P20.23.A THE MANY FACES OF PRIMARY CNS T CELL LYMPHOMA: A MULTICENTRIC, RETROSPECTIVE STUDY OF HISTOPATHOLOGIC, MOLECULAR AND NEUROIMAGING FEATURES
Authors: Müller K J , Forbrig R , Reis J , Gakis G , Englert B , Karschnia P , Kaulen L , Hinz F , Traub B , Ehret F , Dreyling M , Rudelius M , Albert N L , Straube A , Schöberl F , Harter P , Dietrich J , von Baumgarten L 
Published: October 2024

BACKGROUND

Primary CNS T cell lymphoma (PCNSTL) is an extremely rare and aggressive form of non-Hodgkin lymphoma. Diagnosis is often challenging due to a lack of distinctive diagnostic criteria. Its overlapping presentation with other CNS disease highlights the importance of clinical awareness and interdisciplinary work-up. In our study we aimed to analyse the clinical, histopathologic, molecular, and radiographic characteristics of PCNSTL.

MATERIAL AND METHODS

Patients with histologically confirmed PCNSTL and absence of systemic disease were identified at three centres (University Hospital of Munich, Heidelberg University and Massachusetts General Hospital). Retrospective data including histopathology, immunophenotyping as well as multimodal MRI, and PET imaging were extracted.

RESULTS

We evaluated 16 immunocompetent patients (11 male /5 female) with a median age of 50 years (range 19-76) and initial median Karnofsky performance status (KPS) of 70% (20-100). Histopathologic diagnoses included PCNSTL, not otherwise specified (NOS in 13/16, 81.25%), primary ocular T cell lymphoma (1/16, 6.25%), primary CNS NK/T cell lymphoma (1/15, 6.25%) and primary ALK1-positve PCNSTL 1/16, 6.25%). When testing for T-Cell receptor gene rearrangement (TRG), polymerase chain reaction showed T-cell clonality in 7/16 patients (43.75%). Next generation sequencing revealed mutational variants of uncertain significance in 18.75% (available in 3/16), i.e. in BCOR, MED12, and MET genes, so far not described in PCNSTL. 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 (6/16, 37.5%). High intratumoral susceptibility signal was frequently observed (7/16, 43.75%). PET imaging showed a low to moderate tracer uptake in [18F]FET PET (available in 3/16). Kaplan-Meier-analysis exhibited a median progression-free survival of five months and a median overall survival of 96.5 months. While treatment protocols varied, there was evidence of a more favourable overall survival in the subgroup treated with MTX-based chemotherapy combined with autologous stem cell transplant (ASCT; Log-rank-test: p &lt; 0.0275). Further, we observed the first case of an ALK1-positive PCNSTL achieving persistent complete remission after treatment initiation with Lorlatinib.

CONCLUSION

Although PCNSTL represents an exceptionally rare entity, we identified certain neuroimaging patterns together with histopathologic and molecular profiles, which may assist in identifying future PCNSTL cases in clinical practice. The best therapeutic response was observed using MTX-based chemotherapy combined with ASCT. We report on the first case with persistent complete remission after initiating targeted therapy with Lorlatinib in ALK1-positive PCNSTL.