Colonic aberrant crypts may originate from impaired fissioning: Relevance to increased risk of neoplasia

Colonic aberrant crypt foci (ACF) can be identified on the unembedded mucos al surface as clusters of abnormal crypts with enlarged, surface openings. Because dysplasia is frequent, and may be a precursor of carcinoma, epithel ial changes have been well studied. However, the basis for the distinctive changes in crypt architecture remain unclear. We hypothesized that some of the architectural alterations of aberrant crypts may reflect impaired fissi oning during normal crypt duplication cycles. Fissioning begins at the cryp t base. Using morphometric and immunocytochemical approaches, we examined 5 5 human ACF, both dysplastic and nondysplastic, for their architectural fea tures. Non-ACF mucosa was compared. Microscopically, all lesions contained crypts that were attached, paired, dilated, and angulated. In 3 dimensions, these features related to multiple, individual complexes of connected cryp ts, referred to as connected crypt structures (CCSs). CCSs terminated in en larged surface openings (2 to 5x normal) which are morphometrically equival ent to the macroscopic aberrant crypts (P > .1). These openings trap marker dye. Support for an origin of CCSs in impaired basal fissioning is 3-fold. Crypt profiles in ACF are twice as frequent in basal mucosa as superficial ly (P < .001); in normal mucosa, the ratio is 1. In a CCS with vertically c onnected, co-planar crypts, the upper parent crypt diameter was the stun of diameters of inferiorly attached daughter crypts (P >.1). Proliferating ce ll marker, Ki-67, is not expressed at attachment points. In non-ACF mucosa, isolated CCSs consistently occur at foci of mechanical crypt distortion su ch as mucosal folds. We conclude that a CCS is a fundamental component of A CF of all histotypes. Impairment of normal crypt fissioning is probably a m ajor factor in the histogenesis of CCSs, which often occurs in settings of mechanical distortion of the mucosa. The pathological significance of this process may be in the formation of enlarged crypt openings. The latter coul d trap dietary carcinogens as they trap dye, and thereby predispose the CCS to dysplasia. Copyright (C) 1999 by W.B. Saunders Company.