Prognostic significance of immunohistochemical subtypes based on the stage of B-cell differentiation in primary CNS lymphoma.

: Primary central nervous system lymphoma (PCNSL) has been immunohistochemically classified into two subtypes, germinal center (GC) B-cell and non-GC B-cell, but the prognostic impact of these subtypes remains debated. We investigated clinical features and prognostic significance of immunohistochemical subtypes that were identified by expression patterns of three B-cell differentiation markers in PCNSL. We also analyzed a factor related to responsiveness to high-dose methotrexate (HD-MTX) chemotherapy. Tumors from 32 PCNSL patients were immunohistochemically evaluated for expression of cluster of differentiation (CD) 10, B-cell lymphoma-6 (BCL-6), and multiple myeloma oncogene-1 (MUM-1) and classified into subtypes according to the expression patterns of these markers. Clinical features and prognostic outcome of these subtypes were investigated. Twenty-three patients were treated with HD-MTX-based chemotherapy followed by whole-brain radiation therapy (WBRT), and nine were treated with WBRT alone. Three immunohistochemical subtypes were identified, including A-type expressing CD10, BCL-6, and MUM-1 (12 patients), B-type expressing BCL-6 and MUM-1 (12 patients) and C-type expressing MUM-1 only (8 patients). Response rate in the HD-MTX therapy group was 57.1% (4/7) in A-type, 87.5% (7/8) in B-type, and 75% (6/8) in C-type. C-type with the lowest metabolic activity showed significantly longer overall survival than A-type with the higher uptake of methionine (71.6 versus 39.6 months) (P<0.05). Immunohistochemical identification of PCNSL based on the B-cell differentiation stage revealed three types of tumors, showing different metabolic activity and survival time. Refined immunohistochemical classification of PCNSL subtypes may become a useful tool for predicting more accurate prognosis and accessing sensitivity to HD-MTX therapy.