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Results of histopathology, immunohistochemistry, and molecular clonality testing of small intestinal biopsy specimens from clinically healthy client-owned cats

Marsilio S, Ackermann MR, Lidbury JA, Suchodolski JS, Steiner JM. Results of histopathology, immunohistochemistry, and molecular clonality testing of small intestinal biopsy specimens from clinically healthy client-owned cats. J Vet Intern Med. 2019 Feb 28

Inflammatory Bowel Disease (IBD) and Small Cell Lymphoma (SCLSA) are both common intestinal diseases of cats. While the causes and progression of these conditions are not fully understood, they are known to cause similar clinical signs in feline patients but have different prognoses and treatment options. Diagnosis of IBD/SCLSA and differentiation from other chronic enteropathies is important to properly treat and prognosticate for cats affected by diarrhea, vomiting, weight loss, and other GI signs. Diagnosis of these conditions involves examination of biopsy samples of the gut and potential advances testing such as Immunohistochemistry (IHC) and PCR for Antigen Receptor Rearrangement (PARR). While full-thickness samples are often considered ideal, endoscopic samples are less invasive to collect.

The purpose of this study was to determine if healthy adult cats with no evidence of GI disease had histologic, IHC, or PARR evidence of IBS/SCLSA on endoscopic biopsies. 20 cats were recruited to this prospective study.

Eligible cats were clinically healthy and >3y of age. A physical exam, questionnaire on GI history, and CBC/Chem/T4/FIV/FelV test were performed, as was evaluation of folate, cobalamin, fPL, and TLI. Cats were excluded if they had any GI signs, NSAIDs, steroids, antacids, or antibiotics in the last 6 months, or if cobalamin was <350g/L. Cats had a median age of 9.5 years, 12 female spayed and 8 male neutered.

After routine dental procedures (the reason for anesthesia) cats had upper GI endoscopy performed and had biopsies of the stomach and duodenum collected. Samples were submitted for lab testing, and pathologists were not told that these samples were form healthy cats. Owner follow up was maintained for a median of 709 days post endoscopy.

Histologic samples were reported descriptively and given a numerical score as per WSAVA scoring criteria. IHC was performed in a step-wise approach (for CDa, CD79a, and Granzyme B) and PARR evaluated on all samples. Results from all of these tests were integrated and a final diagnosis determined by an external pathologist.

All cats evaluated had abnormalities reported on histopathology, to the extent that a diagnosis of SCLSA was given in 2 cats. When integrating results of all tests, 12 cats were diagnosed with SCLSA; 1 cat with emerging SCLSA, 6 cats had lymphocytic enteritis, and 1 cat had uninterpretable results. This corresponds to 65% of apparently healthy cats being given a diagnosis of lymphoma and 30% lymphocytic enteritis.

Of the 20 cats, 2 were ultimately euthanized for signs attributable to GIZ disease (at 295 and 654 days post endoscopy). Both of these cats had been diagnosed with SCLSA during this study. Another cat developed non self-limiting vomiting that responded to dietary therapy. This cat had been diagnosed with enteritis. The remaining 17 cats had no GI signs during follow up.

There were several drawbacks to this study. One was that full upper and lower GI endoscopy was not performed in all patients, limiting full sampling of the GI tract. The cats used in the study were apparently healthy, but several abnormalities (ie elevated lipase and folate, occasional vomiting) were present. The use of “healthy” cats means that the pre-test probability of disease was low, which may decrease the positive predictive value of the testing performed. The scoring system used to evaluate samples was designed for full thickness biopsies and may not be appropriate to apply to endoscopic samples.

While the purpose of this study was to evaluate endoscopic biopsies, replication with full thickness samples would be interesting to determine if the nature and location of sampling play a role in the diagnoses.

Despite some limitations, this study presents valuable and surprising information. While it demonstrates that a large amount of significant subclinical inflammation is present in the feline GI tract, the lack of clinical signs before or after sample collection in the majority of animals suggesting that significant changes are likely needed to how we collect and interpret GI biopsy samples in cats.

See Also

Day MJ, Bilzer T, Mansell J, et al. Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: a report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group. J Comp Pathol. 2008;138(Suppl 1):S1-S43

Waly NE, Gruffydd-Jones TJ, Stokes CR, et al. Immunohistochemical diagnosis of alimentary lymphomas and severe intestinal inflammation in cats. J Comp Pathol. 2005;133:253-26