Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2.

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.

Eosinophil-Rich Acute Febrile Neutrophilic Dermatosis in a Patient With Enteropathy-Associated T-cell Lymphoma, Type 1.

The presence of eosinophils within the neutrophilic infiltrates of acute febrile neutrophilic dermatosis (Sweet syndrome) is documented in the literature. Here, the authors describe a case of eosinophil-rich acute febrile neutrophilic dermatosis in the setting of new onset enteropathy-associated T-cell lymphoma (EATL), type 1. Histopathologic evaluation of the skin biopsies demonstrated a mixed superficial perivascular and inflammatory infiltrate composed of neutrophils, lymphocytes, and abundant eosinophils. EATL, type 1 is an aggressive although rare primary intestinal lymphoma that may be associated with celiac disease. This lymphoma is associated with a poor prognosis due to treatment resistance or bowel perforation. To the authors' knowledge, Sweet syndrome has not been reported in a patient with EATL.

Refractory celiac disease and EATL patients show severe malnutrition and malabsorption at diagnosis.

BACKGROUND & AIMS: Refractory celiac disease type II (RCDII) and EATL (Enteropathy Associated T-cell Lymphoma) are (pre)malignant complications of celiac disease (CD). Data on malnutrition and intestinal absorption is lacking in these patients. Therefore, the aim of the study is to comprehensively assess nutritional status and intestinal absorption capacity of patients with RCDII and EATL, compared with data of newly diagnosed CD patients. METHODS: Observational study in tertiary care setting in RCDII (n = 24, 63.8 ± 8.2 y), EATL (n = 25, 62.3 ± 5.7 y) and CD patients (n = 43, 45.6 ± 14.8 y). At diagnosis, anthropometry (BMI, unintentional weight loss, fat-free mass index (FFMI), handgrip strength (HGS), nutritional intake, fecal losses and Resting Energy Expenditure (REE)) were assessed. RESULTS: Low BMI (<18.5) was more often observed in RCDII patients than in CD or EATL patients (in 33%, 12% and 12%, respectively, p = 0.029). EATL patients more frequently had unintentional weight loss (>10%) than CD or RCDII patients (in 58%, 19% and 39% of patients, respectively; p = 0.005/0.082). Energy malabsorption (<85%) was detected in 44% and 33% of RCDII and EATL patients, vs 21.6% in CD (NS). Fecal energy losses were higher in RCDII than in CD patients (589 ± 451 vs 277 ± 137 kcal/d, p = 0.017). REE was underestimated by predicted-REE with>10% in 60% of RCDII, 89% of EATL, and 38% of CD patients (p = 0.006). Low FFMI and HGS were detected in one third and two thirds of all patients, respectively. CONCLUSIONS: The nutritional status of patients with RCDII and EATL is inferior compared with untreated naïve CD patients at presentation. Both malabsorption as well as hypermetabolism contribute to malnutrition.

Type II enteropathy-associated T-cell lymphoma: a multicenter analysis from the Asia Lymphoma Study Group.

Enteropathy-associated T-cell lymphoma (EATL) is a rare primary gastrointestinal T-cell lymphoma. A multicenter study from the Asia Lymphoma Study Group identified 38 EATL patients within a 19-year period. All cases were type II EATL. Men were affected twice as common as women, at a median age of 59 (23-89) years. None had a history of celiac disease. The sites of involvement were small bowel and stomach (5%), small bowel (63%), small and large bowel (16%), and large bowel (18%). Common presenting features were bowel perforation (34%), pain (32%), and obstruction (21%). Lymphomas showed monomorphic neoplastic lymphoid infiltrates that were CD3⁺ (100%), CD56⁺ (91%), TIA-1⁺ (96%), CD4⁻CD8⁺ (63%), CD4⁺CD8⁺ (19%), CD4⁻CD8⁻ (16%), and CD4⁺CD8⁻ (3%). Epstein Barr virus was demonstrable in three cases. Despite chemotherapy and/or surgical resection, the overall response and complete response rates were poor at 46% and 38%. The median overall survival (OS) was 7 months and progression-free-survival (PFS) 1 month. Five patients underwent hematopoietic stem cell transplantation all were alive. Age and the prognostic index for peripheral T-cell lymphoma were not prognostically significant. Good performance status was associated with better OS (P = 0.03), and response to initial treatment led to better OS and PFS (P < 0.001).