Spigelman stage IV duodenal polyposis does not precede most duodenal cancer cases in patients with familial adenomatous polyposis

Abstract

The greatest known risk factor for duodenal cancer in familial adenomatous polyposis (FAP) is Spigelman stage (SS) IV duodenal polyposis. Endoscopic surveillance is recommended in FAP patients with SS 0 to IV, and prophylactic duodenectomy should be considered in SS IV. Cancer occurs in patients without SS IV polyposis. We assessed the relationship of SS and other factors with duodenal cancer in FAP. We performed a case-control study on 18 FAP patients with duodenal cancer and 85 randomly selected FAP control subjects with similar age characteristics. Demographic, clinical, and endoscopic features were compared using univariate and logistic regression analyses to assess factors associated with duodenal cancer. Fifty-three percent of cases had no SS IV history. SS components positively associated with cancer included duodenal polyp size (77% vs 47%, P= .015), and high-grade dysplasia (HGD; 29% vs 6%, P= .003) but not polyp number or histology. In the papilla, the frequency of tubulovillous or villous histology (80% vs 22%, P< .001) and HGD (30% vs 4%, P= .010) was greater in cases than control subjects. SS IV polyposis was absent in half of FAP patients with duodenal cancer. Only 2 of 4 SS components (large duodenal polyp size and HGD) were positively associated with duodenal cancer. Advanced pathology of the papilla appears to be an important feature. Revision of SS to emphasize these findings should be considered to better estimate cancer risk.