T-cell lymphoma in Singapore: pathology, clinical findings and association with HTLV-1 antibodies

Of 128 cases of malignant lymphomas studied in Singapore between 1986 and 1988, 28 were identified as peripheral T-cell lymphomas. Sera from two of the 128 cases were positive for HTLV-1 antibodies and both cases had the clinical and pathological features of adult T-cell leukaemia/lymphoma. The pathological and clinical features of the 28 cases of peripheral T-cell lymphoma are presented in detail. Survival data indicated no significant difference between the low grade and high grade histological types. Three of the patients had previous or concomitant malignancies. The percentage of T-cell lymphomas associated with HTLV-1 infection in Singapore is low compared to those areas in which HTLV-1 is endemic.     

Gastric T-cell lymphoma with cytotoxic phenotype

Primary gastric lymphoma usually originates from B cells of mucosa-associated lymphoid tissue (MALT) infected with Helicobacter pylori. When T-cell lymphomas develop in the stomach, they usually occur in association with infection by human T-lymphotropic virus type 1 and gastric involvement of adult T-cell leukemia. Reported herein is a unique and informative case of gastric peripheral T-cell lymphoma with a cytotoxic phenotype that histologically mimicked, and had to be carefully distinguished from, MALT-type B-cell lymphoma. The patient, a 73-year-old woman, underwent a gastric endoscopy examination, and the histological findings suggested MALT-type gastric lymphoma. Analysis of the immunoglobulin heavy chain (IgH) gene and T cell receptor gamma (TCRgamma) gene revealed monoclonal rearrangement of the TCRgamma gene. The tumor cells exhibited mild atypia and immunoreactivity with anti-CD3, anti-CD8, anti-T-cell intracellular antigen-1, antigranzyme B and antiperforin antibodies, but not with anti-CD20, anti-CD10, and anti-CD79a antibodies. The case was finally diagnosed as gastric T-cell lymphoma with cytotoxic phenotype, and this was confirmed after surgical resection. In cases such as this, small biopsy specimens from the stomach should be examined carefully for low grade B-cell-type malignant lymphoma (MALT lymphoma), because sometimes the proliferating B cells can hide the truly malignant T cells, and rearrangement analysis is useful for diagnosing T-cell malignancy.     

Sequential development of diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma

Lymphoma of different histologic type can occur in the same patient. Here, we describe a 64-year-old male patient with angioimmunoblastic T-cell lymphoma (AITL) who subsequently developed diffuse large B-cell lymphoma (DLBCL). At the time of initial diagnosis, histologic examination of a left inguinal lymph node of the patient and a monoclonal pattern of TCRβ gene rearrangement showed typical features of AITL, and there was no evidence of a monoclonal B-cell population. Twenty-six months later, he had generalized lymphadenopathy and organs involvement by DLBCL. A monoclonal IgH gene rearrangement proved de novo development of secondary B-cell lymphoma and excluded relapse of a primary composite lymphoma. The in situ hybridization analysis showed Epstein-Barr-encoded RNA (EBER) sporadic positivity in sample collected from AITL but extensive positivity in the immunoblasts collected from DLBCL. Our observation supports the hypothesis that Epstein-Barr virus (EBV) is etiologically related to AITL in this case. Clonal expansion of EBV-associated DLBCL is a secondary event in AITL via EBV infection or reactivation.     

Gene rearrangements in T-cell lymphoblastic lymphoma

This study presents an examination of the Ig heavy chain (IgH) and T-cell receptor gamma (TCRγ) genes in a series of 39 CD3-positive T-cell acute lymphoblastic leukaemia (ALL) cases with and without co-expression of CD79a; 30/39 cases had a rearrangement of the TCRγ genes and two of these 30 cases also demonstrated an IgH rearrangement. No cases had solely an IgH rearrangement. The conclusion of the study is that lymphoblastic lymphoma cases that are positive for CD3 are of T-cell lineage, regardless of CD79a expression. Copyright © 1999 John Wiley & Sons, Ltd.     

T-cell lymphoma developing in Hodgkin's disease: Evidence for two clones

A case of peripheral T-cell lymphoma (PTL) occurring in a patient with Hodgkin's disease (HD) in relapse is described. The second neoplasm developed 25 months after the diagnosis of HD. Cytogenetic analysis on the lymph node biopsy at the time of diagnosis of PTL revealed the co-existence of two distinct, abnormal cell clones. The first clone was characterized by a reciprocal translocation t(5;7)(q13;q35) involving 7q35, namely the TCR-β gene, as expected in T-cell lymphomas. The second cell clone carried trisomies for chromosomes 2, 5, 7, and 14. By immunophenotypic and molccular analysis as well as by in situ hybridization, it was possible to prove that the malignant T-cells and the Reed-Sternberg cells corresponded to different cell clones, one carrying the structural chromosome abnormalities and one carrying the numerical chromosome anomalies. These results indicate that the present case represented a true composite lymphoma.     

Monocytoid/marginal zone B-cell differentiation in follicle centre cell lymphoma

We report on two cases of low grade follicle centre cell lymphoma with a pronounced parafollicular monocytoid/marginal zone B-cell component. One patient had a history of preceeding follicular high grade B-cell lymphoma of centroblastic type showing the same light chain restriction and identical immunoglobulin heavy chain gene rearrangement as the low grade lymphoma diagnosed 15 months later. Morphologically, in both cases the two constituents of the low grade tumours were clearly distinguishable. Immunohistochemically, the follicular component strongly expressed bcl-2 protein in contrast to a weak staining of the marginal zone B-cell component. Performing PCR, a rearrangement of the major breakpoint region of bcl-2 was not found. Identical light chain restriction of the follicular and the monocytoid B-cell/marginal zone components strongly indicates a clonal relationship between them. A monocytoid/marginal zone B-cell component in follicular lymphoma probably results from differentiation of the follicle centre cells and does not indicate a composite lymphoma.     

The anaplastic variant of centrocytic lymphoma is marked by frequent rearrangements of the bcl-1 gene and high proliferation indices

Ten cases of classic centrocytic lymphoma as defined in the Kiel classification system were investigated for their immunophenotype, their proliferation activity and by means of molecular diagnostics. The findings were compared to those obtained from a group of nine cases of anaplastic centrocytic lymphoma. Both groups showed virtually identical immunohistochemical characteristics with positivity for CD5 and negativity for CD10 and CD23. In the group of anaplastic centrocytic lymphoma, there were considerably higher proliferation indices as documented by staining for the Ki-67 antigen, up to 80% of the tumour cells being positive. Moreover, the cases of anaplastic centrocytic lymphoma had bcl-1 gene rearrangements in eight out of nine cases compared with three out of 10 cases of classic centrocytic lymphoma. DNA analysis was not able to detect bcl-2 gene rearrangement in any case, pointing to a difference compared with lymphomas of germinal centre origin. The coincidence of anaplastic and sometimes blast-like morphology of the tumour cells, high proliferation index and a rearranged bcl-1 gene in nearly all cases of anaplastic centrocytic lymphoma support their classification as high-grade malignant variants of centrocytic lymphoma and suggest a possible role for the bcl-1 locus not only in the origin but also in the progression of centrocytic lymphomas.     

Mediastinal large-cell lymphoma with sclerosis

Summary The Southern blot hybridization technique has been applied to study the configuration of immunoglobulin and T-cell receptor genes in 6 cases of the so called mediastinal large cell lymphoma with sclerosis. This lymphoma has been recently recognized as a separate entity among non-Hodgkin lymphomas mainly affecting young adult patients. The B-cell origin of this neoplasm was suggested by means of immunohistochemical analysis. However, the immunophenotypical B-cell related markers used do not always exhibit lineage fidelity. The Southern blot analysis demonstrated the presence of unique heavy and k-light chain immunoglobulin gene rearrangements, establishing genotypically their B-cell origin.This work was supported by the Associazione Italiana per la Ricerca sul Cancro, Milano, Italy, and Progetto finalizzato Oncologia (contratto n^o 86.00461.44), CNR, Rome, Italy. Aldo Scarpa and Maurizio Lestani are supported by a Scholarship from the Associazione Italiana per la Ricerca sul Cancro, Milano, Italy     

Composite lymphoma: the interface between Hodgkin's and non-Hodgkin's lymphoma

Hodgkin's lymphoma is a rare neoplasm mainly affecting young people. Within the last decade, nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) has been separated from all other cases of the so-called classical type. Moreover, the derivation of Hodgkin's lymphoma from germinal centre B-cells has been established, giving rise to a possible clonal relationship between Hodgkin's lymphoma and the non-Hodgkin's lymphomas (NHLs). The interface between them therefore has both diagnostic and biological aspects. Diagnostic difficulties arise, due to overlapping definitions, between biologically unrelated entities, e.g. classical Hodgkin's lymphoma and NLPHL or anaplastic large cell lymphoma, respectively. On the other hand, there is a biological grey zone regarding composite lymphomas consisting of Hodgkin's lymphoma and any NHL. This simultaneous or subsequent occurrence of Hodgkin's lymphoma and non-Hodgkin's lymphomas may, or may not, be clonally related. For management purposes lymphomas, e.g. NLPHL and T cell-rich B-cell lymphoma, must be distinguished along a continuous spectrum of progression.     

原发性睾丸恶性淋巴瘤克隆性IgH基因重排的检测

目的：探讨原发性睾丸淋巴瘤克隆性IgH基因重排的检测方法。方法：用半巢式PCR方法和聚丙烯凝胶（PAGE）－银染法检测14例睾丸恶性淋巴瘤的IgH基因重排。结果：与免疫组化对照，PCR检测的睾丸原发性B细胞淋巴瘤FR3A检出测率为85.71%，FR2的检出率为64.29%，而二者的综合检出率为100％，互补性较强。结论：半巢式PCR方法及PAGE－银染法对于原发性睾丸细胞淋巴瘤IgH基因的检出率有较高的灵敏度，FR3A和FR2引物的共同应用可以有效提高综合检出率，在目前情况下，应用PCR方法来鉴别恶性淋巴瘤，必须结合HE形态和免疫表型等综合判断。     

Intravascular large B-cell lymphoma secondary to lymphoplasmacytic lymphoma: a case report and review of literature with clonality analysis

Intravascular large B-cell lymphoma (IVLBCL) can be a fatal malignancy mainly because of difficulty in early detection. Due to the lack of specific clinical manifestations, early detection of IVLBCL remains a challenge, especially in the presence of comorbidities. Lymphoplasmacytic lymphoma (LPL) is an indolent B-cell lymphoma accompanied by monoclonal immunoglobulin M protein in most patients, and known to be associated with high risk of secondary hematological malignancies. Here, we report a patient who developed IVLBCL during treatment for LPL that presented a diagnostic challenge. Rearrangement analysis of the immunoglobulin heavy chain revealed the different clonal origins of two lymphomas, implying a predisposition of LPL to develop unrelated secondary lymphoma. Secondary lymphoma including IVLBCL during the treatment for LPL deserves consideration in order to facilitate early diagnosis and intervention.     

T细胞淋巴瘤伴黏液间质1例及文献复习

目的 报道1例罕见的臀部伴黏液间质的T细胞淋巴瘤并文献复习,探讨其诊断要点。方法 应用组织学、免疫组化、基因重排检测技术进行诊断与鉴别诊断。结果经多项免疫组化排除了软组织肿瘤（纤维、平滑肌、横纹肌、脂肪、滑膜肉瘤及肌纤维母细胞瘤）及恶性黑色素瘤等以后,进行了淋巴瘤标记：CD45、CD45RO、CD3、CD20、CD79α、CD68、和TCRγ基因重排检测。显示CD45、CD45RO、CD3阳性,TCRγ克隆性基因重排。结论 本例与文献报道4例资料提示：伴黏液间质的非霍奇金淋巴瘤好发于淋巴结外软组织,由弥漫性淋巴瘤样片状区与黏液间质区组成,必需应用免疫组化排除间叶源性肿瘤,加用淋巴瘤标记和基因重排检测阳性确诊。     

原发性脑内淋巴瘤临床病理、免疫组化、基因重排分析

目的：研究脑内原发性恶性淋巴瘤临床病理、免疫且化及免疫性基因重排特征。方法：对６例脑原发性恶性淋巴瘤作了临床病理形态观察和免疫组化分析（Ｓ－Ｐ法）,并用ＰＣＲ技术单轮及半巢式扩增法进行了ＩｇＨ及ＴＣＲ－β基因重排检测。结果：６例皆为非霍奇金Ｂ细胞淋巴瘤。瘤细胞大部分是中心或中心母细胞型,常伴浆样分化,往往围绕血管排列。ＰＣＲ克隆性基因重排,ＩｇＨ单轮法（２／６例）阳性,半巢式（６／６例）阳性,ＴＣ     

Discordant lymphoma: MALT lymphoma of the stomach and follicular lymphoma of the parotid gland

More than one histological type of malignant lymphoma can occur simultaneously in an individual. The entity is classified as either composite or discordant lymphoma. Both types of lymphoma, particularly discordant lymphoma comprised of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma (MALT-L) and follicular lymphoma (FL), are rare. We report a case of discordant lymphoma comprising MALT-L in the stomach and FL in the parotid gland. The patient was a 50-year-old Japanese woman who visited the University Hospital of Showa (Tokyo, Japan) because a barium study showed erosive gastric lesions. A gastro-intestinal endoscopy was performed 2 months after the barium study, which showed irregular erosions throughout the stomach body. A gastric biopsy showed MALT-L, and Helicobacter pylori (H. pylori) infection was confirmed. The patient had noticed a painless and elastic hard tumor mass of about 2 cm in diameter in the area of the left parotid gland 6 months before the barium study. We removed the parotid gland tumor and diagnosed it as FL 6 months after the barium study. We were able to diagnose the MALT-L and FL by morphological, immunohistochemical and molecular analyses of paraffin-embedded sections. This appears to be the first reported case of MALT-L and FL occurring together as a discordant lymphoma.     

Monoclonal antibody HML-1 reactivity with adult T-cell leukaemia/lymphoma and other lymphomas

Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1), a causative virus of adult T-cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast-feeding. Using a monoclonal antibody HML-1 which labels human intestinal intra-epithelial T lymphocytes, we have immunohistochemically examined ATLL tissues in order to evaluate the possibility that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Previously this antibody was reported to react with intestinal T-cell malignant lymphomas but not with peripheral tumours, or any B-cell lymphomas. We investigated 181 patients with malignant lymphomas and found that 19 out of 113 ATLLs were positive for HML-1. T-cell malignant lymphomas excluding ATLL also reacted with HML-1 (7/24), but all the B-cell lymphomas 0/33) and non-neoplastic lymph node and skin lesions (0/10) were negative for HML-1. In patients with ATLL and other T-cell malignant lymphomas, the positivity level of HML-1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph nodes (15/100) and skin (8/47). We observed one HML-1 positive ATLL patient with tumour formation in the skin and lymphadenopathy and marked infiltration of the large intestine but minimal involvement of other organs. Although HML-1 was frequently expressed in gastric infiltration of ATLL, the level of positivity was too low in lymph nodes to support the hypothesis that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Some of the HML-1 positive ATLL cases co-expressed CD30. Furthermore, three of six cases of Ki-1 lymphoma (large anaplastic cell lymphoma) were positive for HML-1. We conclude that expression of HML-1 in ATLL reflects an activated state of the lymphoma cells, but not the intestinal origin of ATLL cells.     

TCR基因重排检测在T细胞淋巴瘤病理诊断中的作用

基因重排现象是每个淋巴细胞在早期经历的一个正常的过程,由于机体每个淋巴细胞的重排基因都是特有的,使每个淋巴细胞都有独特的重排形式。如若机体在某些致瘤因素的作用下失去对某个基因重排细胞的控制,则该细胞就会出现无控制的、单克隆性增生,最终导致淋巴瘤的形成。所以淋巴瘤所具有的是单克隆性重排。因此通过聚合酶链反应（polymerase chain reaction,PCR）技术进行T细胞抗原受体（T cell receptor,TCR）基因克隆性重排分析,尤其在常规HE形态学与免疫组化结果都不能确诊时,显得尤为重要。该文对其在T细胞淋巴瘤病理诊断中的作用作一综述。     

Epidemiology of human T-cell leukaemia/lymphoma virus type 1 (HTLV-1) infections in a subpopulation of Afro-Caribbean origin in England

Epidemiological studies on neurological diseases in residents of Afro-Caribbean origin in the West Midlands region of England have identified eight patients with tropical spastic paraparesis (TSP), all of whom were found to be infected with human T-cell leukaemia/lymphoma virus type 1 (HTLV-1). The husband of one of the patients with TSP was also infected with HTLV-1 and had a T-cell lymphoma. In addition, six asymptomatic HTLV-1-infected first-degree relatives of the TSP patients have been found. By anonymous testing of over 700 sera obtained from individuals of Afro-Caribbean, African, or Asian ethnic origin, seven HTLV-1-infected individuals were detected, who were all immigrants from the Caribbean. Overall, these numbers yielded a seroprevalence of HTLV-1 infections of 3.4% among the immigrant population of Afro-Caribbean origin, which is comparable with the prevalence of HTLV-1 in Jamaica in an equivalent age and sex cohort. Sera were tested for HTLV-1 antibody by means of three different procedures: passive particle agglutination test (Serodia), indirect enzyme-labeled immunosorbent assay (ELISA; Dupont), and indirect immunofluorescence test (in-house, using HTLV-1-infected MT2 cells). The results of all three tests correlated very well with each other. HTLV-1 antibody titres in TSP patients were on the whole significantly higher than those of asymptomatic carriers, but some of the apparently healthy first-degree relatives and one anonymously tested individual had titres as high as most of the TSP patients.