Intestinal S100/Calgranulin Expression in Cats with Chronic Inflammatory Enteropathy and Intestinal Lymphoma

Abstract

Diagnosing chronic inflammatory enteropathies (CIE) in cats and differentiation from intestinal lymphoma (IL) using currently available diagnostics is challenging. Intestinally expressed S100/calgranulins, measured in fecal samples, appear to be useful non-invasive biomarkers for canine CIE but have not been evaluated in cats. We hypothesized S100/calgranulins to play a role in the pathogenesis of feline chronic enteropathies (FCE) and to correlate with clinical and/or histologic disease severity. This retrospective case-control study included patient data and gastrointestinal (GI) tissues from 16 cats with CIE, 8 cats with IL, and 16 controls with no clinical signs of GI disease. GI tissue biopsies were immunohistochemically stained using polyclonal α-S100A8/A9 and α-S100A12 antibodies. S100A8/A9+ and S100A12+ cells were detected in all GI segments, with few significant differences between CIE, IL, and controls and no difference between diseased groups. Segmental inflammatory lesions were moderately to strongly correlated with increased S100/calgranulin-positive cell counts. Clinical disease severity correlated with S100A12+ cell counts in cats with IL (ρ = 0.69, p = 0.042) and more severe diarrhea with colonic lamina propria S100A12+ cells with CIE (ρ = 0.78, p = 0.021) and duodenal S100A8/A9+ cells with IL (ρ = 0.71, p = 0.032). These findings suggest a role of the S100/calgranulins in the pathogenesis of the spectrum of FCE, including CIE and IL.

ACVIMconsensus statement guidelines on diagnosing and distinguishing low‐grade neoplastic from inflammatory lymphocytic chronic enteropathies in cats

“…Jejunal lymph nodes in cats with LGITL were significantly thicker (LGITL: median, 6.7 mm; range, 2.9‐12 mm; LPE: median, 4.2 mm; range, 1.8‐8.8 mm), significantly rounder and more hypoechoic compared with cats with LPE (Figure 2). 40 The same study showed that the presence of mild abdominal effusion tended to be associated with a final diagnosis of LGITL (45% in cats with LGITL vs 14% in cats with LPE) 40,94 . Specific lesions in liver and spleen that allow for differentiation of LPE from LGITL have not been reported in cats.…”

“…Hypocobalaminemia frequently has been documented in cats with CE with a reported prevalence between 18% and 80% 40,47,67,73,75,86‐93 . In studies that compared serum cobalamin concentrations between cats with LPE and those with LGITL, the prevalence of hypocobalaminemia was reported to be significantly higher in cats with LGITL 40,67,88,89,94 . An increase in serum methylmalonic acid (MMA) concentration indicates cellular cobalamin deficiency and hence has been investigated in correlation with serum cobalamin concentrations in cats 87,88,95,96 .…”

“…Common immunohistochemical markers used in diagnostic samples from cats with lymphoplasmacytic enteritis and low-grade intestinal T-cell lymphoma (LGITL).Recent studies investigated additional diagnostic and prognostic markers including TIA1 cytotoxic granule-associated RNA binding protein and S100/Calgranulin. The presence of intraepithelial TIA1 + cytotoxic lymphocytes was associated with poor prognosis in cats with LGITL 166 ; S100/Calgranulin was not discriminant between LGITL and LPE 94. …”

“…LGITL. 40,67,88,89,94 An increase in serum methylmalonic acid (MMA) concentration indicates cellular cobalamin deficiency and hence has been investigated in correlation with serum cobalamin concentrations in cats. 87,88,95,96 Serum cobalamin concentrations of <209 and 290 ng/L have been shown to have sensitivities of 51% and 74% and specificities of 96% and 80% for an increase of serum MMA indicating cellular cobalamin deficiency.…”

“…40 The same study showed that the presence of mild abdominal effusion tended to be associated with a final diagnosis of LGITL (45% in cats with LGITL vs 14% in cats with LPE). 40,94 Specific lesions in liver and spleen that allow for differentiation of LPE from LGITL have not been reported in cats. No studies currently are available on the merit of other imaging modalities such as computer tomography (CT) or magnetic resonance imaging (MRI) for the diagnosis or differentiation of cats with LPE or…”