewer MUs, and shorter delivery time.

  1. Subcutaneous Panniculitis-like T Cell Lymphoma: Report of A Case and Review of the Literature%皮下脂膜炎样T细胞淋巴瘤1例及文献复习

    Institute of Scientific and Technical Information of China (English)

    田华; 王晓彦; 乌日娜

    2011-01-01

    患者男,73岁.左侧臀部及右足底部出现多发性红色皮下结节及斑块,伴发热.曾被误诊为"血管炎"及"结节性脂膜炎".皮损组织病理示:肿瘤浸润皮下脂肪组织,真皮深层及皮下脂肪层小叶间隔及小叶内大量淋巴细胞及组织细胞浸润,呈团块状,见散在异型淋巴细胞.免疫组化示:CD3(+),CD45RO(+),CD30(+),CD8(+),CD20(-)和CD4(-).患者于化疗半月后因继发严重肺部感染而死亡.诊断:皮下脂膜炎样T细胞淋巴瘤.本文对本病进行相关的文献复习.%This case reported is a 73-year-old male, who had presented with multiple erythematous plaques on left buttock and right foot with fever.This patient has been misdiagnosed as vasculitis and nodular panniculitis.The histopathologic findings showed that both deep dermis and subcutaneous fat was infiltrated with lots of lymphocytes and histiocytes, in which there are interspersed atypical lymphocytes.Immunohistochemical studies showed CD3 ( + ), CD45RO ( + ), CD30 ( + ), CD8 ( + ), CD20 ( - ) and CD4 ( - ).Unfortunately,this patient died from serious lung infection after combined chemotherapy.Diagnose: Subcutaneous panniculitis-like T cell lymphoma (SPTCL).Furthermore, literatures about SPTCL were also reviewed.

  2. A Case of Multiple Extranodal NK/T-cell Lymphoma,Nasal Type%多发性结外鼻型NK/T细胞淋巴瘤1例

    Institute of Scientific and Technical Information of China (English)

    孟慧敏; 王琳; 刘宏杰; 郭在培

    2011-01-01

    患者男,60岁,藏族.全身斑块、结节及肿块6月,肿块破渍伴疼痛2月.皮损病理组织示:表皮变薄,基底层液化变性,瘤细胞在真皮及皮下脂肪层呈弥漫性浸润,瘤细胞形态不一,核深染,可见血管中心性浸润及凝固性坏死.免疫组化标记瘤细胞CD3,CD3e,CD56,TIA-1,粒酶B均为(+),CD30约10%(+).CD8(-),CD79a(-),EBER1/2原位杂交(+).TCR-γ重排未见明确克隆性重排条带.诊断:皮肤结外鼻型NK/T细胞淋巴瘤.%A 60-year-old Tibetan nationality male patient presented with an over six month's history of plaque, nodules and lumps all over his body. Two months ago, the lumps developed to ulceration and accompanied pain. The pathologic features consist of thinning epidermis, liquefaction degeneration of basal cell, diffuse infiltrations of tumor cells in dermis and subcutaneous lipid tissue, which with various shapes and nucleolus hyperchromatism, blood vessels with centricity infiltrations, coagulation necrosis. The immunohistochemitry mark showed the tumor cells were positive with CD3, CD3ε, CD56, TIA-1, GrB and 1/2EBER in situ hybridization, about 10% tumor cells positive with CD30,but negative with CD8 and CD79a, TCR-rearrangement were not identify clone rearrange stripes. Extranodal nasal-type NK/T-cell lymphoma was diagnosed.

  3. Lymphoma in acquired generalized lipodystrophy.

    Science.gov (United States)

    Brown, Rebecca J; Chan, Jean L; Jaffe, Elaine S; Cochran, Elaine; DePaoli, Alex M; Gautier, Jean-Francois; Goujard, Cecile; Vigouroux, Corinne; Gorden, Phillip

    2016-01-01

    Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression.

  4. Interleukin-12 in Treating Patients With Previously Treated Non-Hodgkin's Lymphoma or Hodgkin's Disease

    Science.gov (United States)

    2015-04-14

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  5. Expression patterns of nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase in human malignant lymphomas

    DEFF Research Database (Denmark)

    Olesen, Uffe Høgh; Hastrup, Nina; Sehested, Maxwell

    2011-01-01

    lymphomas (diffuse large B-cell lymphoma, follicular B-cell lymphoma, Hodgkin's lymphoma and peripheral T-cell lymphoma). The expression of NAMPT was generally high in the more aggressive malignant lymphomas, with >80% strong expression, whereas the expression in the more indolent follicular lymphoma (FL...

  6. 皮肤T细胞淋巴瘤外周血免疫表型CD7缺失的临床分析%CD7 Deficiency in Peripheral Blood of Patients with Cutaneous T Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    李可嘉; 沈小雁; 施若非; 李霞; 郑捷

    2011-01-01

    目的:比较不同分期的皮肤T细胞淋巴瘤( cutaneous T cell lymphoma,CTCL)患者外周血淋巴细胞表面抗原CD7的缺失情况.方法 回顾性分析2006年1月-2010年7月本科收治的41例CTCL患者及9例炎症性皮肤病患者外周血淋巴细胞免疫表型的流式细胞检测结果,分析外周血CD7表达.结果 41例CTCL患者中,早期(ⅠA~ⅡA)23例和进展期(ⅡB~ⅣB)18例,CD3+ CD7 -T细胞比例进展期组与炎症性皮肤病组及早期组比较,均明显升高(P<0.05).进展期18例患者中6例CD7缺失(33.33%),早期23例患者中仅1例CD7缺失(4.35%),提示CD7缺失在进展期显著高于早期(P<0.05).无外周血累及的25例蕈样肉芽肿(mycosis fungoides,MF)患者中有2例CD7缺失,均为进展期,提示进展期MF较早期MF更易出现CD7缺失(P<0.05);在进展期MF的CD3+ CD7-T细胞比例均高于早期MF和炎症性皮肤病组(P<0.05).结论 进展期CTCL和无外周血累及的进展期MF外周血CD3+ CD7 -T细胞比例明显高于早期及炎症性皮肤病组,CTCL进展期较早期更容易发生外周血CD7缺失.

  7. Retrospective analysis of 91 patients with T cell non-Hodgkin's lymphoma%T细胞非霍奇金淋巴瘤91例回顾性分析

    Institute of Scientific and Technical Information of China (English)

    杨萍; 王晶; 董菲; 景红梅; 克晓燕

    2012-01-01

    Objective To analyse treatments and prognostic factors of T cell non-Hodgkin lymphoma (T-NHL). Methods Ninety-one patients with T-NHL were retrospectively analyzed, and clinical features,histopathology, laboratory data were included in Kaplan-Meier and prognostic analysis. Results Median age was 38 years,58 (63.7 %) had high-intermediate and high risk by IPI,72 (79.1%) presented with advanced stage disease,extranodal disease was present in 64.8 % of patients.The overall response rate (ORR) for the whole group was 63.8 %,and the estimated 3,5-year ORR were 55.5 %,41.3 % respectively.Compared with CHOP-like regimen, the addition of etoposide could improve the survival of patients, meanwhile radiation therapy could improve the outcome of patients with NK/T cell lymphoma and mediastinal bulky disease, and consolidation chemotherapy with HSCT could improve the survival and reduce the recurrence of patients.Clinical stage,B symptoms,ECOG score,the level of LDH,extranodal involvment,anemia,initial treatment outcome, IPI score, the level of serum albumin and fibrinogen were predictive to overall survival. Cox multivariate analysis showed initial treatment outcome and B symptoms were independent prognostic factors.IPI and m-PIT were useful for stratified patients into different prognostic risk groups. Conclusion T-NHL is a heterogeneous group of malignancies with an inferior long term outcome. New treatment modality needs to be explored for these patients,and new drugs and HSCT may be good choices.%目的 探讨T细胞非霍奇金淋巴瘤(T-NHL)的治疗和预后因素.方法 回顾性分析91例T-NHL患者的临床资料,对患者的临床特征、病理类型及实验室指标以及生存、预后因素进行分析.结果 91例T-NHL患者中位年龄38岁,国际预后指数(IPI)评分中高危/高危58例(63.7%),72例(79.1%)处于疾病进展期,59例(64.8%)存在结外侵犯.治疗总体反应率为63.8%(51例),预计3年及5年生存率分别为55

  8. Current treatment and blueprint of CD30+ T-cell lymphomas: reports from the 19th European Hematology Association annual congress%CD30+T细胞淋巴瘤的治疗现状及展望:第19届欧洲血液学会年会报道

    Institute of Scientific and Technical Information of China (English)

    陈峰; 吴德沛

    2014-01-01

    There is still no agreed standard of care for CD30+ T-cell lymphomas which are dominant in peripheral T-cell lymphoma.The combination of multidrug or dose-intensified chemotherapy regimen and consolidation of hematopoietic stem cell transplantation are widely used at present.In recent years,several clinical trails included certain new agents,such as etoposide,alemtuzumab,denileukin diftitox,bortezomib,romidepsin,lenalidomide,brentuximab vedotin,and so on,have demonstrated the promising outcome.Referring targeted therapies for relapsed/refractory CD30 + T-cell lymphomas,certain agents have been approved,such as pralatrexate,romidepsin,brentuximab vedotin (ALCL),belinostat,and the most encouraging agent is brentuximab vedotin.%外周T细胞淋巴瘤中以CD30+T细胞淋巴瘤居多,目前尚无统一的标准治疗方案.常用的策略是多种药物组成的剂量增强的化疗方案,联合造血干细胞移植进行巩固.近年,多个包含新药附加方案的临床试验,如依托泊苷、阿仑单抗、地尼白介素-毒素连接物、硼替佐米、罗米地辛、来那度胺、brentuximab vedotin等,结果令人鼓舞.针对难治性/复发性CD30+T细胞淋巴瘤,获批的药物有普拉曲沙、罗米地辛、brentuximab vedotin(对间变大细胞淋巴瘤)、belinostat等,其中以brentuximab vedotin前景最为乐观.

  9. Therapy and Prognosis Analysis of 47 Patients with Extranodal NK/T-Cell Lymphoma%47例结外NK/T细胞淋巴瘤治疗和预后分析

    Institute of Scientific and Technical Information of China (English)

    张松松; 于力; 魏敏; 李红华; 靖彧; 李菲; 黄文荣; 陆晓林; 刘占祥; 周颖

    2011-01-01

    本研究探讨结外NK/T细胞淋巴瘤的临床特征、治疗和预后情况.对中国人民解放军总医院血液科自1995年10月到2008年12月收治的47例结外NK/T细胞淋巴瘤患者进行回顾性分析.运用Kaplan-Meier方法行生存分析,COX回归分析模型对预后进行多变量分析.采用的临床参数分别为CD56、Ann Arbor分期、国际预后指标和B组症状.结果表明,全组2年、5年总生存(OS)率分别为91%和71%.单纯放疗患者的累积生存率较单纯化疗患者明显提高,二者相比有统计学差异;而放疗与放化疗结合治疗之间无统计学差异.COX回归分析模型多变量分析显示,CD56、Ann Arbor分期是独立的预后因素;单纯化疗中使用CHOP方案治疗的患者以分期为单因素分析显示,分期≥ⅢE期为预后的因素之一;以B症状为单因素分析3种疗法的生存曲线显示,B症状亦为预后因素之一.结论:单纯放疗的近期疗效明显优于单纯化疗.放化疗结合对近期生存率没有显著提高;CD56阴性和Ann Arbor分期较早是患者预后良好的指标,改善病人的一般状况可以使患者的预后更佳.%This study was purposed to explore the clinical characteristics, therapy and prognosis of patients with extranodal NK/T cell lymphoma (ENKL). 47 patients with ENKL from October 1995 to December 2008 in our hospital were analyzed retrospectively. The survival of patients was analyzed by using Kaplan-Meier methods, the prognosis of patients was evaluated by multivariate analysis using COX regression model. The clinical parameters used included CD56, Ann Arbor stage, international prognostic index (IPI) and B symptom. The results showed that the 2- year and 5-year overall survival (OS) rates were 91% ,71% respectively. Multivariant analysis by COX regression showed the CD56 and Ann Arbor stage were independent prognostic factors. Single factor analysis with staging in CHOP chemotherapy group indicated that more than stage

  10. Pediatric lymphomas in Brazil

    Directory of Open Access Journals (Sweden)

    Gabriela Gualco

    2010-01-01

    Full Text Available OBJECTIVE: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. METHODS: A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. RESULTS: Non-Hodgkin lymphomas represented 68% of the cases, including those of precursor (36% and mature (64% cell origin. Mature cell lymphomas comprised 81% of the B-cell phenotype and 19% of the T-cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central-west region. The distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. Among mature B-cell lymphomas, most of the cases were Burkitt lymphomas (65%, followed by diffuse large B-cell lymphomas (24%. In the mature T-cell group, anaplastic large cell lymphoma, ALK-positive was the most prevalent (57%, followed by peripheral T-cell