Adenocarcinoma in situ of the uterine cervix

Abstract

Human papillomaviruses, particularly types 16 and 18, play a role in the development of adenocarcinomas of the uterine cervix. HPVs probably infect individual groups of cells of the undifferentiated reserve cell (basal cell) layer where they can remain latent for longer periods of time. As in squamous cervical intraepithelial neoplasia (CIN), but apparently much less often than in CIN, first individual cells and than groups of cells with notable large, polychromatic, atypical nuclei develop underneath the normal columnar epithelium. This indirect metaplasia from normal to atypical columnar epithelium is seen in the glandular-endometroid type of cervical adenocarcinomas and less often in the endocervical-intestinal, adenoepidermoid or adenosquamous types. This mode of malignant transformation is not seen in the other variants of cervical adenocarcinoma. Dysplasias of the columnar epithelium can occur. In CIGN or ACIS, as in CIN, atypical columnar epithelium successively replaces normal columnar epithelium. Thus the entire area and depth of the cervical glands is successively replaced by malignant epithelium while the original glandular architecture is preserved for a long period. This process occurs at multiple foci in the normal cervical gland population. The atypical columnar epithelium is separated from the normal cervical glands by sharp borders; there are no gradual transitions between the two types of epithelia. The transition to invasive growth is much more difficult to determine in ACIS and CIGN than in CIN. The diagnosis of early stromal invasion is possible only for the most common types of ACIS or CIGN, namely glandular-endometrioid or endocervical-intestinal ACIS. The development of CIGN and ACIS is bound to the entire gland field of the cervix including areas of ectopy. They are usually located on the cervical canal side of the external os. Diagnosis of CIGN and ACIS by cytology is straightforward only for well differentiated forms which slough atypical glands or gland components. Pure CIGN or ACIS of the uterine cervix are rare because they usually cecxist with CIN. Colposcopy shows only the features of abnormal squamous epithelium; CIGN or ACIS cannot be diagnosed by colposcopy alone. Only larger, already invasive glandular cancerous regions can be recognized on the basis of an irregular papillary surface.