Clonal T-cell populations in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma.

Ten cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and AILD-like lymphoma were studied by immunophenotypic and immunogenotypic analysis. All specimens were found to have a predominance of T cells by immunophenotypic analysis. DNA hybridization analyses showed three of five specimens of AILD and five of six specimens of AILD-like lymphoma to contain clonal rearrangements of the beta T-cell receptor gene. No rearrangements of the heavy or light chain immunoglobulin genes were seen in any case. A single case showed a progression of AILD with a germ-line pattern of beta T-cell receptor DNA to AILD-like lymphoma with detectable clonal rearrangements for beta T-cell receptor DNA. These results suggest that many, but not all, cases diagnosed histologically as AILD or AILD-like lymphoma contain a clonal proliferation of T-lymphocytes.     

Composite angioimmunoblastic T-cell lymphoma and diffuse large B-cell lymphoma: a case report and review of the literature

We report a rare case of composite angioimmunoblastic T-cell lymphoma (AILT) and diffuse large B-cell lymphoma occurring in a 48-year-old woman with generalized lymphadenopathy and hepatosplenomegaly. The patient initially sought care at a local hospital with a single enlarged left cervical lymph node. Histologic examination of the node was interpreted as an atypical immunoblastic proliferation. She developed generalized lymphadenopathy 10 months later and was referred to our institution for further evaluation. The recent biopsy of the cervical node showed typical features of AILT Flow cytometric immunophenotyping identified an aberrant CD4+ T-cell population that lacked surface CD3. Polymerase chain reaction analysis of the T-cell receptor gamma gene revealed a clonal rearrangement. In addition to the AILT, the lymph node showed partial involvement by a diffuse large B-cell lymphoma. The B lymphoma cells and admixed immnunoblasts and Reed-Sternberg-like B cells in the AILT were positive for Epstein-Barr virus (EBV) by in situ hybridization. Ourfindings raise the possibility that the EBV-associated large B-cell lymphoma is a secondary event in AILT via EBV infection or reactivation followed by clonal expansion of an immortalized EBV-infected B cell clone.     

In angioimmunoblastic T-cell lymphoma,neoplastic T cells may be a minor cell population. A molecular single-cell and immunohistochemical study

The significance of T-cell proliferations in angioimmunoblastic lymphoma (AILD) is still enigmatic. Although classified as a malignant T-cell lymphoma in the World Health Organisation lymphoma classification, some cases of AILD lack dominant T-cell clones. In a previous study, based on single-cell polymerase chain reaction (PCR), we obtained similar results as studies of AILD using Southern blot or conventional PCR: some cases of AILD contained large T-cell clones, and, in other cases, T-cell clones were undetectable. As in single-cell studies, only a limited number of cells could be investigated; thus, we wanted to gain more insight into the amount and distribution of tumour cells. By applying triple immunofluorescent staining with antibodies directed against T-cell receptor V-family-specific epitopes, we investigated T-cell populations in AILD and their localisation in the tissue in relation to B cells (CD20) and follicular dendritic cells (CD21). In two of five cases investigated, only a minority of the T-cells compartment belonged to the tumour clone. Neoplastic T cells were found throughout the tissue, including areas dominated by B cells.     

血管免疫母细胞淋巴结病样T细胞淋巴瘤1例动态临床病理观察

目的 探讨血管免疫母细胞淋巴结病样T细胞淋巴瘤(AILD-TCL)的临床病理学特点和鉴别诊断要点。方法 对1例AILD-TCL病程的不同时期进行临床病理学观察与免疫组织化学检测。结果 病变早期淋巴结表现为多形性细胞(中、小淋巴细胞、嗜酸性细胞、浆细胞、免疫母细胞及组织细胞)浸润伴分支状毛细血管后小静脉的明显增生而导致正常结构的部分破坏，细胞无明显异型。病变中期出现散在分布的胞质透明、紧密排列的免疫母细胞簇，细胞中度异型。病变后期，免疫母细胞成簇或弥漫分布．细胞异型性大，核分裂象易见。免疫组化标记示淋巴结内弥漫性浸润的细胞胞质表达CD3、CD45RO、CD4、CD8，增生的滤泡树突细胞表达CD21，CD23阳性的中心细胞稀少。结论 AILD-TCL是一种发展快、预后差的周围T细胞淋巴瘤，熟悉其组织学特点对早期诊断和治疗具有重要意义。     

A case of angioimmunoblastic T-cell non-Hodgkin lymphoma with a neocentric inv dup(1)

Neocentromeres are rare epigenetic phenomena in which functional centromeres are formed onto novel chromosomal locations without any α-satellite DNA. To date, constitutional human neocentromeres have been reported in at least 90 cases. In cancer, however, the knowledge is much more limited. Acquired neocentromeres have been described in a particular class of lipomatous tumors (atypical lipomas and well-differentiated liposarcomas; ALP-WDLPS), three cases of acute myeloid leukemia (AML), one case of non-Hodgkin lymphoma (NHL), and one case of lung carcinoma. Here, we report on a 66-year-old male with angioimmunoblastic T-cell NHL. Cytogenetic analysis of his bone marrow showed multiple aberrations, including the presence of a supernumerary chromosome. Using the fluorescence in situ hybridization technique, the supernumerary chromosome was demonstrated to be entirely composed of material derived from chromosome 1. It represented an inverted duplication of the segments between 1q21 and 1qter with a neocentromere in band 1q31. To our knowledge, this is the second reported case of NHL (both T-cell) with the presence of a neocentromere. The occurrence of neocentromeres in tumor cells, however, may be underestimated because of technical limitations during the routine diagnostic chromosomal analysis. The prognostic impact is therefore currently unknown.     

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.     

Peripheral T-cell lymphoma complicated by a proliferation of large B cells

We studied 14 cases that showed a morphologic appearance of peripheral T-cell lymphoma and contained substantial numbers of CD20+ large B cells. In all but 2 cases, the CD20+ large cells showed a mix of kappa and lambda light chain expression. Two cases showed a focal predominance of kappa expression. In situ hybridization using the EBER1 probe for detection of Epstein-Barr virus (EBV) RNA was performed on every case. EBV RNA was present in 10 cases. Of 8 cases with EBV RNA stained by immunohistochemistry for the latent membrane protein of EBV, 6 were positive. Double-labeling immunohistochemistry and in situ hybridization confirmed that EBV was present in the large B cells. Polymerase chain reaction (PCR) analysis showed a clonal rearrangement of the T-cell receptor (TCR)-gamma chain gene in 12 of 13 cases tested. One additional case showed a clonal rearrangement of the TCR-beta chain gene by Southern blot hybridization. PCR analysis showed a clonal immunoglobulin gene rearrangement in 5 cases, a suggestion of a clonal rearrangement in 1, an oligoclonal pattern in 4, and a polyclonal pattern in 4. The finding of large B and T cells may result in a misdiagnosis of a reactive process or of T-cell-rich B-cell lymphoma. The presence of EBV in some cases could cause further confusion with the reactive T- and B-immunoblastic proliferation of infectious mononucleosis.     

Development of angioimmunoblastic T-cell lymphoma after treatment of diffuse large B-cell lymphoma: a case report and review of literature

Cases of diffuse large B-cell lymphoma (DLBCL) arising after the initial diagnosis of angioimmunoblastic T-cell lymphoma (AITL) and DLBCL synchronous with AITL have been reported. To date, there is no report on the subsequent development of AITL in patients with DLBCL. Here we presented a rare case of AITL developing six months after the initial diagnosis of DLBCL. In order to investigate the clinical and molecular features of patients with AITL and DLBCL, we also reviewed the literature on AITL patients developing DLBCL, and patients with composite AITL and DLBCL.     

Expression of CXCL13, a chemokine highly upregulated in germinal center T-helper cells, distinguishes angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified.

The germinal center T-helper cell has been proposed as the cell of origin for angioimmunoblastic T-cell lymphoma. Our recent report of expression of CXCL13, a chemokine critical for germinal center formation and one of the most highly upregulated genes in the germinal center T-helper cell subset, in the majority of angioimmunoblastic T-cell lymphoma cases, provided further support for this theory. To determine the specifity of this marker for angioimmunoblastic T-cell lymphoma, we evaluated CXCL13 expression in 26 nodal-based peripheral T-cell lymphomas and 14 lymph nodes showing paracortical lymphoid hyperplasia. No significant paracortical CXCL13 staining was seen in the reactive lymph nodes. By WHO classification criteria, 20 of the lymphoma cases were considered peripheral T-cell lymphoma, unspecified, and six were reclassified as angioimmunoblastic T-cell lymphoma after immunohistochemical detection of disorganized follicular dendritic cell meshworks. Combining the results of our studies, 31 of 35 angioimmunoblastic T-cell lymphoma cases (89%) showed CXCL13 expression, in contrast to two out of 20 peripheral T-cell lymphoma, unspecified cases (10%). The two peripheral T-cell lymphoma, unspecified cases that were positive for CXCL13 showed a Lennert lymphoma-like histology. While these cases did not meet all histologic criteria for angioimmunoblastic T-cell lymphoma, they did show an increase in EBV-positive B cells, suggesting they may be histologic variants of angioimmunoblastic T-cell lymphoma. In conclusion, CXCL13 expression is a distinctive feature of angioimmunoblastic T-cell lymphoma, providing further support for the germinal center T-helper cell as the cell of origin for this neoplasm. Given its specificity when compared to cases of peripheral T-cell lymphoma, unspecified as well as paracortical lymphoid hyperplasia, it may be a useful marker in the diagnosis of angioimmunoblastic T-cell lymphoma.     

Vascular endothelial growth factor-A is expressed both on lymphoma cells and endothelial cells in angioimmunoblastic T-cell lymphoma and related to lymphoma progression

Vascular endothelial growth factor-A (VEGF-A), a main stimulator of endothelial cell proliferation, plays an important role on tumor angiogenesis. Angioimmunoblastic T-cell lymphoma (AITL) show the most prominent vascular component among lymphomas and their prognosis is difficult to predict. To assess the clinical significance of VEGF-A in AITL, VEGF-A gene expression was studied in the tumoral lymph nodes of 24 patients using laser microdissection and quantitative polymerase chain reaction. VEGF-A gene was overexpressed in both microdissected lymphoma and endothelial cells. Increased levels of VEGF-A gene expression in lymphoma cells, as in endothelial cells, were related to extranodal involvement and to short survival time. Accordingly, VEGF-A protein expression was also found in both types of cells in lymph nodes and bone marrows with lymphomatous involvement. Triple immunofluorescent labeling on lymph node sections showed that VEGF-A protein and its receptor VEGF-R1 were coexpressed on endothelial cells of microvessels in the areas of lymphoma invasion. In these areas, ultrastructural study showed dystrophic microvessels. Taken together, the value of VEGF-A gene expression as an adverse prognostic marker in AITL should thus be considered. In addition to lymphoma cells themselves, the vascular component, a critical pathologic characteristic in AITL, also contributes to lymphoma progression.     

血管免疫母细胞性T细胞淋巴瘤骨髓/外周血瘤细胞免疫表型分析

血管免疫母细胞性T细胞淋巴瘤(AITL)是一类以异形T淋巴细胞增生伴显著血管增生,以及滤泡树突状细胞增生为主要表现,为一类来源于成熟T细胞的淋巴瘤[1].过去AITL瘤细胞形态学诊断缺乏特异性的鉴别特征,而近来AITL瘤细胞CD10[2]和CXCL13表达意义的发现为AITL的诊断提供了有力的支持,为了更深入了解AITL瘤细胞的免疫表型特征及发病机制,我们利用流式细胞术分析AITL患者骨髓及外周血有核细胞表面CD分子标志,期望获得更多信息.     

CD10 and BCL6 expression in the diagnosis of angioimmunoblastic T-cell lymphoma: utility of detecting CD10+ T cells by flow cytometry

Angioimmunoblastic T-cell lymphoma (AITCL) is a histologically distinct and relatively common subtype of T-cell lymphoma. Although the putative normal cell counterpart is a mature CD4+ T cell, the precise cell of origin remains elusive. We evaluated cases with a diagnosis of AITCL to determine the specificity and utility of CD10 coexpression, particularly by flow cytometry (FCM), in facilitating this diagnosis. Coexpression of BCL6 was also assessed. Eight AITCL cases were evaluated histologically, immunohistochemically, and by 4-color FCM. Four cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), were also analyzed. The lymphoma cells in all 8 AITCL cases were CD4+, CD45RO+ T cells, with classic extrafollicular meshworks of CD21/CD23/CD35+ follicular dendritic cells. Furthermore, all cases of AITCL cases contained interfollicular CD10+ cells by immunohistochemistry, and increased coexpression of CD10 on T cells was also detected in 6 of 8 cases by FCM. CD10 coexpression was not observed in all 4 PTCL-NOS cases. Although not specific for AITCL, increased numbers of BCL6+ cells were seen in AITCL as compared with PTCL-NOS. Double immunohistochemistry performed on an AITCL case with high numbers of BCL6+ cells highlighted coexpression of BCL6 and CD4 on the same cells. The finding suggests that AITCL may be a neoplasm of (possibly intrafollicular) CD10+, BCL6+, and CD4+ memory T cells. Although our series is small, our results suggest that CD10 coexpression may be a useful discriminant, particularly if the differential diagnosis is PTCL-NOS, and demonstrate that this can be determined by FCM.     

Relapsed angioimmunoblastic T-cell lymphoma with acquired expression of CD20: a case report and review of the literature

Background

Angioimmunoblastic T-cell lymphoma is one of the most common types of peripheral T-cell lymphomas, usually presenting at an older age with an aggressive clinical course. Its characteristic morphological presentation and follicular helper T-cell phenotype help to distinguish it from other T-cell lymphomas.

Case presentation

We recently encountered the unique case of a 63-year old patient with relapsed tumour-cell rich angioimmunoblastic T-cell lymphoma, presenting with a “classical” phenotype and, in addition, an acquired, strong, aberrant expression of CD20.“Lineage infidelity” of phenotypic markers is a well-documented phenomenon in lymphomas and leukemias, a circumstance currently still poorly understood and with the potential to bring about erroneous interpretations, causing diagnostic havoc. This case represents one of the few documented angioimmunoblastic T-cell lymphomas with strong CD20 expression. Of interest, CD20 expression was only detected in the recurrent lymphoma and not upon initial diagnosis. The clinical importance of this finding lies in the potential for treatment with an anti-CD20 antibody, for instance Rituximab, in addition to standard chemotherapy protocols for angioimmunoblastic T-cell lymphoma.

Conclusion

Diagnostic work-up of lymphomas to determine their lineage should therefore consider morphology, pheno- as well as genotypic characteristics, where appropriate, and in particular signs of progression and change in marker profile in relapsed cases e.g. acquisition of “non-lineage” markers such as CD20 in T-cell lymphoma.

     

BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma

The angiogenic microenvironment has been known to be a component of angioimmunoblastic T-cell lymphoma since its initial characterization. We have shown that angioimmunoblastic T-cell lymphoma endothelial cells produce vascular endothelial growth factor-A (VEGFA), and participate in lymphoma progression. In squamous cell carcinoma, endothelial BCL2 expression induces a crosstalk with tumor cells through VEGFA, a major mediator of tumoral angiogenesis. In the present study, we analyzed BCL2 and VEGFA in 30 angioimmunoblastic T-cell lymphomas, using triple immunofluorescence to identify protein coexpression in well-characterized lymphoma cells and microenvironment neoangiogenic endothelial cells. Using quantitative real-time PCR, we assessed mRNA expression levels in laser-microdissected endothelial and lymphoma cells. In lymphoma cells, as in endothelial cells, BCL2 and VEGFA proteins were coexpressed. BCL2 was expressed only in neoangiogenic CD34(+)CD105(+) endothelial cells. In laser-microdissected cells, mRNA studies showed a significant relationship between BCL2 and VEGFA levels in CD34(+) endothelial cells, but not in CD3(+)CD10(+)lymphoma cells, or in CD34(+) endothelial cells from lymph node hyperplasia. Further study showed that, in AITL, BCL2 mRNA levels in CD34(+)CD105(+) neoangiogenic endothelial cells also correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH. BCL2 expression by CD105(+) neoangiogenic endothelial cells is related to tumor progression in angioimmunoblastic T-cell lymphoma.     

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

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.     

Bcl-6 expression in reactive follicular hyperplasia, follicular lymphoma, and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: heterogeneity of intrafollicular T-cells and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma

BACKGROUND: The Bcl-6 gene product, a nuclear phosphoprotein, is expressed independently of Bcl-6 gene rearrangement. In lymph nodes, expression of Bcl-6 protein is restricted to germinal center (GC) B-cells and 10% to 15% of CD3/CD4+ intrafollicular T cells. Interfollicular cells are negative for Bcl-6 protein, except for rare CD3+/CD4+ T cells. Recently, we reported cases of angioimmunoblastic T-cell lymphoma (AITL) with hyperplastic GCs (AITL/GC), and observed that borders of enlarged GCs were ill defined, with features suggestive of an outward migration of GC cells to surrounding interfollicular zones. This prompted a study of follicular borders with Bcl-6 staining in reactive follicular hyperplasias and follicular lymphomas to compare with AITL/GC. MATERIALS AND METHODS: Formalin-fixed paraffin sections were used for immunostaining of Bcl-6. Six cases of AITL/GC, 12 nonspecific reactive follicular hyperplasia (FH), 7 HIV adenopathy, 10 follicular lymphoma (FL), and 8 typical AITL (ie, AITL without GC) were studied. Double staining for Bcl-6/CD20, Bcl-6/CD3, and Bcl-6/CD57 was performed in selected cases. RESULTS: In FH and HIV adenopathy, staining for Bcl-6 revealed densely populated GCs with well-defined and regular GC borders, whereas Bcl-6+ cells were rare in the interfollicular areas. An occasional GC with an ill-defined border was invariably surrounded by a broad mantle zone; those with indistinct mantle zones had well-defined, regular borders. In FL, follicles were densely populated, and their borders were irregular, with some Bcl-6+ cells in the interfollicular zones. In AITL/GC, GCs were less dense, GC borders were ill defined and irregular, and the number of interfollicular Bcl-6+ cells was markedly increased. Double staining revealed that these interfollicular Bcl-6+ cells in AITL/GC were Bcl6+/CD3+/CD20-/CD57- T cells. Moreover, CD3+ intrafollicular T cells were depleted in AITL/GC, whereas they were abundant in FH. Intrafollicular CD57+ cells did not stain for Bcl-6, and were also depleted in AITL/GC. In typical AITL, some neoplastic cells were positive for Bcl-6, showing variable degrees of staining. CONCLUSIONS: (1) GCs of AITL/GC differed from those of other reactive follicular hyperplasias and follicular lymphomas, and staining for Bcl-6 was useful to discern them. (2) Intrafollicular CD3+ T cells, many of which were also positive for Bcl-6, were markedly depleted in AITL/GC, with increased interfollicular Bcl-6+/CD3+ cells, suggesting an outward migration of intrafollicular T cells in this condition. (3) Interfollicular Bcl-6+/CD3+ cells in AITL/GC were too numerous to be accounted for by migration alone, suggesting local proliferation. (4) Intrafollicular CD57+ cells were negative for Bcl-6, indicating heterogeneity of the intrafollicular T-cell population. (5) Some neoplastic cells in AITL stained for Bcl-6, suggesting up-regulation of Bcl-6 expression in this tumor.     

T-cell receptor variable (V) gene usage by lymphoid populations in T-cell lymphoma.

A panel of monoclonal antibodies specific for TcR V gene families was used to study TcR V region expression in 28 cases of malignant and reactive T-cell expansions including four cases of mixed cellularity Hodgkin's disease (HD) and five reactive cases. TcR V beta 5 gene products were represented in three cases of lymphoblastic malignancy (V beta 5.1, V beta 5.2) and two cases of peripheral T-cell lymphoma (PTCL) (V beta 5.1). In the PTCL cases, the expanded family was found in the absence of clonal TcR gene rearrangements and in one of these cases with Ig JH and Ck clonal gene rearrangements consistent with the presence of a phenotypically and histologically undetectable clonal B-cell population. In a third PTCL case not investigated for genotype, the TCR V alpha 12 family was overrepresented. Expanded TcR V alpha 2 and V beta 5.1 families were identified in HD and V beta 8 and V beta 5.2/V beta 5.3 families in a reactive lymph node and CD3 and CD8-positive blood lymphocytosis respectively. Further study of PTCL and related entities are needed to establish whether expanded TcR families are common in those cases that fail to exhibit clonal TcR gene rearrangement.     

Analysis of T-cell subpopulations in T-cell non-Hodgkin's lymphoma of angioimmunoblastic lymphadenopathy with dysproteinemia type by single target gene amplification of T cell receptor- beta gene rearrangements

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is defined in the current lymphoma classifications as a T-cell non-Hodgkin's lymphoma. However, in approximately one third of the cases of this lymphoproliferative disease rearrangements of T-cell receptor (TCR) genes indicating clonal expansion of T cells are not detectable. It is currently believed that these cases may represent early stages of a lymphoma with a minor oligoclonal T-cell population. In the present study, 18 lymph nodes with the characteristic histology of AILD were investigated for clonal T-cell receptor gene rearrangements by analysis of DNA extracted from whole tissue sections. Dominant T-cell clones were detected in 12 of these cases. Single CD4(+) and CD8(+) T cells and proliferating Ki67(+) cells of seven cases were micromanipulated from frozen tissue sections. TCRbeta gene rearrangements were amplified from these cells by polymerase chain reaction and sequenced. In all informative cases, the clonal gene rearrangements were only detected among CD4(+), and not among CD8(+) T cells, indicating that the tumor clones in AILD usually derive from CD4(+) T cells. Minor clonal T-cell populations in those cases in which no clone was found by whole-tissue DNA analysis were not detectable even at single cell resolution. T-cell clones in 4 of 10 cases were found to express similar TCRbeta chains, indicating a potential role of (super) antigen triggering in at least some cases of AILD.     

Monoclonality and oligoclonality of T cell receptor beta gene in angioimmunoblastic T cell lymphoma

Angioimmunoblastic T cell lymphoma (AILT) is an aggressive T cell lymphoma with an incidence of approximately 1-2% of all non-Hodgkin lymphoma. The detection of clonal T cell receptor (TCR) gene rearrangements helps in the diagnosis of T cell malignancies such as AILT, where morphological and immunohistological investigations are not always sufficient to reach a definitive diagnosis. TCR beta (TCRB) and TCR gamma (TCRG) gene rearrangements were analysed from 17 WHO-defined cases of AILT by PCR for the presence of TCR clonality. TCRB gene rearrangements were sequenced to identify molecular signature(s) common among this patient group. Monoclonal and oligoclonal TCRB and TCRG gene rearrangements were detected in all cases. BV17S1 was slightly over-represented compared to the use of other Vbeta gene segments; however, no preferential usage of J gene segment(s) was detected. The results of this study emphasise that TCR clonality and oligoclonality is a diagnostic feature of AILT and that BV17S1 is over-represented with no other common molecular findings.     

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.