Targeted Next-generation Sequencing Reveals a Wide Morphologic and Immunophenotypic Spectrum of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma
Journal
The American journal of surgical pathology
Journal Volume
46
Journal Issue
9
Pages
1207
Date Issued
2022-09-01
Author(s)
Hang, Jen-Fan
Chang, Kung-Chao
Wang, Ren-Ching
Chen, Bo-Jung
Hsieh, Pin-Pen
Huang, Wan-Ting
Chuang, Wen-Yu
Chen, Tsung-Wei
Yeh, Yi-Chen
Lin, Shih-Yao
Hsiao, Cheng-Hsiang
Chou, Shih-Cheng
Tseng, Chih-En
Pan, Shien-Tung
Chang, Shih-Lung
Chuang, Shih-Sung
Abstract
Primary intestinal T-cell lymphoma (PITL) is highly aggressive and includes celiac disease-related enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), and primary intestinal peripheral T-cell lymphoma, not otherwise specified (ITCL-NOS). MEITL is the most common PITL in Asia, comprising of monomorphic medium-sized cells typically expressing CD8, CD56, and cytotoxic granules. Occasional cases with intermediate features between MEITL and ITCL-NOS are difficult to be classified and warrant further investigation. We collected 54 surgically resected PITLs from Taiwan, with 80% presenting with bowel perforation. The overall outcome was poor with a median survival of 7 months. Based on histopathology (monomorphic vs. pleomorphic) and immunophenotype, we classified these cases into 4 groups: MEITL with typical immunophenotype (n=34), MEITL with atypical immunophenotype (n=5), pleomorphic PITL with MEITL-like immunophenotype (n=6), and ITCL-NOS (n=9). There was no EATL in our cohort. Targeted next-generation sequencing of the first 3 groups showed highly prevalent loss-of-function mutations for SETD2 (85%, 80%, and 83%, respectively) and frequent activating mutations for STAT5B (64%, 60%, and 50%, respectively) and JAK3 (38%, 20%, and 50%, respectively). In contrast, ITCL-NOS cases had less frequent mutations of SETD2 (56%) and STAT5B (11%) and rare JAK3 mutations (11%). Our results suggest that there is a wider morphologic and immunophenotypic spectrum of MEITL as currently defined in the 2017 WHO classification. MEITL with atypical immunophenotype and PITL with MEITL-like immunophenotype shared clinicopathologic and molecular features similar to MEITL but distinct from ITCL-NOS, indicating that such cases may be considered as immunophenotypic or histopathologic variants of MEITL.
Subjects
primary intestinal T-cell lymphoma; celiac disease-related enteropathy-associated T-cell lymphoma; monomorphic epitheliotropic intestinal T-cell lymphoma; primary intestinal peripheral T-cell lymphoma; not otherwise specified; SETD2; NATURAL-KILLER-CELL; MALIGNANT HISTIOCYTOSIS; CELIAC-DISEASE; NK-CELL; ENTEROPATHY; FEATURES
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Type
journal article