Abstract
BACKGROUND AND OBJECTIVES: Primary CNS T-cell lymphoma (PCNSTL) is an extremely rare and aggressive form of non-Hodgkin lymphoma. Diagnosis is often challenging because of the nonspecific clinical presentation, which can lead to delays in treatment. This study aims to analyze the clinical, histopathologic, and neuroimaging characteristics of PCNSTL. METHODS: In this retrospective, multicentric cohort study, histologically confirmed PCNSTL cases without evidence of systemic disease were selected from pathology databases at 3 academic neuro-oncology centers (University Hospital of Munich, University Hospital of Heidelberg, Massachusetts General Hospital in Boston) during the period from 2008 to 2024. Retrospective data, including demographics, histopathology, immunophenotyping, multimodal MRI, and PET imaging, treatment lines, and outcome data were extracted from medical records and analyzed. RESULTS: We evaluated 16 patients (11 male) with a median age of 50 years (19-76 years) and a median Karnofsky performance status of 80% (20%-100%). T-cell clonality was confirmed in 9/15 (60%) tested patients with typical T-cell receptor gene rearrangement patterns. MRI scans at primary diagnosis showed predominantly supratentorial parenchymal lesions with prominent contrast enhancement in 14/16 (87.5%) and in more than one-third multifocal lesions (7/16, 43.75%). High intratumoral susceptibility signal was frequently observed (7/16, 43.75%). [(18)F]fluorodeoxyglucose-PET and [(18)F]fluoroethyltyrosine-PET imaging revealed only low to moderate tracer uptake in 7/8 examined patients (87.5%). Median progression-free survival was 4 months, and median overall survival was 97.5 months. Although treatment protocols varied, the use of methotrexate (MTX)-based chemotherapy combined with autologous stem-cell transplant (ASCT) was associated with most favorable outcome (95% CI 2-87, p < 0.0275). In 1 case of ALK1-positive PCNSTL, persistent complete remission was achieved after treatment with the ALK-inhibitor lorlatinib. DISCUSSION: Although PCNSTL is exceptionally rare, we identified distinct neuroimaging patterns showing highly aggressive features on MRI but hypometabolic PET imaging, which may assist in identifying future PCNSTL cases. Despite the limited cohort size, our findings suggest that MTX-based chemotherapy with ASCT may translate into favorable outcome. We report on an ALK1-positive PCNSTL case with sustained complete remission after targeted therapy with lorlatinib.