Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and aggressive T-cell lymphoma with incompletely characterized features. We analyzed 120 Chinese patients (88 males, 32 females; median age 58y), including 43% at stage I. All patients had gastrointestinal (GI) involvement, with 78% confined to the small intestine. The tumor cells were typically monomorphic and medium-sized, expressing CD3 (99%), CD7 (90%), CD8 (94%), CD56 (90%), and TIA-1 (97%). Low expression rates were noted for CD4 (9%) and CD5 (13%). CD20 was aberrantly expressed in 4% cases. TCRαβ expression was more common than TCRγδ (1.1:1). The next-generation sequencing (NGS) results showed that all cases had loss-of-function mutations in SETD2 (100%). Other frequently mutated genes included STAT5B (67%), JAK3 (50%), TP53 (33%), and KRAS (22%). All patients had detectable single nucleotide polymorphisms (SNPs). Copy number variations (CNVs) were detected in TSC2 (11%), CDH1 (5%), STK11 (5%), CDKN2B (5%), and SDHD (5%). In addition, novel fusions involving PML-RPH3A (5%), TP63-PRKAR2A (5%), MAD2L1-CD28 (5%), and DPP6-TP63 (5%), were identified. Among these patients, 89% underwent surgery, 83% received systemic chemotherapy, and 7% received stem cell transplantation (SCT). The median overall survival (OS) of 77 patients was 9 months. Age 58 years or older and Ki-67 >50% were significantly associated with poor prognosis in univariate analysis, while Ki-67 >50% and the presence of B symptoms were independent adverse prognostic factors in multivariate analysis. Our findings expand the molecular spectrum of MEITL and support precision medicine approaches for this therapy-resistant disease.