CD75: A B‐cell marker which should not be forgotten in lymphocyte predominant Hodgkin lymphoma

Abstract

To the Editor The derivation of lymphocyte predominant (LP) cells of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) from germinal center (GC) B cells is supported by the following features: the expression of the BCL6 gene product and CD40 by LP cells 1, 2; the occurrence of numerous CD4+/PD1 T cells surrounding the LP cells, as seen in normal GCs and progressively transformed GCs (PTGCs); the presence of a follicular dendritic cell (FDC) meshwork (CD21+) within the tumor nodules 3; and the global gene expression profile 3. On these grounds, immunophenotyping by immunohistochemical analysis using B-cell markers for detecting LP cells is generally considered the golden standard in the diagnosis of NLPHL 3. LP cells are positive for CD20, CD79a, CD75, BCL6, Pax5, and OCT2. To evaluate the impact of B-cell markers in detecting LP cells of NLPHL, we analyzed the histopathologic and immunophenotypic patterns of NLPHL from 42 patients (total of 52 samples). These cases were obtained from our files at Aviano Centro di Riferimento Oncologico (CRO) during the period from 1986 to 2005. Immunohistochemical studies were performed on paraffin-embedded sections from formalin-fixed samples and Bouin-fixed samples. Informed written consent was obtained from the patients, and tissue collection was approved by Aviano CRO Institutional Review Board. Immunohistochemical stains were performed with a panel of monoclonal and polyclonal antibodies, listed in Supporting Information, using an automated immunostainer (Ventana Medical Systems, Tucson, AZ) according to the company's protocols. Serial sections were used for assessment of antigen coexpression. The diagnosis of NLPHL was based on the established WHO criteria 3. Typical NLPHL patterns were recognized in 31 patients, while histopathologic variants were found in the remaining 11 patients. The typical NLPHL patterns, including pattern A and pattern B according to Fan et al. 4, consisted of a predominantly nodular growth with non-neoplastic B-cells and LP cells located within the B-cell nodules. The LP cells were rarely found outside the nodules. Conversely, histopathologic NLPHL variants were characterized by the presence of LP tumor cells outside the B-cell nodules. LP cells were positive for all the B cell markers tested in all cases. CD75, also known as CDw75, a marker of mature B cells of GC derivation, was useful in detecting LP cells, especially those admixed with reactive B cells and FDCs in nodules of typical NLPHL patterns (31 out of 42) (Fig. 1). LP cells expressed CD75 strongly, while small reactive B cells with a mantle cell phenotype in the nodules showed weak cytoplasmic positivity in the Golgi area but no membranous staining. The consequence was that in B-cell nodules of typical NLPHL patterns CD75 selectively highlighted LP cells through their cytoplasmic and membranous staining (Fig. 1). CD20 was expressed in LP cells and in the small reactive B cells in the background with an equal intensity of staining. CD20 could be difficult to interpret in B-cell nodules of typical NLPHL patterns, while in areas with B-cell depletion of histopathologic variants of NLPHL the CD20 stained LP cells were detected easier. LP cells stained for CD75 were more numerous than those stained for CD20. The OCT2 and PAX5, B-cell transcription factors were consistently coexpressed. However, their expression was even worse than CD20 in detecting LP cells because these markers preferentially stained small reactive B cells. Our results lead us to conclude that CD75 is superior to other B-cell markers in detecting LP cells, especially in typical NLPHL patterns. Therefore, CD75 should not be forgotten in the immunohistochemical panel for detecting LP cells. Recognizing histopathologic NLPHL patterns is clinically relevant because of the adverse prognostic impact displayed by the histopathologic NLPHL variants as demonstrated by the German Hodgkin Study Group 5 and also because of the favorable prognostic impact displayed by the typical NLPHL patterns as recently reported by us in the American Journal of Haematology 6. Antonino Carbone1* Annunziata Gloghini2 1Department of Pathology, Centro di Riferimento Oncologico Aviano, Istituto Nazionale Tumori, IRCCS, I-33081 Aviano, Italy; 2Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS, Istituto Nazionale Tumori, I-20133 Milano, Italy Additional Supporting Information may be found in the online version of this article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.