Primary CNS T-Cell Lymphomas: A Clinical Morphologic Immunophenotypic and Molecular Analysis

摘要

Primary central nervous system (CNS) lymphomas are relatively rare with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) account for <5% of CNS lymphomas. We report the clinical, morphologic, immunophenotypic and molecular characteristics of 18 PCNSTLs. Fifteen cases were classified as peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), 2 of which were of γδ T-cell derivation and 1 was TCR silent; there was 1 anaplastic large cell lymphoma (ALCL), ALK-positive and 2 ALCL, ALK-negative. Median age was 58.5 years (range 21-81), with M:F ratio of 11:7. By imaging 15 patients had supratentorial lesions. Regardless of subtype, necrosis and perivascular cuffing of tumor cells were frequently observed (11/18 cases). CD3 was positive in all cases but 1; 10/17 were CD8-positive and 5/17 were CD4-positive. Most cases studied had a cytotoxic phenotype with expression of TIA1 (13/15) and granzyme-B (9/13). PCR analysis of TRG rearrangement confirmed a T-cell clone in 14 cases with adequate DNA quality. Next Generation Sequencing (NGS) showed somatic mutations in 36% of cases studied; 2 had more than one mutation and none showed overlapping mutations. These included mutations in DNMT3A, KRAS, JAK3, STAT3, STAT5B, GNB1 and TET2 genes, genes implicated previously in other T-cell neoplasms. The outcome was heterogeneous; 2 patients are alive without disease, 4 are alive with disease and 6 died of disease. In conclusion, PCNSTL are histologically and genomically heterogeneous with frequent phenotypic aberrancy and a cytotoxic phenotype in most cases.