Histopathologic, phenotypic, and molecular criteria to discriminate low-grade intestinal T-cell lymphoma in cats from lymphoplasmacytic enteritis

Abstract

Background: Differentiation of low-grade intestinal T-cell lymphoma (LGITL) from lymphoplasmacytic enteritis (LPE) in cats is a diagnostic challenge for pathologists.

Objective: Characterize histologic, immunohistochemical, and molecular features of LGITL and LPE.

Animals: Forty-four client-owned cats, 22 diagnosed with LGITL and 22 with LPE.

Methods: Prospective, cohort study. Clinical suspicion of LGITL or LPE was based on persistent gastrointestinal signs, unresponsive to empirical treatments. All cats underwent a standardized diagnostic evaluation, including biopsy (preferentially full-thickness), and were diagnosed with LGITL or LPE after review of clinical, laboratory, sonographic, histologic, immunohistochemical, and clonality results.

Results: A monomorphic lymphocytic population (22/22, 100%) and in-depth mucosal infiltration (15/22, 68%) were hallmarks of LGITL. Epithelial patterns (nests and plaques) were significantly more frequent in LGITL (11/22, 50%) than in LPE (1/22, 5%) cases (P = .001). A CD3+ lymphocytic apical-to-basal gradient was observed in 9/22 (41%) of LGITL vs 1/22 (5%) of LPE cases (P = .004). Most LPE cases (17/18, 94%) featured marked fibrosis in the superficial part of the lamina propria. The Ki-67 20%- and 30%-thresholds discriminated between LGITL and LPE within both the epithelium (specificity >95%) and lamina propria (specificity >95%), respectively. All LGITL cases were CD3+ pSTAT3- and pSTAT5+. T-cell receptor gamma chain gene rearrangements indicated monoclonality in 86% of LGITL cases. Surprisingly, 70% of LPE cases featured monoclonality (40%) or monoclonality on a polyclonal background (30%).

Conclusions and clinical importance: We identified new histologic, immunohistochemical, and clonality criteria to distinguish LGITL from LPE.

Keywords: CD20; CD3; JAK-STAT; Ki-67; PARR; alimentary lymphoma; clonality; epithelium; fibrosis; full-thickness intestinal biopsies; gradient; histology; immunohistochemistry; inflammatory bowel disease; lamina propria; monoclonal; nest; plaque; polyclonal.