Nodal T/NK-cell lymphoma of nasal type: a clinicopathological study of six cases

Aims:  To investigate the clinicopathological features of six unusual cases of nodal CD56+ and Epstein–Barr virus (EBV)+ T/natural killer (NK)-cell lymphoma, a putative nodal counterpart of nasal NK/T-cell lymphoma (nodal T/NK-cell lymphoma of nasal type) in comparison with nasal NK/T-cell lymphoma with secondary lymph node involvement ( n  = 24) and peripheral T-cell lymphoma (PTCL) of cytotoxic molecule (CTM)+ and EBV+ type ( n  = 21).
Methods and results:  All cases of nodal T/NK-cell lymphoma of nasal type exhibited diffuse infiltration of pleomorphic medium-sized to large tumour cells, reminiscent of those in CTM+ EBV+ PTCL. The tumour cells had a typical phenotype of nasal NK/T-cell lymphoma: CD2+, CD3ε+, CD4−, CD5−, CD56+, T-cell intracellular antigen-1+, granzyme B+, perforin+ and EBV+. However, four of six cases demonstrated clonal T-cell receptor γ-gene rearrangement on polymerase chain reaction analysis, unlike nasal NK/T-cell lymphoma. Comparison of clinical parameters and overall survival among the three groups demonstrated only minor differences.
Conclusions:  Nodal T/NK-cell lymphoma may occupy the grey zone between extranodal nasal-type NK/T-cell lymphoma and nodal CTM+ PTCL in a spectrum of NK to T-cell lymphomas that are EBV+. The close relationship between NK/T-cell lymphomas and cytotoxic T-cell lymphomas was also substantiated.     

Genomic profiling of peripheral T-cell lymphoma, unspecified, and anaplastic large T-cell lymphoma delineates novel recurrent chromosomal alterations

To characterize genetic alterations in peripheral T-cell lymphoma, not otherwise specified (PTCL NOS), and anaplastic large T-cell lymphoma (ALCL), 42 PTCL NOS and 37 ALCL [17 anaplastic large cell kinase (ALK)-negative ALCL, 9 ALK-positive ALCL, 11 cutaneous ALCL] were analyzed by comparative genomic hybridization. Among 36 de novo PTCL NOS, recurrent chromosomal losses were found on chromosomes 13q (minimally overlapping region 13q21, 36% of cases), 6q and 9p (6q21 and 9p21-pter, in 31% of cases each), 10q and 12q (10q23-24 and 12q21-q22, in 28% of cases each), and 5q (5q21, 25% of cases). Recurrent gains were found on chromosome 7q22-qter (31% of cases). In 11 PTCL NOS, high-level amplifications were observed, among them 3 cases with amplification of 12p13 that was restricted to cytotoxic PTCL NOS. Whereas cutaneous ALCL and ALK-positive ALCL showed few recurrent chromosomal imbalances, ALK-negative ALCL displayed recurrent chromosomal gains of 1q (1q41-qter, 46%), and losses of 6q (6q21, 31%) and 13q (13q21-q22, 23%). Losses of chromosomes 5q, 10q, and 12q characterized a group of noncytotoxic nodal CD5+ peripheral T-cell lymphomas. The genetics of PTCL NOS and ALK-negative ALCL differ from other T-NHLs characterized genetically so far, among them enteropathy-type T-cell lymphoma, T-cell prolymphocytic leukemia, and adult T-cell lymphoma/leukemia.     

Immunophenotyping of angioimmunoblastic T-cell lymphomas by multiparameter flow cytometry

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct form of peripheral T-cell lymphoma (PTCL) frequently involving lymph nodes, spleen and bone marrow, and is associated with systemic symptoms. Its histologic features may be subtle at an early phase and difficult to diagnose. Despite the success of flow cytometry (FCM) in diagnosing B-cell neoplasm, FCM has not been widely accepted as a useful method for establishing the diagnosis of PTCL. Recently, the neoplastic T-cells in AITL have been shown to express CD10. We prospectively applied multiparameter FCM immunophenotyping to three cases of histologically confirmed AITL and identified a small (5-7%) population of CD4+/CD10+ T-cells in two cases. In one case, the CD4+/CD10+ population lacked surface signals of CD3 and CD7, but strongly expressed CD2, whereas CD45 expression was very weak; partial loss of surface CD3 was observed in the other. None of the lymph nodes with reactive hyperplasia, B-cell lymphomas, or Hodgkin's lymphoma studied during the same time period contained the CD4+/CD10+ population. These findings suggest that addition of CD4/CD10 and CD3/CD10 to FCM immunophenotyping panels is useful in the diagnosis of AITL. To the best of our knowledge, this is the first report to demonstrate CD10-expressing T-cells in AITL by FCM.     

皮下脂膜炎样T细胞淋巴瘤的免疫表型、基因重排检测及其在诊断中的意义

目的 探讨免疫表型和基因重排检测在皮下脂膜炎样T细胞淋巴瘤(SPTL)的诊断和鉴别诊断中的意义.方法 参照2005年世界卫生组织-欧洲癌症研究与治疗组织(WHO-EORTC)皮肤淋巴瘤分类标准收集20例SPTL.采用10种抗原标记进行免疫表型检测,运用PCR技术检测TCRγ、IgH基因重排,并用EB病毒编码的小RNA1/2(EBER1/2)原位杂交检测EB病毒感染.结果 (1)本组病例中男9例、女11例,平均年龄29.5岁;(2)所有病例的瘤细胞均表达1个或多个T细胞分化抗原(CD2、CD3或CD45RO),18/19病例表达BF1,18/20病例表达CD8,20/20、16/20病例分别表达细胞毒颗粒相关蛋白TIA-1、颗粒酶B,瘤细胞不表达CD4、CD20和CD56;(3)16/20病例检出TcRγ基因重排,未检出IgH基因重排;(4)5/20病例EBERl/2原位杂交阳性.结论 SPTL的瘤细胞具有克隆性TCR基因重排,综合临床病理、免疫表型及基因重排检测有助于本病确诊.     

Differential expression of T-bet, a T-box transcription factor required for Th1 T-cell development, in peripheral T-cell lymphomas

We studied T-bet expression in 91 cases of peripheral T-cell lymphoma (PTCL) by immunostaining and found expression in 42 cases (46%), including all 5 lymphoepithelioid lymphoma cases and 12 (86%) of 14 angioimmunoblastic lymphoma cases, but only 9 (25%) of 36 anaplastic large cell lymphoma cases. Expression of T-bet in PTCL correlates with expression of other markers of Th1 T-cell differentiation, including CXCR3 (P < .0001), CD69 (P = .0013), LEF-1 (P = .0007), and OX40/CD134 (P = .005), and absence of expression of markers of Th2 T-cell differentiation, including CD30 (P = .0001) and CXCR4 (P = .0144). Of 22 cases of PTCL immunoreactive for all Th1-associated markers previously studied and nonreactive for Th2-associated markers, 20 (91%) were immunoreactive for T-bet. Of 22 PTCL cases immunoreactive for Th2-associated markers studied and nonreactive for all Th1-associated markers studied, 4 (18%) were immunoreactive for T-bet. The remaining 47 PTCL cases (52%) exhibited incomplete or mixed staining for Th1- and Th2-associated markers, with 18 (38%) of 47 immunoreactive for T-bet. T-bet is a new marker that may contribute to the diagnosis and subtyping of PTCLs. T-bet expression in these neoplasms provides further support for a model of PTCL in which tumor subsets express markers of, and may be derived from, Th1- or Th2-committed T cells.     

CD8+, CD56+ (natural killer-like) T-cell lymphoma involving the small intestine with no evidence of enteropathy: clinicopathology and molecular study of five Japanese patients

The present study reports five CD8+, CD56+ (natural killer (NK)-like) T-cell lymphomas involving the small intestine without evidence of enteropathy, from Japan. Three were intestinal T-cell lymphoma. The site of origin of the other two was not definitive. Four of five patients underwent emergency operation because of intestinal perforation. The small intestines of these patients had multiple ulcerative lesions with or without demarcated tumors. Histologically, the lymphoma cells were monomorphic or slightly pleomorphic and displayed epitheliotropism of varying degrees. Lymphoma cells of all patients shared the common phenotype: CD3+, CD4-, CD5-, CD8+, CD56+, CD57-, T-cell intracellular antigen-1+, granzyme B+. In contrast to nasal/nasal type NK-cell lymphomas, they had clonal rearrangement of T-cell receptor(TCR) genes and were negative for EBV-encoded RNA. Immunohistochemistry and genetics suggested that three cases were of alpha beta T-cell origin and two cases were of gamma delta T-cell origin. There was no evidence of enteropathy in any patient. The cases followed a clinically aggressive course with a frequent involvement of lung. According to the classification based on the recent genetic studies of European enteropathy-type intestinal T-cell lymphoma (ETL), the present cases could be classified as type 2 ETL.     

CXCL13、CD10和bcl-6在血管免疫母细胞性T细胞淋巴瘤的诊断及鉴别诊断中的作用

目的 探讨CXCL13、CD10、bcl-6等标志物在血管免疫母细胞性T细胞淋巴瘤(AITL)的诊断和鉴别诊断中的作用.方法 对四川大学华西医院病理科1990年1月至2008年1月诊断的115例AITL、30例非特指外周T细胞淋巴瘤(PTCL,NOS)和30例以副皮质区增生为主的反应性增生(RH)进行回顾性分析.按2008版WHO关于淋巴造血组织肿瘤分类进行组织学分型,采用9种抗原标志物的免疫组织化学(SP法)染色及TCR-γ基因重排检测.结果 (1)7.8%(9/115)的AITL、6.7%(2/30)的PTCL,NOS和83.3%(25/30)的RH病例观察到生发中心;98.3%(113/115)的AITL、63.3%(19/30)的FTCL,NOS和76.7%(23/30)的RH病例观察到显著血管增生.(2)CXCL13、CD10、bcl-6在RH病例的表达局限在生发中心,在AITL的表达率分别为96.5%(111/115)、50.4%(58/115)和78.3%(90/115),在PTCL,NOS的表达率分别为26.7%(8/30)、3.3%(1/30)和3.3%(1/30),以上三个标记在两种淋巴瘤的表达率差异均具有统计学意义.115例AITL病例均见到滤泡外不规则分布的CD21阳性的滤泡树突状细胞网(FDC).TCR-γ基因克隆性重排在AITL中检出率为83%(83/100).结论 AITL是一种来源于生发中心辅助性T细胞(TFH)的高度侵袭性肿瘤,CXCL13、CD10、bcl-6是AITL诊断和鉴别诊断有用标志物.     

Gene mutations in lymphoproliferative disorders of T and NK/T cell phenotypes developing in renal transplant patients

Post-transplantation lymphoproliferative disorder (PT-LPD) is characterized by lymphoid proliferation after organ or bone marrow transplantation. In Western countries, most cases of PT-LPD are B-cell-derived and Epstein-Barr virus-associated, in which alterations of c-myc, p53, and N-ras genes might play a role in disease progression. In Japan, PT-LPD of T- and NK/T-cell types are not uncommon in renal transplant patients. Mutations of p53 (exons 4 through 8), K-ras (exons 1 and 2), c-kit (exons 11 and 17), and beta-catenin genes (exon 3) in 12 cases of these diseases were analyzed by PCR single strand conformation polymorphism and then by direct sequencing. p53 gene mutations were detected in 5 of 5 cases of peripheral T-cell lymphoma, 3 (60%) of 5 cases of adult T-cell leukemia/lymphoma, and 1 of 2 cases of NK/T cell lymphoma. Twenty-five percent of T and NK/T cell lymphomas showed K-ras mutations. Mutations of c-kit and beta-catenin genes were found in 33% of cases. Among a total of 42 substitution mutations, 40 were transitions with involvement of CpG sites in 20 to 30% of cases. Most cases had at least one mutation that changed an amino acid, which might have provided the selection pressure for expansion. These findings suggested that p53 gene mutations might play a central role in development of peripheral T-cell lymphoma including adult T-cell leukemia/lymphoma in renal transplant patients.     

小细胞性非特指外周T细胞淋巴瘤病理形态和免疫表型分析

目的 探讨小细胞性非特指外周T细胞淋巴瘤(PTCL,NOS)的临床病理与免疫表型及其病理诊断和鉴别诊断.方法 对5例小细胞性PTCL,NOS进行临床病理回顾性研究和随访,免疫表型检测(SP和EnVision法),以及EBER原位杂交和T细胞受体(TCR)基因重排分析.结果 5例均为男性,平均年龄52.6岁.中位病程1个月.5例中3例为临床Ⅳ期,2例为临床Ⅲ期.4例有全身浅表淋巴结及脾脏肿大,1例有肝肿大.2例有浆膜腔积液.行骨髓检查的4例中,3例有肿瘤累及.1例有外周血自细胞总数和淋巴细胞分类计数升高.主要病理改变为淋巴结结构的破坏和单一形态的小淋巴细胞弥漫性浸润,4例可见少数大的异形细胞散在分布,2例见小血管增生现象.5例之肿瘤细胞均表达两种以上T细胞分化抗原和CD43,表达CD99(3/4),均不表达CD20、末端脱氧核苷酸转移酶、CD56和粒酶B.Ki-67指数为5%-15%.4例行TCR基因重排分析,均存在TCRy基因克隆性重排,1例检出TCRβ基因克隆性重排.EBER原位杂交检测均为阴性.获得3例随访资料,且患者均死亡,平均生存时间21.7个月.结论 小细胞性PTCL,NOS少见,呈高临床分期,预后差,组织形态表现为惰性淋巴瘤.     

Aggressive Lennert's lymphoma: report of three cases in comparison to non-aggressive Lennert's lymphoma

The present article describes three cases of Lennert's lymphoma exhibiting aggressive clinical courses. These cases were accompanied by disseminated intravascular coagulation (DIC) or hemophagocytic syndrome (HPS). These cases were compared to non-aggressive type of Lennert's lymphoma. Of the three cases, two demonstrated involvement of the liver and the other possessed bone marrow involvement. In one patient, while a lymph node biopsy revealed Lennert's lymphoma histologically, a liver biopsy obtained 2 months later revealed a high-grade large cell cytotoxic T-cell lymphoma. Two of these cases showed HPS and the other exhibited DIC. All patients died within 1 year of diagnosis, with the shortest survival period being 1.5 months. Immunohistochemically, lymphoma cells were CD8+, CD4-, granzyme B+, and T-cell intracellular antigen-1 (TIA-1)+, showing a cytotoxic T-cell phenotype. Two cases demonstrated positive reactivity for Epstein-Barr virus in lymphoma cells by in situ hybridization. These cases were compared with eight cases of non-aggressive Lennert's lymphoma. In comparison to non-aggressive disease, these three cases displayed a higher percentage of Ki-67-positive cells. In conclusion it was found that a subset of Lennert's lymphoma cases share common features with high-grade cytotoxic T-cell lymphoma, indicating that Lennert's lymphoma may be part of the spectrum of cytotoxic T-cell lymphoma.     

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.     

Histological and immunophenotypic profile of nasal NK/T cell lymphomas from Peru: high prevalence of p53 overexpression.

Nasal NK/T-cell lymphoma is a unique form of lymphoma highly associated with Epstein-Barr virus (EBV). These lymphomas are rare in Western populations and much more prevalent in some Asian and Latin American countries. Although there are several sizable studies from Asian countries, the same is not true from South America. The aim of this study was to analyze a series of 32 cases of nasal T-cell lymphoma from Peru and to further extend the characterization of this disease. Immunohistochemistry was performed on paraffin sections using the following antibodies: CD20 (L26), CD45RO, CD3, Ki67, CD57, CD56, TIA-1, bcl-2, and p53. The presence of EBV was investigated with immunohistochemical analysis for latent membrane protein (LMP)-1 and in situ hybridization using an antisense riboprobe to EBER 1. The 32 patients included 18 men and 14 women (M:F ratio, 1.2:1), with a median age of 43 years (11 to 72). Three categories were identified: (1) Nasal NK/T cell lymphomas (28 cases): The morphology ranged from small or medium-sized cells to large transformed cells. Necrosis was present in 86% of the cases, and angioinvasion was seen in 36% of the cases. All cases were positive for CD45RO, CD3, and for TIA-1. CD56 was positive in 21 of 27 cases (78%), and CD57 was negative in all cases. EBER 1 positivity was identified in most of the tumor cells in 27 of 28 cases (96%), including the six cases in which CD56 was negative. Overexpression of p53 was detected in 24 cases (86%). (2) Blastic NK cell lymphoma (1 case): The neoplastic cells resembled those of lymphoblastic lymphoma. CD56 and CD45RO were positive; TIA-1, TdT, and EBER-1 were negative. (3) Peripheral T-cell lymphoma (PTCL) unspecified (3 cases): CD56, TIA-1, and EBER-1 were negative. Nasal lymphomas from Peru with a T cell phenotype are predominantly EBV-associated NK/T cell lymphomas, similar to those described in Asian countries. The expression of CD56, TIA-1, and EBER-1, in combination, are very useful markers for the diagnosis of nasal NK/T cell lymphoma in paraffin-embedded tissue. The differential diagnosis of T-cell lymphomas in the nasal region should include rare cases of PTCL unspecified and the blastic variant of NK cell lymphoma. P53 is overexpressed in 86% of the cases. The significance of this finding with regard to clinical behavior and prognosis remains to be determined.     

The usefulness of flow cytometric CD10 detection in the differential diagnosis of peripheral T-cell lymphomas

We studied the histologic and multiparameter flow cytometry (MFC) features of 12 cases of angioimmunoblastic T-cell lymphoma (AITL), 13 of mature T-cell lymphoma, and 25 control cases of reactive lymphoid hyperplasia to evaluate the role of CD10 in the differential diagnosis of peripheral T-cell lymphomas (PTCLs). A characteristic immunophenotypic profile (CD2+/CD4+) with recurrent phenotypic aberrancies (eg, CD3 and CD7 loss) was identified in most AITL cases; MFC documented CD10 coexpression on T cells in 10 (83%). Mature T-cell lymphoma showed a more heterogeneous altered immunophenotypic pattern, and 2 cases of PTCL, unspecified, had clear evidence of aberrant CD10 expression on T cells. A small physiologic CD3+/CD4+/CD10+ T-cell population was detected by MFC in all control cases tested (range, 0.28%-4.71%), suggesting that a normal subset of peripheral CD10+ T cells exists. CD10 was a highly sensitive but incompletely specific phenotypic marker for diagnosing AITL; the differential diagnosis of PTCL, unspecified, must be related with traditional histologic features. A small number of CD10+ T cells in reactive lymph nodes suggests that this subpopulation may be the normal counterpart of neoplastic T cells in AITL. The biologic role of CD10+ T cells should be studied further.     

First reported cases of intravascular large cell lymphoma of the NK cell type: clinical, histologic, immunophenotypic, and molecular features

Most cases of intravascular large cell lymphoma are of B-cell phenotype, with a few cases of T-cell lineage and rare cases with histiocytic features described. A definitive natural killer (NK) cell variant has not been recognized. This report is the first to describe the clinical, histologic, immunophenotypic, and molecular features of 2 cases of intravascular lymphoma with an NK cell phenotype (CD3epsilon+, CD2+, CD7+, CD56+, T-cell intracytoplasmic antigen-1+, perforin+, granzyme B+, CD20-, CD4-, CD5-, CD8-, T-cell receptor [TCR]betaF1-). Molecular studies for TCR gene rearrangements revealed a germline configuration. A 41-year-old man had erythematous plaque-like subcutaneous lesions of the lower extremities in which biopsy revealed Epstein-Barr virus-positive intravascular lymphoma. Following chemotherapy and stem cell transplantation, he was alive with no evidence of disease at 1 year. A 47-year-old woman had myalgias, arthralgias, weakness, fever, altered mental status, and pancytopenia. Bone marrow biopsy demonstrated intravascular lymphoma. Therapy was initiated; however, her condition deteriorated rapidly, and she died. Autopsy revealed involvement of multiple organs, including brain, kidneys, ovaries, and bone marrow. These cases represent the first documented examples of an NK cell variant of intravascular lymphoma.     

Peripheral T-cell lymphoma with extensive dendritic cell network mimicking follicular dendritic cell tumor: a case report with pathologic, immunophenotypic, and molecular findings

Peripheral T-cell lymphoma (PTCL) with a nodular pattern of growth is uncommon and may be misdiagnosed initially as a B-cell lymphoma or reactive process. We report a case of a rapidly growing PTCL with a distinctly nodular pattern in an axillary lymph node from an 89-year-old man. Immunohistochemical stains for CD21, CD23, and CD35 highlighted an extensive dendritic cell network that imparted the nodular appearance and, in addition, was associated intimately with the neoplastic cells. The neoplastic cells otherwise had an immunophenotype similar to previously reported cases of PTCL with a nodular pattern and germinal center origin (CD3+, CD4+, CD5+, bcl-6+, CD31+, subset CD10+, subset CXCL13+, and subset CD79a+). Molecular studies confirm a clonal T-cell receptor g gene rearrangement. This case emphasizes unusual morphologic features in a PTCL that may be mistaken for follicular lymphoma or a tumor of follicular dendritic cell origin.     

Epstein-Barr virus-associated lymphoproliferative disorder presenting with classical Hodgkin lymphoma and developing as peripheral T-cell lymphoma 9 years later: a case report of composite lymphoma

We describe a patient who was diagnosed with classical Hodgkin lymphoma (CHL) at 67-years-old and peripheral T-cell lymphoma, not otherwise specified (PTCL) at 76-years-old, and died 5 months later. Both tumors showed prominent epithelioid cell reaction admixed with neoplastic cells. Hodgkin and Reed-Sternberg cells in the swollen lymph node were positive for CD30 and EBV-encoded RNA (EBER). PTCL cells in the skin tumor were positive for cytoplasmic CD3ε, CD4 and EBER. A rearrangement band of the T-cell receptor gene was detected in the skin tumor. This case is the first documented EBV-associated composite lymphoma composed of CHL and PTCL. The patient may show the possibility that both EBV infection and/or immunodeficiency induce the development of CHL and PTCL.     

963例成熟T和自然杀伤细胞/T细胞淋巴瘤的临床病理特征分析

目的 观察广东地区不同类型成熟T和自然杀伤(NK)细胞/T细胞淋巴瘤及其亚型的临床病理特点.方法 按WHO(2008版)标准重新评估广东地区2002-2006年1137例成熟T和NK/T细胞淋巴瘤患者.由多名血液病理医师复查,补做必要的免疫组织化学染色及原位杂交.结果 963例确诊为成熟T和NK/T细胞淋巴瘤,占同期所有淋巴瘤20.1%(963/4801),发生于结内319例(33.1%),结外644例(66.9%);非特殊型外周T细胞淋巴瘤293例(30.4%);结外鼻型NK/T细胞淋巴瘤281例(29.2%);间变性大细胞淋巴瘤(ALCL)198例(20.6%);血管免疫母细胞性T细胞淋巴瘤(AILT)46例(4.8%).男女比为1.99:1,发病中位年龄为44岁.非特殊型外周T细胞淋巴瘤好发于55～64岁;结外鼻型NK/T细胞淋巴瘤好发于25～54岁;间变性淋巴瘤激酶(ALK)阳性ALCL多见于年轻人而阴性多见于中老年人;AIIJT好发于65～74岁.结论 广东地区成熟T和 NK/T细胞淋巴瘤多见于结外,好发于男性,总体发病与年龄增长无明显关系,但具体类型有不同的年龄侧重群;常见的类型依次为非特殊型外周T细胞淋巴瘤、结外鼻型NK/T细胞淋巴瘤及ALCL;EB病毒感染与NK/T细胞淋巴瘤关系密切.     

Specific phenotyping of T-cell proliferations in formalin-fixed paraffin-embedded tissues. Use of antibodies to the T-cell receptor beta F1.

Antibody beta F1 to a common framework determinant of the beta subunit of the T-cell receptor (TCR) was used as a specific phenotypic marker for T-cell differentiation in malignant lymphomas. Sensitivity of immunoperoxidase staining in paraffin sections was enhanced by pronase pretreatment, overnight incubation of primary antibody in Tween 20, and use of streptavidin horseradish peroxidase complexes to amplify the reaction. All 43 cases of B-cell lymphoma were negative for TCR. Reed Sternberg (RS) cells in 3 of 20 cases of Hodgkin's disease exhibited cell membrane staining for TCR (all nodular sclerosis type), further evidence that some RS cells may be T-cell derived. Twenty-nine of 44 cases of T-cell lymphoma expressed TCR (66%). These included 11 of 12 cases of peripheral T-cell lymphoma (PTCL) of small and mixed cell type, 8 of 9 cases of lymphoepithelioid cell (Lennert's) lymphoma, and 2 of 4 cases of T-cell lymphoblastic lymphoma. Loss of immunoreactivity for TCR occurred in lymphomas of large or activated T-cell type, including 7 of 9 cases of T-cell immunoblastic lymphoma and 3 of 4 cases of large cell PTCL. Antibody beta F1 is a specific and relatively sensitive marker of T-cell phenotype in formalin-fixed paraffin sections of malignant lymphomas.     

B-cell lymphoma with hyaline vascular Castleman disease-like features: a clinicopathologic study

Hyaline vascular Castleman disease (HV-CD) is a localized benign mass characterized by follicular hyperplasia with atrophic germinal centers, mantle zone hyperplasia, hyaline deposits, and vascular proliferation. Before establishing a diagnosis of CD, several B-cell lymphomas (BCLs) must be considered, including follicular lymphoma (FL), mantle cell lymphoma (MCL), and nodal marginal zone lymphoma (NMZL). Conversely, BCLs with prominent atrophic germinal centers and hyaline vascular penetration may closely resemble HV-CD, leading to misdiagnosis. We report 6 cases of BCL with prominent HV-CD-like features, including FL (2 cases), MCL, NMZL (2 cases), and interfollicular large B-cell lymphoma. Histologically, all were initially considered to be HV-CD before additional tests revealed a neoplastic B-cell proliferation. We highlight the clinicopathologic features of these cases in comparison with cases diagnostic of HV-CD. In contrast with HV-CD, BCLs with HV-CD-like features are more likely to manifest clinically with systemic symptoms or generalized lymphadenopathy. Careful histopathologic examination, supported with immunohistochemical studies, flow cytometric immunophenotyping, and judicious use of cytogenetic and molecular analyses, allows identification of the masked neoplastic process. A multifaceted approach, integrating clinical, histologic, and ancillary tests, can help avoid this diagnostic pitfall.     

Primary bony peripheral T-cell lymphoma mimicking nasal type NK/T-cell lymphoma: a case report

Primary bony lymphomas are rare, and nearly all are high-grade B-cell lymphomas. Natural killer (NK)/T-cell lymphomas are highly aggressive lymphomas of NK- or T-cell lineage with predominant extranodal presentation and are divided into nasal and nasal-type (extra-nasal). We report a primary bony peripheral T-cell lymphoma mimicking NK/T-cell lymphoma, nasal type. A 22-year-old Taiwanese male presented with a frontal skull bone mass noted for 3 weeks, and received craniectomy with tumor removal. His tumor showed extensive coagulative necrosis with angioinvasion by large lymphoma cells expressing CD2, CD8, CD16, CD43, CD45, CD45RO, CD56, T-cell intracellular antigen-1, and granzyme B, but not CD3, CD4, CD20, CD57, CD68, and betaF1. In situ hybridization for Epstein-Barr virus-encoded mRNA was negative. Polymerase chain reaction study of formalin-fixed tissue showed clonal rearrangement of the T-cell receptor-gamma chain gene. The diagnosis was peripheral T-cell lymphoma, unspecified subtype. The initial stage was I(EA). His lymphoma was refractory to chemotherapy, and bony metastases developed in the right iliac bone 2 months later. He died of disease after 6 months without autopsy. We emphasize the importance of detailed immunohistochemical and gene rearrangement studies for the classification of malignant lymphomas via a very rare primary bony lymphoma of peripheral T-cell subtype.