Clinicopathologic Determinants of Survival in Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL): Analysis of a Pooled Database

Abstract

Introduction: MEITL is a rare and rapidly progressive extranodal T-cell lymphoma that arises from the intestinal intraepithelial T lymphocytes. Established in the 2016 WHO classification, this entity was carved out of what was previously known as type 2 enteropathy-associated T-cell lymphoma. MEITL usually affects the young-old and is not associated with celiac disease. We conducted this analysis to explore the clinicopathologic determinants of survival in this newly established T-cell entity. Methods: In order to study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 116 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 116 patients with confirmed MEITL were identified. The median age was 59.5 years with a peak incidence between ages 56 and 68. There was a male predominance with M:F ratio of 2. The jejunum was the most commonly involved site (71%). Median OS of the whole group was 11 months. The most common presentations were abdominal pain, followed by perforation, diarrhea, and weight loss. The majority presented at stages I&II (78%). The median duration of symptoms prior to diagnosis was 4 months. Compared to no treatment, combination chemotherapy and stem cell transplant (SCT) were statistically superior with a median OS of 2, 9, and 34 months respectively (p=0.0005). Further analysis revealed that surgical resection imparted a survival advantage on its own and in conjunction with combination chemotherapy and SCT. When surgical resection was incorporated in the analysis, median OS amounted to 2, 5, 7, 11, 13, 24 months for no treatment, surgery alone, chemotherapy, surgery+chemotherapy, SCT, and surgery+SCT respectively (p=0.0015). The quality of response to treatment also seemed to impact the outcome (p=0.0005) with median OS of 6, 36, and 60 months for none/transient, PR, and CR respectively. OS was not impacted by sex, presentation with obstruction or perforation, or anatomic site involvement. While older age, weight loss, and TCRγδ seemed to negatively impact OS, they did not reach statistical significance. Conclusions: This study presents an updated clinicopathologic data from a pooled cohort of patients with MEITL. It identifies quality of response, treatment modalities as well as surgical resection as major determinants of OS in this rare disease. Disclosures No relevant conflicts of interest to declare.

Cellular Origins and Pathogenesis of Gastrointestinal NK- and T-Cell Lymphoproliferative Disorders

“…This is an intestinal T-cell lymphoma that arises from IELs and exhibits epitheliotropism, usually with a CD8+ CD56+ phenotype [221,222]. It primarily arises in older male adults (median age: 58-69) [220,[223][224][225][226] and is more commonly reported in Asia, although there is a global distribution [220,222,223,227].…”

“…Similar to EATL, patients present with gastrointestinal symptoms such as abdominal pain, diarrhoea, bleeding, weight loss and bowel perforation [220,[223][224][225][226]228,229], but the mean duration of symptoms is short (4 months) [224]. The commonest site of involvement is the small intestine [220,[222][223][224][225][226], but multifocal lesions are common [220,223,228]. Other than regional lymph nodes, distant dissemination to liver, lung and brain has been reported [222,225,[230][231][232][233][234][235].…”

“…Other than regional lymph nodes, distant dissemination to liver, lung and brain has been reported [222,225,[230][231][232][233][234][235]. The prognosis is poor, with a median survival of less than a year [220,[223][224][225][226].…”

An unusual lymphoma involving the GI tract and bone marrow

“…1,2 Mutations in these genes have been detected in over 50% of MEITLs. 3 However, these mutations are not exclusive to MEITL and may be encountered in hepatosplenic T-cell lymphomas, 4 rarely in EATL 5,6 and other T-cell lymphomas. 7 The clinical-pathologic correlation in addition to the molecular studies is what aided in the ultimate diagnosis of MEITL.…”