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PURPOSE Primary central nervous system lymphoma (PCNSL) has been immunohistochemically classified into two subtypes, germinal center (GC) B-cell and non-GC B-cell, but prognostic impact of these subtypes remains debated. We investigated clinical features and prognostic significance of newly defined immunohistochemical subtypes that were identified by expression patterns of three B-cell differentiation markers in PCNSL. In addition, we analyzed a factor related to responsiveness to high-dose methotrexate (HD-MTX) chemotherapy. METHODS Tumors from 32 PCNSL patients were immunohistochemically evaluated regarding expression of CD10, BCL-6, and MUM-1 and classified into subtypes according to the expression patterns of these markers. Clinical features and prognostic outcome of these subtypes were investigated. RESULTS 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). CONCLUSIONS 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 the sensitivity to HD-MTX therapy.

ML-04 PROGNOSTIC SIGNIFICANCE OF IMMUNOHISTOCHEMICAL SUBTYPES BASED ON THE STAGE OF B-CELL DIFFERENTIATION IN PRIMARY CNS LYMPHOMA