Intestinal hypomotility in systemic sclerosis: a histological study into the sequence of events.

OBJECTIVES: The pathogenesis of intestinal involvement in systemic sclerosis (SSc) is thought to be a sequential process (vascular, neuronal, and consecutive muscular impairment), but understanding of the underlying histological changes and how they translate to symptoms, is still lacking. Therefore, we systematically investigated histological characteristics of SSc in the intestines, compared to controls. METHODS: Autopsy material from the small bowel and colon was used for histological semiquantitative evaluation of the vasculature, enteric nervous system, interstitial cells of Cajal (ICC), and muscle layers, using a combination of histochemical and immunohistochemical stainings, according to guidelines of the Gastro 2009 International Working Group. RESULTS: Vascular changes were most frequently encountered, represented by intima fibrosis in both arteries and small vessels, and represented by venous dilatation. Second, generalized fibrosis of the circular muscle layer was significantly more found in SSc patients than in controls. Third, reduction of submucosal nerve fibers and myenteric neurons was shown in the colon of four SSc patients, which may explain severe symptoms of intestinal dysmotility. The density of myenteric ICC network was decreased in the small bowel of SSc patients. CONCLUSIONS: The postulated sequential processes of intestinal involvement in SSc could not be supported by our histological evaluation. The interpatient diversity suggests that parallel processes occur, explaining the variety of histological features and clinical symptoms. Key Points • Histological analysis showed vascular changes, fibrosis in the muscularis propria, and reduction of the ENS and ICC network in the intestines of SSc patients. • Pathophysiological mechanisms leading to intestinal dysmotility in SSc may be parallel rather than sequential. • The interpatient diversity suggests parallel pathophysiological processes, explaining the variety of histological features and clinical symptoms.

Practical and reproducible estimation of myenteric interstitial cells of Cajal in the bowel for diagnostic purposes.

BACKGROUND: Histological assessment of the interstitial cells of Cajal (ICCs) in the bowel is important for diagnosing patients with gastrointestinal neuromuscular diseases (GINMD). Although the International Working Group on GINMD proposed reporting a decrease in ICC number of more than 50%, quantitative methods used in literature are not practical for daily routine of the pathologist. Consequently, this study presents a straightforward semiquantitative estimation method for myenteric ICCs of the bowel. METHODS: Formalin-fixed paraffin-embedded sections from small bowel (n = 87) and colon (n = 159) were collected to create two control groups and four groups composed of patients with gastrointestinal motility disorders. The control groups included material of resection and autopsy origin, respectively. Samples were stained with CD117 (c-kit) antibody to estimate the myenteric ICC network. Scores of two observers were compared to analyze inter- and intraobserver agreement and reliability. KEY RESULTS: Interobserver reliability was almost perfect for small bowel (intraclass correlation coefficient 0.847; 95% confidence interval [CI]: 0.774-0.897) and substantial for colon (0.683; 95% CI: 0.591-0.758). Almost perfect intraobserver reliability was found (intraclass correlation coefficient 0.918; 95% CI: 0.874-0.947). The small bowel showed more myenteric ICCs than the colon. Neither significant differences between colonic regions were found nor were there any differences in the orientation of the sections. CONCLUSIONS & INFERENCES: The proposed estimation method for the myenteric ICC network showed generally good agreement and reliability. As the method is semiquantitative, simple, and capable to differentiate between normal and diseased tissue, it can be used in routine diagnostics of gastrointestinal neuromuscular disorders.