Biclonality of Composite B- and T-cell Lymphomas A Case Report

Most composite lymphomas which are composed morphologically of two different tumor cell types are considered to represent different morphological expressions of a single clone. However, in recent years, composite B- and T cell lymphomas and biclonality of B cell lymphoma have been reported. We experienced a case of composite lymphoma which initially developed as cutaneous lymphoma composed of lymphoplasmacytes associated with large clear cells. It was confirmed that the tumor cells of these two systems were biclonal on the basis of surface markers and DNA rearrangements, i.e. B cells of the IgG kappa type, showing IgH and kappa chain DNA rearrangement, and Tcells with CD4 surface marker, showing rearrangement of the T cell receptor beta chain gene. This case showed a predominant B cell pattern at the initial stage, and terminated in T cell lymphoma, as revealed at autopsy. Therefore we considered this case to be a unique composite lymphoma showing biclonality of both B- and T-cell systems, providing a number of suggestions for future study of malignant lymphoma.     

Paraffin-immunohistochemical Analysis of 26 Non-Hodgkin's Malignant Lymphomas n the Endemic Area of Human T-cell Leukemia Virus Type 1

A study was conducted to evaluate the usefulness of paraffin immunohistochemistry for histopathological classification of non Hodgkin's malignant lymphomas (NHML). The phenotypes of lymphoma cells and other cells were examined using 11 monoclonal and 3 polyclonal antibodies by the ABC method on paraffin-embedded tissue sections of 226 cases of NHML, comprising 94 B cell lymphomas (B ML) and 132 T cell lymphomas (T-ML). In 219 NHML cases (96.8%), lymphoma cells reacted with more than one of these antibodies. A set of MB 1, Mx pan B, L26, LN 1, LN 2 and antiimmunoglobulin light chain antibodies characterized each subtype of B MLs, categorized according to the Kiel classification. Mantle-zone lymphoma (MzML) was added as one subtype. L26 stained the largest number of B MLs (82.8%). B cell chronic lymphocytic leukemia (B CLL) was labeled most frequently by MB 1. MzML was characterized by reactivity of lymphoma cells with LN 2 and by the appearance of monoclonal immunoglobulin light chain along the cell membrane. Follicle center cell lymphomas were stained by LN 1 and LN 2, although a small number of proliferating cells were labeled by LN 1 in B CLL, MzML and the im-munocytoma lymphoplasmacytic/cytoid variant. MT 1 and/or UCHL-1 showed various degrees of reactivity with the cell membranes of lymphoma cells in 94.8% of T-MLs. Among the T cell pleomorphic lymphomas of Suchi and Lennert, the adult T cell leukemia/lymphoma type, defined by stippled heterochromatin distribution and peculiar huge cells, reacted selectively (p<0.05) with anti phospho-kinase C antibody. Anaplastic large cell T-ML reacted with a set of Ber H2, LN 2 and Leu Ml. In T zone lymphomas without hyperplastic follicles, angioimmuno-blastic lymphadenopathy with dysproteinemia type T-ML, lymphoepithelioid cell lymphomas and some pleomorphic lymphomas comprising clear large lymphoma cells, there were many intermingling B cells, and their constitution varied. In some lymphoblastic lymphomas of both the T cell and B cell type, phenotypes of T cells and B cells were expressed. Consequently, it was shown that paraffin immunohistochemistry was useful for the practical histopathological diagnosis of NHML even in the area where human T cell leukemia virus type 1 is endemic.     

Peripheral T-cell Lymphoma of AILD (Angioimmunoblastic Lymphadenopathy with Dysproteinemia) Type Involving Gastrointestinal Tract

A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) which showed widespread involvement of the gastrointestinal tract is reported. A lymph node biopsy specimen showed the characteristic histological features of AILD. During the progression of the illness, lymphomatous lesions developed in the gastrointestinal tract, complicated by cytomegalovirus infection. A double immunoenzymatic study using a combination of Ki 67 antibody and antibodies against surface antigens demonstrated that CD3⁺, CD4., and/or T cell receptor (TCR) beta⁺ cells were predominant (67–68%) among the population of proliferating Ki 67⁺ cells, rather than CD8⁺ or CD22⁺ cells. Clonal rearrangement of the TCR beta chain gene was also detected. These findings provide further evidence for the neoplastic nature of lesions of this type, and the diagnosis of peripheral T cell lymphoma.     

蝎毒及蝎毒多肽对小鼠免疫功能和外周血细胞计数的作用

目的　观察蝎毒 (SV)及蝎毒多肽 (PSV)对正常小鼠免疫功能和外周血细胞计数的作用 .方法　取正常小鼠 4 5只 ,随机分为 3组 :SV组、PSV组、对照组 ,分别腹腔注射 ,1次 /d ,连续 5d .于首次给药 6h、2 4h、8d后 ,每组取小鼠 5只 ,称体重 ,眼球取血 ,计数外周血细胞、处死后脾脏、胸腺 ,计算脾重指数、胸腺指数 .8d取外周血后测试体能 .结果　SV组 6h、2 4h、8d白细胞计数增加 (p <0 .0 5 ) ;PSV组略高于对照组 .SV组 6h中性粒比例明显增多 ,2 4h淋巴细胞比例明显增加 (p<0 .0 5 ) ,8d二者比例恢复正常 ;PSV组 6h、2 4h中性粒略有增加 ,8d恢复正常 .两组单核细胞均有增高 .血小板计数SV组维持正常 ,PSV组升高 .SV、PSV组脾重指数、胸腺指数和红细胞计数与对照组相比均不减少或略有增加 (p >0 .0 5 ) ,两组体能增强明显 .结论　SV及PSV均可提高正常小鼠的免疫功能 ,维持或增加外周血各类细胞数目 ,改善机体整体功能状态     

Peripheral T-cell lymphomas. Immunologic and enzyme histochemical analysis of 15 cases

Fifteen cases of peripheral T-cell lymphoma were studied to evaluate the respective properties of various histologic types using enzyme histochemical and ultrastructural examinations in addition to immunological methods. Eleven cases in an ATLA-negative group manifested various histologic patterns such as IBL-like, pleomorphic and Lennert's lymphomas in comparison with the relatively monomorphic proliferation of neoplastic lymphoid cells in the 4 ATLA-positive cases. The presence of neoplastic clear cells is characteristic of peripheral T-cell malignancies, and is likely to be found in CD4+ lymphomas. There is an occasional reaction of epithelioid histiocytes and plasma cells with eosinophils, the former being designated Lennert's lymphoma and the latter IBL-like T-cell lymphoma. Immunological examination revealed four immunophenotypic patterns: (1) CD2+3+4+8-, (2) CD2+3-4+8-, (3) CD2+3+4-8+, and (4) CD2+3+4+8+, but did not provide information concerning the intimate relationship between histologic types and immuno-phenotypes. beta-Glucuronidase reactivity, however, contributed to the distinction between helper and suppressor T-cell malignancies, suggesting its usefulness for distinguishing these two cell types and their malignant counterparts.     

Enzyme histochemical demonstration of hairy cell leukaemia in paraffin-embedded tissue sections

Summary Hairy cell leukaemia is a form of leukaemia difficult to diagnose since pancytopenia is often present. Hairy cells contain tartrate-resistant acid phosphatase, and this factor is utilised in the diagnosis of the condition. This study confirms that it is also possible to demonstrate tartrate-resistant acid phosphatase in leukaemic infiltrates in formalin fixed paraffin-embedded tissue sections.     

Peripheral T-cell lymphoma of Lennert type complicated by monoclonal proliferation of large B-cells

A 69-year-old man presented with lymph node swelling in the right inguinal region. A biopsy was made (LN1) and diagnosed as peripheral T-cell lymphoma. The lesion remitted completely over a period of about 51 months after combination chemotherapy, but erythematous papules, systemic lymphadenopathy, and fever of 38° appeared. Skin (S1) and lymph nodes (LN2) were biopsied. Erythematous papules once disappeared spontaneously, but appeared again and were biopsied (S2). LN1 displayed the typical histologic and immunohistochemical features of Lennert lymphoma, i.e., diffuse proliferation of small to large lymphoid cells of CD3+, CD4+, CD8− immunophenotype accompanied by numerous clusters of epithelioid histiocytes. In LN2, the large cells with CD3+, CD4+, CD8− decreased in number, while numerous CD20+ large cells were discernible. Clonality analysis revealed the persistent presence of an identical T-cell clone in LN1 and LN2. Clonal bands of immunoglobulin heavy (IgH) chain gene were detected in LN2 but not in LN1. S1 and S2 showed diffuse proliferation of small to large lymphoid cells of CD20−, CD3+, CD4+, CD8− in the upper dermis, with obvious epidermotropism. Clonality analysis revealed the presence of a T-cell clone identical to LN1 and LN2 with no B-cell clone, indicating the recurrence of PTCL. In situ hybridization (ISH) for Epstein-Barr virus (EBV) genome revealed that positive signals in the nucleus of large B-lymphoid cells appeared only in LN2.     

Ultrastructure of 26 Cases of Ki-1 Lymphomas: Morphoimmunologic Correlation

Twenty-six cases of high-grade lymphomas with activation markers (CD30) classified and immunophenotyped according to the Kiel classification were studied to determine their fine structural features. Transmission electron microscopy showed in 17 cases anaplastic nuclear and cytoplasmic changes identical to those observed in Hodgkin's disease, it being impossible to determine by the morphology a B, T, or null nature. Four high-grade B-centroblastic and immunoblastic cases and five T-pleomorphic cases showed nuclear changes and cytoplasmic differentiation that suggested a T or B nature. An immunogold-labeling technique showed CD30-positive particles primarily in the Golgi complex and occasionally in the cell membrane.     

Ultrastructure of 26 Cases of Ki-1 Lymphomas: Morphoimmunologic Correlation

Twenty-six cases of high-grade lymphomas with activation markers (CD30) classified and immunophenotyped according to the Kiel classification were studied to determine their fine structural features. Transmission electron microscopy showed in 17 cases anaplastic nuclear and cytoplasmic changes identical to those observed in Hodgkin's disease, it being impossible to determine by the morphology a B, T, or null nature. Four high-grade B-centroblastic and immunoblastic cases and five T-pleomorphic cases showed nuclear changes and cytoplasmic differentiation that suggested a T or B nature. An immunogold-labeling technique showed CD30-positive particles primarily in the Golgi complex and occasionally in the cell membrane.     

Peripheral T-cell lymphoma arising from an intraglandular lymph node in the parotid gland: a case report and literature review

T/NK-cell lymphoma of the salivary gland is rare. A 58-year-old man complained of a tumor mass in the left parotid gland region and he was diagnosed to have a left parotid tumor. The tumor was subsequently resected, revealing a diffuse growth pattern of medium to large sized atypical cells. The tumor was surrounded by fibrous connective tissue in the form of a capsule, and those were positive for CD3, CD4, CD5 and CD30, but negative for Bcl2, CD8, CD10, CD15, CD20, CD25, CD56, CD79a, CD246, EMA, granzyme B, TdT and TIA-1. There was no molecular evidence of Epstein-Barr virus (EBV) infection. It was diagnosed as peripheral T-cell lymphoma (PTCL) arising from an intraglandular lymph node in the parotid gland. In conclusion, Only 17 cases of primary T/NK-cell lymphoma of the salivary glands have been recorded until now, and the characteristics of these are not clear yet. Additional study is needed.     

T、B细胞表型抗体免疫组化敏感性与特异性分析

目的：探讨Ｔ、Ｂ细胞非霍奇金淋巴瘤免疫表型染色的特异性和交叉反应性。方法：应用Ｓ－Ｐ免疫组织化学方法对６２例非霍奇金淋巴瘤进行ＣＤ２０、ＣＤ７４、ＣＤ４５ＲＯ、ＣＤ４３和ＣＤ３免疫表型测定。结果：发现Ｂ细胞表型抗体ＣＤ２０和ＣＤ７４对Ｂ细胞非霍奇金淋巴瘤染色阳性率达８８．２％～１００％,但ＣＤ７４的特异性不强,与Ｔ细胞有２６．７％（４／１５）～３５．７％（５／１４）的交叉反应,而ＣＤ２０表现出高度的特异性,交叉反应为０。Ｔ细胞表型抗体ＣＤ４５ＲＯ、ＣＤ４３和ＣＤ３对Ｔ细胞非霍奇金淋巴瘤染色阳性率达８５．７％～１００％,但ＣＤ４５ＲＯ和ＣＤ４３对Ｂ细胞的交叉反应高达４０％（６／１５）～４７．１％（８／１７）,特异性不强,而多克隆抗体ＣＤ３与Ｂ细胞仅有５．９％（１／１７）的交叉反应,表现出明显的特异性。结论：提示在进行Ｔ、Ｂ细胞免疫表型划分时,应使用一组包括ＣＤ２０、ＣＤ７４,ＣＤ４５ＲＯ、ＣＤ４３和ＣＤ３等抗体,ＣＤ３是一种具有高度敏感性和高度特异性的Ｔ细胞标志抗体,值得推荐。     

结外鼻型NK/T细胞淋巴瘤28例临床病理分析

目的：探讨结外鼻型NK/T细胞淋巴瘤( extranodal natural killer/T-cell lymphoma, nasal type, EN-NK/TCL)的临床病理学特征、诊断及鉴别诊断。方法应用免疫组化、EBER原位杂交技术检测28例EN-NK/TCL,依据WHO(2008)淋巴造血组织肿瘤分类进行临床病理学分析。结果28例EN-NK/TCL中,男性13例,女性15例,男女之比为1∶1．2,平均年龄46岁,中位年龄44．5岁。18例发生于鼻腔,5例发生于皮肤,扁桃体、上腭、舌根、肾上腺、胃各1例。临床主要表现为鼻塞,皮肤病变可表现为皮疹、溃疡、斑块或结节形肿物。可伴有B症状、淋巴结肿大,可累及多个部位。肿瘤细胞为小、中、大淋巴细胞或呈混合型,常见血管中心性或血管破坏的生长方式及坏死,多伴有炎细胞浸润。免疫表型：T细胞标志物( CD3ε最敏感)、CD56及细胞毒性标志物均阳性,原位杂交EBER呈阳性。10例获得随访,其中1例死亡。结论 EN-NK/TCL好发于上呼吸道,其次是皮肤。结合形态学、免疫表型及EBER原位杂交结果可确诊。     

Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics

AIMS: To identify distinguishing histological, immunophenotypic and molecular genetic features between angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma (PTL). METHODS: Nodal T-cell lymphomas examined (n =137), included AITL (n = 89), PTL (n = 22), anaplastic large cell lymphoma (n = 16) and 'AITL/PTL indeterminate' (n = 10) with overlapping features between AITL and PTL, showing morphology typical of AITL but lacking follicular dendritic cell expansion. Immunohistochemistry for CD3, CD20, CD21 and CD10, in situ hybridization for Epstein-Barr virus encoded RNA (EBER) and polymerase chain reaction for T-cell and B-cell clonality analysis were performed. RESULTS: Of the AITLs, 74/89 showed typical morphology, whereas 15/89 showed hyperplastic follicles. AITL and 'AITL/PTL indeterminate' showed a polymorphous infiltrate and prominent vascularity in all cases. In both groups, CD10 was present in the majority and clear cells and EBER positivity were specific (but not universal) features lacking in PTL. Detection of T-cell clonality was significantly higher in AITL (90%) compared with PTLu (59%). CONCLUSION: Clear cells and EBV infection (when present) are useful distinguishing features and CD10 a sensitive and specific marker of AITL. Hyperplastic follicles are present in a significant minority of AITL. AITL/PTL indeterminate probably falls within the spectrum of AITL rather than PTL.     

Diagnosis of NK and cytotoxic T-cell disorders: a review

A number of NK- and T-cell lymphomas with diverse clinical, histologic, and immunophenotypic features express one or more cytotoxic markers. Because these lymphomas are rare they can be challenging to diagnose for clinicians and pathologists. Though the common theme among the neoplasms discussed in this review is expression of one or more cytotoxic markers, expression of other markers such as cytoplasmic CD3, EBV-associated molecules, CD56, and CD30 tend to provide more important clues to the correct diagnosis. In this review, we discuss NK- and T-cell lymphomas and highlight certain key features that can aid in arriving at the correct diagnosis of these malignancies.     

Expression of T-cell Receptor (TCR)α Chain on Normal Human Tonsils and T-cell Lymphomas

We analyzed immunohistologically the expression of T cell receptor (TCR)α chain on human tonsils and on T cell lymphoma (T ML) tissues using the avidin biotin peroxidase method. A murine monoclonal antibody αF1, specific for the constant region of the JCRα chain, was employed. On normal tonsil, αF1 positive cells were observed mainly in T zones and germinal centers. In T zones, the staining intensities varied markedly, with heavy staining evident in less than one fourth. In germinal centers, a proportion of stained cells showed a histiocytic pattern with small cytoplasmic projections. All the T ML tissues expressed TCRα, whereas the staining intensities varied among cases and among lymphoma cells. No correlations were observed in the expressions of TCRα chain and other T-cell markers including CD3, CD4 and CD8. Acta Pathol Jpn 40: 722-728, 1990.     

反应性淋巴组织和滤泡性淋巴瘤中T细胞的分布及其生物学意义

应用6种抗体的免疫组织化学及形态学定量方法,对19例反应性淋巴组织及11例滤泡性淋巴瘤组织中T细胞的分布及其生物学意义进行探讨,结果表明:在反应性淋巴滤泡中的了细胞90％以上分布于核分裂象较少的明区,而在核分裂象较多的暗区,T细胞仅占10％。在滤泡性淋巴瘤组织中,T细胞失去上述极性分布特点。组织学观察发现与肿瘤细胞的增殖相对应,T细胞呈弥漫型、边缘优势型、边缘型、部分边缘型、散在型等5种分布样式。根据上述结果推论T细胞主要介入正常及肿瘤性B细胞的分化过程。