Primary CNS T-cell Lymphomas: A Clinical, Morphologic, Immunophenotypic, and Molecular Analysis.

Area of Science:

• Neuropathology
• Hematology
• Oncology

Background:

• Primary central nervous system (CNS) lymphomas are uncommon, with diffuse large B-cell lymphoma being the most frequent subtype.
• Primary CNS T-cell lymphomas (PCNSTLs) represent less than 5% of all primary CNS lymphomas.
• Understanding the characteristics of PCNSTLs is crucial for diagnosis and treatment.

Purpose of the Study:

• To comprehensively analyze the clinical, morphologic, immunophenotypic, and molecular features of 18 PCNSTL cases.
• To identify common mutations and phenotypic profiles in PCNSTLs.
• To correlate these findings with patient outcomes.

Main Methods:

• Clinical data review, morphologic assessment, and immunophenotyping (CD3, CD8, CD4, TIA1, granzyme-B).
• T-cell receptor (TCR) γ rearrangement analysis using polymerase chain reaction.
• Next-generation sequencing (NGS) for somatic mutation profiling.

Main Results:

• Fifteen cases were peripheral T-cell lymphoma, not otherwise specified; 1 was ALK-positive anaplastic large cell lymphoma; 2 were ALK-negative anaplastic large cell lymphoma.
• Common findings included supratentorial lesions, necrosis, and perivascular cuffing.
• Most cases exhibited a cytotoxic phenotype (TIA1+, granzyme-B+).
• NGS identified mutations in genes such as DNMT3A, KRAS, JAK3, STAT3, and TET2 in 36% of cases.
• Outcomes were heterogeneous, with varying survival rates.

Conclusions:

• PCNSTLs are histologically and genomically diverse, often presenting with a cytotoxic phenotype.
• Frequent phenotypic aberrancies and specific gene mutations are characteristic of PCNSTLs.
• Further research is needed to elucidate the full spectrum and therapeutic targets for PCNSTLs.