Aberrant crypt foci in patients with neoplastic and nonneoplastic colonic disease

Aberrant crypt foci (ACF) are putative preneoplastic lesions that might rep resent the earliest morphological lesion visible in colonic carcinogenesis. However, findings concerning the growth and morphological features of thes e lesions in human studies suggest that ACF are highly heterogeneous in nat ure. In this study, we evaluated the morphological features of a large numb er of ACF in colon mucosa of 26 patients with colorectal carcinoma (CRC), f our patients with adenoma as well as seven patients with nonneoplastic colo nic diseases. By dissecting microscope, 508 ACF were identified, and of the se, 378 were sampled for histological examination. The median ACF density ( number of ACF/cm(2)) was significantly higher in the left colon than in the right colon (0.047 v 0.014 ACF/cm(2)). Unexpectedly, in our series, the ov erall ACF density was higher in the nonneoplastic colonic diseases than in CRC (0.13 v 0.032 ACF/cm(2), P=.0087), cases of nonneoplastic diseases, how ever, being limited to 7 patients. ACF were significantly larger in colons with CRC or adenoma than in colons with nonneoplastic disease (P<.03). On h istological examination, we observed 133 ACF with normal epithelium, 189 AC F with hyperplasia, 27 ACF with atypical hyperplasia, and 29 ACF with dyspl asia. We noted a progressive increase of median ACF size from normal mucose to hyperplasia, atypical hyperplasia, and dysplasia. Dysplastic ACF were m ore frequently observed in patients with CRC or adenoma and showed predomin antly elongated crypt orifices (P < .0001). We conclude that ACF are histol ogically heterogeneous, encompass a spectrum of lesions of which only a sub set are associated with dysplasia and then represent an early step in color ectal carcinogenesis. ACF with dysplasia are characterized by larger size, elongated crypt orifices, and an association with CRC. HUM PATHOL 30:66-71. Copyright (C) 1999 by W.B. Saunders Company.