Peripheral T-cell lymphoma with unusual clinical presentation of rhabdomyolysis.

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Liu, Zhiyu; Medeiros, L Jeffrey; Young, Ken H

2017-03-01

Primary extranodal lymphoma is known to occur in nose, gastrointestinal tract, skin, bone, and central nervous system. However, it is extremely rare for primary lymphoma to arise in skeletal muscle. We report a case of a 32-year-old man who presented initially with fever and fatigue. He had a history of alcohol abuse. Laboratory studies and computerized tomography scan showed results consistent with rhabdomyolysis, but the cause of the rhabdomyolysis was undetermined. After biopsy of abdominal skeletal muscle with histologic examination and T-cell receptor gamma chain gene rearrangement analysis, the diagnosis of peripheral T-cell lymphoma was established. After two cycles of the cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide regimen, the patient's symptoms greatly improved. This is the third reported case of peripheral T-cell lymphoma arising in skeletal muscle reported in the literature and which presented clinically with rhabdomyolysis. The alcohol abuse during the clinical course likely worsens the pathologic process of the rhabdomyolysis. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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

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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.

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

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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.

Primary cutaneous smoldering adult T-cell leukemia/ lymphoma.

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Gittler, Julia; Martires, Kathryn; Terushkin, Vitaly; Brinster, Nooshin; Ramsay, David

2016-12-15

HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches.

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

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Duygu Mert, Mehmet Sinan Dal, Fazilet Duygu

2016-09-01

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

Peripheral T cell lymphoma: clinical utility of romidepsin

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Sawey K

2012-06-01

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

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

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

2008-06-01

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

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

NARCIS (Netherlands)

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

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

Use of Monoclonal Antibodies for the Diagnosis of T-cell Malignancies: Applications and Limitations.

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Hastrup, N; Pallesen, G; Ralfikiaer, E

1990-01-01

Biopsy samples from 136 peripheral T-cell lymphomas have been examined and compared with benign inflammatory T-cell infiltrates in an attempt to establish whether immunohistological methods may help to improve the distinction between these conditions. The results confirm and extend previous reports and indicate that the aberrant T-cell phenotypes constitute the single most reliable criterion for the distinction between benign and malignant T-cell infiltrates. These phenotypes are expressed frequently in T-cell malignancies in. lymphoid organs and are also seen in a substantial number of biopsy samples from advanced cutaneous T-cell lymphomas (CTCL). In contrast, early CTCL do not express aberrant T-cell phenotypes and are indistinguishable from benign cutaneous conditions in terms of their immunophenotypic properties. It is concluded that immunophenotypic techniques form a valuable supplement to routine histological methods for the diagnosis of T-cell lymphomas in lymphoid organs. The methods may also help to improve the diagnosis of advanced CTCL, but are of no or only limited help for the recognition of the early stages.

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

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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.

[Primary peripheral T-cell lymphoma of the penis: a case report and review of the literature].

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Shi, Yan-Lin; Yin, Hong-Lin; Zhou, Xiao-Jun; Zhou, Hang-Bo; Lu, Zhen-Feng

2008-11-01

To report a case of primary peripheral T-cell lymphoma of the penis. We analyzed the clinicopathological characteristics of the case of primary peripheral T-cell lymphoma using histological, cytochemical and immunohistochemical methods and by review of the literature. The patient was a 65 years old man and presented with a diffuse enlargement of the penis as the initial sign, followed by erosive ulcer in the caput penis and inguinal lymphadenectasis. The tumor was pathohistologically manifested as an epidermal ulcer, with tumorous necrosis around the capillary, infiltrative growth and atypical changes of the neoplastic cells and proliferation of capillaries. Immunohistochemically, the tumor cells were positive for CD43 and CD3, but negative for CD20, CD79a, CD34, CD30, CD56 and CD34. Clinically it responded to the chemotherapy designed for peripheral T-cell lymphoma. Primary peripheral T-cell lymphoma of the penis is an extremely rare malignant tumor, the diagnosis of which relies on histopathological examination, immunohistochemical staining and differentiation between squamous cell carcinoma and other types of lymphoma.

OPD4-positive T-cell lymphoma of the liver in systemic lupus erythematosus.

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Tsutsumi, Y; Deng, Y L; Uchiyama, M; Kawano, K; Ikeda, Y

1991-11-01

Primary malignant lymphoma of the liver occupying the right lobe, 14 x 9 x 7 cm in size, developed in a 30-year-old man with a 4-year history of autoimmune hemolytic anemia. The diagnosis of systemic lupus erythematosus (SLE) accompanying thrombocytopenia had been made clinically 10 months earlier. The liver biopsy specimen revealed diffuse proliferation of large lymphoma cells expressing the activated helper/inducer T-cell phenotype (LCA+, UCHL1+, OPD4+, LN3+, MT1-, L26-, MB1-, Leu M1-, Ki-1-, KP1-). The lymphoma was successfully treated by chemotherapy and irradiation. Intractable thrombocytopenia provoked fatal esophageal hemorrhage. At autopsy, no lymphomatous lesion was identified, and the hepatic right lobe contained an encapsulated necrotic lesion without any viable tumor cells. The bone marrow revealed marked hyperplasia of erythroid and megakaryocytic series. Extramedullary hematopoiesis was demonstrated in the liver, spleen and lymph nodes. This is the second case of primary hepatic T-cell lymphoma associated with SLE.

Expression of activating natural killer-cell receptors is a hallmark of the innate-like T-cell neoplasm in peripheral T-cell lymphomas.

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Uemura, Yu; Isobe, Yasushi; Uchida, Akiko; Asano, Junko; Nishio, Yuji; Sakai, Hirotaka; Hoshikawa, Masahiro; Takagi, Masayuki; Nakamura, Naoya; Miura, Ikuo

2018-04-01

Peripheral T- or natural killer (NK)-cell lymphomas are rare and difficult-to-recognize diseases. It remains arduous to distinguish between NK cell- and cytotoxic T-lymphocyte-derived lymphomas through routine histological evaluation. To clarify the cells of origin, we focused on NK-cell receptors and examined the expression using immunohistochemistry in 22 cases with T- and NK-cell neoplasms comprising angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-positive and -negative anaplastic large-cell lymphomas, extranodal NK/T-cell lymphoma, nasal type, monomorphic epitheliotropic intestinal T-cell lymphoma, aggressive NK-cell leukemia, and other peripheral T-cell lymphomas. Inhibitory receptor leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) was detected in 14 (64%) cases, whereas activating receptors DNAM1, NKp46, and NKG2D were expressed in 7 (32%), 9 (41%), and 5 (23%) cases, respectively. Although LILRB1 was detected regardless of the disease entity, the activating NK-cell receptors were expressed predominantly in TIA-1-positive neoplasms (DNAM1, 49%; NKp46, 69%; and NKG2D, 38%). In addition, NKp46 and NKG2D were detected only in NK-cell neoplasms and cytotoxic T-lymphocyte-derived lymphomas including monomorphic epitheliotropic intestinal T-cell lymphoma. One Epstein-Barr virus-harboring cytotoxic T-lymphocyte-derived lymphoma mimicking extranodal NK/T-cell lymphoma, nasal type lacked these NK-cell receptors, indicating different cell origin from NK and innate-like T cells. Furthermore, NKG2D expression showed a negative impact on survival among the 22 examined cases, which mainly received the standard chemotherapy regimen (log-rank test, P = .024). We propose that the presence of activating NK-cell receptors may provide new insights into understanding peripheral T-cell lymphomas and characterizing them as innate-like T-cell neoplasm. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on

Primary T cell central nervous system lymphoblastic lymphoma in a child: case report and literature review.

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Mazur, Marcus D; Ravindra, Vijay M; Alashari, Mouied; Raetz, Elizabeth; Poppe, Matthew M; Bollo, Robert J

2015-06-01

Primary central nervous system lymphoma (PCNSL) of T cell origin is rare in pediatric patients. We report a case of T cell PCNSL in a 12-year-old boy and review the literature to highlight the importance of brain biopsy to definitively establish the diagnosis when PCNSL is suspected. A 12-year-old boy presented with worsening left-sided weakness, nausea, vomiting, headache, blurred vision, and diplopia. Magnetic resonance imaging revealed right parietal gyral thickening with faint meningeal contrast enhancement. No clear diagnosis was identified after serum testing, cerebrospinal fluid analysis, and cerebral angiography. To establish the diagnosis definitively, a right craniotomy and open, frameless stereotactic biopsy were performed, which yielded the diagnosis of lymphoblastic T cell lymphoma. PCNSL of T cell origin in children remains poorly studied, with only 18 detailed cases reported over the last three decades, including this case. Establishing a definitive diagnosis of PCNSL is challenging, and a brain biopsy is often required to obtain enough tissue for pathological analysis. Increasing awareness and identification of children diagnosed with T cell PCNSL is needed to better understand the molecular biology of this disease and develop more standardized treatment regimens.

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

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Pedro Dantas Oliveira

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

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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.

[Prostatic granulomas revealing a peripheral T-cell lymphoma].

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Foguem, C; Curlier, E; Rouamba, M-M; Regent, A; Philippe, P

2009-02-01

The presence of granulomas on tissue biopsie has been reported in a wide range of disorders. The clinical presentation and the diagnostic work-up of granulomatosis can be difficult as it is illustrated in the following report. A 59-year-old patient was referred in 2002 for a granulomatous prostatitis. Physical examination was normal. Except for the increase of prostate-specific antigen (which motivated a biopsy), the laboratory results were normal. Thoracic CT-scan disclosed mediastinal lymph nodes. A minor salivary gland biopsy was consistent with the diagnosis of sarcoidosis. In 2004, the patient presented an epidermal necrolysis, and in 2005 the deterioration of general status raised suspicion of a lymphoproliferative disorder. Liver and bone marrow biopsies revealed a granulomatous process. Despite steroid therapy, the patient died. Autopsy discloses a anaplasic T cell lymphoma. This report illustrates the relationship between sarcoidosis and lymphoma as a mode of presentation, a complication, or an accidental but misleading association? The association between anaplastic lymphoma and sarcoidosis is exceptional.

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

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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...

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

International Nuclear Information System (INIS)

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

2016-01-01

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

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

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Katherine Devitt

2014-01-01

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

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

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Devitt, Katherine; Cerny, Jan; Switzer, Bradley; Ramanathan, Muthalagu; Nath, Rajneesh; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

2014-01-01

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.

Adult T-Cell Leukemia/Lymphoma. Review of the Literature.

Science.gov (United States)

Rodríguez-Zúñiga, M J M; Cortez-Franco, F; Qujiano-Gomero, E

2018-06-01

Adult T-cell Leukemia/Lymphoma (ATLL) is an aggressive neoplasm of T lymphocytes associated with Human T-lymphotropic virus type1 (HTLV-1) infection. HTLV-1 is a public health problem because it is endemic in native groups in Latin America, and its infection leads to several chronic diseases as ATLL. We aimed to review current literature of ATLL in order to consider it as a differential diagnosis in front of patients with compatible symptoms. Prognosis is still poor in aggressive and indolent variants, with survival rates from months to few years. Treatment based on chemotherapy, antiretroviral, and allogenic stem cell transplantation are currently improving survival rates, but with limited results. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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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.

Primary NK/T cell lymphoma nasal type of the colon

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Ana María Chirife

2013-02-01

Full Text Available Since nasal NK/T-cell lymphoma and NK/T-cell lymphoma nasal type are rare diseases, colonic involvement has seldom been seen. We report a case of a patient with a primary NK/T-cell lymphoma nasal type of the colon. The patient had no history of malignant diseases and was diagnosed after exhaustive study in the context of fever of unknown origin. The first therapeutic approach followed the DAEPOCH-protocol: etoposide, prednisone, doxor-rubicin, vincristine and cyclophosphamide. The persistence of constitutional symptoms after the first treatment course motivated the switch to a second line following the SMILE-protocol: dexamethasone, metotrexate, ifosfamide, E.coli L-asparaginase, and etoposide. Despite intensive chemotherapy, the patient died 2 months after the diagnose of an extranodal NK/T-cell lymphoma of the colon and 4 months after the first symptomatic appearance of disease.

Primary orbital precursor T-cell lymphoblastic lymphoma

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Stenman, Lisa; Persson, Marta; Enlund, Fredrik

2016-01-01

Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical...... examination revealed left-sided exophthalmus, periorbital edema, chemosis, and reduced motility of the left eye. A magnetic resonance imaging scan revealed thickening of the left orbital muscles and a positron emission tomography-computed tomography scan also demonstrated activity in a subclavicular lymph....... There was no involvement of the bone marrow. Based on the clinical and histopathological findings, a diagnosis of T-LBL was made. There was no evidence of NOTCH1 mutation or rearrangements of the ETV6 and MLL genes and high-resolution array-based comparative genomic hybridization (arrayCGH) analysis revealed a normal...

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

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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.

[Adult T-cell leukemia/lymphoma associated with unusual positivity of anti-ATLA (adult T-cell leukemia-cell-associated antigen) antibodies].

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Eto, T; Okamura, H; Okamura, T; Gondo, H; Kudo, J; Shibuya, T; Harada, M; Niho, Y

1990-03-01

A 56-year-old female was admitted because of generalized lymphadenopathy. Based upon histological findings of biopsied lymph node, malignant lymphoma, diffuse large cell type was diagnosed. The surface marker analysis showed that malignant cells were positive for CD4 and CD2 but negative for CD8. Although anti-ATLA (adult T-cell leukemia associated antigen) antibody was negative with the use of a gelatin particle agglutination method (P.A.), other methods such as an indirect immunofluorescence assay (I.F.), an enzyme-linked immunosorbent assay (E.I.A.) and a Western blotting assay revealed the positivity for anti-ATLA antibody. Adult T-cell leukemia/lymphoma (ATL/L) was confirmed by the presence of monoclonal integration of HTLV-I proviral DNA in biopsied specimen. This case, showing a pattern of P.A. (-) and I.F. (+), is extremely unusual, because I.F. and P.A. show highly close correlation. Thus, it is important to employ different methods for screening of anti-ATLA antibodies in the diagnosis of ATL/L.

Terminal deoxynucleotidyl transferase in the diagnosis of leukemia and malignant lymphoma.

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Kung, P C; Long, J C; McCaffrey, R P; Ratliff, R L; Harrison, T A; Baltimore, D

1978-05-01

Neoplastic cells from 253 patients with leukemia and 46 patients with malignant lymphoma were studied for the presence of terminal deoxynucleotidyl transferase (TdT) by biochemical and fluorescent antibody technics. TdT was detected in circulating blast cells from 73 of 77 patients with acute lymphoblastic leukemia, 24 of 72 patients with chronic myelogenous leukemia examined during the blastic phase of the disorder and in cell suspensions of lymph nodes from nine of nine patients with diffuse lymphoblastic lymphoma. Blast cells from six of 10 patients with acute undifferentiated leukemia were TdT positive, but the enzyme was found in only two of 55 patients with acute myeloblastic leukemia. TdT was not detected in other lymphocytic or granulocytic leukemias or in other types of malignant lymphomas. The fluorescent antibody assay for TdT permits rapid and specific identification of the enzyme in single cells. The TdT assay is clinically useful in confirming the diagnosis of acute lymphoblastic leukemia, evaluating patients with blastic chronic myelogenous leukemia, and distinguishing patients with lymphoblastic lymphoma, whose natural history includes rapid extranodal dissemination, from patients with other poorly differentiated malignant lymphomas.

Primary hepatic peripheral T-cell lymphoma mimicking hepatocellular carcinoma: a case report.

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Lee, Jisun; Park, Kil Sun; Kang, Min Ho; Kim, Yook; Son, Seung-Myoung; Choi, Hanlim; Choi, Jae-Woon; Ryu, Dong Hee

2017-08-01

Peripheral T-cell lymphomas (PTCLs) are aggressive neoplasms which may involve the liver. The imaging manifestations of hepatic lymphoma are highly variable and show overlapping appearances of numerous other hepatic diseases. As the management and prognosis of lymphoma differ markedly from those of other malignant diseases, prompt diagnosis and early effective treatment are very important. Here, we report an atypical case of primary PTCL not otherwise specified involving the liver that exhibited a solitary hepatic mass mimicking hepatocellular carcinoma (HCC) on CT. Liver biopsy is not commonly recommended in highly suspicious cases of HCC. However, in a patient without risk factors for HCC, consideration of other diagnostic possibilities is required and needle biopsy may be a more rational choice. An imaging approach, based on a careful review of clinical and laboratory findings is essential to prevent false-positive diagnosis of HCC and subsequent invasive treatment.

Mantle Cell Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Peripheral T cell lymphoma: Not otherwise specified

Directory of Open Access Journals (Sweden)

Anusha H Pai

2015-01-01

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

Cerebellar T-cell lymphoma: an unusual primary intracranial neoplasm

International Nuclear Information System (INIS)

Knorr, J.R.; Ragland, R.L.; Stone, B.B.; Woda, B.A.; Gelber, N.D.

1992-01-01

Primary T-cell lymphoma within the central nervous system is extremely rare. Imaging characteristics appear indistinguishable from the more common B-cell lymphoma. A case of such a primary tumor is discussed and the MRI and CT findings presented. (orig.)

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.

Clinico pathological spectrum of mycosis fungoides type cutaneous t-cell lymphoma

International Nuclear Information System (INIS)

Shaikh, Z.I.; Rahman, S.B.

2006-01-01

Objective: To determine the clinical, histological, and immuno phenotypic characteristics of mycosis fungoides type cutaneous T-cell lymphoma. Design: Descriptive study. Place and Duration of Study: This study was conducted from January 2000 to December 2004 at the Department of Dermatology, Military Hospital and the Department of Dermatopathology, Armed Forces Institute of Pathology, Rawalpindi. Materials and Methods: The medical case records of patients with mycosis fungoides diagnosed during the period of study were surveyed. Data was collected pertaining to patients' characteristics, clinical descriptions, histopathological features, immuno phenotypic analysis and stage of disease at the time of diagnosis. Results: A total of 33 cases of mycosis fungoides were diagnosed between the years 2000 and 2004. There were 24 male and 9 female patients with male to female ratio of 2.6:1 The age ranged from 24 to 68 years and the duration of disease prior to diagnosis varied between 2 to 36 months. The number of skin biopsies performed for definite diagnosis ranged from 01 to 5. The various clinical presentations recorded in these patients were hypo pigmented patches in 7 (21.3%), infiltrated papules and plaques in 6 (18.2%), erythroderma in 5 (15.2%), psoriasiform lesions in 3 (9%), and nodular lesions in 3 (9%) patients. There were 2 (6%) cases respectively of noduloulcerative, ichthyosiform and poikilodermatous lesions, and 1 (3%) case each of follicular, morphoea-like and purpuric skin lesions. The predominant histological features were lymphocytic infiltrate in the upper dermis, epidermotropism, haloed lymphocytes in epidermis, Pautrier's micro abscesses, and interface dermatitis. The immunohistochemical studies (n=12) showed predominantly T helper cell immuno phenotype (CD3+, CD45RO+) in 11 (92%) cases and T suppressor cell immuno phenotype (CD3+, CD8+) in 1 (8%) patient. Conclusion: The mycosis fungoides type cutaneous T-cell lymphoma has a wide clinico

Current and Emerging Therapeutics for Cutaneous T-Cell Lymphoma: Histone Deacetylase Inhibitors

OpenAIRE

Annabelle L. Rodd; Katherine Ververis; Tom C. Karagiannis

2012-01-01

Cutaneous T-cell lymphoma is a term that encompasses a spectrum of non-Hodgkin’s T-cell lymphomas with primary manifestations in the skin. It describes a heterogeneous group of neoplasms that are characterised by an accumulation of malignant T cells of the CD4 phenotype that have the propensity to home and accumulate in the skin, lymph nodes, and peripheral blood. The two most common variants of cutaneous T-cell lymphoma include mycosis fungoides and the leukemic variant, the Sézary syndrome....

Hematopoietic Cell Transplantation for Systemic Mature T-Cell Non-Hodgkin Lymphoma

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Smith, Sonali M.; Burns, Linda J.; van Besien, Koen; LeRademacher, Jennifer; He, Wensheng; Fenske, Timothy S.; Suzuki, Ritsuro; Hsu, Jack W.; Schouten, Harry C.; Hale, Gregory A.; Holmberg, Leona A.; Sureda, Anna; Freytes, Cesar O.; Maziarz, Richard Thomas; Inwards, David J.; Gale, Robert Peter; Gross, Thomas G.; Cairo, Mitchell S.; Costa, Luciano J.; Lazarus, Hillard M.; Wiernik, Peter H.; Maharaj, Dipnarine; Laport, Ginna G.; Montoto, Silvia; Hari, Parameswaran N.

2013-01-01

Purpose To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma. Patients and Methods Outcomes of 241 patients (112 anaplastic large-cell lymphoma, 102 peripheral T-cell lymphoma not otherwise specified, 27 angioimmunoblastic T-cell lymphoma) undergoing autologous HCT (autoHCT; n = 115; median age, 43 years) or allogeneic HCT (alloHCT; n = 126; median age, 38 years) were analyzed. Primary outcomes were nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Patient, disease, and HCT-related variables were analyzed in multivariate Cox proportional hazard models to determine association with outcomes. Results AutoHCT recipients were more likely in first complete remission (CR1; 35% v 14%; P = .001) and with chemotherapy-sensitive disease (86% v 60%; P < .001), anaplastic large-cell histology (53% v 40%; P = .04), and two or fewer lines of prior therapy (65% v 44%; P < .001) compared with alloHCT recipients. Three-year PFS and OS of autoHCT recipients beyond CR1 were 42% and 53%, respectively. Among alloHCT recipients who received transplantations beyond CR1, 31% remained progression-free at 3 years, despite being more heavily pretreated and with more refractory disease. NRM was 3.5-fold higher (95% CI, 1.80 to 6.99; P < .001) for alloHCT. In multivariate analysis, chemotherapy sensitivity (hazard ratio [HR], 1.8; 95% CI, 1.16 to 2.87) and two or fewer lines of pretransplantation therapy (HR, 5.02; 95% CI, 2.15 to 11.72) were prognostic of survival. Conclusion These data describe the roles of autoHCT and alloHCT in T-cell non-Hodgkin lymphoma and suggest greater effectiveness earlier in the disease course, and limited utility in multiply relapsed disease. Notably, autoHCT at relapse may be a potential option for select patients, particularly those with anaplastic large-cell lymphoma histology. PMID:23897963

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

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Ryan L Bjordahl

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

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

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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.

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

DEFF Research Database (Denmark)

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

2002-01-01

Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation, defines a distinct type of T/null-cell lymphoma (TCL). The resulting nucleophosmin (NPM) /ALK chimeric kinase is constitutively active and oncogenic. Downstream effector mol...

Anaplastic Large Cell Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Therapeutic options in peripheral T cell lymphoma

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Yaping Zhang

2016-04-01

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

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.

Celiac Disease, Enteropathy-Associated T-Cell Lymphoma, and Primary Sclerosing Cholangitis in One Patient: A Very Rare Association and Review of the Literature

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N. Majid

2013-01-01

Full Text Available Enteropathy-associated T-cell lymphoma (EATL is a very rare peripheral T-cell lymphoma which is mostly associated with celiac disease. However, the association of primary sclerosing cholangitis and enteropathy-associated T-cell lymphoma is uncommon. Herein we report and discuss the first case of patient who presented simultaneously with these two rare diseases. It is a 54-year-old man who stopped gluten-free diet after 15 years history of celiac disease. The diagnosis was based on the histological examination of duodenal biopsy and the diagnosis of primary sclerosing cholangitis was made on liver biopsy, as well as the magnetic resonance cholangiogram. The treatment of EATL is mainly based on chemotherapy in addition to the optimal management of complications and adverse events that impact on the response to treatment and clinical outcomes, although the prognosis remains remarkably very poor.

MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance

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Zi-Xun Yan

2015-01-01

Full Text Available MicroRNAs (miRs play an important role in tumorogenesis and chemoresistance in lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n=32, T-cell lymphoblastic lymphoma (n=16, peripheral T-cell lymphoma, not otherwise specified (n=45, anaplastic large cell lymphoma (n=15, and angioimmunoblastic T-cell lymphoma (n=22. Irrespective to histological subtypes, miR181a overexpression was associated with increased AKT phosphorylation. In vitro, ectopic expression of miR181a in HEK-293T cells significantly enhanced cell proliferation, activated AKT, and conferred cell resistance to doxorubicin. Meanwhile, miR181a expression was upregulated in Jurkat cells, along with AKT activation, during exposure to chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment, such as doxorubicin, cyclophosphamide, cytarabine, and cisplatin. Isogenic doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also presented with miR181a overexpression and cross-resistance to cyclophosphamide and cisplatin. Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9 cell sensitivity to chemotherapeutic agents, further indicating that miR181a was involved in acquired chemoresistance. Collectively, miR181a functioned as a biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway. Related to tumor cell chemoresistance, miR181a could be a potential therapeutic target in treating T-cell malignancies.

Posttransplantation primary cutaneous CD30 (Ki-1)-positive large-cell lymphoma.

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Seçkin, D; Demirhan, B; Oğuz Güleç, T; Arikan, U; Haberal, M

2001-12-01

We describe the case of a 51-year-old female renal transplant recipient with primary cutaneous CD30-positive large-cell lymphoma of T-cell origin. Cutaneous T-cell lymphomas are rarely reported in organ transplant recipients, and we believe they should be considered in the differential diagnosis of cutaneous neoplastic and infectious diseases affecting this patient group.

New targeted treatments for cutaneous T-cell Lymphomas

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Martine Bagot

2017-01-01

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

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

Science.gov (United States)

2017-11-10

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

TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

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Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

2016-07-07

Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. © 2016 by The American Society of Hematology.

Subcutaneous panniculitis-like T-cell lymphoma

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Francis Abel

2010-01-01

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

Regulation of Id2 expression in EL4 T lymphoma cells overexpressing growth hormone.

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Weigent, Douglas A

2009-01-01

In previous studies, we have shown that overexpression of growth hormone (GH) in cells of the immune system upregulates proteins involved in cell growth and protects from apoptosis. Here, we report that overexpression of GH in EL4 T lymphoma cells (GHo) also significantly increased levels of the inhibitor of differentiation-2 (Id2). The increase in Id2 was suggested in both Id2 promoter luciferase assays and by Western analysis for Id2 protein. To identify the regulatory elements that mediate transcriptional activation by GH in the Id2 promoter, promoter deletion analysis was performed. Deletion analysis revealed that transactivation involved a 301-132bp region upstream to the Id2 transcriptional start site. The pattern in the human GHo Jurkat T lymphoma cell line paralleled that found in the mouse GHo EL4 T lymphoma cell line. Significantly less Id2 was detected in the nucleus of GHo EL4 T lymphoma cells compared to vector alone controls. Although serum increased the levels of Id2 in control vector alone cells, no difference was found in the total levels of Id2 in GHo EL4 T lymphoma cells treated with or without serum. The increase in Id2 expression in GHo EL4 T lymphoma cells measured by Id2 promoter luciferase expression and Western blot analysis was blocked by the overexpression of a dominant-negative mutant of STAT5. The results suggest that in EL4 T lymphoma cells overexpressing GH, there is an upregulation of Id2 protein that appears to involve STAT protein activity.

T cell lymphoblastic lymphoma/leukemia within an adrenocorticotropic hormone and thyroid stimulating hormone positive pituitary adenoma: A cytohistological correlation emphasizing importance of intra-operative squash smear.

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Gupta, Rakesh K; Saran, Ravindra K; Srivastava, Arvind K; Jagetia, Anita; Garg, Lalit; Sharma, Mehar C

2017-08-01

We present a rare case of primary pituitary T cell lymphoma/leukemia (T-LBL) in association with adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) expressing pituitary adenoma in a 55-year-old woman highlighting the importance of intra-operative squash smears examination. The patient presented with complaints of headache, diminution of vision and recent onset altered sensorium. MRI revealed a mass lesion in the sellar-suprasellar region with non-visualization of pituitary gland separately, extending to involve adjacent structures diagnosed as invasive pituitary macroadenoma. Intra-operative tissue was sent for squash smear examination. The cytology showed a tumor comprising of sheets of immature lymphoid cells intermixed with clusters of pituitary acinar cells with many mitoses and tingible body macrophages. A diagnosis of presence of immature lymphoid cells within the pituitary was offered and differentials of infiltration by lymphoma cells from systemic disease versus primary central nervous lymphoma-like lymphoma arising in the pituitary adenoma were considered. Later paraffin section examination and immunohistochemistry corroborated with the squash findings and a final diagnosis of primary pituitary T cell lymphoma/leukemia in association with ACTH and TSH expressing pituitary adenoma was made. To date, only six cases of primary pituitary T cell lymphomas, including three T-LBL cases, have been reported. This is the seventh case and first one additionally describing cytohistological correlation and importance of intra-operative cytology. © 2017 Japanese Society of Neuropathology.

Primary focal T-cell lymphoma of the liver: a case report and review of the literature.

Science.gov (United States)

Cerban, Razvan; Gheorghe, Liana; Becheanu, Gabriel; Serban, Valentin; Gheorghe, Cristian

2012-06-01

We present the case of a previously healthy 62 year old man who developed primary non-Hodgkin lymphoma of the liver. Biopsy confirmed that it was a diffuse large anaplastic T-cell lymphoma of an extremely rare type. The diagnosis of this type of lesions is suggested by the presence of a hepatic mass without lymphadenopathy, splenomegaly or bone marrow involvement associated with normal tumor markers (carcinoembryonic antigen, alpha-fetoprotein and CA 19-9 levels). Histological examination of tissue is essential to confirm the diagnosis. Treatment options are surgical resection and/or chemotherapy but the rate of response to treatment varies widely. Some patients can achieve prolonged remission.

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

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

2017-06-01

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

Human adipose tissue-derived mesenchymal stem cells inhibit T-cell lymphoma growth in vitro and in vivo.

Science.gov (United States)

Ahn, Jin-Ok; Chae, Ji-Sang; Coh, Ye-Rin; Jung, Woo-Sung; Lee, Hee-Woo; Shin, Il-Seob; Kang, Sung-Keun; Youn, Hwa-Young

2014-09-01

Human mesenchymal stem cells (hMSCs) are thought to be one of the most reliable stem cell sources for a variety of cell therapies. This study investigated the anti-tumor effect of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) on EL4 murine T-cell lymphoma in vitro and in vivo. The growth-inhibitory effect of hAT-MSCs on EL4 tumor cells was evaluated using a WST-1 cell proliferation assay. Cell-cycle arrest and apoptosis were investigated by flow cytometry and western blot. To evaluate an anti-tumor effect of hAT-MSCs on T-cell lymphoma in vivo, CM-DiI-labeled hAT-MSCs were circumtumorally injected in tumor-bearing nude mice, and tumor size was measured. hAT-MSCs inhibited T-cell lymphoma growth by altering cell-cycle progression and inducing apoptosis in vitro. hAT-MSCs inhibited tumor growth in tumor-bearing nude mice and prolonged survival time. Immunofluorescence analysis showed that hAT-MSCs migrated to tumor sites. hAT-MSCs suppress the growth of T-cell lymphoma, suggesting a therapeutic option for T-cell lymphoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Subcutaneous Panniculitis-Like T-Cell Lymphoma of the Breast

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Jeong, Seo In; Lim, Hyo Soon [Department of Radiology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 519-763 (Korea, Republic of); Choi, You Ri [Department of Radiology, Chonnam National University Hospital, Gwangju 501-757 (Korea, Republic of); Kim, Jin Woong [Department of Radiology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 519-763 (Korea, Republic of); Park, Min Ho; Cho, Jin Seong [Department of Surgery, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 519-763 (Korea, Republic of); Lee, Ji Shin [Department of Pathology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 519-763 (Korea, Republic of); Kang, Heoung Keun [Department of Radiology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 519-763 (Korea, Republic of)

2013-07-01

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous lymphoma. There have been a few case reports describing the radiologic imaging findings of SPTCL. We report a case of SPTCL, rarely presented with a breast mass. Here, we review her clinical history and radiologic (mammography and ultrasound) findings.

A novel xenograft model of cutaneous T-cell lymphoma

DEFF Research Database (Denmark)

Krejsgaard, Thorbjørn; Kopp, Katharina; Ralfkiaer, Elisabeth

2010-01-01

Cutaneous T-cell lymphomas (CTCLs) are characterized by accumulation of malignant T cells in the skin. Early disease resembles benign skin disorders but during disease progression cutaneous tumors develop, and eventually the malignant T cells can spread to lymph nodes and internal organs. However...... and lymphatic tumors, originated from the transplanted malignant T cells. In conclusion, we describe a novel mouse model of tumor stage CTCL for future studies of disease dissemination and preclinical evaluations of new therapeutic strategies....

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

Science.gov (United States)

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

2016-10-06

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

Silicone-induced granuloma of breast implant capsule (SIGBIC: similarities and differences with anaplastic large cell lymphoma (ALCL and their differential diagnosis

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Fleury EF

2017-03-01

Full Text Available Eduardo de Faria Castro Fleury,1 Milena Morais Rêgo,1 Luciana Costa Ramalho,1 Veronica Jorge Ayres,1 Rodrigo Oliveira Seleti,2 Carlos Alberto Pecci Ferreira,2 Decio Roveda Jr 2 1Radiology Department, IBCC – Instituto Brasileiro de Controle do Câncer, 2Irmandade Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil Abstract: Primary breast lymphoma is a rare disease and accounts for 0.5% of cases of breast cancer. Most primary breast lymphomas develop from B cells, and the involvement of T cells is rare. Anaplastic large cell lymphoma (ALCL is a recently discovered T-cell lymphoma associated with breast implants. Only a few cases have been reported to date. It is believed that the incidence of ALCL is increasing because of the increasing number of breast implants. The clinical presentation is variable and can manifest as a palpable mass in the breast or armpit, breast pain, or capsular contracture. Because of the rarity of the disease and the lack of knowledge to date, clinical diagnosis is often delayed, with consequent delays in treatment. The cause and pathogenesis have not been fully elucidated, and there are no evidence-based guidelines for diagnosis, treatment, or follow-up of this disease. We present a review of cases of patients with silicone breast implants, including ALCL, a rare type of breast cancer that is still under study, and silicone-induced granuloma of breast implant capsule and its differential diagnosis, and discuss if a silicone-induced granuloma of breast implant capsule could be the precursor of the disease. Keywords: lymphoma, granuloma, breast cancer, implant

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.)

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

NARCIS (Netherlands)

Peh, SC; Kim, LH; Poppema, S

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

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....... The malignant CTCL cells express MHC class II molecules that are high-affinity receptors for SE. Although treatment with SE has no direct effect on the growth of the malignant CTCL cells, the SE-treated CTCL cells induce vigorous proliferation of the SE-responsive nonmalignant T cells. In turn, the nonmalignant...... T cells enhance proliferation of the malignant cells in an SE- and MHC class II-dependent manner. Furthermore, SE and, in addition, alloantigen presentation by malignant CTCL cells to irradiated nonmalignant CD4(+) T-cell lines also enhance proliferation of the malignant cells. The growth...

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.

Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma

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Long Zheng

2017-12-01

Full Text Available T cells expressing chimeric antigen receptors (CARs recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR on the surface of human B-cell lymphomas. Lym-1 CAR T cells were thus generated for evaluation of cytotoxic activity towards lymphoma cells in vitro and in vivo. Human T cells from healthy donors were transduced to express a Lym-1 CAR, and assessed for epitope-driven function in culture and towards Raji xenografts in NOD-scidIL2Rgammanull (NSG mice. Lym-1 CAR T cells exhibited epitope-driven activation and lytic function against human B-cell lymphoma cell lines in culture and mediated complete regression of Raji/Luciferase-Green fluorescent protein (Raji/Luc-GFP in NSG mice with similar or better reactivity than CD19 CAR T cells. Lym-1 CAR transduction of T cells is a promising immunotherapy for patients with Lym-1 epitope positive B-cell malignancies.

The Value and Relevance of the T Cell Lymphoma Registries and International Collaborations: the Case of COMPLETE and the T-Cell Project.

Science.gov (United States)

Bellei, Monica; Nabhan, Chadi; Pesce, Emanuela Anna; Conte, Luana; Vose, Julie M; Foss, Francine; Federico, Massimo

2015-12-01

Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of lymphoid malignancies that portend a poor prognosis and have an undefined optimal therapeutic strategy. Data on best practices stem from prior studies that have generally included B cell lymphomas. However, the enhanced ability to diagnose PTCLs, the development of newer agents specific for PTCLs, and its increased incidence have called the scientific community to develop better strategies to combat these neoplasms. To that end, T cell lymphoma registries were developed in an attempt to answer relevant questions on the prognosis and management of PTCLs. The largest registries currently enrolling patients are the Comprehesive Oncology Measures for PeripheraL T-cEll Lymphoma TrEatment (COMPLETE) and the T-Cell Project. Despite the inherent limitations of these studies, valuable information are being collected to refine our management approaches and to aid in designing future clinical trials. This review illustrates the value of these registries and describes the critical questions that need to be answered.

Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature

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Yang Qing-Xu

2012-01-01

Full Text Available Abstract Only a few cases of extranodal Epstein-Barr virus (EBV-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone, but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1197421158639299

Natural killer/T-cell lymphoma invading the orbit and globe.

Science.gov (United States)

Lyons, Lance J; Vrcek, Ivan; Somogyi, Marie; Taheri, Kevin; Admirand, Joan H; Chexal, Saradha; Loukas, Demetrius F; Nakra, Tanuj

2017-10-01

Natural killer/T-cell lymphomas are extremely rare and carry high mortality rates. Epidemiologically, these cancers tend to affect mainly Asian and South American patients and are associated with Epstein-Barr virus seropositivity. This report details a 78-year-old Vietnamese woman who presented initially with vitritis of unknown cause, but later developed proptosis and conjunctival involvement as her disease spread. Biopsies of the orbit, ethmoid sinus, and conjunctiva were found to be significant for natural killer/T-cell lymphoma. The case highlights the diagnostic difficulty of this tumor given its rarity and ability to mimic other disorders.

Orbital T-Cell Lymphoma with Discrete Enlargements of All Extraocular Muscles Bilaterally in Patient with Moon Face Countenance

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Hideaki Kawakami

2017-01-01

Full Text Available Purpose. To report our findings in a case of orbital T-cell lymphoma in which all of the extraocular muscles (EOMs were bilaterally and discretely enlarged and the patient had a moon face countenance. Case. A 59-year-old woman presented with visual disturbances in her left eye, hyperemia in both eyes, and a moon face countenance. Examinations showed limited upward gaze in the right eye, blepharoptosis, hypertropia, and limited downward and rightward gaze in the left eye. Slit-lamp examination showed only chemosis and hyperemia of both eyes. Magnetic resonance imaging with contrast revealed discrete enlargements of the muscle bellies in all EOMs without abnormalities of the orbital fat in both eyes. Blood examinations excluded thyroid- and IgG4-related ophthalmopathy, and EOM biopsy revealed peripheral T-cell lymphoma. After beginning aggressive chemotherapy, the enlarged EOMs, limited eye motility, and moon face countenance improved. Unfortunately, the patient died of sepsis during the chemotherapy. Conclusions. A lymphoma should be included in the differential diagnosis of eyes with enlarged EOMs. Because lymphomas can lead to death, it is important for clinicians to consider lymphomas in eyes with enlarged EOMs.

Diagnosing lymphoma in a setting with a high burden of infection: a pediatric case of Epstein-Barr virus-associated aggressive B-cell lymphoma with t(8;14 (q23;q32 and extensive necrosis mimicking tuberculosis

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Mário Henrique Magalhães Barros

2015-02-01

Full Text Available The association of lymphoma with necrotic granuloma can pose diagnostic challenges and delay treatment, especially in settings with a high burden of infection. In these settings, the timely use of cytogenetic and molecular methods is most relevant. Here, we report a case of B-cell lymphoma with t (8;14 in a 5-year-old male child. The lymphoma was associated with necrotic granuloma and was initially misdiagnosed as tuberculosis. Polymerase chain reaction was used to detect clonal lymphoproliferation and to rule out Mycobacterium tuberculosis infection. Tumor cells harbored Epstein-Barr virus and expressed CD20, CD10, BCL6, and Ki67 (30%, leading to the diagnosis of B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

Epstein-Barr virus-associated peripheral T-Cell lymphoma involving spleen in a renal transplant patient.

Science.gov (United States)

Lee, Hye Kyung; Kim, Hee Jung; Lee, Eun Hee; Kim, Suk Young; Park, Tae In; Kang, Chang Suk; Yang, Woo Ick

2003-01-01

The incidence of posttransplantation lymphoproliferative disorders (PTLDs) has increased in recent years. Although rare, various types of T-cell lymphoma have been reported and their association with Epstein-Barr virus (EBV) has been compared with B-cell PTLDs. We report a case of splenic peripheral T-cell lymphoma occurring in a 47-yr-old male patient 7 yr after renal allograft transplantation. The spleen showed sinusoidal proliferation of focal CD30 positive, large, atypical lymphoid cells. Positivity for CD3 and cytolytic granule-associated proteins was also demonstrated in the tumor cells, while anaplastic large cell lymphoma kinase (ALK) and CD8 were not expressed. Strong nuclear signals for EBV mRNA were noted by EBER1 in situ hybridization. A molecular genetic study demonstrated a rearrangement of the gamma T-cell receptor gene. To our knowledge, this case is unique in terms of a posttransplant T-cell lymphoma that shows focal CD30, cytolytic granule-associated proteins, and EBV positivity. PMID:12692428

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 PTL...... cases) (p > 0.05). In the ALK+ ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ-secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment...... with Notch inhibitors has cytotoxic effects....

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 epide...... in CTCL.Journal of Investigative Dermatology accepted article preview online, 09 July 2014; doi:10.1038/jid.2014.284....

Immunological aspects of adult T-cell leukemia/lymphoma (ATLL), a possible neoplasm of regulatory T-cells

OpenAIRE

Yamada, Yasuaki; Kamihira, Shimeru

2008-01-01

Adult T-cell leukemia/lymphoma (ATLL) is a distinct disease caused by the first discovered human oncogenic retrovirus, human T-cell leukemia virus type-1 (HTLV-1). The peculiarity of this disease is not only in its causative agent HTLV-1 but also in the character of leukemia cells. ATLL cells express the mature helper/inducer T-cell antigens, CD2, CD3, CD4 and CD5 but usually lacking CD8. Despite CD4 expression, it has long been known that ATLL cells exhibit strong immunosuppressive activity ...

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...

The CD4+CD26-T-cell population in classical Hodgkin's lymphoma displays a distinctive regulatory T-cell profile

NARCIS (Netherlands)

Ma, Yue; Visser, Lydia; Blokzijl, Tjasso; Harms, Geert; Atayar, Cigdem; Poppema, Sibrand; van den Berg, Anke

Little is known about the gene expression profile and significance of the rosetting CD4+CD26- T cells in classical Hodgkin's lymphoma (cHL). To characterize these T cells, CD4+CD26- and CD4+CD26+ T-cell populations were sorted from lymph node (LN) cell suspensions from nodular sclerosis HL (NSHL)

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

Science.gov (United States)

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

2017-06-01

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

NKT Cell Responses to B Cell Lymphoma.

Science.gov (United States)

Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B; Page, Carly; Younger, Kenisha M; Tiper, Irina V; Frieman, Matthew; Kimball, Amy S; Webb, Tonya J

2014-06-01

Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

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

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

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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

'Adult T-cell leukemia/lymphoma' with bone demineralization

International Nuclear Information System (INIS)

Ohuchida, Toshiyuki; Nishitani, Hiromu; Matsuura, Keiichi

1985-01-01

Two patients with T-cell malignancy having radiographic manifestations of generalized and localized bone demineralization are reported. One, a 53-year-old-man, had marked osteoporosis and severe hypercalcemia, but no clinical evidence of leukemia throughout his illness. At autopsy there was no definite evidence of bone involvement. Histologic proof was obtained from abdominal skin which revealed ''adult T-cell leukemia/lymphoma (ATLL).'' The second case, a 33-year-old man, complained of arthralgia in his hands and feet; radiographs showed severe localized demineralization and pathologic fractures. Specimens of his peripheral blood, cervical lymph nodes, and bone marrow revealed ATLL cells. (orig.)

Identification of a subset of perpheral T-cell lymphoma, not otherwise specified, characterized by FOXP3-positive regulatory T-cell phenotype, HTLV-1 negativity and poor outcome

DEFF Research Database (Denmark)

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

2014-01-01

Identification of a subset of perpheral T-cell lymphoma, not otherwise specified, characterized by FOXP3-positive regulatory T-cell phenotype, HTLV-1 negativity and poor outcome.......Identification of a subset of perpheral T-cell lymphoma, not otherwise specified, characterized by FOXP3-positive regulatory T-cell phenotype, HTLV-1 negativity and poor outcome....

Orbital involvement by non-Hodgkin lymphoma NK T cells.

Science.gov (United States)

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

2014-11-01

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

Interaction between host T cells and Reed-Sternberg cells in Hodgkin lymphomas

NARCIS (Netherlands)

Poppema, S; van den Berg, Anke

2000-01-01

Recent studies provide evidence that Reed-Sternberg (R-S) cells produce factors that may explain the characteristic inflammatory infiltrate in the affected tissues of Hodgkin lymphoma. The various chemokines and cytokines that are produced lead to a preferential influx of Th2-type T cells and

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%, P<0.001). Notably, the survival time of the 5 nodal lymphoma patients with γδ T-cell phenotype was within 3 months, which was inferior to those of αβ T and TCR-silent types (P=0.003), and 3 of those with available clinical information were all found to be associated with autoimmune diseases. These data suggest that nodal EBV CTL is distinct from ENKTL.

Primary Cutaneous CD4-Positive Small/Medium Pleomorphic T-cell Lymphoma – A Case Report

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Micković Milena

2016-12-01

Full Text Available Primary cutaneous CD4-positive small- to medium-sized pleomorphic T-cell lymphoma is a provisional entity in the 2005 WHO-EORTC classification for cutaneous lymphomas. It is a rare condition and, in most cases, it has a favorable clinical course and prognosis. Primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoma (PCSM-TCL is defined as a cutaneous T-cell lymphoma with predominantly small- to medium-sized CD4-positive pleomorphic T-cells without a history of patches and plaques typical of mycosis fungoides. PCSM-TCL usually presents as a solitary plaque or tumor on the head, neck, trunk or upper extremities and it is considered to have indolent clinical behavior. Histologically, it is characterized by a dense infiltration of small/medium-sized pleomorphic T-cells that involves the entire dermal thickness, often with nodular extension into the hypodermis. Using immunohistochemical staining, the majority of the reported cases proved to be CD3, CD4 positive and CD8, CD30 negative. However, due to the rarity and heterogeneity of the PCSM-TCL, precise clinicopathologic characteristics of PCSM-TCL have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatments.

Neurofibromin 1 Impairs Natural Killer T-Cell-Dependent Antitumor Immunity against a T-Cell Lymphoma

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Jianyun Liu

2018-01-01

Full Text Available Neurofibromin 1 (NF1 is a tumor suppressor gene encoding a Ras GTPase that negatively regulates Ras signaling pathways. Mutations in NF1 are linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. In terms of antitumor immunity, CD1d-dependent natural killer T (NKT cells play an important role in the innate antitumor immune response. Generally, Type-I NKT cells protect (and Type-II NKT cells impair host antitumor immunity. We have previously shown that CD1d-mediated antigen presentation to NKT cells is regulated by cell signaling pathways. To study whether a haploinsufficiency in NF1 would affect CD1d-dependent activation of NKT cells, we analyzed the NKT-cell population as well as the functional expression of CD1d in Nf1+/− mice. Nf1+/− mice were found to have similar levels of NKT cells as wildtype (WT littermates. Interestingly, however, reduced CD1d expression was observed in Nf1+/− mice compared with their WT littermates. When inoculated with a T-cell lymphoma in vivo, Nf1+/− mice survived longer than their WT littermates. Furthermore, blocking CD1d in vivo significantly enhanced antitumor activity in WT, but not in Nf1+/− mice. In contrast, a deficiency in Type-I NKT cells increased antitumor activity in Nf1+/− mice, but not in WT littermates. Therefore, these data suggest that normal NF1 expression impairs CD1d-mediated NKT-cell activation and antitumor activity against a T-cell lymphoma.

Primary Hepatosplenic B-cell Lymphoma: Initial Diagnosis and Assessment of Therapeutic Response with F-18 FDG PET/CT

International Nuclear Information System (INIS)

Kang, Sung Min; Lee, Hong Je; Seo, Ji Hyoung; Lee, Sang Woo; Ahn, Byeong Cheol; Lee, Jae Tae

2008-01-01

A 52-year-old woman with a history of general weakness, fatigue, weight loss, elevated serum levels of liver transaminase enzyme for three months underwent an F-18 FDG PET/CT to evaluate a cause of the hepatosplenomegaly found on abdominal ultrasonography. Initial PET/CT revealed markedly enlarged liver and spleen with intense FDG uptake. Otherwise, there were no areas of abnormal FDG uptake in whole body image. Histological evaluation by a hepatic needle biopsy demonstrated diffuse large B cell type lymphoma and final diagnosis for this patient was hepatosplenic B-cell lymphoma. She received five cycles of CHOP chemotherapy, and second PET/CT was followed after then. Follow-up PET-CT revealed normal sized liver with disappearance of abnormal FDG uptake. Hepatosplenic B-cell lymphoma is relatively rare and mostly presents as single or multiple nodules. Diffuse type hepatosplenic lymphoma is extremely rare and poorly recognized entity. The diagnosis is very difficult and complicated by the presence of misleading symptoms.4 In this rare hepatosplenic B-cell lymphoma case, F-18 FDG PET/CT provided a initial diagnostic clue of hepatosplenic lymphoma and an accurate chemotherapy response

Primary Hepatosplenic B-cell Lymphoma: Initial Diagnosis and Assessment of Therapeutic Response with F-18 FDG PET/CT

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Kang, Sung Min; Lee, Hong Je; Seo, Ji Hyoung; Lee, Sang Woo; Ahn, Byeong Cheol; Lee, Jae Tae [Kyungpook National University Hospital, Daegu (Korea, Republic of)

2008-08-15

A 52-year-old woman with a history of general weakness, fatigue, weight loss, elevated serum levels of liver transaminase enzyme for three months underwent an F-18 FDG PET/CT to evaluate a cause of the hepatosplenomegaly found on abdominal ultrasonography. Initial PET/CT revealed markedly enlarged liver and spleen with intense FDG uptake. Otherwise, there were no areas of abnormal FDG uptake in whole body image. Histological evaluation by a hepatic needle biopsy demonstrated diffuse large B cell type lymphoma and final diagnosis for this patient was hepatosplenic B-cell lymphoma. She received five cycles of CHOP chemotherapy, and second PET/CT was followed after then. Follow-up PET-CT revealed normal sized liver with disappearance of abnormal FDG uptake. Hepatosplenic B-cell lymphoma is relatively rare and mostly presents as single or multiple nodules. Diffuse type hepatosplenic lymphoma is extremely rare and poorly recognized entity. The diagnosis is very difficult and complicated by the presence of misleading symptoms.4 In this rare hepatosplenic B-cell lymphoma case, F-18 FDG PET/CT provided a initial diagnostic clue of hepatosplenic lymphoma and an accurate chemotherapy response.

[Autologous regulatory T cells can suppress the proliferation of lymphoma cell line in vitro].

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Ying, Zhi-Tao; Guo, Jun; Ren, Jun; Kong, Yan; Yuan, Zhi-Hong; Liu, Xi-Juan; Zhang, Chen; Zheng, Wen; Song, Yu-Qin; Zhang, Yun-Tao; Zhu, Jun

2009-06-01

This study was aimed to investigate the suppressive effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cell line and to explore its mechanism. C57BL/6 Mouse Treg cells were isolated by MACS (magnetic cell sorting). The purity and the expression of Foxp3 were detected by flow cytometry. The suppressive effect of sorted Treg cells on EL4 cells was detected by MTT assay. The secretion of TGF-beta1 and IL-10 was examined by enzyme-linked immunosorbent assay (ELISA). The results showed that CD4(+)CD25(+) T cells could be successfully isolated by MACS with the purity reaching 91.6% and the expression level of Foxp3 was 78.9%. The ratio of viable cells was more than 95%. Regulatory T cells could suppress the proliferation of EL4 cells effectively in the presence of antigen presenting cells (APCs). And the suppressive effect was most significant at 1:1 ratio. In addition, the suppression still existed without APCs. TGF-beta1 and IL-10 could not be detected by ELISA. It is concluded that the Treg cells can suppress T lymphoma cell in vitro. The suppressive effect of Treg cells works in dose-dependent manner, but not in cytokine-dependent manner. The mechanism of this suppression may take effect through cell-cell contact.

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

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

2015-03-01

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

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

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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.

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

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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

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

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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.

A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma

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Daisuke Usuda

2017-11-01

Full Text Available A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.

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Lee Ratner

Full Text Available Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggested that secondary genetic or epigenetic changes are important in disease pathogenesis.We prospectively investigated combination chemotherapy followed by antiretroviral therapy for this disorder. Nineteen patients were prospectively enrolled between 2002 and 2006 at five medical centers in a phase II clinical trial of infusional chemotherapy with etoposide, doxorubicin, and vincristine, daily prednisone, and bolus cyclophosphamide (EPOCH given for two to six cycles until maximal clinical response, and followed by antiviral therapy with daily zidovudine, lamivudine, and alpha interferon-2a for up to one year. Seven patients were on study for less than one month due to progressive disease or chemotherapy toxicity. Eleven patients achieved an objective response with median duration of response of thirteen months, and two complete remissions. During chemotherapy induction, viral RNA expression increased (median 190-fold, and virus replication occurred, coincident with development of disease progression.EPOCH chemotherapy followed by antiretroviral therapy is an active therapeutic regimen for adult T-cell leukemia-lymphoma, but viral reactivation during induction chemotherapy may contribute to treatment failure. Alternative therapies are sorely needed in this disease that simultaneously prevent virus expression, and are cytocidal for malignant cells.

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

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

2014-12-01

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

Multicentric epitheliotropic T-cell lymphoma in an African hedgehog (Atelerix albiventris).

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Chung, Tae-Ho; Kim, Hyo-Jin; Choi, Ul-Soo

2014-12-01

A 2-year-old female African hedgehog was presented with a 5-month history of pruritus, and diffuse spine and hair loss. A dermatologic examination revealed erythema, excoriation, scales, and crusting affecting the face, flanks, forelimbs, hindlimbs, and dorsal and ventral abdomen. Fine-needle aspiration was performed and skin biopsies were taken from several lesions for cytologic and histologic evaluation. The aspirates yielded smears characterized by a monomorphic population of medium-sized to large lymphocytes with scant to moderate amounts of clear to moderately basophilic cytoplasm and distinct nucleoli along with a low number of cytoplasmic fragments. On histopathologic examination, there were dense dermal lymphoid infiltrates invading the dermis and a monomorphic population of round cells that had infiltrated the overlying epidermis. Epitheliotropic cutaneous lymphoma was diagnosed based on morphologic features. Additional immunochemical analysis using anti-CD3 and anti-CD79a antibodies revealed strong CD3 expression by the tumor cells, which confirmed epitheliotropic cutaneous T-cell lymphoma. This is the first description of a multicentric pattern of epitheliotropic cutaneous T-cell lymphoma in an African hedgehog. © 2014 American Society for Veterinary Clinical Pathology.

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

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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.

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

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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.

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

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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

Impact of Autologous and Allogeneic Stem Cell Transplantation in Peripheral T-Cell Lymphomas

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Peter Reimer

2010-01-01

Full Text Available Peripheral T/NK-cell lymphomas (PTCLs are rare malignancies characterized by poor prognosis. So far, no standard therapy has been established, due to the lack of randomised studies. High-dose therapy and autologous stem cell transplantation (HDT-autoSCT have shown good feasibility with low toxicity in retrospective studies. In relapsing and refractory PTCL several comparison analyses suggest similar efficacy for PTCL when compared with aggressive B-cell lymphoma. In the upfront setting, prospective data show promising results with a long-lasting overall survival in a relevant subset of patients. Achieving a complete remission at transplantation seems to be the most important prognostic factor. Allogeneic stem cell transplantation (alloSCT has been investigated only as salvage treatment. Especially when using reduced intensity conditioning regimen, eligible patients seem to benefit from this approach. To define the role for upfront stem cell transplantation a randomised trial by the German High-Grade Non-Hodgkin Lymphoma Study Group comparing HDT-autoSCT and alloSCT will be initiated this year.

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

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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 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. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells.

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Huang, Yu-Hsuan; Tsai, Kevin; Tan, Sara Y; Kang, Sohyeong; Ford, Mandy L; Harder, Kenneth W; Priatel, John J

2017-01-01

Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8 + T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a - / - CD8 + T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a - / - CD8 + T cells responded equivalently to wild-type CD8 + T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8 + T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8 + T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8 + T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas.

2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells

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2017-01-01

ABSTRACT Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein–Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8+ T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a−/− CD8+ T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a−/− CD8+ T cells responded equivalently to wild-type CD8+ T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8+ T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8+ T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8+ T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas. PMID:28344876

Dysregulated choline metabolism in T-cell lymphoma: role of choline kinase-α and therapeutic targeting

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Xiong, J; Bian, J; Wang, L; Zhou, J-Y; Wang, Y; Zhao, Y; Wu, L-L; Hu, J-J; Li, B; Chen, S-J; Yan, C; Zhao, W-L

2015-01-01

Cancer cells have distinct metabolomic profile. Metabolic enzymes regulate key oncogenic signaling pathways and have an essential role on tumor progression. Here, serum metabolomic analysis was performed in 45 patients with T-cell lymphoma (TCL) and 50 healthy volunteers. The results showed that dysregulation of choline metabolism occurred in TCL and was related to tumor cell overexpression of choline kinase-α (Chokα). In T-lymphoma cells, pharmacological and molecular silencing of Chokα significantly decreased Ras-GTP activity, AKT and ERK phosphorylation and MYC oncoprotein expression, leading to restoration of choline metabolites and induction of tumor cell apoptosis/necropotosis. In a T-lymphoma xenograft murine model, Chokα inhibitor CK37 remarkably retarded tumor growth, suppressed Ras-AKT/ERK signaling, increased lysophosphatidylcholine levels and induced in situ cell apoptosis/necropotosis. Collectively, as a regulatory gene of aberrant choline metabolism, Chokα possessed oncogenic activity and could be a potential therapeutic target in TCL, as well as other hematological malignancies with interrupted Ras signaling pathways

Ocular and multicentric T-cell lymphoma in horse

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Mariana C. Oliveira

2016-11-01

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

Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies.

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Prakash, Ajay; Diefenbach, Catherine S

2018-06-08

The activity of T cell mediated immunotherapies in B cell lymphoma has been limited to date. The novel bi-specific antibody CD20-TCB, has a 2:1 antibody design to maximize T cell engagement, and demonstrates activity in preclinical models. This may represent a novel therapeutic approach for patients with relapsed/refractory NHL. Copyright ©2018, American Association for Cancer Research.

[Regulatory T cells inhibit proliferation of mouse lymphoma cell line EL4 in vitro].

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Zhang, Chen; Kong, Yan; Guo, Jun; Ying, Zhi-Tao; Yuan, Zhi-Hong; Zhang, Yun-Tao; Zheng, Wen; Song, Yu-Qin; Li, Ping-Ping; Zhu, Jun

2010-10-01

This study was aimed to investigate the effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cells and its mechanism in vitro. C57BL/6 mouse Treg cells were isolated by magnetic cell sorting (MACS). The purity of Treg cells and their expression of Foxp3 were identified by flow cytometry (FCM) and PT-PCR respectively. The suppression of Treg cells on EL4 cells was detected by 3H-TdR method. At the same time, enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of cytokine TGF-β1 and IL-10. The results showed that CD4+CD25+ T cells could be successfully isolated by MACS with the purity reaching 94.52% and the expression of Foxp3 reaching 84.72%. After sorting, the expression of Foxp3 mRNA could be detected by RT-PCR. 3H-TdR assay confirmed that regulatory T cells could suppress the proliferation of EL4 cells with or without antigen presenting cells (APC) or dendritic cells (DC), APC or DC might effectively enhance the suppression. In addition, DC alone also suppressed the proliferation. TGF-β1 and IL-10 could be detected in the supernatant by ELISA. It is concluded that the Treg cells can obviously suppress the proliferation of T cell lymphoma cells in vitro, APC or DC can enhance this suppressive effect, while the DC alone also can suppress the proliferation of EL4 cells, the TGF-β1 and IL-10 cytokine pathway may be one of the mechanisms of suppression.

iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo

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Bassiri, Hamid; Das, Rupali; Guan, Peng; Barrett, David M.; Brennan, Patrick J.; Banerjee, Pinaki P.; Wiener, Susan J.; Orange, Jordan S.; Brenner, Michael B.; Grupp, Stephan A.; Nichols, Kim E.

2013-01-01

Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth of tumors. To gain insights into the direct contribution of iNKT cells to tumor immune surveillance, we developed in vitro and in vivo systems to selectively examine the antitumor activity of iNKT cells in the absence of other cytolytic effectors. Using the EL4 T-lymphoma cell line as a model, we find that iNKT cells exert robust and specific lysis of tumor cells in vitro in a manner that is differentially-induced by iNKT cell agonists of varying TCR affinities, such as OCH, α-galactosyl ceramide and PBS44. In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of T cell receptor (TCR) signaling, or loss of perforin expression significantly reduce iNKT cell killing. Consistent with these findings, iNKT cell reconstitution of T, B, and NK cell-deficient mice slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms. Together, these observations establish that iNKT cells are sufficient to control the growth of T-lymphoma in vitro and in vivo. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T-lymphoma. PMID:24563871

iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo .

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Bassiri, Hamid; Das, Rupali; Guan, Peng; Barrett, David M; Brennan, Patrick J; Banerjee, Pinaki P; Wiener, Susan J; Orange, Jordan S; Brenner, Michael B; Grupp, Stephan A; Nichols, Kim E

2014-01-01

Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth of tumors. To gain insights into the direct contribution of iNKT cells to tumor immune surveillance, we developed in vitro and in vivo systems to selectively examine the antitumor activity of iNKT cells in the absence of other cytolytic effectors. Using the EL4 T-lymphoma cell line as a model, we found that iNKT cells exert robust and specific lysis of tumor cells in vitro in a manner that is differentially induced by iNKT cell agonists of varying T-cell receptor (TCR) affinities, such as OCH, α-galactosyl ceramide, and PBS44. In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of TCR signaling, or loss of perforin expression significantly reduce iNKT cell killing. Consistent with these findings, iNKT cell reconstitution of T, B, and NK cell–deficient mice slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms. Together, these observations establish that iNKT cells are sufficient to control the growth of T lymphoma in vitro and in vivo. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T lymphoma. ©2013 AACR.

Allogeneic hematopoietic stem cell transplantation in Primary Cutaneous T Cell Lymphoma.

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Cudillo, Laura; Cerretti, Raffaella; Picardi, Alessandra; Mariotti, Benedetta; De Angelis, Gottardo; Cantonetti, Maria; Postorino, Massimiliano; Ceresoli, Eleonora; De Santis, Giovanna; Nasso, Daniela; Pisani, Francesco; Scala, Enrico; Di Piazza, Fabio; Lanti, Alessandro

2018-06-01

In our retrospective study, 16 patients affected by advanced cutaneous T cell lymphoma (CTCL) underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two patients (12.5%) were in complete remission (CR), nine (56.3%) in partial remission (PR), and five (31.2%) with active disease. The patients were transplanted from an HLA-identical (n = 7) from a mismatched (n = 1) or haploidentical (n = 1) sibling, from matched unrelated donor (n = 5), or from a single cord blood unit (n = 2). Conditioning regimen was standard myeloablative in 6 patients and at reduced intensity in 10. Seven patients died from non relapse mortality (NRM) and four patients relapsed or progressed, three of them achieved a second CR after donor lymphocyte infusion (DLI) or chemotherapy plus DLI. To date, with a median follow-up of 76 months (range 6-130), nine patients are alive, eight in CR, and one with active disease. Overall survival (OS) and disease-free survival (DFS) at 1 and 10 years are 61% (95% CI 40-91%) and 54% (95% CI 33-86%), 40% (95% CI 22-74%), and 34% (95% CI 16-68%), respectively. The time from diagnosis to transplant seems to influence negatively both OS (log-rank p < 0.04) and DFS (log-rank p < 0.05). Our results confirm on a long follow-up that CTCL appears particularly susceptible to the graft versus lymphoma (GVL) effect, so that allogeneic HSCT represents a possibility of cure for advanced CTCL. The timing of HSCT in the clinical course of disease remains an open issue.

Management of patients with non-Hodgkin’s lymphoma: focus on adoptive T-cell therapy

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Perna SK

2015-03-01

Full Text Available Serena Kimi Perna,1 Leslie E Huye,1,† Barbara Savoldo1,2 1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Houston, TX, 2Department of Pediatrics, Texas Children's Hospital, Houston, TX, USA  †Leslie E Huye passed away on January 1st, 2015 Abstract: Non-Hodgkin's lymphoma (NHL represents a heterogeneous group of malignancies with high diversity in terms of biology, clinical responses, and prognosis. Standard therapy regimens produce a 5-year relative survival rate of only 69%, with the critical need to increase the treatment-success rate of this patient population presenting at diagnosis with a median age of 66 years and many comorbidities. The evidence that an impaired immune system favors the development of NHL has opened the stage for new therapeutics, and specifically for the adoptive transfer of ex vivo-expanded antigen-specific T-cells. In this review, we discuss how T-cells specific for viral-associated antigens, nonviral-associated antigens expressed by the tumor, T-cells redirected through the expression of chimeric antigen receptors, and transgenic T-cell receptors against tumor cells have been developed and used in clinical trials for the treatment of patients with NHLs. Keywords: adoptive immunotherapy, cytotoxic T lymphocytes (CTLs, chimeric antigen receptor (CAR, transgenic T-cell receptors 

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

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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.

Spontaneous regression of primary cutaneous diffuse large B-cell lymphoma, leg type with significant T-cell immune response

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Paul M. Graham, DO

2018-05-01

Full Text Available We report a case of histologically confirmed primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT that subsequently underwent spontaneous regression in the absence of systemic treatment. The case showed an atypical lymphoid infiltrate that was CD20+ and MUM-1+ and CD10–. A subsequent biopsy of the spontaneously regressed lesion showed fibrosis associated with a lymphocytic infiltrate comprising reactive T cells. PCDLBCL-LT is a cutaneous B-cell lymphoma with a poor prognosis, which is usually treated with chemotherapy. We describe a case of clinical and histologic spontaneous regression in a patient with PCDLBCL-LT who had a negative systemic workup but a recurrence over a year after his initial presentation. Key words: B cell, lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, regression

F-18 FDG PET/CT Findings of Subcutaneous Panniculitis - Like T- Cell Lymphoma : A Case Report

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Kong, Eun Jung; Cho, Ihn Ho; Chun, Kyung Ah; Bae, Yeung Kyung; Choi, Joon Hyuk; Hyun, Myung Soo

2009-01-01

F-18 FDG PET is a metabolic imaging modality that is efficacious in staging and assessment of treatment response for variety of lymphomas. We report usefulness of F-18 FDG PET/CT in evaluating severity of the disease and response to therapy in a patient with subcutaneous panniculitis- like T-cell lymphoma (SPTCL). Here we describe a case of SPTCL in 24-year-old man who had wide spread firm and tender nodular lesions with increased F-18 FDG uptake. After chemotherapy follow up F-18 FDG PET/CT image shows disseminated malignancy and then the patient died with hemophagocytic syndrome. This report suggests that F-18 FDG PET/CT may be useful in determining disease activity at the time of initial diagnosis, after treatment, and evaluating a suspected outcome of SPTCL

Tofacitinib induces G1 cell-cycle arrest and inhibits tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells.

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Ando, Shotaro; Kawada, Jun-Ichi; Watanabe, Takahiro; Suzuki, Michio; Sato, Yoshitaka; Torii, Yuka; Asai, Masato; Goshima, Fumi; Murata, Takayuki; Shimizu, Norio; Ito, Yoshinori; Kimura, Hiroshi

2016-11-22

Epstein-Barr virus (EBV) infects not only B cells, but also T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoma. These lymphoid malignancies are refractory to conventional chemotherapy. We examined the activation of the JAK3/STAT5 pathway in EBV-positive and -negative B, T and NK cell lines and in cell samples from patients with EBV-associated T cell lymphoma. We then evaluated the antitumor effects of the selective JAK3 inhibitor, tofacitinib, against these cell lines in vitro and in a murine xenograft model. We found that all EBV-positive T and NK cell lines and patient samples tested displayed activation of the JAK3/STAT5 pathway. Treatment of these cell lines with tofacitinib reduced the levels of phospho-STAT5, suppressed proliferation, induced G1 cell-cycle arrest and decreased EBV LMP1 and EBNA1 expression. An EBV-negative NK cell line was also sensitive to tofacitinib, whereas an EBV-infected NK cell line was more sensitive to tofacitinib than its parental line. Tofacitinib significantly inhibited the growth of established tumors in NOG mice. These findings suggest that tofacitinib may represent a useful therapeutic agent for patients with EBV-associated T and NK cell lymphoma.

Use of antibodies against the variable regions of the T-cell receptor alpha/beta heterodimer for the study of cutaneous T-cell lymphomas.

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Ralfkiaer, E; Wollf-Sneedorff, A; Vejlsgaard, G L

1991-11-01

Recent studies have suggested that antibodies against the variable (V) regions of the T-cell antigen receptor (TCR) may be used as markers for clonality and malignancy in T-cell infiltrates. We have investigated this by examining biopsy samples from 45 patients with cutaneous T-cell lymphomas (CTCL) for reactivity with seven antibodies against different V-gene families on the TCR alpha/beta heterodimer, i.e. ICI (V beta 5a), W112 (V beta 5b), OT145 (V beta 6a), 16G8 (V beta 8a), S511 (V beta 12a), F1 (V alpha 2a) and LC4 (alpha beta Va). Serial biopsies were available in 13 patients and a total of 62 samples were studied. The neoplastic cells in five cases were positive for either V beta 5 (one case), V beta 6 (one case), V beta 8 (two cases) or V beta 12 (one case). In the remaining 40 cases, no staining was seen of the neoplastic cells. These findings indicate that while antibodies against the TCR V-regions may be used as clonotypic markers for certain T-cell neoplasms, there is as yet not a sufficient number of anti-TCR V-region antibodies available for the routine diagnosis of these conditions.

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

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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

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

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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

Determination of DNA-synthetizing lymphatic cells as a kinetic and prognostic factor in non-Hodgkin lymphoma

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Heiss, F.

1982-01-01

A differentiated clinical and pathoanatomical classification of non-Hodgkin lymphomas is presented. On this basis, diagnostic, prognostic and pathophysiological information on the main types of lymphoma can be obtained from the measurement of the rosette-forming cell fraction (T-cell fraction) and from the autoradiographic determination of the proliferating cell fraction. This approach under the aspect of proliferation kinetics was employed in 9 patients with chronic B-lymphadenosis, 3 patients with chronic T-lymphadenosis, 14 patients with immunocytoma, 15 patients with different types of non-Hodgkin lymphoma, and 3 patients with angioimmunoblastic lymphadenopathy, both for primary diagnosis and in follow-up examinations. (orig./MG) [de

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

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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.

Baicalein induces cell death in murine T cell lymphoma via inhibition of thioredoxin system.

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Patwardhan, Raghavendra S; Pal, Debojyoti; Checker, Rahul; Sharma, Deepak; Sandur, Santosh K

2017-10-01

We have earlier demonstrated the radioprotective potential of baicalein using murine splenic lymphocytes. Here, we have studied the effect of baicalein on murine T cell lymphoma EL4 cells and investigated the underlying mechanism of action. We observed that baicalein induced a dose dependent cell death in EL4 cells in vitro and significantly reduced the frequency of cancer stem cells. Previously, we have reported that murine and human T cell lymphoma cells have increased oxidative stress tolerance capacity due to active thioredoxin system. Hence, we monitored the effect of baicalein on thioredoxin system in EL4 cells. Docking studies revealed that baicalein could bind to the active site of thioredoxin reductase. Baicalein treatment led to significant reduction in the activity of thioredoxin reductase and nuclear levels of thioredoxin-1 thereby increasing ASK1 levels and caspase-3 activity. Interestingly, CRISPR-Cas9 based knock-out of ASK1 or over-expression of thioredoxin-1 abolished anti-tumor effects of baicalein in EL4 cells. Further, baicalein administration significantly reduced intra-peritoneal tumor burden of EL4 cells in C57BL/6 mice. Thus, our study describes anti-tumor effects of baicalein in EL4 cells via inhibition of thioredoxin system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Epstein-Barr virus-containing T-cell lymphoma presents with hemophagocytic syndrome mimicking malignant histiocytosis.

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Su, I J; Hsu, Y H; Lin, M T; Cheng, A L; Wang, C H; Weiss, L M

1993-09-15

The previously designated malignant histiocytosis (MH) may include lymphoid neoplasms of T-cell lineage as well as patients with benign virus-associated hemophagocytic syndrome (VAHS). In this study, the association of Epstein-Barr virus (EBV) with T cell lymphomas which present with clinicopathologic features indistinguishable from malignant histiocytosis (MH) was investigated further. Four adult patients, three women and one man, were admitted because of fever, cutaneous lesions, hepatosplenomegaly, and jaundice. Laboratory examinations revealed pancytopenia, abnormal liver functions and coagulopathy. All patients ran a fulminant course terminating in a hemophagocytic syndrome within 1 month. Immunophenotypic study, Southern blot analysis, and in situ hybridization were performed on the specimens obtained from the four patients. The biopsy-necropsy specimens from skin, liver, spleen, and bone marrow showed infiltration of atypical large cells with reactive histiocytosis and florid hemophagocytosis activity. Based on the clinical and histologic findings, these cases would have been designated as MH by previous criteria. Immunophenotypic, Southern blot, and in situ hybridization studies, however, showed clonotypic proliferation of EBV genomes in the nuclei of the large atypical cells that expressed T-cell antigens. Therefore, these patients should be diagnosed as a recently described EBV-associated peripheral T-cell lymphoma (EBV-PTCL). EBV-PTCL may present with a fulminant hemophagocytic syndrome indistinguishable from the previously designated MH. This finding represents a step forward in our changing concept regarding MH, some of which only recently has been suggested to be of T-cell lymphoma origin. Differentiation from benign VAHS is clinically important. Features useful in this distinction are tabulated and discussed.

Primary "cutaneous" T-cell anaplastic large cell lymphoma, CD30+, neutrophil-rich variant with subcutaneous panniculitic lesions, in a post-renal transplant patient: report of unusual case and literature review.

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Salama, S

2005-06-01

Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.

Incidence of adult T-cell leukemia/lymphoma in nonendemic areas.

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Yoshida, Noriaki; Chihara, Dai

2015-02-01

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm with extremely poor prognosis caused by human T-cell leukemia virus type 1 (HTLV-1). The distribution of HTLV-1 and the incidence of ATLL in endemic areas have been well described, however, little is known about the incidences and the trends of the disease in nonendemic areas. Recently, studies have shown that the HTLV-1 carriers are increasing in nonendemic areas. Also, the incidence of ATLL seems to be significantly increasing in nonendemic areas suggesting that HTLV-1 carriers have emigrated from endemic areas. These epidemiologic studies indicate the necessity of edification of the disease caused by HTLV-1 and establishing appropriate preventive methods against infection in nonendemic areas.

Genetic alterations in B-cell non-Hodgkin's lymphoma

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Magić Zvonko

2005-01-01

Full Text Available Background. Although the patients with diagnosed B-NHL are classified into the same disease stage on the basis of clinical, histopathological, and immunological parameters, they respond significantly different to the applied treatment. This points out the possibility that within the same group of lymphoma there are different diseases at molecular level. For that reason many studies deal with the detection of gene alterations in lymphomas to provide a better framework for diagnosis and treatment of these hematological malignancies. Aim. To define genetic alterations in the B-NHL with highest possibilities for diagnostic purposes and molecular detection of MRD. Methods. Formalin fixed and paraffin embedded lymph node tissues from 45 patients were examined by different PCR techniques for the presence of IgH and TCR γ gene rearrangement; K-ras and H-ras mutations; c-myc amplification and bcl-2 translocation. There were 34 cases of B-cell non-Hodgkin’s lymphoma (B-NHL, 5 cases of T-cell non-Hodgkin’s lymphoma (T-NHL and 6 cases of chronic lymphadenitis (CL. The mononuclear cell fraction of the peripheral blood of 12 patients with B-NHL was analyzed for the presence of monoclonality at the time of diagnosis and in 3 to 6 months time intervals after an autologous bone marrow transplantation (BMT. Results. The monoclonality of B-lymphocytes, as evidenced by DNA fragment length homogeneity, was detected in 88 % (30/34 of B-NHL, but never in CL, T-NHL, or in normal PBL. Bcl-2 translocation was detected in 7/31 (22.6% B-NHL specimens, c-myc amplification 9/31 (29%, all were more than doubled, K-ras mutations in 1/31 (3.23% and H-ras mutations in 2/31 (6.45% of the examined B-NHL samples. In the case of LC and normal PBL, however, these gene alterations were not detected. All the patients (12 with B-NHL had dominant clone of B-lymphocyte in the peripheral blood at the time of diagnosis while only in 2 of 12 patients MRD was detected 3 or 6 months after

Efficacy of pegaspargase in extra nodal natural killer/T-cell lymphoma nasal type: A case report from China

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Xingan Xiong

2015-01-01

Full Text Available Extranodal natural killer (NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. There is no known satisfactory treatment. The author herein to report one case of L-asparaginase extranodal NK/T-cell lymphoma primary treated with L-asparaginase methotrexate and dexamethasone.

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

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

1990-01-01

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

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

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Ralfkiaer, Ulrik; Hagedorn, Peter; Bangsgaard, Nannie

2011-01-01

from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) mi...

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

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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.

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

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Khanlari Mahsa

2012-12-01

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

Molecular diagnosis of Burkitt's lymphoma

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Dave, SS; Fu, K; Wright, GW; Lam, LT; Kluin, P; Boerma, EJ; Greiner, TC; Weisenburger, DD; Rosenwald, A; Ott, G; Muller-Hermelink, H; Gascoyne, RD; Delabie, J; Rimsza, LM; Braziel, RM; Grogan, TM; Campo, E; Jaffe, ES; Dave, BJ; Sanger, W; Bast, M; Vose, JM; Armitage, JO; Connors, JM; Smeland, EB; Kvaloy, S; Holte, H; Fisher, RI; Miller, TP; Montserrat, E; Wilson, WH; Bahl, M; Zhao, H; Yang, LM; Powell, J; Simon, R; Chan, WC; Staudt, LM

2006-01-01

Background: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.

Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas

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de Masson, Adèle; Beylot-Barry, Marie; Bouaziz, Jean-David; de Latour, Régis Peffault; Aubin, François; Garciaz, Sylvain; d’Incan, Michel; Dereure, Olivier; Dalle, Stéphane; Dompmartin, Anne; Suarez, Felipe; Battistella, Maxime; Vignon-Pennamen, Marie-Dominique; Rivet, Jacqueline; Adamski, Henri; Brice, Pauline; François, Sylvie; Lissandre, Séverine; Turlure, Pascal; Wierzbicka-Hainaut, Ewa; Brissot, Eolia; Dulery, Rémy; Servais, Sophie; Ravinet, Aurélie; Tabrizi, Reza; Ingen-Housz-Oro, Saskia; Joly, Pascal; Socié, Gérard; Bagot, Martine

2014-01-01

The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38–0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41–0.77) and progression-free survival 31% (95%CI: 0.19–0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1–0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3–6.2; P=0.01) but also transplant-related mortality (HR=10−7, 95%CI: 4.10−8–2.10−7; P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides. PMID:24213148

Nodular breast lymphoma

International Nuclear Information System (INIS)

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

1996-01-01

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

Adoptive transfer of murine T cells expressing a chimeric-PD1-Dap10 receptor as an immunotherapy for lymphoma.

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Lynch, Adam; Hawk, William; Nylen, Emily; Ober, Sean; Autin, Pierre; Barber, Amorette

2017-11-01

Adoptive transfer of T cells is a promising cancer therapy and expression of chimeric antigen receptors can enhance tumour recognition and T-cell effector functions. The programmed death protein 1 (PD1) receptor is a prospective target for a chimeric antigen receptor because PD1 ligands are expressed on many cancer types, including lymphoma. Therefore, we developed a murine chimeric PD1 receptor (chPD1) consisting of the PD1 extracellular domain fused to the cytoplasmic domain of CD3ζ. Additionally, chimeric antigen receptor therapies use various co-stimulatory domains to enhance efficacy. Hence, the inclusion of a Dap10 or CD28 co-stimulatory domain in the chPD1 receptor was compared to determine which domain induced optimal anti-tumour immunity in a mouse model of lymphoma. The chPD1 T cells secreted pro-inflammatory cytokines and lysed RMA lymphoma cells. Adoptive transfer of chPD1 T cells significantly reduced established tumours and led to tumour-free survival in lymphoma-bearing mice. When comparing chPD1 receptors containing a Dap10 or CD28 domain, both receptors induced secretion of pro-inflammatory cytokines; however, chPD1-CD28 T cells also secreted anti-inflammatory cytokines whereas chPD1-Dap10 T cells did not. Additionally, chPD1-Dap10 induced a central memory T-cell phenotype compared with chPD1-CD28, which induced an effector memory phenotype. The chPD1-Dap10 T cells also had enhanced in vivo persistence and anti-tumour efficacy compared with chPD1-CD28 T cells. Therefore, adoptive transfer of chPD1 T cells could be a novel therapy for lymphoma and inclusion of the Dap10 co-stimulatory domain in chimeric antigen receptors may induce a preferential cytokine profile and T-cell differentiation phenotype for anti-tumour therapies. © 2017 John Wiley & Sons Ltd.

CAR T-Cell therapy can lead to long-lasting remissions in patients with lymphoma | Center for Cancer Research

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More than three years after treatment, some clinical trial participants who received CAR T-cell therapy for diffuse large B-cell lymphoma remain in remission. These results are reported in a paper in Molecular Therapy by James Kochenderfer, M.D., of CCR's Experimental Transplantation and Immunology Branch. “This raises the possibility that CAR T cells can be curative for diffuse large B cell lymphoma,” Kochenderfer says.

Characterization of hydroxyurea (HYU) S49 T lymphoma cells

International Nuclear Information System (INIS)

Albert, D.A.; Gudas, L.J.

1986-01-01

This paper tests the hypotheses that in vivo ribonucleotide reductase activity and consequent deoxyribonucleoside triphosphate production is rate-limited by the availability of M2 activity. The authors selected and characterized cell lines with variable resistance to hydroxyurea and comparing them with wild type S49 T-lymphoma cells. Ribonucleotide reductase assay was measured and in the process C 14-CDP was added in the final volume of assay mixture. It is shown that hydroxourea reversibly binds to the tyrosine radical of the M2 subunit of ribonucleotide reductase that is required for catalytic activity

Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma

DEFF Research Database (Denmark)

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

2002-01-01

-Hodgkin's lymphoma. METHODS AND RESULTS: We have analysed sequential biopsies from 42 non-Hodgkin's lymphoma patients immunohistochemically for p53 alterations (based on p53 and p21Waf1 expression), as well as for expression of MDM2, p27Kip1 and cyclin D3. Relapse of follicle centre lymphoma was associated with p53...... alterations as 5/6 (83%) follicle centre lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. Of these cases, three showed transformation to diffuse large B-cell lymphoma. p53 alteration was also associated with relapse of de novo diffuse large B-cell lymphoma and T-cell non......-Hodgkin's lymphoma, as 2/5 (40%) diffuse large B-cell lymphomas and 3/9 (33%) T-cell non-Hodgkin's lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. No indolent non-Hodgkin's lymphoma case showed MDM2 over-expression at diagnosis, whereas 4/5 (80%) transformed diffuse large B-cell lymphomas...

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

International Nuclear Information System (INIS)

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

1990-01-01

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

PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro.

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Lina Quan

Full Text Available Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL is an aggressive malignancy that is largely resistant to current therapeutic regimens, and is an attractive target for immune-based therapies. Anti-programmed death-1 (PD-1 antibodies showed encouraging anti-tumor effects in both preclinical models and advanced solid and hematological malignancies, but its efficacy against EBV+DLBCL is unknown. Herein, we performed experiments using co-culture system with T cells and lymphoma cell lines including EBV+DLBCL and EBV-DLBCL [including germinal center B-cell like (GCB-DLBCL and non-GCB-DLBCL] in vitro. We show that lymphoma cells augmented the expression of PD-1 on T cells, decreased the proliferation of T cells, and altered the secretion of multiple cytokines. However, through PD-1 blockade, these functions could be largely restored. Notbaly, the effect of PD-1 blockade on antitumor immunity was more effective in EBV+DLBCL than that in EBV-DLBCL in vitro. These results suggest that T-cell exhaustion and immune escape in microenvironment is one of the mechanisms underlying DLBCL; and PD-1 blockade could present as a efficacious immunotherapeutic treatment for EBV+DLBCL.

Celiac disease and fulminant T lymphoma detected too late in a 35-year-old female patient: Case report

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Marinko Marušić

2011-08-01

Full Text Available Celiac disease is the most common chronic gastroenterological autoimmune disease characterized by gluten intolerance. The diagnosis of celiac disease and enteropathy-associated T cell lymphoma is often made when it is too late.Case report describes a 35-year-old female patient managed for one year under the diagnosis of inflammatory bowel disease and admitted to our hospital for exacerbation of the underlying disease. However, inflammatory bowel disease was ruled out by diagnostic work-up, while the clinical picture and the findings obtained raised suspicion of lymphoma. The patient’s condition was additionally complicated by fulminant course of the disease and ileus.Conclusion:Early diagnosis and appropriate treatment of the disease, and follow up of family members are crucial to prevent intestinal lymphoma development.

Detection of Tax-specific CTLs in lymph nodes of adult T-cell leukemia/lymphoma patients and its association with Foxp3 positivity of regulatory T-cell function.

Science.gov (United States)

Ichikawa, Ayako; Miyoshi, Hiroaki; Arakawa, Fumiko; Kiyasu, Junichi; Sato, Kensaku; Niino, Daisuke; Kimura, Yoshizo; Yoshida, Maki; Kawano, Riko; Muta, Hiroko; Sugita, Yasuo; Ohshima, Koichi

2017-06-01

Human T-cell lymphotropic virus type (HTLV)-1 Tax is a viral protein that has been reported to be important in the proliferation of adult T-cell leukemia/lymphoma (ATLL) cells and to be a target of HTLV-1-specific cytotoxic T lymphocytes (CTLs). However, it is not clear how Tax-specific CTLs behave in lymph nodes of ATLL patients. The present study analyzed the immunostaining of Tax-specific CTLs. Furthermore, ATLL tumor cells are known to be positive for forkhead box P3 (Foxp3)and to have a regulatory T (Treg)-cell-like function. The association between T-reg function and number and activity of Tax-specific CTLs was also investigated. A total of 15 ATLL lymphoma cases with human leukocyte antigen (HLA)-A24, for which Tax has a high affinity, were selected from the files of the Department of Pathology, School of Medicine, Kurume University (Kurume, Japan) using a polymerase chain reaction (PCR) method. Immunostaining was performed for cluster of differentiation (CD) 20, CD3, CD4, CD8, T-cell intracellular antigen-1 and Foxp3 in paraffin sections, and for Tax, interferon γ and HLA-A24 in frozen sections. In addition, the staining of Tax-specific CTLs (HLA-A24-restricted) was analyzed by MHC Dextramer ® assay in frozen sections. In addition, the messenger RNA expression of Tax and HTLV-1 basic leucine zipper factor were also evaluated by reverse transcription-PCR. Immunohistochemical staining of Tax protein in lymphoma tissue revealed the presence of positive lymphoma cells ranging from 5 to 80%, and immunohistochemical staining of HLA-A24 revealed the presence of positive lymphoma cells ranging from 1 to 95%. The expression of Tax and HLA-A24 was downregulated by viral function. Foxp3, a marker for Treg cells, was expressed in 0-90% of cells. Several cases exhibited Tax-specific CTL (HLA-A24-restricted)-positive cells, and there was an inverse correlation between Tax-specific CTLs and Foxp3. However, neither Tax nor HLA-A24 expression was associated with CTL or

Forodesine in the treatment of relapsed/refractory peripheral T-cell lymphoma: an evidence-based review

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Makita S

2018-04-01

Full Text Available Shinichi Makita,1 Akiko Miyagi Maeshima,2 Dai Maruyama,1 Koji Izutsu,1 Kensei Tobinai1 1Department of Hematology, 2Department of Pathology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan Abstract: T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma (PTCL generally have a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP/CHOP-like chemotherapy; once relapse occurs, it is mostly regarded as an incurable disease. To overcome the chemorefractoriness of PTCL, several novel agents have been developed. Since the first approval of pralatrexate, a dihydrofolate reductase inhibitor, for relapsed/refractory PTCL by the US Food and Drug Administration, several new agents, such as romidepsin (histone deacetylase inhibitor, brentuximab vedotin (antibody–drug conjugate targeting CD30, chidamide (histone deacetylase inhibitor, and mogamulizumab (anti-CC chemokine receptor 4 monoclonal antibody, have been approved as a therapeutic option for relapsed/refractory PTCL in several countries, including the US, Europe, China, and Japan. Forodesine is a novel, potent purine nucleoside phosphorylase inhibitor that is effective against T-cell malignancies. Although the clinical development of forodesine was discontinued in the US and Europe, a multicenter Phase I/II study of oral forodesine for relapsed PTCL was recently completed in Japan. The overall response rate was 24% (10 of 41 patients, which included four patients with complete response. In general, the toxicity of forodesine is manageable. As the study met the primary end point, forodesine was approved for the treatment of relapsed/refractory PTCL in Japan in March 2017, which was the first approval of forodesine in the world. As forodesine is an oral formulation, it is more convenient than other novel intravenous agents approved for PTCL

Immunohistochemical Characterization of Canine Lymphomas

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Roxana CORA

2017-11-01

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

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)

2017-11-15

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

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...... therapeutic agents may potentially exploit the phenotypic plasticity of CTCL such that the malignant T cells become vulnerable to antitumor immunity....... cells and other sources. IL-2-type cytokines activate STAT5 to promote expression of Treg-related FoxP3, while various cytokines can activate STAT3 to induce synthesis of IL-10 and IL-17. When the Treg phenotype is activated in the early stages of CTCL, “immune evasion” can occur, allowing the clonal T...

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...

L-type amino-acid transporter 1 (LAT1): a therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia

NARCIS (Netherlands)

Rosilio, C.; Nebout, M.; Imbert, V.; Griessinger, E.; Neffati, Z.; Benadiba, J.; Hagenbeek, T.; Spits, H.; Reverso, J.; Ambrosetti, D.; Michiels, J.-F.; Bailly-Maitre, B.; Endou, H.; Wempe, M. F.; Peyron, J.-F.

2015-01-01

The altered metabolism of cancer cells is a treasure trove to discover new antitumoral strategies. The gene (SLC7A5) encoding system L amino-acid transporter 1 (LAT1) is overexpressed in murine lymphoma cells generated via T-cell deletion of the pten tumor suppressor, and also in human T-cell acute

Extranodal NK/T Cell Lymphoma, Nasal Type (ENKTL-NT): An Update on Epidemiology, Clinical Presentation, and Natural History in North American and European Cases.

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Haverkos, Bradley M; Pan, Zenggang; Gru, Alejandro A; Freud, Aharon G; Rabinovitch, Rachel; Xu-Welliver, Meng; Otto, Brad; Barrionuevo, Carlos; Baiocchi, Robert A; Rochford, Rosemary; Porcu, Pierluigi

2016-12-01

Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with increasing incidence in the United States. Data on epidemiology, disease presentation, and outcome for European and North American ("Western") cases are very limited. We review published landmark clinical studies on ENKTL-NT in the West and report in detail recent data, including our institutional experience. We highlight key observations in its epidemiology, natural history, and trends in clinical management. In the USA, ENKTL-NT is more common among Asian Pacific Islanders (API) and Hispanics compared to non-Hispanic whites. Published studies indicate less heterogeneity in clinical presentation in Western ENKTL-NT compared to Asian patients. While there is variation in age at diagnosis, presence of antecedent lymphoproliferative disorders, and outcomes among racial/ethnic groups, the universal association of ENKTL-NT with EBV and the poor response of this neoplasm to anthracycline-based therapy is consistent across all geographic areas. Data on epidemiology, disease presentation, and clinical outcomes in mature T cell and NK cell (T/NK cell) neoplasms, including ENKTL-NT, in Europe and North America are very limited. As the classification and diagnostic characterization of the currently recognized T/NK cell lymphoma disease entities continue to evolve, gaps and inconsistencies in data reporting across different studies are being recognized. Despite these limitations, several studies from the USA suggest that the incidence of ENKTL-NT is higher in Asian Pacific Islanders (API) and non-white Hispanics and that outcomes may be worse in non-whites. However, the universal association of ENKTL-NT with Epstein-Barr virus (EBV) across all ethnic groups suggests a common pathogenesis. Given the overlap between the entities included in the category of T/NK cell neoplasms, there is a need to further define

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

Science.gov (United States)

Su, Shan; Cheng, Xinlai; Wink, Michael

2015-09-01

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

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

FOXP3 is a unique marker for CD4+CD25+ regulatory T cells (Tregs). In solid tumours, high numbers of Tregs are associated with a poor prognosis. Knowledge about the implications of Tregs for the behaviour of haematological malignancies is limited. In this study, skin biopsies from 86 patients...... 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....... In the remaining 85 cases, the atypical neoplastic infiltrate was either FOXP3 negative (n=80) or contained only very occasional weakly positive cells (n=5). By contrast, all biopsies showed varying numbers of strongly FOXP3+ tumour-infiltrating Tregs. MF with early or infiltrated plaques had significantly higher...

Peripheral T-Cell Lymphoma with Aberrant Expression of CD19, CD20, and CD79a: Case Report and Literature Review

Science.gov (United States)

Matnani, Rahul G.; Stewart, Rachel L.; Pulliam, Joseph; Jennings, Chester D.; Kesler, Melissa

2013-01-01

A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a), which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV) or Human Herpes Virus 8 (HHV-8). At the time of diagnosis, the PET scan demonstrated hypermetabolic neoplastic cells involving the left axilla, bilateral internal jugular areas, mediastinum, right hilum, bilateral lungs, and spleen. However, bone marrow biopsy performed for hemolytic anemia revealed normocellular bone marrow with trilineage maturation. The patient had no evidence of immunodeficiency or infection with EBV or HHV-8. This is the first reported case of a mature T-cell lymphoma with aberrant expression of three B-cell lineage markers. The current report also highlights the need for molecular gene rearrangement studies to determine the precise lineage of ambiguous neoplastic clones. PMID:24066244

Peripheral T-Cell Lymphoma with Aberrant Expression of CD19, CD20, and CD79a: Case Report and Literature Review

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Rahul G. Matnani

2013-01-01

Full Text Available A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a, which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV or Human Herpes Virus 8 (HHV-8. At the time of diagnosis, the PET scan demonstrated hypermetabolic neoplastic cells involving the left axilla, bilateral internal jugular areas, mediastinum, right hilum, bilateral lungs, and spleen. However, bone marrow biopsy performed for hemolytic anemia revealed normocellular bone marrow with trilineage maturation. The patient had no evidence of immunodeficiency or infection with EBV or HHV-8. This is the first reported case of a mature T-cell lymphoma with aberrant expression of three B-cell lineage markers. The current report also highlights the need for molecular gene rearrangement studies to determine the precise lineage of ambiguous neoplastic clones.

Malignant inflammation in cutaneous T-cell lymphoma-a hostile takeover

DEFF Research Database (Denmark)

Krejsgaard, Thorbjørn; Lindahl, Lise M; Mongan, Nigel P

2017-01-01

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage......, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early...... of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We...

Linfoma T subcutâneo do tipo paniculite: relato de um caso acometendo paciente pediátrico Subcutaneous panniculitic T cell lymphoma: a case report affecting a child

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Lúcia de Noronha

2001-01-01

Full Text Available Os autores relatam um caso de linfoma T subcutâneo do tipo paniculite em uma paciente feminina de 3 anos, apresentando havia um mês múltiplos nódulos subcutâneos, indolores, disseminados no abdome, região peitoral e cervical. Ao exame histopatológico, evidenciou-se um linfoma T infiltrando tecido adiposo subcutâneo. Os linfomas T subcutâneos representam uma entidade clinicopatológica distinta, sendo raro o acometimento pediátrico.We report a case of lypotrophic lymphoma affecting a 3-year-old child with 1-month history of nontender subcutaneous nodules disseminated throughout the abdomen, chest and cervical region. Histological examination showed a T-cell lymphoma affecting the subcutaneous tissue. Subcutaneous panniculitis-like T-cell lymphoma is an unusual cutaneous T-cell lymphoma that rarely affects pediatric patients.

A Multicentric T-Cell Lymphoma with a Plasmacytoid Morphology in a Dog

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Alissa Bally

2018-01-01

Full Text Available An 8-year-old male (neutered Labrador with a history of erythematous skin lesions and exercise intolerance for a prolonged period was suddenly found dead. Necropsy findings revealed an infiltrative, focally extensive mass which occupied 25% of the cardiac interventricular septum. Severe endocardiosis was also found on the bicuspid and tricuspid valves. The submandibular lymph nodes and kidneys were bilaterally enlarged, and the pre-hepatic lymph node and spleen were also enlarged. Multiple dermal pustules were present around the mouth and on the ear, and small ulcers were present on the tongue. Histopathological examination detected the presence of neoplastic lymphocytes with a plasmacytoid morphology in these tissues as well as in the tongue and skin lesions. Immunohistochemical (CD3+/CD18+ evaluation was consistent with a T-cell lymphoma, which could be classified as a peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS.

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

DEFF Research Database (Denmark)

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

2012-01-01

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

Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo.

Science.gov (United States)

Kaneko, Hitomi; Hori, Toshiyuki; Yanagita, Soshi; Kadowaki, Norimitsu; Uchiyama, Takashi

2005-03-01

OX40, a member of the TNF receptor superfamily, and its ligand (OX40L) play crucial roles in induction and maintenance of integrated T cell immune response. Engagement of OX40L delivers a costimulatory signal to T cells. In this study, we investigated whether inoculation of OX40L-transfected EL4, a murine T cell lymphoma cell line, could induce anti-lymphoma immunity in mice. Female C57BL/6 mice were inoculated with 1 x 10(5) cells of parental EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4 (EL4-mock), and then the tumor size, overall survival, CTL activity of spleen cells, and the immunohistochemistry were compared. While both parental EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than parental EL4 or EL4-mock. Pretreatment of mice with either anti-CD4 or anti-CD8 mAb accelerated the growth of EL4-OX40L, suggesting that both CD4+ and CD8+ T cells were involved in anti-lymphoma immunity. The immunohistochemical study revealed the infiltration of CD8+ T cells into the tumor of EL4-OX40L. In vitro CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had significant cytotoxic activity against parental EL4. The gene transfer of OX40L into lymphoma cells is an eligible and efficient modality to induce anti-lymphoma immunity.

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...

An Unusual Case of Marginal Zone B-Cell Lymphoma Arising in the Breast - Its Diagnosis and the Role of Radiotherapy in its Management.

LENUS (Irish Health Repository)

Rock, Kathy

2011-10-01

BACKGROUND: Primary lymphoma of the breast accounts for 0.04-0.5% of all breast malignancies and approximately 1% of all extranodal lymphomas. For stage IE node-negative disease, involved field radiotherapy is recommended except for very young women in whom the risk of breast cancer is a concern. The rate of complete response for limited stage extranodal marginal B-cell lymphoma is in excess of 90%. CASE REPORT: We report the case of a 62-year-old lady who presented with a unilateral painless palpable right breast lump. She subsequently underwent a trucut biopsy of the lesion. The histology revealed a low-grade B-cell non-Hodgkin\\'s lymphoma (NHL). Immunohistochemistry showed that more than 95% of the cells were B cells which were CD 20+\\/CD 45+ and BC L6+. This confirmed the diagnosis of marginal zone lymphoma. Staging work-up was negative for distant metastases. Serum alkaline phosphatase and lactate dehydrogenase were normal. The patient had no \\'B\\' symptoms. Her final diagnosis was clinical stage IAE NHL, and she was referred for curative radiotherapy. CONCLUSION: Radiation treatment is a safe and extremely effective modality of treatment for early stage I marginal zone B-cell lymphomas of the breast.

Safety and efficacy of pralatrexate in the management of relapsed or refractory peripheral T-cell lymphoma.

Science.gov (United States)

Rodd, Annabelle L; Ververis, Katherine; Karagiannis, Tom C

2012-01-01

Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas, with generally poor prognosis. Historically, there has been a lack of consensus regarding appropriate therapeutic measures for the disease, with conventional frontline chemotherapies being utilized in most cases. Following promising results obtained in 2009, the methotrexate analogue, pralatrexate, became the first drug to gain US FDA approval for the treatment of refractory PTCL. This antimetabolite was designed to have a higher affinity for reduced folate carrier (RFC) and folylpolyglutamate synthetase (FPGS). RFC is the principal transporter for cell entrance of folates and antifolates. Once inside the cell, pralatrexate is efficiently polyglutamated by FPGS. Pralatrexate has demonstrated varying degrees of efficacy in peripheral T-cell lymphoma, with response rates differing between the multiple subtypes of the disease. While phase III studies are still to be completed, early clinical trials indicate that pralatrexate is promising new therapeutic for PTCL.

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

Science.gov (United States)

2018-01-25

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

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

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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

Hydroa vacciniforme-like lymphoma with primarily periorbital swelling: 7 cases of an atypical clinical manifestation of this rare cutaneous T-cell lymphoma.

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Plaza, Jose A; Sangueza, Martin

2015-01-01

Hydroa vacciniforme-like lymphoma (HVL) is a rare cutaneous T-cell lymphoma that is usually seen in children of Hispanic or Asian origin. Association between chronic latent Epstein-Barr virus infection in both hydroa vacciniforme (HV) and HVL has been demonstrated and has recently been categorized by the World Health Organization as one of the Epstein Barr virus-positive lymphoproliferative disorders of childhood. Patients with HVL present with a cutaneous rash characterized by edema, blisters, ulcers, and scars mainly seen on the face and extremities that mimic HV; however, unlike in HV, the lesions tend to be extensive and deeper and are associated with severe scarring, necrosis, and systemic manifestations. We are reporting 7 cases of an unusual clinical variant of HVL with primarily periorbital edema. All of our patients in this series presented with progressive periorbital edema that was accompanied with systemic symptoms including fever, malaise, and lymphadenopathy. Most cases were initially misinterpreted as inflammatory processes including cellulitis, arthropod bite reactions, and periorbital lupus erythematosus. The biopsy of these lesions revealed an atypical lymphocytic infiltrate predominantly distributed in the deep dermis and in subcutaneous fat. Immunohistochemistry studies revealed a cytotoxic T-cell (CD8) profile. All cases were associated with Epstein-Barr virus infection. Our study presents a rare clinical variant of HVL with predominant periorbital edema. This variant could potentially be overlooked and misdiagnosed as an inflammatory condition; thus, it needs to be included in the differential diagnosis of periorbital edema in young patients.

Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models.

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Ng, Samuel Y; Yoshida, Noriaki; Christie, Amanda L; Ghandi, Mahmoud; Dharia, Neekesh V; Dempster, Joshua; Murakami, Mark; Shigemori, Kay; Morrow, Sara N; Van Scoyk, Alexandria; Cordero, Nicolas A; Stevenson, Kristen E; Puligandla, Maneka; Haas, Brian; Lo, Christopher; Meyers, Robin; Gao, Galen; Cherniack, Andrew; Louissaint, Abner; Nardi, Valentina; Thorner, Aaron R; Long, Henry; Qiu, Xintao; Morgan, Elizabeth A; Dorfman, David M; Fiore, Danilo; Jang, Julie; Epstein, Alan L; Dogan, Ahmet; Zhang, Yanming; Horwitz, Steven M; Jacobsen, Eric D; Santiago, Solimar; Ren, Jian-Guo; Guerlavais, Vincent; Annis, D Allen; Aivado, Manuel; Saleh, Mansoor N; Mehta, Amitkumar; Tsherniak, Aviad; Root, David; Vazquez, Francisca; Hahn, William C; Inghirami, Giorgio; Aster, Jon C; Weinstock, David M; Koch, Raphael

2018-05-22

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models.

MicroRNA Expression in Early Mycosis Fungoides Is Distinctly Different from Atopic Dermatitis and Advanced Cutaneous T-Cell Lymphoma

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Ralfkiaer, Ulrik; Lindahl, Lise Maria; 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...... is often impossible. MF usually takes an indolent course, but for unknown reasons may turn into an aggressive disease with a poor prognosis. Herein, we used a global quantitative real-time polymerase chain reaction platform to study microRNA (miR) expression in patients with early MF (n=13), more advanced...... CTCL (n=42), and atopic dermatitis (AD, n=20). Thirty-eight miRs were differentially expressed (≥2-fold) in early MF vs. AD and 36 in early MF vs. more advanced disease. miRs that distinguish early MF from AD included both up-regulated (miR-155, miR-146a, 146b-5p, miR-342-3p, let-7i*) and down...

Histone deacetylase inhibitors potentiate photochemotherapy in cutaneous T-cell lymphoma MyLa cells.

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Sung, Jane J; Ververis, Katherine; Karagiannis, Tom C

2014-02-05

Cutaneous T cell lymphomas (CTCL) represent rare extranodal non-Hodgkin's lymphomas, which are characterised by pleomorphic skin lesions and distinct T-cell markers. CTCL is a relatively benign disease in its early stages, but survival rates decrease significantly with progression. Histone deacetylase inhibitors (HDACi) have recently emerged as a new class of targeted anticancer therapies for CTCL, which have been shown to induce growth inhibition, terminal differentiation and apoptosis in various cancers in vitro and in vivo. In addition to the intrinsic anticancer properties of HDACi, recent studies have demonstrated its ability to synergise with phototherapy. In particular, we examine the therapeutic potential of HDACi in combination with ultraviolet A (UV-A) phototherapy, employing a halogenated DNA minor groove binding ligand called UVASens as a photosensitiser. In vitro studies have demonstrated that UVASens is approximately 1000-fold more potent than current psoralens. The extreme photopotency of UVASens allows the use of lower radiation doses minimising the carcinogenic risks associated with the long-term use of phototherapy. Considering, previous findings using the photosensitiser UVASens and potential synergy of HDACi with phototherapy, it was hypothesised that HDACi will augment photochemotherapy-induced cytotoxicity in CTCL MyLa cells. The findings indicated that combinations of UVASens/UV-A photochemotherapy and HDACi significantly decreased cell viability and increased apoptosis and DNA double-strand breaks in MyLa cells. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Usefulness of MRI compared with CT for diagnosis of mesenteric lymphoma in a dog.

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Yasuda, Daiji; Fujita, Michio; Yasuda, Shuichi; Taniguchi, Akiko; Miura, Harumi; Hasegawa, Daisuke; Orima, Hiromitsu

2004-11-01

We evaluated the usefulness of MRI and compared it with CT for diagnosis of mesenteric lymphoma in a dog. The results in the plain CT, dynamic CT and plain MR (T1WI and T2WI) images suggested that the mass was a large single nodular lesion with abundant blood perfusion. On enhanced MRI(T1WI) , the mass was depicted as a tumor with adhesion to the gut wall. Exploratory laparotomy confirmed the mass was consistent with the findings on enhanced MRI. We think that MRI might be a useful imaging tool for diagnosis of canine mesenteric lymphoma.

Primary cutaneous anaplastic large-cell lymphoma.

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

2013-10-01

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

Diagnosis of lymphoma in paraffin wax sections by nested PCR and immunohistochemistry.

OpenAIRE

Kitamura, Y; Nanba, E; Inui, S; Tanigawa, T; Ichihara, K

1996-01-01

AIMS: To investigate whether nested polymerase chain reaction (PCR) and immunohistochemistry can be used to diagnose malignant lymphoma. METHODS: Paraffin wax embedded tissue sections from 31 patients with malignant lymphoma were analysed by nested PCR and immunohistochemistry using standard protocols. RESULTS: Nested PCR amplification of 1 pg DNA confirmed monoclonality in B cell lymphoma; PCR amplification of 10 pg DNA confirmed monoclonality in T cell lymphoma. Twenty seven (87%) samples w...

Primary testicular diffuse large B-cell lymphoma: A case report

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Muhammad Sadiq

2017-12-01

Full Text Available Primary testicular diffuse large-B cell lymphoma (DLBCL is an uncommon and aggressive disease with predominant manifestation in the older age. Herein, we report a case of 47-year-old male patient who presented with three months history of left testis swelling. The patient underwent unilateral (left radical orchiectomy. Histopathological examination revealed extensive involvement and replacement of testicular parenchyma by a tumor composed of large discohesive sheets of cells with pleomorphic, hyperchromatic nuclei and prominent nucleoli. Immunohistochemical (IHC staining showed reactivity for LCA & Pan B (CD20 and negativity for OCT 3/4, SALL4 and Inhibin. Moreover, Pan T (CD3 highlighted reactive T-cells. These features rendered the diagnosis of DLBCL of testis. The hybrid 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG positron emission tomography/computed tomography (PET/CT demonstrated two para-aortic FDG avid lymph nodes on the left side at the level of L2 vertebra. Presently, the patient has been planned for doxorubicin-based chemotherapy (i.e., cyclophosphamide, doxorubicin, vincristine and prednisone; CHOP along with intrathecal Methroxate (MTX, which would presumably improve the prognosis. Our study would expand the pool of this uncommon tumor towards its better understanding. Keywords: Primary testicular lymphoma, Diffuse large-B cell lymphoma, Orchiectomy, Doxorubicin-based chemotherapy

The changing landscape of peripheral T-cell lymphoma in the era of novel therapies.

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Karlin, Lionel; Coiffier, Bertrand

2014-01-01

Peripheral T-cell lymphomas (PTCLs) are the most common sub-entity of mature T-cell lymphomas, and apart from particular presentations, share a poor prognosis with frequent short-term, agressive, and chemorefractory relapses. Because of the rarity and also the heterogeneity of the disease, we lack randomized clinical trials. However, to date, neither intensification of frontline chemotherapy or autologous transplant has led to any improvement of survival, and the standard CHOP (cyclophosphamide, doxorubicine, vincristine, and prednisone) regimen remains the most employed as induction therapy. In the past few years, new chemotherapeutic agents, with the capability to encompass the resistance to conventional chemotherapy, such as pralatrexate or bendamustine, have been evaluated. Furthermore, identification of cell surface molecular markers (CD52, CD30, CCR4) has led to the development of new monoclonal antibodies. Similarly, the better comprehension of physiopathological mechanisms and detection of deregulated intracellular pathways encouraged the use of novel therapies such as histone deacetylase inhibitors or immunomodulatory drugs. Some of these compounds have been approved for relapse, and are currently evaluated upfront in ongoing clinical trials. Despite these efforts, the global prognosis still remains much inferior to those of B-cell lymphomas, highlighting the necessity of multicenter clinical trials. © 2013 Elsevier Inc. All rights reserved.

Predictive value of PET response combined with baseline metabolic tumor volume in peripheral T-cell lymphoma patients

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Cottereau, Anne-Segolene; El-Galaly, Tarec C; Becker, Stéphanie

2018-01-01

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas with poor outcomes with current therapy. We investigated if response assessed with Positron Emission Tomography/computed tomography (PET/CT) combined with baseline total metabolic tumor volume (TMTV) co...

Expression pattern of immunosurveillance-related antigen in adult T cell leukaemia/lymphoma.

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Asano, Naoko; Miyoshi, Hiroaki; Kato, Takeharu; Shimono, Joji; Yoshida, Noriaki; Kurita, Daisuke; Sasaki, Yuya; Kawamoto, Keisuke; Ohshima, Koichi; Seto, Masao

2018-05-01

Adult T cell leukaemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leucocyte antigen (HLA) and β2 microglobulin (β2M) serve as key molecules in tumour immunity, and their expression is reduced frequently in tumour cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumour cells from T cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and β2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL. We analysed a total of 123 biopsy samples from patients newly diagnosed with ATLL by using immunohistochemical analysis. Of the patients enrolled, 91 (74%) were positive for HLA (in cell membrane, 60 patients), 89 (72%) were positive for β2M (in cell membrane, 54 patients) and 48 (39%) were positive for both HLA and β2M in the cell membrane (HLA m+ β2M m+ ). No significant clinical differences other than prognosis were found between the HLA m+ β2M m+ group and the other groups. Immunophenotypical evaluation revealed significantly higher rates of CD30-positive lymphoma cells (P = 0.003) and PD-L1-positive stromal cells in microenvironments (miPD-L1 high ) (P = 0.011) of the HLA m+ β2M m+ group than in the other groups. The HLA m+ β2M m+ group had a significantly better prognosis that the other groups (P = 0.0096), and patients showing HLA m+ β2M m+ with miPD-L1 high had the most favourable prognosis among all groups. The membranous expression of HLA and β2M is likely to reflect the immune response and would be useful to predict prognosis before starting ATLL therapy. © 2018 John Wiley & Sons Ltd.

Lymphoma of the eyelid

DEFF Research Database (Denmark)

Svendsen, Frederik Holm; 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 lymphoma (18 cases-9%). T-cell lymphomas are most frequently mycosis fungoides (25 cases-13%), extranodal natural killer/T-cell, nasal-type lymphoma (12 cases-6%), and primary cutaneous anaplastic large-cell lymphoma (12 cases-6%). This distribution differs from the distribution of ocular adnexal lymphoma...... and that of cutaneous lymphoma. The majority of subtypes occur in elderly patients, except for lymphoblastic lymphoma of B-cell and T-cell origin and Burkitt lymphoma, which occur in children and adolescents. Several subtypes have a male predominance, including peripheral T-cell lymphoma and Burkitt lymphoma. Only...

Natural Killer/T-cell Neoplasms: Analysis of Incidence, Patient Characteristics, and Survival Outcomes in the United States.

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Kommalapati, Anuhya; Tella, Sri Harsha; Ganti, Apar Kishore; Armitage, James O

2018-05-04

Limited data are available regarding the incidence, survival patterns, and long-term outcomes of natural killer (NK)/T-cell neoplasms in the United States. We performed a retrospective study of patients with NK/T-cell neoplasms diagnosed from 2001 to 2014 using the Surveillance, Epidemiology, and End Results program database. The Kaplan-Meier method was used to estimate the overall survival difference among the subgroups. Multivariate analyses were used to determine the factors affecting survival. For the 797 patients with NK/T-cell lymphoma, nasal type, the median age at diagnosis was 53 years, and males tended to be younger at diagnosis (P < .0001). The incidence of the disease increased from 0.4 in 2001 to 0.8 in 2014 per 1,000,000 individuals. The incidence was significantly greater in Hispanic patients compared with that in non-Hispanic patients (rate ratio, 3.03; P = .0001). The median overall survival was 20 months (range, 2-73 months) and varied significantly according to the primary site (P < .0001) and the disease stage at diagnosis (P < .0001). NK/T-cell lymphoma patients had an increased risk of acute myeloid leukemia (standardized incidence ratio, 18.77; 95% confidence interval, 2.27-67.81). For the 105 NK/T-cell leukemia patients, the median age at diagnosis was 58 years (range, 4-95 years). The overall incidence of the disease was 0.09 per 1,000,000 individuals and was significantly greater in males (rate ratio, 0.41; P < .0001). Unlike NK/T-cell lymphoma, no racial disparities were found in the incidence. The median overall survival was 17 months (range, 0-36 months). The incidence of NK/T-cell lymphoma, nasal type, in the United States has at least doubled in the past decade, with the greatest predilection among Hispanics. Patients with NK/T-cell lymphoma might have an increased risk of the subsequent development of acute myeloid leukemia. Copyright © 2018 Elsevier Inc. All rights reserved.

Intracerebral lymphoma with two patients. CT and MRI diagnosis

International Nuclear Information System (INIS)

Yanakiev, A.; Popovska, T.; Zasheva, I.

2012-01-01

Full text: Lymphoma (Hodgkin's and non-Hodgkin's) is a disease of the lymphatic system where the central neural system is affected in very rare cases. According to different authors the frequency of cases with lymphoma where the neural system is affected varies between 0.2% and 0.5%, and the primary cerebral lymphoma accounts for about 1-2% of all brain neoplasms. The intracranial form of lymphoma is usually a late onset of the disease with serious and potentially fatal complications for the patient. These complications usually appear several years after diagnosing the disease, but the cerebral lymphoma may occur even in patients who are in remission, which is actually the case with our patients. We present you two cases - a 38-year-old female and a 48-year-old male, who were hospitalized in Neuro ward with the following complaints: loss of speech for a few minutes, dizziness, weakness, tingling and shuffling of one of the legs. Those patients were diagnosed with histological B-cell non-Hodgkin's lymphoma and Hodgkin's lymphoma, several years ago. CT and MRI were carried out on the patients. Despite both clinical and radiographic suspicions for intracranial forms of lymphoma, the patients were still difficult to diagnose. A definitive diagnosis was given after a surgery and histological examination, i.e. non- Hodgkin's lymphoma - large B-cell lymphomas, and Hodgkin's lymphoma. These cases are of interest because of their rare intracranial localization of the lymphoma. The knowledge of CT and MRI images with the intracranial form of lymphoma may help diagnosing, but images should be interpreted together with the clinical and paraclinical results

[A morphometric analysis of the nuclei and nucleoli in tumor cells in lymphogranulomatosis, diffuse large B-cell lymphoma and anaplastic large cell lymphoma].

Science.gov (United States)

Gorgidze, L A; Vorob'ev, I A

2009-01-01

To make a comparative morphometric analysis of the nuclei and nucleoli of tumor cells in lymphogranulomatosis (LGM), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL) for differential diagnosis of these lymphomas. Biopsy material (lymph node biopsies) was frozen in hexane, fixed and stained, then microscopic pictures were made. Mean area of tumor cell nuclei in LGM was 97.25 +/- 68.77 mcm2, in DLBCL and ALCL--55.89 +/- 20.13 mcm2 and 70.31 +/- 34.64 mcm2, respectively. The area differences were significant (p nucleoli of the former are larger than those of the latter. Mean area of the nucleoli in DLBCL was 3.05 +/- 1.58, in ALCL--5.53 +/- 4.94 mcm2. The differences are significant (p Nucleoli in Hodgkin 's cells are significantly larger than those in the tumor cells in ALCL and DLBCL and the nucleoli with the area more than 12 mcm2 can be used in differential diagnosis between LGM and DLBCL but not between LGM and ALCL.

Imaging Cutaneous T-Cell Lymphoma with Optical Coherence Tomography

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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.

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

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

2009-02-01

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

A rare case of hepatic T-cell rich B-cell lymphoma (TCRBCL) in a juvenile dog.

Science.gov (United States)

Chung, Tae-Ho; Lamm, Catherine; Choi, Young-Chul; Lee, Jung-Woo; Yu, Dohyeon; Choi, Ul-Soo

2014-10-01

A 7-month-old castrated male French Bull dog was presented with vomiting, lethargy, anorexia and weight loss of 2 weeks duration. The patient's history and clinical manifestations of suspected hepatopathy were subjected to ultrasonography, radiography, biochemical investigations and cytology of hepatic lesion. The cytologic impression was hepatic lymphoma, which was later confirmed by histopathology. The neoplastic cells were strongly diffusely immunoreactive for PAX5, but not immunoreactive for CD3, and B lymphocyte specific clonal proliferation was detected using by assay of antigen receptor rearrangement. Large numbers of immunoreactive mature non-neoplastic lymphocytes were admixed with the neoplastic cell population. Therefore, the immunohistochemical results were definitively consistent with a T-cell rich B-cell lymphoma (TCRBCL). This is the first description of a hepatic TCRBCL in a juvenile dog showing a poor response to aggressive chemotherapy.

Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.

Science.gov (United States)

Magro, Cynthia M; Wang, Xuan; Subramaniyam, Shivakumar; Darras, Natasha; Mathew, Susan

2014-04-01

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

Systemic lupus erythematosus and lymphoma not Hodgkin of cells T. Presentation of case and revision of the literature

International Nuclear Information System (INIS)

Serra Valdés, Miguel Angel; Landrian Davis, Alain; Ramos Rivero, Ana Ibis; Reyes Prolong, Yunaykis; Aranguren Barreto, Otmara; Herrera Calderón, Yanet

2016-01-01

The increment in the incidence of the lymphomas associated to rheumatic illnesses is related with the states of immunodeficiency and autoimmunity states. It presents a half-breed 28-years woman with fever, linphadenopathy, arthralgias, vasculitis in skin, ulcerates in the palate, hepatoesplenomegalia and marking of antibodies for the systemic lupus erythematosus. History of familiar cancer. The size of some ganglions decided biopsy of the same, multicorte computerized tomography, Medulograma and other examines. It diagnosed to him moreover lymphoma not Hodgkin of T cells with peripheral owner. It is concluded a case whose form of concomitant debut of systemic lupus erythematosus and a lymphoma not Hodgkin of T cells constitutes a strange and little frequent presentation in the clinic. (author)

Loss of SHP-1 tyrosine phosphatase expression correlates with the advanced stages of cutaneous T-cell lymphoma

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Witkiewicz, Agnieszka; Raghunath, Puthiyaveettil; Wasik, Agnieszka

2007-01-01

Cutaneous T-cell lymphoma (CTCL) comprises distinct and often progressive stages of skin involvement by patches, plaques, and tumors. We have previously demonstrated that CTCL-derived malignant T-cell lines display loss of a tumor suppressor SHP-1 tyrosine phosphatase because of epigenetic...

Primary Hepatosplenic Large B-Cell Lymphoma

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M.R. Morales-Polanco

2008-03-01

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

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.

Plasma Cell-Free DNA in Paediatric Lymphomas

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

2013-01-01

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

Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice.

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Canela, Andrés; Martín-Caballero, Juan; Flores, Juana M; Blasco, María A

2004-05-01

Here we describe a new mouse model with constitutive expression of the catalytic subunit of telomerase (Tert) targeted to thymocytes and peripheral T cells (Lck-Tert mice). Two independent Lck-Tert mouse lines showed higher incidences of spontaneous T-cell lymphoma than the corresponding age-matched wild-type controls, indicating that constitutive expression of Tert promotes lymphoma. Interestingly, T-cell lymphomas in Lck-Tert mice were more disseminated than those in wild-type controls and affected both lymphoid and nonlymphoid tissues, while nonlymphoid tissues were never affected with lymphoma in age-matched wild-type controls. Importantly, these roles of Tert constitutive expression in promoting tumor progression and dissemination were independent of the role of telomerase in telomere length maintenance, since telomere length distributions on a single-cell basis were identical in Lck-Tert and wild-type thymocytes. Finally, Tert constitutive expression did not interfere with telomere capping in Lck-Tert primary thymocytes, although it resulted in greater chromosomal instability upon gamma irradiation in Lck-Tert primary lymphocytes than in controls, suggesting that Tert overexpression may interfere with the cellular response to DNA damage.

Usefulness of MRI compared with CT for diagnosis of mesenteric lymphoma in a dog

International Nuclear Information System (INIS)

Yasuda, D.; Fujita, M.; Yasuda, S.; Taniguchi, A.; Miura, H.; Hasegawa, D.; Orima, H.

2004-01-01

We evaluated the usefulness of MRI and compared it with CT for diagnosis of mesenceric lymphoma in a dog. The results in the plain CT. dynamic CT and plain MR (TIWI and t2W1) images suggested that the mass was a large single nodular lesion with abundant blood perfusion. On enhanced MRI(T1WI) , the mass was depicted as a tumor with adhesion to the gut wall, Exploratory laparotomy confirmed the mass was consistent with the findings on enhanced MRI. We think that MRI might be a useful imaging tool for diagnosis of canine mesenteric lymphoma

Extranodal natural killer/T-cell lymphoma presenting as orbital cellulitis

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Zuhaimy, Hanis; Aziz, Hayati Abdul; Vasudevan, Suresh; Hui Hui, Siah

2017-01-01

Objective: To report an aggressive case of extranodal natural killer/T-cell lymphoma (NKTCL) of the ethmoid sinus presenting as orbital cellulitis Method: Case report Results: A 56-year-old male presented with right eye redness, reduced vision, and periorbital swelling for 5 weeks duration associated with a two-month history of blocked nose. The visual acuity of the right eye was 6/18. The eye was proptosed with periorbital oedema and conjunctival chemosis. The pupil was mid-dilated but there was no relative afferent pupillary defect. The fundus was normal. The extraocular movements were restricted in all directions of gaze. Nasal endoscopy revealed pansinusitis that corresponded with CT scan orbit and paranasal sinuses findings. Despite treatment, he showed no clinical improvement. Ethmoidal sinus biopsies performed revealed extranodal NKTCL. Further imaging showed involvement of the right orbital contents and its adnexa with intracranial extension into the right cavernous sinus and meninges over right temporal fossa. The patient underwent chemotherapy. However he succumbed to his illness two months after the diagnosis. Conclusion: Extranodal NKTCL is a great mimicker. This case demonstrated how an acute initial presentation of extranodal NKTCL can present as orbital cellulitis with pansinusitis. PMID:28194321

Interferon-γ Promotes Inflammation and Development of T-Cell Lymphoma in HTLV-1 bZIP Factor Transgenic Mice.

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Yu Mitagami

2015-08-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is an etiological agent of several inflammatory diseases and a T-cell malignancy, adult T-cell leukemia (ATL. HTLV-1 bZIP factor (HBZ is the only viral gene that is constitutively expressed in HTLV-1-infected cells, and it has multiple functions on T-cell signaling pathways. HBZ has important roles in HTLV-1-mediated pathogenesis, since HBZ transgenic (HBZ-Tg mice develop systemic inflammation and T-cell lymphomas, which are similar phenotypes to HTLV-1-associated diseases. We showed previously that in HBZ-Tg mice, HBZ causes unstable Foxp3 expression, leading to an increase in regulatory T cells (Tregs and the consequent induction of IFN-γ-producing cells, which in turn leads to the development of inflammation in the mice. In this study, we show that the severity of inflammation is correlated with the development of lymphomas in HBZ-Tg mice, suggesting that HBZ-mediated inflammation is closely linked to oncogenesis in CD4+ T cells. In addition, we found that IFN-γ-producing cells enhance HBZ-mediated inflammation, since knocking out IFN-γ significantly reduced the incidence of dermatitis as well as lymphoma. Recent studies show the critical roles of the intestinal microbiota in the development of Tregs in vivo. We found that even germ-free HBZ-Tg mice still had an increased number of Tregs and IFN-γ-producing cells, and developed dermatitis, indicating that an intrinsic activity of HBZ evokes aberrant T-cell differentiation and consequently causes inflammation. These results show that immunomodulation by HBZ is implicated in both inflammation and oncogenesis, and suggest a causal connection between HTLV-1-associated inflammation and ATL.

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

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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.

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

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

2017-10-01

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

Anti-ATLA (antibody to adult T-cell leukemia-lymphoma virus-associated antigen)-negative adult T-cell leukemia-lymphoma.

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Shimoyama, M; Minato, K; Tobinai, K; Nagai, M; Setoya, T; Watanabe, S; Hoshino, H; Miwa, M; Nagoshi, H; Ichiki, N; Fukushima, N; Sugiura, K; Funaki, N

1983-01-01

Five cases of adult T-cell leukemia-lymphoma (ATL) having typical clinicohematologic and morphologic features but negative for anti-ATLA [antibody to ATL virus (ATLV)-associated antigen (ATLA)] are presented. Some differences in immunologic, epidemiologic, and serologic data between anti-ATLA-positive and -negative ATLs are also described. Expression of ATLA in early primary cultured leukemic cells was found to be negative in three patients tested (Cases 1, 2 and 4), however, a long-term cultured cell line, ATL-6A, derived from peripheral blood leukemia cells from Case 1, was found to express ATLA. Mother of Case 1 and a daughter of Case 2 were anti-ATLA negative. These results indicate that ATLV was involved in certain anti-ATLA-negative ATL patients, at least in Case 1, and that the patient had no detectable immune response against ATLV and ATLA. However, in other cases in which no ATLA reactivity of serum and no ATLA expression in cultured leukemic cells were observed, another possibility such as activation of an unknown cellular oncogene specific for ATL without ATLV involvement may be considered. In order to prove these possibilities definitely, it is necessary to elucidate whether or not proviral DNA of ATLV is integrated into chromosomal DNA of ATL cells and to find a cellular oncogene specific for ATL in the future.

The radiographic findings in diagnosis of pulmonary lymphoma

International Nuclear Information System (INIS)

Song Wei; Wang Li; Yan Hongzhen

2001-01-01

Objective: To study the radiographic findings in the diagnosis of pulmonary lymphoma and pseudo lymphoma. Methods: Eight patients with pulmonary lymphoma and 2 with pseudo lymphoma were examined by X-ray film, tomography, and CT. Results: Single or multiple nodules or masses were observed in 8 patients with pulmonary lymphoma, shaggy borders or halo of ground-glass attenuation in 7 patients, 2 patients had multiple patchy infiltrates bilaterally, 2 had diffuse interstitial infiltrates and 1 had miliary nodules. Multiple consolidations with air bronchogram and without hilar and mediastinal lymphadenopathy were observed in 2 patients with pulmonary pseudo lymphoma. Conclusion: Radiographic findings of pulmonary lymphoma were varied, the most common findings were the nodules or masses with shaggy borders or halo of ground-glass attenuation. The specific findings of pulmonary pseudo lymphoma were multiple consolidations with air bronchogram and without hilar and mediastinal lymphadenopathy. The final diagnosis relied on pathology

Notch 1 as a potential therapeutic target in cutaneous T-cell lymphoma

DEFF Research Database (Denmark)

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

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 signalling is involved in the pathogenesis of mycosis fungoides and Sezary syndrome, the most common subtypes of cutaneous T cell lymphoma....... By immunohistochemistry of 40 biopsies taken from skin lesions of mycosis fungoides and Sezary syndrome we demonstrated prominent expression of Notch1 on tumor cells, especially in the more advanced stages. The gamma-secretase inhibitor I blocked Notch signaling and potently induced apoptosis in cell lines derived from...... mycosis fungoides (MyLa) and Sezary syndrome (SeAx, HuT-78)and in primary leukemic Sézary cells. Specific downregulation of Notch1 (but not Notch2 and Notch3) by siRNA induced apoptosis in SeAx. The mechanism of apoptosis involved the inhibition of NF-kappaB, which is the most important prosurvival...

Exacerbation of spontaneous autoimmune nephritis following regulatory T cell depletion in B cell lymphoma 2-interacting mediator knock-out mice.

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Wang, Y M; Zhang, G Y; Wang, Y; Hu, M; Zhou, J J; Sawyer, A; Cao, Q; Wang, Y; Zheng, G; Lee, V W S; Harris, D C H; Alexander, S I

2017-05-01

Regulatory T cells (T regs ) have been recognized as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. The loss of T regs or their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of T regs in the chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of T regs in a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2-interacting mediator (Bim) knock-out mice by transient depleting T regs . Bim is a pro-apoptotic member of the B cell lymphoma 2 (Bcl-2) family. Bim knock-out (Bim -/- ) mice fail to delete autoreactive T cells in thymus, leading to chronic spontaneous autoimmune kidney disease. We found that T reg depletion in Bim -/- mice exacerbated the kidney injury with increased proteinuria, impaired kidney function, weight loss and greater histological injury compared with wild-type mice. There was a significant increase in interstitial infiltrate of inflammatory cells, antibody deposition and tubular damage. Furthermore, the serum levels of cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17α, interferon (IFN)-γ and tumour necrosis factor (TNF)-α were increased significantly after T reg depletion in Bim -/- mice. This study demonstrates that transient depletion of T regs leads to enhanced self-reactive T effector cell function followed by exacerbation of kidney disease in the chronic spontaneous kidney disease model of Bim-deficient mice. © 2017 British Society for Immunology.

Cutaneous B-cell lymphoma : classification, prognostic factors and management recommendations

NARCIS (Netherlands)

Senff, Nancy Johanna

2009-01-01

The term primary cutaneous B-cell lymphomas refers to a heterogeneous group of B-cell non-Hodgkin lymphomas, that present in the skin without evidence of extracutaneous disease at the time of diagnosis. In recent years, there has been considerable debate regarding the classification and terminology

Marginal Zone Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Intraocular lymphoma

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Li-Juan Tang

2017-08-01

Full Text Available Intraocular lymphoma (IOL is a rare lymphocytic malignancy which contains two main distinct forms. Primary intraocular lymphoma (PIOL is mainly a sub-type of primary central nervous system lymphoma (PCNSL. Alternatively, IOL can originate from outside the central nervous system (CNS by metastasizing to the eye. These tumors are known as secondary intraocular lymphoma (SIOL. The IOL can arise in the retina, uvea, vitreous, Bruch’s membrane and optic nerve. There are predominantly of B-cell origin; however there are also rare T-cell variants. Diagnosis remains challenging for ophthalmologists and pathologists, due to its ability to masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other metastatic cancers. Laboratory tests include flow cytometry, immunocytochemistry, interleukin detection (IL-10: IL-6, ratio >1, and polymerase chain reaction (PCR amplification. Methotrexate-based systemic chemotherapy with external beam radiotherapy and intravitreal chemotherapy with methotrexate are useful for controlling the disease, but the prognosis remains poor. Therefore, it is important to make an early diagnose and treatment. This review is focused on the clinical manifestations, diagnosis, treatment and prognosis of the IOL.

Frequency and clinical correlates of elevated plasma Epstein-Barr virus DNA at diagnosis in peripheral T-cell lymphomas

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Haverkos, Bradley M.; Huang, Ying; Gru, Alejandro; Pancholi, Preeti; Freud, Aharon G.; Mishra, Anjali; Ruppert, Amy S.; Baiocchi, Robert A.; Porcu, Pierluigi

2016-01-01

Epstein Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis, but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact, and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients. Fifteen of 61 patients (24.5%, 95% CI: 14–37%) were pre-treatment pEBVd+, with no significant differences in baseline characteristics or treatment between pEBVd+ and pEBVd− patients. EBER-ISH was performed on 10 pEBVd+ and 35 pEBVd− tumors. All 10 pEBVd+ patients were EBER+, but 9 pEBVd− patients were also EBER+. With median follow up of 24 months (range 1–96), overall survival (OS) was shorter in pEBVd+ compared to pEBVd− patients (13 vs. 72 months; p=0.04). In this retrospective study, pre-treatment pEBVd was elevated in 25% of PTCL patients, was highly specific for EBER+ tumors, and was associated with shorter survival. pEBVd should be further explored as a prognostic variable and tumor biomarker in PTCL. PMID:27943278

Clinical and otorhinolaryngological aspects of extranodal NK/T cell lymphoma, nasal type.

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Miyake, Marcel Menon; Oliveira, Mariana Vendramini Castrignano de; Miyake, Michelle Menon; Garcia, Julio Oliva de Almeida; Granato, Lidio

2014-01-01

Extranodal NK/T-Cell lymphoma, nasal type (NKTLN) is a disease that mainly affects the nasal cavity and the paranasal sinuses. Early nasal symptoms are nonspecific, simulating sinus infection. With disease progression, necrosis of the nasal mucosa increases, hindering histological diagnosis. Thus, multiple biopsies may be necessary until definitive diagnosis. Most studies on NKTLN address the hematological and immunological aspects of the disease. To present data from a Brazilian quaternary hospital, with emphasis on the clinical aspects of the disease, and to correlate the findings with the most recent literature data. Case study of seven patient files. Patients were evaluated on their medical history, number of biopsies necessary, association with Epstein-Barr virus, treatment, and outcome. All patients had nonspecific nasal complaints and underwent at least three cycles of antibiotic therapy. The earlier a biopsy was performed, the fewer biopsies were required to diagnose the disease and start treatment. However, this fact did not translate into better prognosis. The otolaryngologist plays a fundamental role in the prognosis of NKTLN and can shorten time between symptom onset and treatment of the patient. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

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

) 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......, 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...... leukemic cell line U937. Expression of SOCS-3 coincides with a constitutive activation of STAT3 in CTCL tumor cells, and stable transfection of CTCL tumor cells with a dominant negative STAT3 strongly inhibits SOCS-3 expression, whereas transfection with wild-type STAT3 does not. Moreover, the reduced SOCS...

A novel splice variant of the Fas gene in patients with cutaneous T-cell lymphoma.

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van Doorn, Remco; Dijkman, Remco; Vermeer, Maarten H; Starink, Theo M; Willemze, Rein; Tensen, Cornelis P

2002-10-01

Defective apoptosis signaling has been implicated in the pathogenesis of primary cutaneous T-cell lymphomas (CTCLs), a group of malignancies derived from skin-homing T cells. An important mediator of apoptosis in T cells is the Fas receptor. We identified a novel splice variant of the Fas gene that displays retention of intron 5 and encodes a dysfunctional Fas protein in 13 of 22 patients (59%) in both early and advanced CTCL. Impairment of Fas-induced apoptosis resulting from aberrant splicing potentially contributes to the development and progression of CTCL by allowing continued clonal expansion of activated T cells and by reducing susceptibility to antitumor immune responses.

MLL duplication in a pediatric patient with B-cell lymphoblastic lymphoma.

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Mater, David Van; Goodman, Barbara K; Wang, Endi; Gaca, Ana M; Wechsler, Daniel S

2012-04-01

Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma seen in children. Approximately, 90% of lymphoblastic lymphomas arise from T cells, with the remaining 10% being B-cell-lineage derived. Although T-cell lymphoblastic lymphoma most frequently occurs in the anterior mediastinum (thymus), B-cell lymphoblastic lymphoma (B-LBL) predominates in extranodal sites such as skin and bone. Here, we describe a pediatric B-LBL patient who presented with extensive abdominal involvement and whose lymphoma cells displayed segmental duplication of the mixed lineage leukemia (MLL) gene. MLL duplication/amplification has been described primarily in acute myeloid leukemia and myelodysplastic syndrome with no published reports of discrete MLL duplication/amplification events in B-LBL. The MLL gene duplication noted in this case may represent a novel mechanism for tumorigenesis in B-LBL.

An association between newly diagnosed cutaneous T cell lymphoma and prior impetigo: a nested case-control study.

Science.gov (United States)

Boursi, Ben; Haynes, Kevin; Mamtani, Ronac; Yang, Yu-Xiao

2016-11-01

Colonization with staphylococcus aureus (SA) is associated with disease activity and progression in patients with cutaneous T-cell lymphoma (CTCL) secondary to T-cell activation by bacterial superantigens. The aim of the current study was to evaluate the possible role of SA as an etiologic factor affecting CTCL initiation. We conducted a nested case-control study in a large population-representative database from the UK. Cases were defined as all patients with an incident diagnosis of mycosis fungoides (MF) or Sezary syndrome (SS) between 1995 and 2013. For every case, four eligible controls matched on age, sex, practice-site, and duration of follow-up were selected. Exposure of interest was clinical diagnosis of impetigo prior to CTCL diagnosis. Conditional logistic regression was used to calculate odds-ratio (ORs) and 95 % confidence-interval (CI) for CTCL risk. The results were further stratified according to age, sex and time interval between impetigo and CTCL diagnosis. The study population included 310 cases with MF or SS and 1223 matched controls. Among cases with CTCL 4.8 % (n = 15) had impetigo prior to cancer diagnosis compared to 2 % (n = 24) of controls. The adjusted OR for CTCL diagnosis among patients with prior impetigo was 2.33 (95 % CI 1.12-4.83). The risk was elevated among individuals with impetigo 1-5 years before cancer diagnosis (OR 3.33, 95 % CI 1.00-11.10). There was no change in risk among patients with impetigo more than 5 years before cancer diagnosis (OR 1.09, 95 % CI 0.35-3.37). Our results suggest a possible association between SA colonization and CTCL initiation that might serve as an important etiological factor for the disease.

Radiation therapy of lethal midline granuloma type nasal T-cell lymphoma

International Nuclear Information System (INIS)

Sakata, Koh-ichi; Hareyama, Masato; Ohuchi, Atushi; Sido, Mitsuo; Nagakura, Hisayasu; Morita, Kazuo; Harabuchi, Yasuaki; Kataura, Akikatsu

1996-01-01

Purpose/Objective: Lethal midline granuloma (LMG) is disorder characterized by progressive, unrelenting ulceration, and necrosis of the nasal cavity and midline facial tissues. Several investigators have demonstrated that LMG (polymorphic reticulosis) is a peripheral T-cell lymphoma, and the term nasal T-cell lymphoma of the LMG type (LMG-NTL) has since been widely used. Recently, expression of the natural killer (NK) cell marker CD56 on tumor cells has been reported in some cases. However, there is very little information about the optimal treatment for this disease. In this study, we report our observations on the clinical behavior of this tumor in comparison with nasal lymphoma of non-LMG-NTL type (non-LMG-NTL) that makes tumor mass and paranasal sinus lymphoma (PSL) to improve management of LMG-NTL. Materials and Methods: Sixteen patients (10 men, 6 women) with LMG-NTL, 8 patients (4 men, 4 women) with non-LMG-NTL, and 6 patients (4 men, 2 women) with PSL were treated with radiation therapy between January 1975 and December 1994. Four of 8 patients with non-LMG-NTL had tumors of B-cell origin and four had T-cell derived tumors. All 6 patients with PSL had B-cell tumors. They had stage I or II disease. The radiation portal encompassed clinically involved areas with a generous margin. The median dose received was 40 Gy (range, 9-74 Gy) and the median TDF delivered was 63.3 (range, 13.7-103.5). One or two courses of VEPA chemotherapy (same drugs as CHOP, however, drugs doses and treatment schedule are a little different) were administered to the patients with non-LMG-NTL after radiotherapy and the patients with PSL before radiotherapy. In patients with LMG-NTL, between 1975 and 1981 one patient was treated with COPP, one with VEMP after radiotherapy, and two with radiotherapy alone. From 1982 to 1986, all three patients treated for LMG-NTL received VEPA before radiotherapy. Since 1987, of 11 patients treated for LMG-NTL, all except one received two courses of

Lymphoma immunotherapy: vaccines, adoptive cell transfer and immunotransplant

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Brody, Joshua; Levy, Ronald

2017-01-01

Therapy for non-Hodgkin lymphoma has benefited greatly from basic science and clinical research such that chemotherapy and monoclonal antibody therapy have changed some lymphoma subtypes from uniformly lethal to curable, but the majority of lymphoma patients remain incurable. Novel therapies with less toxicity and more specific targeting of tumor cells are needed and immunotherapy is among the most promising of these. Recently completed randomized trials of idiotype vaccines and earlier-phase trials of other vaccine types have shown the ability to induce antitumor T cells and some clinical responses. More recently, trials of adoptive transfer of antitumor T cells have demonstrated techniques to increase the persistence and antitumor effect of these cells. Herein, we discuss lymphoma immunotherapy clinical trial results and what lessons can be taken to improve their effect, including the combination of vaccination and adoptive transfer in an approach we have dubbed ‘immunotransplant’. PMID:20636025

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

Science.gov (United States)

2018-01-02

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

Identification of genuine primary pulmonary NK cell lymphoma via clinicopathologic observation and clonality assay.

Science.gov (United States)

Gong, Li; Wei, Long-Xiao; Huang, Gao-Sheng; Zhang, Wen-Dong; Wang, Lu; Zhu, Shao-Jun; Han, Xiu-Juan; Yao, Li; Lan, Miao; Li, Yan-Hong; Zhang, Wei

2013-08-19

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is an uncommon lymphoma associated with the Epstein-Barr virus (EBV). It most commonly involves the nasal cavity and upper respiratory tract. Primary pulmonary NK/T cell lymphoma is extremely rare. If a patient with a NK or T-cell tumor has an unusual reaction to treatment or an unusual prognosis, it is wise to differentiate NK from T-cell tumors. The clinicopathologic characteristics, immunophenotype, EBV in situ hybridization, and T cell receptor (TCR) gene rearrangement of primary pulmonary NK cell lymphoma from a 73-year-old Chinese woman were investigated and the clonal status was determined using female X-chromosomal inactivation mosaicism and polymorphisms at the phosphoglycerate kinase (PGK) gene. The lesion showed the typical histopathologic characteristics and immunohistochemical features of NK/T cell lymphoma. However, the sample was negative for TCR gene rearrangement. A clonality assay demonstrated that the lesion was monoclonal. It is concluded that this is the first recorded case of genuine primary pulmonary NK cell lymphoma. The purpose of the present work is to recommend that pathologists carefully investigate the whole lesion to reduce the likelihood that primary pulmonary NK cell lymphoma will be misdiagnosed as an infectious lesion. In addition, TCR gene rearrangement and clonal analysis, which is based on female X-chromosomal inactivation mosaicism and polymorphisms at PGK and androgen receptor (AR) loci, were found to play important roles in differentiating NK cell lymphoma from T cell lymphoma. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5205300349457729.

Fasting blood glucose is a novel prognostic indicator for extranodal natural killer/T-cell lymphoma, nasal type

Science.gov (United States)

Cai, Q; Luo, X; Liang, Y; Rao, H; Fang, X; Jiang, W; Lin, T; Lin, T; Huang, H

2013-01-01

Background: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease with poor prognosis, requiring risk stratification. However, the prognosis of ENKTL is not fully defined and needs supplementation. We hypothesised that fasting blood glucose (FBG) may be a new prognostic factor for ENKTL. Methods: We retrospectively analysed 130 patients newly diagnosed with ENKTL. Results: Both univariate analysis and multivariate analysis revealed that FBG >100 mg dl−1 was associated with a poor outcome. Patients with FBG >100 mg dl−1 at diagnosis had more adverse clinical features, achieved lower complete remission rates (P=0.003) and had worse overall survival (PKPI) scores with different survival outcomes (PKPI. PMID:23299534

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

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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.

Clinicopathologic features of adult T-cell leukemias/lymphomas at a North American tertiary care medical center: infrequent involvement of the central nervous system.

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Hsi, Andy C; Kreisel, Friederike H; Frater, John L; Nguyen, TuDung T

2014-02-01

Human T-cell lymphotropic virus type 1 is associated with adult T-cell leukemia/lymphoma (ATLL). Published series of ATLLs seen at a United States medical institution are rare. We present the features of 4 ATLLs diagnosed at our North American tertiary care medical center from 1990 to 2012. Despite the absence of a history of origin from an endemic region, all our ATLLs demonstrated evidence of human T-cell lymphotropic virus type 1 infection. Central nervous system (CNS) involvement by ATLL was uncommon in our series, and represented only 1.6% (1/64) of all CNS B-cell or T-cell lymphomas diagnosed over a 20+ year period at our institution. Review of the medical literature reveals that the majority of CNS-involved ATLLs present with the lymphoma or acute subtype, and complete remission is difficult to achieve in these cases. CNS involvement frequently occurs with a systemic disease, which carries an aggressive clinical course with poor prognosis. In addition, CNS involvement by ATLL can be the initial presentation or seen with relapsed disease, can be the only site or be associated with other tissue sites of involvement, and may manifest with variable clinical signs/symptoms. Our retrospective study reveals that ATLLs are rare mature T-cell lymphomas in a native North American population, but the clinical and histopathologic features of ATLLs from this nonendemic region are similar to those seen from other endemic regions. Early recognition of these rare ATLLs involving uncommon sites, such as the CNS, will help optimize treatment for these infrequent mature T-cell lymphomas.

Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous T-cell lymphoma

International Nuclear Information System (INIS)

Lansigan, Frederick; Stearns, Diane M; Foss, Francine

2010-01-01

Denileukin diftitox (Ontak ® ) is indicated for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL), a rare lymphoproliferative disorder of the skin. Denileukin diftitox was the first fusion protein toxin approved for the treatment of a human disease. This fusion protein toxin combines the IL2 protein with diphtheria toxin, and targets the CD25 subunit of the IL2 receptor, resulting in the unique delivery of a cytocidal agent to CD-25 bearing T-cells. Historically, immunotherapy targeting malignant T-cells including monoclonal antibodies has been largely ineffective as cytocidal agents compared to immunotherapy directed against B-cells such as rituximab. This review will summarize the development of denileukin diftitox, its proposed mechanism of action, the pivotal clinical trials that led to its FDA approval, the improvements in quality of life, and the common toxicities experienced during the treatment of patients with CTCL. CTCL is often a chronic progressive lymphoma requiring the sequential use of treatments such as retinoids, traditional chemotherapy, or biological response modifiers. The incorporation of the immunotoxin denileukin diftitox into the sequential or combinatorial treatment of CTCL will also be addressed

Safety and Efficacy of Pralatrexate in the Management of Relapsed or Refractory Peripheral T-cell Lymphoma

OpenAIRE

Tom C. Karagiannis; Katherine Ververis; Annabelle L. Rodd

2012-01-01

Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas, with generally poor prognosis. Historically, there has been a lack of consensus regarding appropriate therapeutic measures for the disease, with conventional frontline chemotherapies being utilized in most cases. Following promising results obtained in 2009, the methotrexate analogue, pralatrexate, became the first drug to gain US FDA approval for the treatment of refractory PTCL. This...

Establishment of imageable model of T-cell lymphoma growing in syngenic mice

Czech Academy of Sciences Publication Activity Database

Větvička, David; Hovorka, Ondřej; Kovář, Lubomír; Říhová, Blanka

2009-01-01

Roč. 29, č. 11 (2009), s. 4513-4518 ISSN 0250-7005 R&D Projects: GA AV ČR IAA400200702; GA AV ČR KAN200200651; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50200510 Keywords : Imageable model * EL-4 T- cell lymphoma * whole body imaging Subject RIV: EC - Immunology Impact factor: 1.428, year: 2009

Adhesion molecule profiles of B-cell non-Hodgkin's lymphomas in the leukemic phase

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D.M. Matos

2006-10-01

Full Text Available We evaluated the expression of 10 adhesion molecules on peripheral blood tumor cells of 17 patients with chronic lymphocytic leukemia, 17 with mantle-cell lymphoma, and 13 with nodal or splenic marginal B-cell lymphoma, all in the leukemic phase and before the beginning of any therapy. The diagnosis of B-cell non-Hodgkin's lymphomas was based on cytological, histological, immunophenotypic, and molecular biology methods. The mean fluorescence intensity of the adhesion molecules in tumor cells was measured by flow cytometry of CD19-positive cells and differed amongst the types of lymphomas. Comparison of chronic lymphocytic leukemia and mantle-cell lymphoma showed that the former presented a higher expression of CD11c and CD49c, and a lower expression of CD11b and CD49d adhesion molecules. Comparison of chronic lymphocytic leukemia and marginal B-cell lymphoma showed that the former presented a higher expression of CD49c and a lower expression of CD11a, CD11b, CD18, CD49d, CD29, and CD54. Finally, comparison of mantle-cell lymphoma and marginal B-cell lymphoma showed that marginal B-cell lymphoma had a higher expression of CD11a, CD11c, CD18, CD29, and CD54. Thus, the CD49c/CD49d pair consistently demonstrated a distinct pattern of expression in chronic lymphocytic leukemia compared with mantle-cell lymphoma and marginal B-cell lymphoma, which could be helpful for the differential diagnosis. Moreover, the distinct profiles of adhesion molecules in these diseases may be responsible for their different capacities to invade the blood stream.

Aggressive Angioimmunoblastic T Cell Lymphomas (AITL) with Soft Tissue Extranodal Mass Varied Histopathological Patterns with Peripheral Blood, Bone Marrow, and Splenic Involvement and Review of Literature.

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Mukherjee, Tanushri; Dutta, Rajat; Pramanik, S

2018-03-01

Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell non-Hodgkin lymphoma with an aggressive fatal course and it has varied clinical presentation with an uncommon presentation when they present as soft tissue masses or when there is spill in the peripheral blood or there are composite lymphomas that are rare presentations. Common presentations include lymphadenopathy, fever and systemic symptoms, hemolytic anemias, skin rashes, and rheumatoid arthritis. The classical histopathology is absence of follicles in lymph nodes with presence of high endothelial venules and the tumor cells of small to medium-sized lymphocytes with pale cytoplasm mixed with reactive T cells. On immunohistochemistry, the cells are positive for CD3, CD4, CD10, BCL2, and CXCL13. In this observational study, the clinicopathologic presentation and the immunohistochemical profile of five cases who initially presented with a soft tissue mass which is an extremely rare presentation of this rare type of non-Hodgkin lymphoma that was diagnosed at our center with peripheral blood and bone marrow involvement and the clinicopathologic presentation, immunohistochemical profile, and response to treatment on follow-up are correlated with the literature review. One case had a fulminant and aggressive course and was fatal within 2 months of diagnosis. The rest of the four cases are on regular chemotherapy and follow-up. Our five cases had presented with soft tissue masses, two in the axillary regio,n two in the hand, and one in the scapular region with an extranodal presentation, and there was associated lymphadenopathy which developed subsequently with classic histomorphology and immunohistochemical findings. The age range was 46-54 years and all five cases were males. Three cases were with anemia (hemoglobin range 6.5-8.0 mg/dl) and all five cases were having peripheral blood plasmacytosis. Histopathology was classic with paracortical involvement with polymorphous population of cells with

Synchronous meningioma and anaplastic large cell lymphoma.

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

2010-06-01

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

Conditional survival of patients with diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

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

2006-01-01

BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survive...... survival probability provides more accurate prognostic information than the conventional survival rate estimated from the time of diagnosis.......BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survived...... a period of time after treatment. Conditional survival data have not been reported for lymphoma patients. METHODS: Conditional survival was estimated for 1209 patients with diffuse large B-cell lymphoma (DLBCL) from the population-based LYFO registry of the Danish Lymphoma Group. The Kaplan-Meier method...

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

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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.

Dose-Effect Relationship of Alkylating Agents on Testicular Function in Male Survivors of Childhood Lymphoma.

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Servitzoglou, Marina; De Vathaire, Florent; Oberlin, Odile; Patte, Catherine; Thomas-Teinturier, Cécile

2015-01-01

The purpose of our study was to assess the gonadal function in male survivors of childhood lymphoma. We studied 171 male survivors of childhood lymphoma (83 with B-cell non-Hodgkin lymphoma [B-NHL], 32 with T-cell non-Hodgkin lymphoma [T-NHL], 50 with Hodgkin lymphoma [HL], and 6 with anaplastic large-cell lymphoma [ALCL]), measuring follicle-stimulating hormone [FSH] and luteinizing hormone [LH] levels at a median age of 21.1 (17-30.4) years after a median delay of 9.3 (2-22.4) years from treatment. FSH levels were above normal range (≥10 IU/L) in 42.1% and LH levels ≥8 IU/L in only 8.9% of survivors. In multivariate analysis, only the following chemotherapeutic agents were associated with higher FSH or LH levels: cyclophosphamide (P alkylating agents on childhood lymphoma survivors is dose dependent and not correlated to diagnosis, age, or pubertal status at diagnosis.

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....

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

Science.gov (United States)

2018-01-26

Adult Grade III Lymphomatoid Granulomatosis; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

Enhanced Autophagy and Reduced Expression of Cathepsin D Are Related to Autophagic Cell Death in Epstein-Barr Virus-Associated Nasal Natural Killer/T-Cell Lymphomas: An Immunohistochemical Analysis of Beclin-1, LC3, Mitochondria (AE-1), and Cathepsin D in Nasopharyngeal Lymphomas

International Nuclear Information System (INIS)

Hasui, Kazuhisa; Wang, Jia; Jia, Xinshan; Tanaka, Masashi; Nagai, Taku; Matsuyama, Takami; Eizuru, Yoshito

2011-01-01

This study investigated autophagy in 37 cases of nasopharyngeal lymphomas including 23 nasal natural killer (NK)/T-cell lymphomas (NKTCL), 3 cytotoxic T-cell lymphomas (cytotoxic-TML) and 9 B-cell lymphomas (BML) by means of antigen-retrieval immunohistochemistry of beclin-1, LC3, mitochondria (AE-1) and cathepsin D. Peculiar necrosis was noted in EBV + lymphomas comprising 21 NKTCL, 2 cytotoxic-TML and 1 BML. Lymphomas without peculiar necrosis showed high expression of beclin-1, macrogranular cytoplasmal stain of LC3 with sporadic nuclear stain, a hallmark of autophagic cell death (ACD), some aggregated mitochondria and high expression of cathepsin D, suggesting a state of growth with enhanced autophagy with sporadic ACD. EBV + NKTCL with the peculiar necrosis, showed significantly low level of macrogranular staining of LC3, aggregated mitochondria and low expression of cathepsin D in the cellular areas when degenerative lymphoma cells showed decreased beclin-1, significantly advanced LC3-labeled autophagy, residual aggregated mitochondria and significantly reduced expression of cathepsin D, suggesting advanced autophagy with regional ACD. Consequently it was suggested that enhanced autophagy and reduced expression of lysosomal enzymes induced regional ACD under EBV infection in NKTCL

Actual approaches in diagnosis and therapy of malignant lymphoma

International Nuclear Information System (INIS)

Moog, F.; Roemer, W.

1998-01-01

Actual molecular strategies in therapy of lymphoma attempt to utilize the immune system to target and eliminate residual lymphoma cells after first line therapy. Therefore lymphoma-specific vaccines are used. Therapy was already successful in vitro, in vivo studies are planned for the near future. In the past two decades, prognosis of lymphoma patients has improved due to advances in staging as well as in therapy control. The introduction of duplex sonography allows the decision on dignity of suspicious lymph nodes not only by size criteria but also by different perfusion pattern. Similar advances have been made in cross sectional imaging like computed tomography and magnetic resonance imaging. The development of lymph node specific contrast agents present new tools for further investigation. In nuclear medicine, functional imaging using positron-emission tomography presents new perspectives especially in diagnosis and treatment control of malignant lymphoma. The visualization of the glucose metabolism using the radiolabeled glucose analogue fluorodeoxyglucose (FDG) allows the detection of involved lymph nodes independent of arbitrary criteria such as lesion diameter. First studies on the use of FDG-PET in staging and restaging of lymphoma patients show promising results. (orig.) [de

Mantle-cell lymphoma.

Science.gov (United States)

Barista, I; Romaguera, J E; Cabanillas, F

2001-03-01

During the past decade, mantle-cell lymphoma has been established as a new disease entity. The normal counterparts of the cells forming this malignant lymphoma are found in the mantle zone of the lymph node, a thin layer surrounding the germinal follicles. These cells have small to medium-sized nuclei, are commonly indented or cleaved, and stain positively with CD5, CD20, cyclin D1, and FMC7 antibodies. Because of its morphological appearance and a resemblance to other low-grade lymphomas, many of which grow slowly, this lymphoma was initially thought to be an indolent tumour, but its natural course was not thoroughly investigated until the 1990s, when the BCL1 oncogene was identified as a marker for this disease. Mantle-cell lymphoma is a discrete entity, unrelated to small lymphocytic or small-cleaved-cell lymphomas.

Radiation leukemia virus and x-irradiation induce in C57BL/6 mice two distinct T-cell neoplasms: a growth factor-dependent lymphoma and a growth factor-independent lymphoma

International Nuclear Information System (INIS)

Haas, Martin; Rothenberg, Ellen; Bogart, M.H.; Jones, O.W.

1987-01-01

Two different classes of neoplastic T cells were isolated from radiation leukemia virus (RadLV)-inoculated and from X-ray-treated C57BL/6 mice. One consisted of growth factor-dependent T-cell lymphoma (FD-TCL) lines which were established from the spleens and thymuses of treated mice within a day of lymphoma detection. Non-thymic, factor-dependent TCL cells produced interleukin-2 upon lectin stimulation, and were autostimulatory because they secreted growth factor(s) constitutively. In vivo, FD-TCL cells that were injected intraperitoneally or intravenously homed to the spleen, proliferated in it and killed the injected mice. The isolation and study of FD-TCL cells was facilitated by their cultivation on stromal hematopoietic monolayers in supplemented ''lymphocyte medium'', until an autostimulating, self-sustaining concentration of FD-TCL cells was obtained. FD-TCL cells could not be grown from lymphoid tissue of normal, control mice. In contrast, T-cell lymphoma (TCL) lines, which were established from virus-induced thymomas which had been kept in situ for 4-6 weeks after detection, consisted of factor-independent cells that possessed an aneuploid karyotype. The phenotypic markers of TCL cells differed from those of FD-TCL cells, suggesting heterogeneity in the stages of differentiation at which cells can give rise to growth factor-independent (TCL) and to growth factor-dependent (FD-TCL) lines. (author)

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

Science.gov (United States)

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

2017-05-01

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

The First Year of the AEVD Primary Cutaneous Lymphoma Registry.

Science.gov (United States)

Peñate, Y; Servitje, O; Machan, S; Fernández-de-Misa, R; Estrach, M T; Acebo, E; Mitxelena, J; Ramón, M D; Flórez, A; Blanes, M; Morillo, M; Medina, S; Bassas, J; Zayas, A; Espinosa, P; Pérez, A; Gónzalez-Romero, N; Domínguez, J D; Muniesa, C; López Robles, J; Combalia, A; Yanguas, I; Suh, H; Polo-Rodríguez, I; Bielsa, I; Mateu, A; Ferrer, B; Descalzo, M A; García-Doval, I; Ortiz-Romero, P L

2018-04-18

Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30 + T-cell lymphoproliferative disorder (CD30 + CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30 + CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate

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

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...... of advanced stage lymphomas showed that delta p53 was independently associated with treatment failure (relative risk, 3.8; P = 0.001). Delta p53 predicted poor survival when analyzing all patients (P = 0.0001), as well as B-cell (P = 0.04) and T-cell NHL (P = 0.000002). In multivariate analysis, delta p53...

HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.

Directory of Open Access Journals (Sweden)

Yorifumi Satou

2011-02-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is the causal agent of a neoplastic disease of CD4+ T cells, adult T-cell leukemia (ATL, and inflammatory diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis, dermatitis, and inflammatory lung diseases. ATL cells, which constitutively express CD25, resemble CD25+CD4+ regulatory T cells (T(reg. Approximately 60% of ATL cases indeed harbor leukemic cells that express FoxP3, a key transcription factor for T(reg cells. HTLV-1 encodes an antisense transcript, HTLV-1 bZIP factor (HBZ, which is expressed in all ATL cases. In this study, we show that transgenic expression of HBZ in CD4+ T cells induced T-cell lymphomas and systemic inflammation in mice, resembling diseases observed in HTLV-1 infected individuals. In HBZ-transgenic mice, CD4+Foxp3+ T(reg cells and effector/memory CD4+ T cells increased in vivo. As a mechanism of increased T(reg cells, HBZ expression directly induced Foxp3 gene transcription in T cells. The increased CD4+Foxp3+ T(reg cells in HBZ transgenic mice were functionally impaired while their proliferation was enhanced. HBZ could physically interact with Foxp3 and NFAT, thereby impairing the suppressive function of T(reg cells. Thus, the expression of HBZ in CD4+ T cells is a key mechanism of HTLV-1-induced neoplastic and inflammatory diseases.

The Diagnosis of Gastric Mucosa-associated Lymphoid Tissue Lymphoma by Flow Cytometry and Fluorescence in situ Hybridization of Biopsy Specimens.

Science.gov (United States)

Matsueda, Katsunori; Omote, Sizuma; Sakata, Masahiro; Fujita, Isao; Horii, Jouichiro; Toyokawa, Tatsuya

2018-04-15

Mucosa-associated lymphoid tissue (MALT) lymphoma and reactive inflammatory lymphoid changes are frequently difficult to distinguish based on a routine histological differential diagnosis. We were unable to diagnose gastric MALT lymphoma histologically using specimens obtained by endoscopy, although a flow cytometry (FCM) analysis demonstrated clonality of neoplastic cells by separating cells by CD45 gating. Furthermore, a fluorescence in situ hybridization (FISH) analysis showed trisomy 18. We therefore diagnosed gastric MALT lymphoma with trisomy 18. We recommend that FCM and FISH analyses of biopsy specimens be considered for diagnosing gastric MALT lymphoma if this diagnosis is suspected based on endoscopic findings.

Computational diagnosis of canine lymphoma

Science.gov (United States)

Mirkes, E. M.; Alexandrakis, I.; Slater, K.; Tuli, R.; Gorban, A. N.

2014-03-01

One out of four dogs will develop cancer in their lifetime and 20% of those will be lymphoma cases. PetScreen developed a lymphoma blood test using serum samples collected from several veterinary practices. The samples were fractionated and analysed by mass spectrometry. Two protein peaks, with the highest diagnostic power, were selected and further identified as acute phase proteins, C-Reactive Protein and Haptoglobin. Data mining methods were then applied to the collected data for the development of an online computer-assisted veterinary diagnostic tool. The generated software can be used as a diagnostic, monitoring and screening tool. Initially, the diagnosis of lymphoma was formulated as a classification problem and then later refined as a lymphoma risk estimation. Three methods, decision trees, kNN and probability density evaluation, were used for classification and risk estimation and several preprocessing approaches were implemented to create the diagnostic system. For the differential diagnosis the best solution gave a sensitivity and specificity of 83.5% and 77%, respectively (using three input features, CRP, Haptoglobin and standard clinical symptom). For the screening task, the decision tree method provided the best result, with sensitivity and specificity of 81.4% and >99%, respectively (using the same input features). Furthermore, the development and application of new techniques for the generation of risk maps allowed their user-friendly visualization.

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

Directory of Open Access Journals (Sweden)

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.

Overexpression of a transcription factor LYL1 induces T- and B-cell lymphoma in mice.

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Zhong, Y; Jiang, L; Hiai, H; Toyokuni, S; Yamada, Y

2007-10-18

LYL1, a member of the class II basic helix-loop-helix transcription factors, is aberrantly expressed in a fraction of human T-cell acute lymphoblastic leukemia. Here, we generated transgenic mice ubiquitously overexpressing LYL1 using a construct expressing full-length cDNA driven by a human elongation factor 1alpha promoter. Four independent lines exhibiting high LYL1 expression were established. Of these transgenic mice, 96% displayed loss of hair with a short kinked tail. Furthermore, 30% of them developed malignant lymphoma, with an average latent period of 352 days. In these mice, histological examination revealed tumor cell infiltration in multiple organs and immunohistochemical analysis showed that the infiltrated tumor cells were either CD3 or CD45R/B220-positive; fluorescence-activated cell sorter analysis indicated that each tumor consisted either of mainly CD4, CD8 double-positive T cells or mature B cells; the clonality of LYL1-induced lymphoma was confirmed by T-cell receptor rearrangement and immunoglobulin heavy-chain gene rearrangement analyses. Mammalian two-hybrid analysis and luciferase assay suggested that excess LYL1 blocked the dimerization of E2A and thus inhibited the regulatory activity of E2A on the CD4 promoter. Reverse transcription-polymerase chain reaction results showed that the expression of certain E2A/HEB target genes was downregulated. Taken together, our results provide direct evidence that aberrant expression of LYL1 plays a role in lymphomagenesis.

Synchronous Pulmonary Malignancies: Atypical Presentation of Mantle Cell Lymphoma Masking a Lung Malignancy.

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Masha, Luke; Zinchuk, Andrey; Boosalis, Valia

2015-09-07

We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given.

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

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

2016-01-01

Primary non-Hodgkin’s lymphoma’s of the tongue is very rare and accounts for 1% of all malignant tumor of the oral cavity. Clinical features are non-specific ulcerative lesions that do not heal. In the literature, the majority of cases are diffuse large B cell type however, T cell phenotype also may occur. We describe a 77 years old man, who presented with an ulcerative mass in the left margin of the tongue the diagnosis diffuse large B cell lymphoma was confirmed. The patient is actually on treatment R-mini CEOP and has favorable evolution. PMID:28292136

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

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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

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

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Kelsen, Jens; Dige, Anders; Schwindt, Heinrich; D'Amore, Francesco; Pedersen, Finn S; Agnholt, Jørgen; Christensen, Lisbet A; Dahlerup, Jens F; Hvas, Christian L

2011-03-31

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. 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. 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 levels may be at an increased risk of developing malignant γδ-T cell lymphomas

Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

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Afonso José Pereira Cortez

2011-02-01

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

Alteration of the gene expression profile of T-cell receptor αβ-modified T-cells with diffuse large B-cell lymphoma specificity.

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Zha, Xianfeng; Yin, Qingsong; Tan, Huo; Wang, Chunyan; Chen, Shaohua; Yang, Lijian; Li, Bo; Wu, Xiuli; Li, Yangqiu

2013-05-01

Antigen-specific, T-cell receptor (TCR)-modified cytotoxic T lymphocytes (CTLs) that target tumors are an attractive strategy for specific adoptive immunotherapy. Little is known about whether there are any alterations in the gene expression profile after TCR gene transduction in T cells. We constructed TCR gene-redirected CTLs with specificity for diffuse large B-cell lymphoma (DLBCL)-associated antigens to elucidate the gene expression profiles of TCR gene-redirected T-cells, and we further analyzed the gene expression profile pattern of these redirected T-cells by Affymetrix microarrays. The resulting data were analyzed using Bioconductor software, a two-fold cut-off expression change was applied together with anti-correlation of the profile ratios to render the microarray analysis set. The fold change of all genes was calculated by comparing the three TCR gene-modified T-cells and a negative control counterpart. The gene pathways were analyzed using Bioconductor and Kyoto Encyclopedia of Genes and Genomes. Identical genes whose fold change was greater than or equal to 2.0 in all three TCR gene-redirected T-cell groups in comparison with the negative control were identified as the differentially expressed genes. The differentially expressed genes were comprised of 33 up-regulated genes and 1 down-regulated gene including JUNB, FOS, TNF, INF-γ, DUSP2, IL-1B, CXCL1, CXCL2, CXCL9, CCL2, CCL4, and CCL8. These genes are mainly involved in the TCR signaling, mitogen-activated protein kinase signaling, and cytokine-cytokine receptor interaction pathways. In conclusion, we characterized the gene expression profile of DLBCL-specific TCR gene-redirected T-cells. The changes corresponded to an up-regulation in the differentiation and proliferation of the T-cells. These data may help to explain some of the characteristics of the redirected T-cells.

Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability

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Woodward, Jessica; Taylor, Gillian C.; Soares, Dinesh C.; Boyle, Shelagh; Sie, Daoud; Read, David; Chathoth, Keerthi; Vukovic, Milica; Tarrats, Nuria; Jamieson, David; Campbell, Kirsteen J.; Blyth, Karen; Acosta, Juan Carlos; Ylstra, Bauke; Arends, Mark J.; Kranc, Kamil R.; Jackson, Andrew P.; Bickmore, Wendy A.

2016-01-01

Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2nes) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4+CD8+ T-cell stage from which tumors initiate. Premalignant CD4+CD8+ T cells show persistent catenations during chromosome segregation, triggering DNA damage in diploid daughter cells and elevated ploidy. Genome sequencing revealed that Caph2 single-mutant tumors are near diploid but carry deletions spanning tumor suppressor genes, whereas P53 inactivation allowed Caph2 mutant cells with whole-chromosome gains and structural rearrangements to form highly aggressive disease. Together, our data challenge the view that mitotic chromosome formation is an invariant process during development and provide evidence that defective mitotic chromosome structure can promote tumorigenesis. PMID:27737961

Type distribution of lymphomas in Lebanon: five-year single institution experience.

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Sader-Ghorra, Claude; Rassy, Marc; Naderi, Samah; Kourie, Hampig Raphael; Kattan, Joseph

2014-01-01

Lymphomas represent the fifth most frequent cancer in Lebanon. However, little is known concerning epidemiologic characteristics and distribution of lymphoid neoplasms according to the 2008 WHO classification. We conducted a retrospective study of lymphoma cases diagnosed from 2008 till 2012 at Hotel-Dieu de France University Hospital. A total of 502 new cases of lymphoma were diagnosed at our institution during a five year period: 119 cases (24%) were Hodgkin lymphomas (HL) and 383 cases (76%) were non-Hodgkin lymphomas (NHL). HLs were equally distributed in both sexes with a mean age at diagnosis of 30 years. Among NHL, 87% (332 cases) were B cell lymphomas, 9% (34 cases) were T cell lymphomas and 4%(17 cases) were classified as precursor lymphoid neoplasms. Among B cell lymphomas, 44% (147 cases) were diffuse large B cell lymphomas (DLBCL), 20% (65 cases) follicular lymphomas and 8% (27 cases) mantle cell lymphomas. DLBCL were equally distributed in both sexes with a mean age of 58 years. Follicular lymphomas were characterized by a male predominance (57%) and a mean age of 60 years. Mantle cell lymphomas showed a pronounced male predominance (85%) with a mean age of 60 years in men and 70 years in women. Some 72% of patients having T cell lymphomas were men, with a mean age of 57 years in men and 45 years in women, while 65% of patients having precursor lymphoid neoplasms were women with a mean age of 22 years in women and 30 years in men. The lymphoma subtype distribution in Lebanon is unique when compared to other countries from around the world. In fact, Hodgkin and follicular lymphomas are more frequent than in most Far Eastern, European and American countries, while T-cell lymphomas and DLBCL are less frequent.

Malignant lymphoma in african lions (panthera leo).

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

2010-09-01

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

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

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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.

Malignant lymphoma of the conjunctiva

DEFF Research Database (Denmark)

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

2015-01-01

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

Total Skin Electron Beam for Primary Cutaneous T-cell Lymphoma

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Elsayad, Khaled; Kriz, Jan; Moustakis, Christos; Scobioala, Sergiu; Reinartz, Gabriele; Haverkamp, Uwe; Willich, Normann [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Weishaupt, Carsten [Department of Dermatology, University Hospital of Muenster, Muenster (Germany); Stadler, Rudolf [Department of Dermatology, Johannes-Wesling-Klinikum Minden, Minden (Germany); Sunderkötter, Cord [Department of Dermatology, University Hospital of Muenster, Muenster (Germany); Eich, Hans Theodor, E-mail: Hans.Eich@ukmuenster.de [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany)

2015-12-01

Purpose: Recent trials with low-dose total skin electron beam (TSEB) therapy demonstrated encouraging results for treating primary cutaneous T-cell lymphoma (PCTCL). In this study, we assessed the feasibility of different radiation doses and estimated survival rates of different pathologic entities and stages. Methods and Materials: We retrospectively identified 45 patients with PCTCL undergoing TSEB therapy between 2000 and 2015. Clinical characteristics, treatment outcomes, and toxicity were assessed. Results: A total of 49 courses of TSEB therapy were administered to the 45 patients. There were 26 pathologically confirmed cases of mycosis fungoides (MF) lymphoma, 10 cases of Sézary syndrome (SS), and 9 non-MF/SS PCTCL patients. In the MF patients, the overall response rate (ORR) was 92% (50% complete remission [CR]), 70% ORR in SS patients (50% CR), and 89% ORR in non-MF/SS patients (78% CR). The ORR for MF/SS patients treated with conventional dose (30-36 Gy) regimens was 92% (63% CR) and 75% (25% CR) for low-dose (<30-Gy) regimens (P=.09). In MF patients, the overall survival (OS) was 77 months with conventional dose regimens versus 14 months with low-dose regimens (P=.553). In SS patients, the median OS was 48 versus 16 months (P=.219), respectively. Median event-free survival (EFS) for MF in conventional dose patients versus low-dose patients was 15 versus 8 months, respectively (P=.264) and 19 versus 3 months for SS patients (P=.457). Low-dose regimens had shorter treatment time (P=.009) and lower grade 2 adverse events (P=.043). A second TSEB course was administered in 4 MF patients with 100% ORR. There is a possible prognostic impact of supplemental/boost radiation (P<.001); adjuvant treatment (P<.001) and radiation tolerability (P=.021) were detected. Conclusions: TSEB therapy is an efficacious treatment modality in the treatment of several forms of cutaneous T-cell lymphoma. There is a nonsignificant trend to higher and longer clinical benefit

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

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Kumai, Takumi; Kobayashi, Hiroya; Harabuchi, Yasuaki

2016-01-01

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

Clinico-Radiologic Findings in Primary Cutaneous Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type Mimicking Cellulitis of the Left Arm

International Nuclear Information System (INIS)

Kim, Soo Hyun; Seon, Hyun Ju; Choi, Yoo Duk; Yun, Sook Jung

2015-01-01

Extranodal natural killer (NK)/T-cell lymphoma is a very rare and aggressive disease characterized histopathologically by an Epstein-Barr virus (EBV)-positive atypical lymphoid cytotoxic infiltrate, extensive vascular destruction, and prominent tissue necrosis. It commonly shows cutaneous lesions that primarily or secondarily mimic cellulitis at the primary site. We report on a very rare case of extranodal NK/T-cell lymphoma, nasal type of skin/soft tissue, in a 64-year-old man, and describe the radiological findings. The condition was misdiagnosed as cellulitis of the left arm based on initial noninvasive clinical and radiologic work-up

Synchronous pulmonary malignancies: atypical presentation of mantle cell lymphoma masking a lung malignancy

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Luke Masha

2015-09-01

Full Text Available We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given.

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

NARCIS (Netherlands)

Yssel, H.; de Waal Malefyt, R.; Duc Dodon, M. D.; Blanchard, D.; Gazzolo, L.; de Vries, J. E.; Spits, H.

1989-01-01

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

T Cell Lymphoma and Leukemia in Severe Combined Immunodeficiency Pigs following Bone Marrow Transplantation: A Case Report

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Ellis J. Powell

2017-07-01

Full Text Available After the discovery of naturally occurring severe combined immunodeficiency (SCID within a selection line of pigs at Iowa State University, we found two causative mutations in the Artemis gene: haplotype 12 (ART12 and haplotype 16 (ART16. Bone marrow transplants (BMTs were performed to create genetically SCID and phenotypically immunocompetent breeding animals to establish a SCID colony for further characterization and research utilization. Of nine original BMT transfer recipients, only four achieved successful engraftment. At approximately 11 months of age, both animals homozygous for the ART16 mutation were diagnosed with T cell lymphoma. One of these ART16/ART16 recipients was a male who received a transplant from a female sibling; the tumors in this recipient consist primarily of Y chromosome-positive cells. The other ART16/ART16 animal also presented with leukemia in addition to T cell lymphoma, while one of the ART12/ART16 compound heterozygote recipients presented with a nephroblastoma at a similar age. Human Artemis SCID patients have reported cases of lymphoma associated with a “leaky” Artemis phenotype. The naturally occurring Artemis SCID pig offers a large animal model more similar to human SCID patients and may offer a naturally occurring cancer model and provides a valuable platform for therapy development.

Development of Ultra-Super Sensitive Immunohistochemistry and Its Application to the Etiological Study of Adult T-Cell Leukemia/Lymphoma

International Nuclear Information System (INIS)

Hasui, Kazuhisa; Wang, Jia; Tanaka, Yuetsu; Izumo, Shuji; Eizuru, Yoshito; Matsuyama, Takami

2012-01-01

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

Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation.

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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

2017-07-01

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 in order 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 levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new 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. Copyright© 2017 Ferrata Storti Foundation.

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

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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.

Multiparametric flow cytometry in the diagnosis and characterization of low-grade pulmonary mucosa-associated lymphoid tissue lymphomas.

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Zaer, F S; Braylan, R C; Zander, D S; Iturraspe, J A; Almasri, N M

1998-06-01

Primary mucosa associated lymphoid tissue (MALT) lymphomas are rare neoplasms that seem to have a better prognosis than nodal lymphomas. Morphologic diagnosis of these lesions may be difficult because of features that overlap with those of benign lymphoid infiltrates. In this study, we assessed the contribution of multi-parametric flow cytometry in demonstrating clonality and further characterizing pulmonary MALT lymphomas. Based on a clinical or pathologic suspicion of MALT-lymphoma, 3 transbronchial biopsies, 4 fine needle aspirates, 1 core needle biopsy, and 13 wedge excisions of lung were submitted fresh (unfixed) to our laboratory for evaluation. Among the 13 cases diagnosed as MALT lymphomas, B-cell monoclonality was established by identifying expression of a single immunoglobulin light chain on CD20 or CD19-positive cells in 12 cases. One case lacked expression of both light chains on B-cells. Of 11 lymphoma cases in which CD5 and CD10 surface antigens were assessed, no cases expressed CD10, and 1 case demonstrated weak CD5 expression. Nine of 10 cases studied were diploid and 1 case was hyperdiploid. All of the lymphomas displayed low (< or = 3%) S-phase fractions consistent with low grade processes. In 10 patients with short follow-up, none died of their disease and the majority had no evidence of lymphoma dissemination. In seven of the remaining eight cases, B-cells were polyclonal consistent with reactive processes. In one morphologically reactive case, flow cytometric analysis was unsuccessful because of poor cell viability. The pulmonary MALT lymphomas in this study represent a group of B-cell tumors with distinctive morphologic, immunophenotypic, and cell kinetic characteristics. Multi-parametric flow cytometry is useful for confirming B-cell monoclonality and illustrating an antigenic profile compatible with this diagnosis. Flow cytometry can be particularly helpful when working with small biopsies and cytologic samples with limited diagnostic

Histopathological Assessment and Immunohistochemical Study of Nasopharyngeal Low Grade MALT Lymphoma

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El-Hawary, A.K.

2006-01-01

Introduction: MALT lymphoma arises in a variety of body tissues, but most often in the stomach. Though relatively rare, these MALT lymphomas may arise within several sites in the head and neck, and often present diagnostic and therapeutic challenges. Immunohistochemical analysis are helpful in confirming the diagnosis between the MALT-lymphoma and the reactive lymphoid hyperplasia. MALT-type lymphoma demonstrated characteristic negative staining for CD3, CD5 and CD43, positive staining for CD20, and monotypic staining for either kappa or lambda light chain immunoglobulin markers, whereas reactive lymphoid hyperplasia all expressed Band T cell markers. Material and Methods: 41 cases of nasopharyngeal masses were obtained from the files at pathology department, Mansoura Faculty of Medicine through the period from 2002 till 2006. 31 cases were corresponded histomorphologically to low-grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT) type and 10 patients with reactive lymphoid hyperplasia of the adenoid. Hematoxylin-eosin-stained slides were reviewed to confirm the diagnosis. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded sections using the labeled streptavidin-biotin-peroxidase complex method with DAB as chromogen. The following antibodies were evaluated CD20, CD3, Kappa, lambda and cytokeratin antibodies. Results: All cases of low grade MALT lymphoma show Iymphoepitheliallesion and proliferation of centrocyte like cells. 14 cases (45.1 %) show subepithelial plasma cells. Dutcher bodies were demonstrated in 10 cases (32.2%). Monocytoid B-cells were seen in 12 cases (38.7%). Six (60%) out of the ten cases of adenoids show transmigrating lymphocyte without formation of lymphoepithelial lesion. All cases with MALT-type lymphoma expressed CD20 and not CD3 whereas 10 cases of adenoid, all expressed Band T cell markers. Immunohistochemical staining showed that 31 cases of low grade MALT lymphoma were positive for immunoglobin

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

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

1980-01-01

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

Modulation of radiation-induced apoptosis and G2/M block in murine T-lymphoma cells

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Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N.

1995-01-01

Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to 137 Cs γ irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of γ radiation. We studied the effect of several pharmacological agents on the radiation-induced G 2 /M block and DNA fragmentation. The agents which reduced the radiation-induced G 2 /M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G 2 /M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G 2 /M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G 2 /M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs

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

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

2018-02-01

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

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

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Million, Lynn, E-mail: lmillion@stanford.edu [Stanford Cancer Institute, Stanford, California (United States); Yi, Esther J.; Wu, Frank; Von Eyben, Rie [Stanford Cancer Institute, Stanford, California (United States); Campbell, Belinda A. [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Dabaja, Bouthaina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsang, Richard W. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Ng, Andrea [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Wilson, Lynn D. [Department of Therapeutic Radiology/Radiation Oncology, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut (United States); Ricardi, Umberto [Department of Oncology, University of Turin, Turin (Italy); Kirova, Youlia [Institut Curie, Paris (France); Hoppe, Richard T. [Stanford Cancer Institute, Stanford, California (United States)

2016-08-01

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

Expression of MCM-3 and MCM-7 in Primary Cutaneous T-cell Lymphomas.

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Jankowska-Konsur, Alina; Kobierzycki, Christopher; Reich, Adam; Grzegrzolka, Jedrzej; Maj, Joanna; Dziegiel, Piotr

2015-11-01

Primary cutaneous T-cell lymphomas is a group of rare non-Hodgkin lymphomas, originally affecting the skin. Increased proliferation activity is a hallmark of diverse tumors and the proliferation rate, measured by the expression of various markers has a predictive value regarding the malignancy course. The aim of the present study was to evaluate the prognostic value and the potential correlation between the expression of proliferation markers Ki-67, MCM-3 and MCM-7, and clinicopathological data for different types of primary cutaneous T-cell lymphomas. Immunohistochemical reactions were performed on paraffin blocks obtained from 90 patients with mycosis fungoides (MF) and 21 patients with other CTCL (oCTCL), in comparison to 19 patients with benign inflammatory dermatosis (lichen planus, eczema), serving as control. Statistically significant differences in the expression of Ki-67, MCM-3 and MCM-7 were observed between oCTCL vs. the control group (29% vs. 5%; 17% vs. 5%; 13% vs. 1.5%, respectively, ANOVA with Scheffé post-hoc test: pMCM-3 (r=0.83; pMCM-7 (r=0.84; pMCM-3 and MCM-7 (r=0.81, pMCM-3 expression was significantly higher in advanced compared to early stages (11% vs. 3% and 15.5% vs. 5.0%, respectively, Student's t-test: pMCM-3 and MCM-7 compared to benign inflammatory dermatoses (Student's t-test: pMCM-3 and MCM-7 than T1a (pMCM-3 expression in MF showed a positive relationship with both nodal and distant metastases (ANOVA with Scheffé post hoc test: pMCM-3 expression correlated with shorter survival in MF, although the latter did not reach statistical significance (10-year survival 0.38 vs. 0.82, p=0.02, and 0.46 vs. 0.81, p=0.06, respectively; log rank test). All studied proliferation markers may had predictive values regarding the disease severity and prognosis. Further studies are required to analyze their implementation into patient stratification and treatment process such that will improve prognosis in CTCL. Copyright© 2015 International

Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

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Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

2018-02-01

We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

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.

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Dammy Pinheiro

Full Text Available 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.

A unique case of primary effusion lymphoma-like lymphoma showing disappearance and recurrence of the body cavity effusion.

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Koeda, Chikahiko; Sato, Takashi; Matsumoto, Yuki; Usui, Yuta; Kunugida, Fusanori; Ogawa, Muneyoshi

2017-03-01

Primary effusion lymphoma-like lymphoma (PEL-LL) is a rare B-cell lymphoma that the etiology remains unclear. We describe a case of PEL-LL with a pleuropericardial effusion. Diagnosis required long period of time as it followed a unique progress of disappearance and recurrence of the body cavity effusion. We finally had a diagnosis of B-cell lymphoma by the immunocytochemistry of effusion using the cell block procedure. Authors consider that it is valuable to actively try the cell block procedure at the time of the first drainage for early diagnosis, if the body cavity effusion due to the malignancy is suspected.

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

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Jovanović Svetlana

2013-01-01

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

Primary mantle cell lymphoma of tonsil: Case report

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Knežević Snežana B.

2017-01-01

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

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

Circulating Tfh1 (cTfh1 cell numbers and PD1 expression are elevated in low-grade B-cell non-Hodgkin's lymphoma and cTfh gene expression is perturbed in marginal zone lymphoma.

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Elliot T Byford

Full Text Available CD4+ T-cell subsets are found in the tumour microenvironment (TME of low-grade B-cell non-Hodgkin's lymphomas such as marginal zone lymphoma (MZL or follicular lymphoma (FL. Both numbers and architecture of activating follicular helper T-cells (Tfh and suppressive Treg in the TME of FL are associated with clinical outcomes. There has been almost no previous work on CD4+ T-cells in MZL. It is now recognised that circulating CD4+CXCR5+ T-cells are the memory compartment of Tfh cells. We determined differences in number of circulating Tfh (cTfh cells and cTfh subsets between normal subjects and patients with FL or MZL. Lymphoma patients showed increased numbers of cTfh1 and reduced cTfh17 cells due to decreased expression of the subset-defining marker CCR6 in patients. PD1, a surface marker associated with Tfh cells, showed increased expression on cTfh subsets in patients. Focusing on MZL we determined expression of 96 T-cell associated genes by microfluidic qRT-PCR. Analysis of differentially expressed genes showed significant differences between normal subjects and patients both for bulk cTfh (CCL4 and the cTfh1 subset (JAK3. While our findings require confirmation in larger studies we suggest that analysis of number and gene expression of circulating T-cells might be a source of clinically useful information as is the case for T-cells within lymphoma lymph nodes.

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

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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)-express...

Primary Intra-aortic Epstein-Barr Virus-Positive Large B-Cell Lymphoma Presenting as Aortic Mural Thrombosis: An Entity Distinct From Intravascular Large B-Cell Lymphoma.

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Nakao, Ryuta; Sakashita, Aki; Omoto, Atsushi; Sato, Osamu; Hino, Yoko; Yanagisawa, Akio; Urata, Yoji

2017-12-01

Intravascular selective growth of neoplastic B lymphocytes is a characteristic finding of intravascular large B-cell lymphoma (IVLBCL). However, because neoplastic B cells of IVLBCL grow merely in the lumina of capillaries or small vessels, primary IVLBCL of the great vessels is considered exceptional. To our knowledge, only 2 primary B-cell lymphomas in the lumina of the vena cava have been reported. However, there has been no report of primary B-cell lymphoma with intra-aortic growth. We describe a novel manifestation of primary Epstein-Barr virus-positive large B-cell lymphoma mainly affecting the lumina of the aorta and its major branches in a 76-year-old man. He had a long-term fever that was refractory to antibiotics and aortic mural thrombosis with visceral embolization. Because he had no detectable mass suggesting a malignancy, it was difficult to diagnose while he was alive. He died without anticancer treatment, and the confirmed diagnosis was made at autopsy.

FDG-PET in lymphomas

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Knapp, W. H.

2009-01-01

Lymphomas are a heterogeneous group of neoplasms in which two major subtypes are distinguished, Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL). The incidence of lymphomas is about 20 per 100000 inhabitants (Jemal et al 2002) and 7-8 times higher than that of HD. Since NHL has a worse prognosis, the death rates of NHL are 14 times higher than those for HD. Lymphomas account for about 4 % of all cancer incidences. In USA, lymphomas are the fifth most frequent cancer type diagnosed and the third most frequent form of cancer death (Jemal et al 2002). Concerning HD, there is a preponderance for males with a gender ratio of 1.33 for incidence and 1.12 for mortality. For NHL incidences and mortality rates of genders are almost equal. HL comprises different subtypes among which nodular sclerosis is the most frequent one (60-70 %). Other histopathologic subtypes are those of mixed cellularity, lymphocyte reach and lymphocyte depleted characteristics. The most frequent subgroup of NHL are B-cell lymphomas (80-90 % of all NHL). Two thirds of this subgroup are diffuse large B-cell lymphomas, one third follicular lymphomas. Other (less frequent) subtypes are mantle cell, peripheral T-cell, anaplastic large-cell-lymphomas etc. For NHL increasing incidence has been observed in the last decades. Within 15 years the incidence increased by 50 % in the USA (Jemal et al 2002). Etiology of lymphomas is still unknown. In a certain proportion of NHL viral causes are assumed. Diagnosis is based on histology (needle biopsy) with consecutive sub typing. Prognosis depends on stage, expansion state, histology and proliferation rates. (author)

Clinical significance of cyclooxygenase-2 expression in extranodal natural killer (NK)/T-cell lymphoma, nasal type

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Shim, Su Jung; Yang, Woo-Ick; Shin, Eunah; Koom, Woong Sub; Kim, Yong Bae; Cho, Jae Ho; Suh, Chang Ok; Kim, Joo Hang; Kim, Gwi Eon

2007-01-01

Purpose: To determine whether there are any differences in therapeutic response, patterns of systemic recurrence, and prognosis of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, by the cyclooxygenase-2 (COX-2) expression. Patients and Methods: Thirty-four patients with Ann Arbor Stage I and II extranodal NK/T-cell lymphoma who underwent chemotherapy or radiotherapy, or both, were retrospectively reviewed. These patients were divided into two groups according to their immunohistochemical staining for COX-2 expressions: a COX-2-negative group (n = 10 patients) and a COX-2-positive group (n = 24 patients). The treatment response, patterns of treatment failure, and survival data for the patients were compared between the COX-2-positive and negative groups. Results: There was no significant difference in the clinical profiles between the COX-2-negative and COX-2-positive groups. All patients (100%) in the COX-2-negative group achieved complete response after initial treatment, whereas only 14 patients (58%) in the COX-2-positive group achieved complete response (p = 0.03). Compared with the patients in the COX-2-negative group, those in the COX-2-positive group had a significantly lower 2-year systemic recurrence-free survival rate (100% for the COX-2-negative group vs. 54% for the COX-2-positive group) (p = 0.02) and a decreased 5-year overall survival rate (70% for the COX-2-negative group vs. 32% for the COX-2-positive group) (p = 0.06). Conclusion: Cyclooxygenase-2 expression can serve as a predictive factor for poor treatment response, higher systemic recurrence, and unfavorable prognosis in patients with extranodal NK/T-cell lymphoma, nasal type

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

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2018-04-23

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

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

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Illidge, T.M.

1999-06-01

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

Mechanisms of lymphocytotoxicity induced by extracorporeal photochemotherapy for cutaneous T cell lymphoma

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Marks, D.I.; Rockman, S.P.; Oziemski, M.A.; Fox, R.M.

1990-01-01

Extracorporeal photochemotherapy is an effective treatment for cutaneous T cell lymphoma but its mode of action is uncertain. The reduction in viability of patients' photoirradiated buffy coat lymphocytes was correlated with a 35% increase in DNA single-strand breaks and marked decreases in cellular ATP and NAD levels (to 58 and 34% of control, respectively) immediately after photoirradiation. Complementary in vitro studies were conducted with normal human peripheral blood lymphocytes using a Therakos ultraviolet A (UVA) light box. UVA light was cytotoxic on its own but was potentiated by 8-methoxysporalen. 3-aminobenzamide, a poly (ADP-ribose) synthetase inhibitor, mitigated the cytotoxic effect of ultraviolet A light in the presence of 8-methoxypsoralen in lymphocytes and reduced the amount of nucleotide depletion they caused. 10 J/cm2 of UVA light in the presence of 300 ng/ml 8-methoxypsoralen increased the poly (ADP-ribose) synthetase activity of peripheral blood lymphocytes. Exposing lymphocytes to deoxycoformycin and deoxyadenosine was found to induce biochemical and physical effects similar to those of photochemotherapy. In summary, we have shown that the lymphocytotoxic effect of extracorporeal photochemotherapy for cutaneous T cell lymphoma is apparently mediated by DNA damage, subsequent poly (ADP-ribosyl)ation and adenine nucleotide depletion. It is not known how the DNA damage and resultant biochemical effects relate to the possible immunological mechanism of extracorporeal photochemotherapy; however, it is possible that its effects can be mimicked by other DNA-damaging agents

Hodgkin's lymphoma arising in a case of mycosis fungoides: An unusual association

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Preeti Sharma

2018-01-01

Full Text Available Mycosis fungoides is a cutaneous T-cell lymphoma with a high risk for developing secondary malignancies, especially B-cell lymphoproliferative disorders. About 40 cases of Hodgkin's lymphoma associated with mycosis fungoides have been reported in literature till date. We report a case of a 35-year-old gentleman who presented with intensely itchy reddish lesions all over the body. Multiple skin biopsies taken from the lesions on scalp and back confirmed the clinical diagnosis of mycosis fungoides. While on treatment, he presented with multiple bilateral cervical, axillary and inguinal lymphadenopathy 9 years after the primary diagnosis of mycosis fungoides. Excision biopsy of a cervical lymph node revealed partial effacement of architecture by a tumor comprising polymorphous background. Histopathology and immunohistochemistry revealed a diagnosis of Hodgkin's lymphoma - nodular sclerosis subtype. The patient was started on chemotherapy for stage IV Hodgkin's lymphoma. Our case emphasizes the importance of keeping secondary Hodgkin's lymphoma in mind while dealing with a patient of mycosis fungoides. Our case immunohistochemically supports the distinct etiopathogenesis of Epstein–Barr virus-negative Hodgkin's lymphoma vis-à-vis cutaneous mycosis fungoides.

A leukemic double-hit follicular lymphoma associated with a complex variant translocation, t(8;14;18)(q24;q32;q21), involving BCL2, MYC, and IGH.

Science.gov (United States)

Minakata, Daisuke; Sato, Kazuya; Ikeda, Takashi; Toda, Yumiko; Ito, Shoko; Mashima, Kiyomi; Umino, Kento; Nakano, Hirofumi; Yamasaki, Ryoko; Morita, Kaoru; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Ashizawa, Masahiro; Hatano, Kaoru; Oh, Iekuni; Fujiwara, Shin-Ichiro; Ohmine, Ken; Kawata, Hirotoshi; Muroi, Kazuo; Miura, Ikuo; Kanda, Yoshinobu

2018-01-01

Double-hit lymphoma (DHL) is defined as lymphoma with concurrent BCL2 and MYC translocations. While the most common histological subtype of DHL is diffuse large B-cell lymphoma, the present patient had leukemic follicular lymphoma (FL). A 52-year-old man was admitted to our hospital due to general fatigue and cervical and inguinal lymph node swelling. The patient was leukemic and the pathological diagnosis of the inguinal lymph node was FL grade 1. Chromosomal analysis revealed a complex karyotype including a rare three-way translocation t(8;14;18)(q24;q32;q21) involving the BCL2, MYC, and IGH genes. Based on a combination of fluorescence in situ hybridization (FISH), using BCL2, MYC and IGH, and spectral karyotyping (SKY), the karyotype was interpreted as being the result of a multistep mechanism in which the precursor B-cell gained t(14;18) in the bone marrow and acquired a translocation between der(14)t(14;18) and chromosome 8 in the germinal center, resulting in t(8;14;18). The pathological diagnosis was consistently FL, not only at presentation but even after a second relapse. The patient responded well to standard chemotherapies but relapsed after a short remission. This patient is a unique case of leukemic DH-FL with t(8;14;18) that remained in FL even at a second relapse. Copyright © 2017 Elsevier Inc. All rights reserved.

Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS). A new prognostic model developed by the International T cell Project Network.

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Federico, Massimo; Bellei, Monica; Marcheselli, Luigi; Schwartz, Marc; Manni, Martina; Tarantino, Vittoria; Pileri, Stefano; Ko, Young-Hyeh; Cabrera, Maria E; Horwitz, Steven; Kim, Won S; Shustov, Andrei; Foss, Francine M; Nagler, Arnon; Carson, Kenneth; Pinter-Brown, Lauren C; Montoto, Silvia; Spina, Michele; Feldman, Tatyana A; Lechowicz, Mary J; Smith, Sonali M; Lansigan, Frederick; Gabus, Raul; Vose, Julie M; Advani, Ranjana H

2018-04-19

Different models to investigate the prognosis of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) have been developed by means of retrospective analyses. Here we report on a new model designed on data from the prospective T Cell Project. Twelve covariates collected by the T Cell Project were analysed and a new model (T cell score), based on four covariates (serum albumin, performance status, stage and absolute neutrophil count) that maintained their prognostic value in multiple Cox proportional hazards regression analysis was proposed. Among patients registered in the T Cell Project, 311 PTCL-NOS were retained for study. At a median follow-up of 46 months, the median overall survival (OS) and progression-free survival (PFS) was 20 and 10 months, respectively. Three groups were identified at low risk (LR, 48 patients, 15%, score 0), intermediate risk (IR, 189 patients, 61%, score 1-2), and high risk (HiR, 74 patients, 24%, score 3-4), having a 3-year OS of 76% [95% confidence interval 61-88], 43% [35-51], and 11% [4-21], respectively (P < 0·001). Comparing the performance of the T cell score on OS to that of each of the previously developed models, it emerged that the new score had the best discriminant power. The new T cell score, based on clinical variables, identifies a group with very unfavourable outcomes. © 2018 The Authors British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Secondary pancreatic involvement by a diffuse large B-cell lymphoma presenting as acute pancreatitis

Institute of Scientific and Technical Information of China (English)

M Wasif Saif; Sapna Khubchandani; Marek Walczak

2007-01-01

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. More than 50% of patients have some site of extra-nodal involvement at diagnosis,including the gastrointestinal tract and bone marrow.However, a diffuse large B-cell lymphoma presenting as acute pancreatitis is rare. A 57-year-old female presented with abdominal pain and matted lymph nodes in her axilla. She was admitted with a diagnosis of acute pancreatitis. Abdominal computed tomography (CT) scan showed diffusely enlarged pancreas due to infiltrative neoplasm and peripancreatic lymphadenopathy. Biopsy of the axillary mass revealed a large B-cell lymphoma.The patient was classified as stage Ⅳ, based on the Ann Arbor Classification, and as having a high-risk lymphoma,based on the International Prognostic Index. She was started on chemotherapy with CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone). Within a week after chemotherapy, the patient's abdominal pain resolved. Follow-up CT scan of the abdomen revealed a marked decrease in the size of the pancreas and peripancreatic lymphadenopathy. A literature search revealed only seven cases of primary involvement of the pancreas in B-cell lymphoma presenting as acute pancreatitis. However, only one case of secondary pancreatic involvement by B-cell lymphoma presenting as acute pancreatitis has been published. Our case appears to be the second report of such a manifestation.Both cases responded well to chemotherapy.

Lennert's Lymphoma

International Nuclear Information System (INIS)

Narayanrao, Suresh T.; Pillai, R.; Nada, Aymen; Hasan, Suhel

2005-01-01

Lymphoepithelioid cell lymphoma (Lennert's lymphoma) is a rare morphological variant of peripheral T-cell lymphoma characterized by the presence of numerous clusters of epithelioid histiocytes without formation of discrete granulomas and the intervening atypical lymphocytes. Lennert's lymphoma is often misinterpreted as granulomatous lymphadenitis or Hodgkin's disease. This report describes fine needle aspiration cytology and histological findings in a case of Lennert's lymphoma. (author)

Intravascular Large B-Cell Lymphoma

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Maria S. Khan MD, FACP

2014-03-01

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

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

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Manfè, Valentina; Biskup, Edyta; Willumsgaard, Ayalah

2013-01-01

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 c...

Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

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Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

2012-11-01

The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

Dual diagnosis of sarcoidosis and lymphoma.

LENUS (Irish Health Repository)

Brady, B

2013-06-01

Sarcoidosis is a multisystem granulomatous disease of unknown origin with pulmonary and extrapulmonary manifestations. Worldwide it is most often diagnosed in the third and fourth decades and most often affects Swedish, Danish and black patients. The association between malignancy and sarcoidosis has not been conclusively proven. Cancer can eventually occur in patients who have an established diagnosis of sarcoidosis for example, in sarcoidosis-lymphoma syndrome. Sarcoidosis can also subsequently develop in an oncology patient. There are multiple obstacles to confirming epidemiologically the linkage between sarcoidosis and malignancy. Histological verification and clinical acumen are needed to avoid misdiagnosis. The 18 fluorodeoxyglucose (18-FDG) PET has failed to provide a non invasive diagnostic method to differentiate neoplasia from benign sarcoid lesions and tissue diagnosis is essential before commencing a new therapeutic intervention in patients with lymphoma.

T-cell non-Hodgkin lymphomas: Spectrum of disease nd the role of imaging in the management of common subtypes

Energy Technology Data Exchange (ETDEWEB)

Park, Hye Sun [Dept. of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; Shinagare, Atul B. [Dept. of Imaging, Dana Farber Cancer Institute, Harvard Medical School, Boston (United States)

2017-01-15

T-cell non-Hodgkin lymphomas (NHLs) are biologically diverse, uncommon malignancies characterized by a spectrum of imaging findings according to subtype. The purpose of this review is to describe the common subtypes of T-cell NHL, highlight important differences between cutaneous, various peripheral and precursor subtypes, and summarize imaging features and the role of imaging in the management of this diverse set of diseases.

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.

Modulation of radiation-induced apoptosis and G{sub 2}/M block in murine T-lymphoma cells

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Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N. [Harvard Medical School, Boston, MA (United States)

1995-03-01

Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to {sup 137}Cs {gamma} irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of {gamma} radiation. We studied the effect of several pharmacological agents on the radiation-induced G{sub 2}/M block and DNA fragmentation. The agents which reduced the radiation-induced G{sub 2}/M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G{sub 2}/M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G{sub 2}/M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G{sub 2}/M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs.

Non-Hodgkin's Lymphoma of the Tongue Presenting as an Ulcerative Lesion

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Bijan Khademi

2011-10-01

Full Text Available Malignant lymphoma may occur in the oral cavity and oropharynx, but is most commonly located in Waldeyer's ring, particularly in the palatine and lingual tonsil. The occurrence of malignant lymphoma in the tongue is very rare. Clinical features are nonspecific ulcerative lesions that do not heal. In the literature, the majority of casesare non-Hodgkin’s lymphoma, diffuse large B cell type; however T-cell phenotype also may occur. We describe a 60-year-old man who presented with an ulcerative mass in the left lateral aspect of his tongue, unresponsive to medical therapy. After tissue biopsy, histopathological and immunohistochemical analyses confirmed a diagnosis of non-Hodgkin’s lymphoma, diffuse large B cell type.

FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma.

Science.gov (United States)

Park, Myoung-Ja; Taki, Tomohiko; Oda, Megumi; Watanabe, Tomoyuki; Yumura-Yagi, Keiko; Kobayashi, Ryoji; Suzuki, Nobuhiro; Hara, Junichi; Horibe, Keizo; Hayashi, Yasuhide

2009-04-01

Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL-97 and NHL-98. FBXW7 and/or NOTCH1 mutations were found in 22 (40.0%) of 55 T-ALL and 7 (50.0%) of 14 T-NHL patients. FBXW7 mutations were found in 8 (14.6%) of 55 T-ALL and 3 (21.4%) of 14 T-NHL patients, and NOTCH1 mutations in 17 (30.9%) of 55 T-ALL and 6 (42.9%) of 14 T-NHL patients. Three (5.4%) T-ALL and two (1.4%) T-NHL patients had mutations in both FBXW7 and NOTCH1. FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five-year event-free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95.5% (95% CI, 71.9-99.4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63.6%, P = 0.007 and 78.8%, P = 0.023, respectively).

Reduction of myeloid-derived suppressor cells and lymphoma growth by a natural triterpenoid.

Science.gov (United States)

Radwan, Faisal F Y; Hossain, Azim; God, Jason M; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

2015-01-01

Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A's anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen (Ag) presentation and CD4+ T cell recognition of lymphoma cells in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. © 2014 Wiley Periodicals, Inc.

Non Hodgkin T cell lymphoma: an atypical clinical presentation Linfoma não Hodgkin de células T citotóxico: uma apresentação clínica atípica

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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.

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

DEFF Research Database (Denmark)

Savorani, Cecilia; Manfé, Valentina; Biskup, Edyta

2015-01-01

(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....

Contribution of flow cytometry to the diagnosis of gastric lymphomas in endoscopic biopsy specimens.

Science.gov (United States)

Almasri, N M; Zaer, F S; Iturraspe, J A; Braylan, R C

1997-07-01

Gastric lymphomas seem to have unique clinical, pathologic, and immunophenotypic features that set them apart from nodal lymphomas. Microscopic examination of endoscopic biopsy specimens is the most frequent procedure used to diagnose gastric tumors, but it is very difficult, and sometimes impossible, to recognize lymphomas in endoscopic samples by histologic or even immunohistologic methods. Because most gastric lymphomas are of B-cell origin, we used flow cytometry to assess B-cell clonality in gastric biopsy specimens containing dense lymphocytic infiltrates thought to represent lymphoma. We prepared viable cell suspensions from unfixed specimens obtained from 29 consecutive patients who had a previous microscopic diagnosis of suspicious gastric lymphoid infiltrates. We performed immunophenotypic studies with multicolor flow cytometry, and we assessed clonality by examination of immunoglobulin (Ig) light-chain expression analyzed exclusively on B cells identified by anti-CD20 or CD19 antibodies. The mean number of cells recovered was 1.04 x 10(6), from an average of 5.5 gastric biopsy fragments per patient. In 26 of the 29 patients, the number of cells was adequate for analysis. We detected B-cell monoclonality in 16 cases, including 5 in which the percentage of clonal B cells was less than 5%. Of the 16 cases, only 8 could be diagnosed as lymphomas on morphologic grounds alone; the remaining 8 patients had either suspicious lymphoid infiltrates or chronic gastritis. The three cases with an insufficient number of cells were considered non-neoplastic either on histologic grounds alone or in conjunction with Southern analysis of Ig genes. We conclude that flow cytometric immunophenotypic analysis of freshly prepared cell suspensions obtained from endoscopic biopsy specimens can be used to evaluate gastric lymphocytic infiltrates. Specifically, the analysis of surface Ig light-chain expression on B cells distinguishes between monoclonal (lymphoma) and polyclonal

CD7 Positive Diffuse Large B-Cell Lymphoma Arising in a Background of Follicular Lymphoma: A Case Report and Review of the Literature

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Elham Vali Betts

2016-01-01

Full Text Available Diffuse large B-cell lymphoma (DLBCL is a neoplasm of large B-lymphocytes with a diffuse growth pattern. The neoplastic cells express B-cell markers such as CD20 and PAX-5 and there may be coexpression of BCL-2, BCL-6, CD10, and MUM-1. With the exception of CD5, other T-cell markers are not commonly expressed in this neoplasm. Here, we describe the first reported case of a DLBCL with abnormal expression CD7 arising in a background of follicular lymphoma in an 81-year-old male who presented with a nontender left axillary mass. Additionally, no other T-cell antigens were expressed in this B-cell lymphoma. Expression of CD7 in DLBCL is exceptionally rare and its prognostic significance is unknown. Here, we describe this rare case with review of literature of known DLBCLs with expression of T-cell antigens.

Reduction of Myeloid-derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid

Science.gov (United States)

Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

2016-01-01

Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A’s anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen presentation and CD4+ T cell recognition of lymphoma in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. PMID:25142864