Evaluation of Histology, Immunohistochemistry, Clonality and STAT5B Mutation Detection in Cats with Chronic Enteropathy

Abstract: Background: Differentiation of feline enteritis and intestinal small cell T-cell lymphoma (SCL) by histology can be difficult and often relies on immunohistochemistry (IHC) and clonality testing. An activating mutation in STAT5B was described in feline SCL.
Hypothesis/Objectives: Hypothesis: histologic diagnosis of SCL varies across pathologists and detection of clonality and STAT5B mutation will aid in diagnosis. Objective: compare histology, CD3/CD20 IHC, clonality and STAT5B mutation results in feline intestinal biopsies.
Animals: 66 endoscopic duodenal and ileal biopsies from 41 client-owned cats seen at a tertiary hospital with chronic enteropathy, which failed a 2-week diet trial and did not have significant concurrent disease.
Methods: Three pathologists blindly categorized biopsy samples as enteritis, suspicious for SCL or definitive SCL, clonality was assessed by PCR for antigen receptor rearrangements, and detection of a STAT5B mutation was assessed by droplet-digital PCR (cohort study).
Results: All pathologists agreed on the diagnosis in 41% of samples by histology. 28/66 (42%) samples were diagnosed with SCL by at least 1 pathologist via histology; of these, 93% had a clonal T-cell receptor rearrangement and 79% had mutant STAT5B detected. Among 14 samples diagnosed as enteritis histologically by all pathologists, 9/14 had suspicion for SCL following IHC, 5/14 had T-cell clonality, and 2/14 carried mutant STAT5B.
Conclusions and clinical importance: Histologic diagnosis was often discordant across pathologists. Clonality and STAT5B mutation were detected in cats with suspicion but not definitive diagnosis of SCL. Cats with SCL frequently carry the STAT5B mutation and detection may be a useful ancillary test.