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

Summary

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.

Introduction

Although angioimmunoblastic T-cell lymphoma (AITCL) is a rare disease entity comprising 1% to 2% of lymphomas, overall, it is one of the more common subsets (15%-20%) of peripheral T-cell lymphoma (PTCL) [1]. Patients typically present with advanced-stage disease characterized by generalized lymphadenopathy, fever, weight loss, hepatosplenomegaly, rashes, polyclonal gammopathy, circulating immune complexes, and severe immunodeficiency. The latter is believed to be a consequence, rather than a cause, of the neoplastic process [2], [3]. The clinical course is aggressive, with a median survival of less than 3 years.

Morphologically, lymph nodes show partial or complete effacement of normal nodal architecture by a prominent interfollicular infiltrate. The lymph nodes contain a polymorphous population of lymphoid cells, including small nonneoplastic lymphocytes and neoplastic cells that are usually medium-sized, with abundant clear cytoplasm, distinct cell membranes, and round nuclei. Typically, the neoplastic cells express CD3 and CD4 [4]. There is often a mixed inflammatory background of eosinophils, plasma cells, and macrophages as well as pronounced vascular arborization of high endothelial venules and prominent extrafollicular meshworks of follicular dendritic cells. Scattered Epstein-Barr virus–positive B-cell immunoblasts, which are thought to be a manifestation of the secondary immunodeficiency, are frequently present. Remnant follicles can often be identified compressed around the periphery of the node, although early cases may have hyperplastic, as opposed to atrophic, germinal centers [5].

The diagnosis of AITCL is not always straightforward. Overt morphological and/or cytological features of malignancy may not be present. Furthermore, unlike the situation in many B-cell lymphomas, until recently, no distinctive immunophenotypic or molecular markers had been identified to assist in the diagnosis. The recent important immunophenotypic observation that appears to be quite specific for AITCL is that the neoplastic T cells coexpress CD10 [6], [7]. Finally, as with most mature T-cell lymphomas, the normal counterpart of the neoplastic cell in AITCL remains to be elucidated.

We evaluated CD10 and BCL6 expression in a total of 8 cases with a diagnosis of AITCL and compared this with 4 cases of PTCL not otherwise specified (PTCL-NOS). We describe the utility of both immunohistochemical and flow cytometric analyses in the distinction of AITCL from other PTCLs and propose a putative cell of origin for AITCL.