Collagenous colitis is a rare cause of chronic watery diarrhea. In this con
dition, endoscopic findings are usually normal. Currently, the diagnosis re
lies on the histological presence of thick subepithelial bands of collagen
deposits and an inflammatory infiltrate within the mucose. However, these s
ubepithelial bands may be developed only focally and may be too subtle to a
llow a definitive diagnosis upon routine hematoxylin and eosin (HE) and van
Gieson's stainings. Recently, we and others were able to show a prominent
staining of tenascin and type-VI collagen in the subepithelial band-like st
ructures. In this study, we tested the diagnostic value of tenascin stainin
g and type-VI collagen immunolocalization for the identification of collage
nous colitis and compared it with conventional histology and histochemical
detection of collagens. The analysis was based on 434 biopsy specimens of c
ollagenous colitis, other forms of colitis, and normal mucosa. We were able
to show that the immunohistochemical detection of increased amounts of ten
ascin, selectively in the subepithelial zone, is a specific test for collag
enous colitis, with a sensitivity superior to conventional histological and
histochemical detection, especially in minimal collagenous colitis (P<0.00
1). Of note, tenascin staining also allows the diagnosis of collagenous col
itis in biopsies obtained only from the rectum and sigmoid colon, thus avoi
ding the need for colonoscopic investigations. Tenascin immunostaining is a
simple and safe tool to complement conventional histological diagnostics i
n clinically and histopathologically unclear cases of diarrhea.