MIXED EPITHELIAL POLYPS IN ASSOCIATION WITH HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER PROVIDING AN ALTERNATIVE PATHWAY OF CANCER HISTOGENESIS

A member of a hereditary non-polyposis colorectal cancer (HNPCC) famil y developed two colorectal cancers and multiple polyps within four yea rs of a negative colonoscopic examination, One of the cancers was only 4 mm in diameter and showed the gross and endoscopic appearances of a de novo carcinoma. Microscopic examination of multiple levels reveale d a mixed hyperplastic polyp/adenoma (mixed polyp) in contiguity with the cancer, The colon harboured additional polyps of which five were t ubular adenomas, seven were hyperplastic polyps and seven were mixed p olyps (architecturally compatible with hyperplastic polyps but with at ypical cytology), Atypical features of the mixed polyps included tripo lar mitoses, bizarre chromatin aggregations and multinucleation, One m ixed polyp showed DNA microsatellite instability. Under the influence of the mutator defect, hyperplastic polyps may develop atypical or ade nomatous features and show progression to carcinoma, Such an alternati ve morphogenetic pathway could explain the differing molecular and pat hological profiles of cancers showing DNA microsatellite instability.