title: Primary CNS T-cell Lymphomas: A Clinical, Morphologic, Immunophenotypic, and Molecular Analysis.
abstract: 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, 2 of which were of γδ T-cell derivation and 1 was TCR silent; there was 1 anaplastic large cell lymphoma, ALK-positive and 2 anaplastic large cell lymphoma, ALK-negative. Median age was 58.5 years (range, 21 to 81 y), with an M:F ratio of 11:7. Imaging results showed that 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). Polymerase chain reaction analysis of T-cell receptor γ rearrangement confirmed a T-cell clone in 14 cases with adequate DNA quality. Next-generation sequencing showed somatic mutations in 36% of cases studied; 2 had >1 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 heterogenous; 2 patients are alive without disease, 4 are alive with disease, and 6 died of disease. In conclusion, PCNSTLs are histologically and genomically heterogenous with frequent phenotypic aberrancy and a cytotoxic phenotype in most cases.
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health.
authors.forename: Madhu P
authors.initials: MP
authors.lastname: Menon
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health.
authors.forename: Alina
authors.initials: A
authors.lastname: Nicolae
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health.
authors.forename: Hillary
authors.initials: H
authors.lastname: Meeker
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health.
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xi
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health.
authors.forename: Armin G
authors.initials: AG
authors.lastname: Jegalian
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Miller
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D016543:Central Nervous System Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D016399:Lymphoma, T-Cell / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016692:Receptors, Antigen, T-Cell, gamma-delta