Primary CNS T-cell Lymphomas

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 (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.

Cytoskeleton structure and total methylation of mouse cardiac and lung tissue during space flight

“…Moreover, Menon M.P. et al [ 67 ] showed that patients with primary central nervous system T-cell lymphomas had tumor cell necrosis as well as mutations of a number of genes, in particular TET2, the products of which are involved in the regulation of transcription efficiency. Thus, in our experiment, we can only assume that the mechanism of the change in total methylation levels in the cardiac and lung tissue of mice was associated with the decrease in the Tet2 mRNA content under space flight conditions.…”

EBV driven natural killer cell disease of the central nervous system presenting as subacute cognitive decline

“…The diagnosis was particularly difficult in this case because apart from subacute infarction and gliosis, the other helpful features such as a mass lesion and perivascular cuffing were absent. Most primary CNS mature T and NK-cell lymphomas are PTCL NOS, with EBV-positive NK/T-cell lymphoma being extremely rare [ 3 ]. Of the 6 previously reported cases all have been highly aggressive, presenting with discrete intracranial masses (87% supratentorial).…”

“…Primary CNS lymphomas (PCNSL) are rare, accounting for only 2–6% of all primary brain tumours. They are almost always Non-Hodgkin in type and B-cell (98%) in origin [ 3 ]. Primary CNS diffuse large B-cell lymphoma may be EBV-positive, particularly in the setting of HIV infection [ 4 ].…”

“…The precise mechanism by which EBV induces T-cell or NK-cell proliferation is unknown [ 7 ]. T-cell PCNL are much rarer than B-cell lymphoma and account for < 5% of all PCNSL’s [ 3 ]. Most primary CNS T-cell lymphomas are peripheral T cell lymphoma not otherwise specified (PTCL, NOS).…”

New developments in the pathology of malignant lymphoma. A review of the literature published from September 2015–December 2015

“…Menon et al [ 32 ] report the clinical, morphologic, immunophenotypic, and molecular characteristics of 18 cases of the rare primary central nervous system T-NHL (PCNSTL). Fifteen cases were classified as peripheral T-NHL, not otherwise specified, two of which were of γδ T cell derivation and one was TCR silent; there was one ALCL, ALK-positive and two ALCL, ALK-negative.…”