[Monomorphic epitheliotropic intestinal T-cell lymphoma: a clinicopathological and genetic mutation characteristics analysis of forty-two cases]

Abstract

Objective: To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). Methods: The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed. Results: Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29). Conclusions: MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.