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

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.