[Anal cancer: diagnostic and differential diagnostic issues]

Tumors of the anal canal are mostly epithelial in origin. The transition of gland-forming rectal mucosa via specialized urothelium-like cells at the dentate line to anal non-keratinized and finally perianal keratinized squamous epithelium implies a broad spectrum of tumor types, with most cancers exhibiting a mixture of different histological features. Moreover, secondary neoplasias extending into or metastasizing to the anal region need to be considered. Based on epithelial metaplasia at the transformation zone, poorly differentiated squamous anal carcinomas may show co-expression of both the squamous (CK5/6) and glandular type keratins (CK7). Since HPV infection of high-risk types (often 16 and 18) is etiologically associated with anal cancer, p16(INK4a) is highly sensitive and specific in the detection of high-grade anal squamous intraepithelial neoplasias (ASIN) and corresponding invasive squamous carcinomas. Diagnosis of secondary malignancies, including pagetoid extension into the anogenital region, requires the application of specific immunohistochemical marker panels.