Do all colorectal carcinomas arise in preexisting adenomas?

In this article, the underlying nature of the adenoma is defined and evidence in support of the adenoma-carcinoma sequence is presented. Emphasis is placed on recent findings from the field of molecular biology which fortify the concept of the adenoma as a step in the evolution of large bowel cancer. Despite the considerable body of indirect evidence in support of the adenoma-carcinoma sequence, the de novo theory still has some support. Although differences between the de novo and adenoma carcinoma concept are largely semantic, the fact that infiltrating carcinoma can arise within small, flat foci of severely dysplastic epithelium (indistinguishable from carcinoma in situ) may be of considerable clinical importance. Other routes of morphogenesis exist also, but these make a relatively small contribution to the overall incidence of colorectal cancer. Even if it is accepted that the majority of colorectal cancers develop in a preexisting adenoma, the systematic removal of adenomas would pose a number of practical difficulties. First, adenomas are extremely common, particularly in populations at high risk of colorectal cancer. A second factor is the recently recognized existence of flat or depressed adenomas which may be small and difficult to visualize endoscopically. A simple screening program based on our knowledge of the evolution of colorectal cancer is outlined.