Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significance

Abstract
Background Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the most common type of cutaneous B‐cell lymphoma. There is ongoing discussion on the origin of the neoplastic B cells in these PCFCCLs, and consequently on their relation to the groups of primary cutaneous marginal zone B‐cell lymphomas (PCMZLs) and nodal follicular lymphomas. Objectives To define better the neoplastic B cells in PCFCCLs, and to find out if differences in the expression of the antiapoptopic protein Bcl‐2, and Bcl‐6 and CD10, molecules which are normally expressed by the neoplastic B cells in nodal follicular lymphomas, might have diagnostic or prognostic significance in cutaneous B‐cell lymphoproliferative disorders. Methods Pretreatment biopsies of well‐defined groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B‐cell lymphoma of the leg (PCLBCL‐leg; n = 19), secondary cutaneous follicular lymphoma (n = 3) and cutaneous pseudo‐B‐cell lymphoma (n = 6) were investigated by immunohistochemistry for expression of Bcl‐2, Bcl‐6 and CD10. Results The PCFCCLs consistently expressed Bcl‐6, whereas CD10 and Bcl‐2 were expressed in only one and two of 24 cases, respectively. In contrast, PCMZLs were always negative for Bcl‐6 and CD10, but were Bcl‐2 positive, whereas skin and lymph node localizations of secondary cutaneous follicular lymphomas consistently expressed all of Bcl‐2, Bcl‐6 and CD10. Reactive follicle centre cells in pseudo‐B‐cell lymphomas expressed Bcl‐6 (six of six cases) and CD10 (five of six cases), but not Bcl‐2. PCLBCL‐leg was Bcl‐6 positive and CD10 negative in all cases, irrespective of clinical outcome, and strongly expressed Bcl‐2 protein in all but two cases. Conclusions The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL‐leg, and indicate that staining for Bcl‐2, Bcl‐6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B‐cell lymphoproliferative disorders.