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The incidence of CNS lymphoma has increased significantly in the past 30 years, primarily in the elderly and immunocompromised. While T-cell lymphomas comprise 15-20% of systemic lymphomas, they comprise less than 4% of primary CNS lymphomas, suggesting that they may be under-recognized compared to their systemic counterparts. To investigate this, we studied brain biopsies from three patients who were diagnosed with T-cell lymphoma confined to the brain. They had enhancing lesions by MRI, arising in the cerebellum and brainstem in one and temporal lobe in two. We compared these to biopsies from three patients who had reactive lymphoid infiltrates and who had clinical signs/symptoms and radiographic findings that were indistinguishable from the lymphoma group. Biopsies from both the lymphoma group and reactive group showed considerable cytomorphologic heterogeneity. Although one lymphoma case contained large atypical cells, the other two contained small, mature lymphocytes within a heterogeneous infiltrate of neoplastic and reactive inflammatory cells. Surface marker aberrancies were present in two lymphoma cases, but this alone could not reliably diagnose T-cell lymphoma. The proliferation index was not useful for differentiating lymphoma from reactive infiltrates. In five of the six cases the diagnosis was most influenced by clonality studies for T-cell receptor-gamma gene rearrangements. We conclude that because of the high degree of overlap in cytomorphologic and immunophenotypic features between T-cell lymphoma and reactive infiltrates, T-cell lymphoma may not be recognized unless studies for T-cell receptor gene rearrangements are performed for CNS lesions composed of a polymorphous but predominantly T-cell infiltrate.

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