Risk of second malignancy after cutaneous T-cell lymphoma

Risk of second primary malignancy was assessed in a population-based follow-up survey of all persons who developed cutaneous T-cell lymphoma (CTCL) in nine geographic areas of the United States covered by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute during the period 1973 to 1983. Among 544 patients with a first primary tumor reported as CTCL, a second cancer developed in 35 (6%), yielding a significantly elevated relative risk (RR) of 1.7, which reflects excesses for cancers of the lung and colon and non-Hodgkin's lymphoma. Although the excess of lymphoma may be related to the evolution of CTCL to less differentiated T-cell lymphoma, additional studies are needed to clarify the immunologic, genetic, viral, and environmental factors that may contribute to the development of second cancers.     

Correlation of aberrant proliferation with T-cell growth factor in adult T-cell leukemia cells

Peripheral blood lymphocytes from seven patients with adult T-cell leukemia (ATL) were found to lack PHA-responsiveness. However, in most of the cases, minute but distinct proliferation could be induced and maintained by human spleen cell conditioned medium containing PHA or by a combination of PHA and conditioned medium of gibbon cell line, MLA-144 (MLA-144 CM). These results indicate that the lack of response to mitogens of ATL cells might be attributed not only to the failure of these cells to produce T-cell growth factor (TCGF) upon activation, but also to their poor responsiveness to TCGF. Furthermore, a direct proliferative response to mitogen-free MLA-144 CM was shown in two out of seven patients; these two patients experienced rapidly progressive clinical courses. This observation raises the possibility that TCGF promotes the growth of ATL cells in vivo, and is related to the clinical course of the disease.     

Correlation of T-cell immune response with spontaneous resolution and subsequent relapse of Hodgkin's lymphoma

To our knowledge, there has been no report of spontaneous regression in a non-immunocompromised adult with classical Hodgkin's lymphoma (HL) in the absence of chemotherapy. We describe spontaneous regression and subsequent relapse of Epstein - Barr virus (EBV)-positive HL in an otherwise healthy male adult. The clinical course was associated with an increase in regulatory T-cell markers within the peripheral blood and diseased lymph node at the time of relapse and with a concomitant reduction in cellular immunity against relevant EBV latent membrane protein tumor-associated antigens. Our findings are in keeping with previous observations that implicate impaired cellular immunity in the immunopathogenesis of EBV-positive HL.     

Peripheral T-cell lymphoma together with myelofibrosis with elevated plasma transforming growth factor-beta1

Myelofibrosis is usually observed in myeloproliferative disorders, such as chronic myeloid leukemia. However, there are only a few reports showing an association between T-cell lymphoma and myelofibrosis. We report a case of peripheral T-cell lymphoma, unspecified (diffuse large cell) type, involving the bone marrow that was associated with severe myelofibrosis. In the present case, the plasma concentration of transforming growth factor-beta1 (TGF-beta1) was increased to 8.95 ng/ml (normal range: 1.56-3.24 ng/ml). No lymphadenopathy or skin lesions were observed during the entire clinical course. Although the mechanism of secondary myelofibrosis is still unclear, elevated plasma TGF-beta1 might be involved in the pathogenesis of bone marrow fibrosis in the present case.     

血管内皮生长因子与非霍奇金淋巴瘤浸润的相关性研究

目的检测非霍奇金淋巴瘤（NHL）患者血清中血管内皮细胞生长因子（sVEGF）的浓度,探讨其与NHL浸润的关系。方法采用夹心酶联免疫吸附法（ELISA）检测81例NHL初治患者和36例健康对照sVEGF的水平。同时检测81例NHL初治患者血浆乳酸脱氢酶（LDH）浓度。比较NHL患者与对照组sVEGF的差别及不同临床分期、治疗效果、血浆LDH浓度、sVEGF水平的差别,分析NHL患者sVEGF水平、LDH浓度的相关性。结果NHL患者组sVEGF水平（282．90±29．80）Pg／ml,较对照组升高[（180．20±14．91）Pg／ml],且差异具有统计学意义（P〈0．05）;Ⅲ、IV期患者sVEGF水平为（304．35±143．21）Pg／ml高于I、Ⅱ期的（257．86±168．10）Pg／ml,但差异无统计学意义;未完全缓解患者组sVEGF水平为（323．26±159．89）Pg／ml,明显高于达完全缓解者组[（228．21±143．21）pg／ml]（P〈0．05）;LDH升高组sVEGF水平（385．40±157．87）pg／ml较LDH正常组（234．18±158．87）Pg／ml明显升高（P〈0．05）;VEGF水平与LDH浓度间有显著的相关性（P〈0．01）。结论血管生成在NHL的侵袭转移机制中具有重要作用;sVEGF水平可作为NHL了解病情、观察疗效和预后的指标。     

Establishment and characterization of four human bladder tumor cell lines and sublines with different degrees of malignancy

We have established four human bladder tumor cultures, designated MGH-U1 to -U4 (also known as EJ, HM, RN, and RB in some previous reports). All have been grown in culture for over 30 passages and were free of Mycoplasma contamination. Characterizations of these cell lines were performed. These include isozyme profile, morphology with light and scanning electron microscopes, karyotype, growth rate, DNA content by flow cytometry, presence of cell surface ABH isoantigens, tumorigenicity in nude mice, lactic acid dehydrogenase isozymes, and colony formation in soft agar. Results obtained from these characterizations confirm that MGH-U1 and -U2 are sublines of a previously established bladder tumor cell line, T-24. These results also show that MGH-U3 and -U4, derived respectively from a grade 1 tumor and an urothelium biopsy with severe atypia, are likely to be independent human bladder cell lines and different from other transitional cell bladder carcinoma cell lines reported. The study further demonstrates that these four cell lines/sublines have different degrees of malignancy and a close correlation, in biological and malignant characteristics, between the cells in culture and those in the original tumors. Therefore these cultures may represent cells at different stages of malignant progression. These can be useful models for studies of the development and progression of bladder tumors and detection and treatment of bladder tumors of different grades and stages.     

Clinical characteristics of T-cell lymphoma associated with hemophagocytic syndrome: comparison of T-cell lymphoma with and without hemophagocytic syndrome.

T-cell lymphoma-associated hemophagocytic syndrome (T-LAHS) has been frequently reported in Asian countries and is considered with extremely poor prognosis. To summarize its clinical characteristics and explore its early diagnosis and treatment, we retrospectively analyzed the records of 113 patients with aggressive T cell lymphoma, of which 28 were associated with LAHS. According to WHO classification (2001), 22 cases were classified into peripheral T-cell lymphoma (unspecified), 2 into extranodal NK/T-cell lymphoma, and 4 into systemic anaplastic large cell lymphoma. The median survivals of the LAHS and no-LAHS groups were 40 days and 8 months, respectively. The elevating rates of serum lactate dehydrogenase (LDH) (100% vs. 55%), ferritin (100% vs. 64%), fasting triglycerides (79% vs. 43%), and hypofibrinogen (43% vs. 14%) levels were higher in the LAHS group than in the no-LAHS group (P < 0.05), so were bone marrow involvement (57% vs. 32%, P < 0.05) and liver dysfunction (40% vs. 13%, P < 0.05). Eleven of the 28 LAHS patients did not receive any chemotherapy, and 14 received CHOP regimen as initial chemotherapy. Three patients in critical conditions were given plasma exchange and gained the chance of initial chemotherapy. We suggest that in patients presenting with fever, hepatosplenomegaly, cytopenia, and constantly increasing levels of serum LDH, CA125, ferritin, transglutaminase, and beta2-microglobulin, T-LAHS should be taken into account. Repeating biopsies of multiple parts of bone marrow may help diagnosis. The therapeutic result of chemotherapy alone or combined for T-LAHS was discouraging and the survival time of most cases was no more than 1 year. Plasmapheresis as initial therapy is worth considering in critical cases.     

非霍奇金淋巴瘤免疫分型与骨髓细胞形态学的相关性研究

目的:探讨非霍奇金淋巴瘤免疫分型与骨髓细胞形态学的相关性。方法:选择2015年3月至2017年3月我院收治的NHL骨髓侵犯患者63例,进行骨髓涂片细胞形态学检测与流式细胞（FCM）免疫分型检测,分析两种检测之间的联系。结果:按照骨髓细胞形态学分型结果,63例NHL骨髓侵犯患者其中小细胞成熟细胞型40例（63.49%）、大细胞原始型患者6例（9.52%）、大细胞幼稚型10例（15.87%）以及组织细胞型7例（11.11%）。FCM检测根据骨髓瘤细胞特异性抗原表达情况,诊断为B细胞淋巴瘤患者48例（76.19%）、T细胞淋巴瘤患者10例（15.87%）、NK细胞淋巴瘤患者4例（6.35%）以及间变性大细胞淋巴瘤患者1例（1.59%）。FCM诊断48例B细胞淋巴瘤患者中,小细胞成熟细胞型37例（77.08%）、大细胞原始型4例（8.33%）、大细胞幼稚型5例（10.42%）、组织细胞型2例（4.17%）;10例T细胞淋巴瘤患者中,小细胞成熟细胞型3例（30.00%）、大细胞原始型2例（20.00%）、大细胞幼稚型1例（10.00%）、组织细胞型4例（40.00%）;4例NK细胞淋巴瘤患者中,均为大细胞幼稚型（100.00%）;1例间变性大细胞淋巴瘤患者为组织细胞型（100.00%）。结论:非霍奇金淋巴瘤免疫分型与骨髓细胞形态学之间具有着一定的联系,二者联合运用,可提高临床诊断准确性并为临床提供相应的病理分型意见,值得临床推广。     

Glutamate receptor-mediated effects on growth and morphology of human histiocytic lymphoma cells

Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS) and binds to a variety of receptors, which recently have also been detected in peripheral, non-excitable cells. New research suggests that this abundant amino acid might also be involved in the growth of tumor cells acting via novel receptor-mediated autocrine/paracrine signal transduction pathways. We report here that glutamate, as well as glutamate receptor reactive drugs, differentially modulate growth and morphology of human histiocytic lymphoma-derived U937 cells. These effects were different depending on the culture milieu: in glutamine-free medium the glutamate receptor agonists, kainate (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), but also the antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), significantly decreased the proliferation of U937 cells. In contrast, in cultures devoid of glutamate, glutamine and serum, the agonists significantly increased cell proliferation whereas the antagonist CNQX showed no effect. These data point to a significant role of peripheral glutamate receptors in tumor cell proliferation.     

Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades--should peripheral T-cell lymphoma be considered separately?

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.     

Nasal T-cell lymphoma associated with hemophagocytic syndrome

A patient with immunohistochemically confirmed nasal T-cell lymphoma is reported. He developed systemic histiocytosis with marked hemophagocytosis, simulating malignant histiocytosis. The differential diagnosis from the latter is discussed.     

放射治疗上呼吸道T细胞淋巴瘤34例临床预后分析

目的：分析上呼吸道T细胞淋巴瘤放射治疗的远期疗效和影响其预后的相关因素。方法：对经病理证实的34例上呼吸道T细胞淋巴瘤病例，按病变累及部位，有无发热，不同照射剂量和服用CCNU合并化疗等因素将病例分组，经放射治疗后观察其生存期。结果：病变累及两个或以上解剖部位病例组的生存率低于累及一个部位的病例组；无发热症状的病例组3年和5年生存率高于有发热病例组，放射剂量以50－60Gy的病例组生存率较高，结论：放射治疗是上呼吸道T细胞淋巴瘤的首选治疗，发病越早，临床症状越轻，预后越好。     

Therapeutic outcome of extranodal NK/T-cell lymphoma initially treated with chemotherapy--result of chemotherapy in NK/T-cell lymphoma

The therapeutic outcome of chemotherapy in NK/T cell lymphoma (NTCL) has not been well documented until now. The aims of this study were to investigate the outcome of chemotherapy and to evaluate the clinical factors influencing the responsiveness to chemotherapy. Between 1995 and 2000, 59 patients received anthracycline-based chemotherapy as an initial treatment. Forty-five patients had nasal NTCL, whereas 14 had extranasal NTCL. Forty-one patients had stage I/II and 18 had stage III/IV disease. Epstein-Barr virus status was positive in 67.6% of cases. The results of initial chemotherapy were complete remission in 35.6% of the patients, 2-year disease-free survival in 22.9% and 2-year overall survival in 44.2%. Adjuvant radiotherapy after chemotherapy did not improve outcome in stage I/II nasal NTCL. The International Prognostic Index was a significant prognostic factor of complete remission rate, and stage was also significant for disease-free survival.