Anal carcinoma--a histological review.

Epidemiological evidence of an association between anal carcinoma and symptomatic HIV-related disease suggests that the number of cases of this disease may increase significantly over the next few years. The role of oncogenic HPV types in the pathogenesis of anal carcinoma is substantiated by both epidemiological evidence that tumours are associated with a past history of anal warts and by experimental evidence showing that over 85% of tumours contain HPV 16/18 DNA on PCR. The physical state of the virus in the tumour cell genome is currently under investigation, and cellular interactions between HPV, HIV and other sexually transmitted viruses require further research. Clinical studies have shown that patients with anal warts and those who are HIV positive also show an increased tendency to develop dysplasia within the anal epithelium. However, the malignant potential of dysplasia remains unclear and, it presents problems in management, particularly when multifocal and high grade. Problems in classification of anal carcinomas involve both the site of the tumours and the histological appearance. Despite the difficulties which exist in estimating the origin of a tumour from canal or margin, this information does appear to have clinical significance and should therefore continue to be assessed. Recent morphological and keratin studies have emphasized the heterogeneity of these tumours and have revealed a similar heterogeneous profile of keratin expression in the normal anal epithelium. These results support the body of opinion which suggests that, with the exception of small cell carcinoma and adenocarcinoma, anal carcinomas should be considered as squamous cell tumours which are able to display a range of further morphological characteristics within which ductal differentiation and mucin production appear to carry the worst prognosis. Although there is no universally accepted staging system for anal carcinoma, depth of invasion and extent of spread at the time of diagnosis are the most important clinical factors determining survival and response to therapy. Randomized clinical trials are now under way to compare the outcome of various combinations of radiotherapy and chemotherapy, which have replaced radical surgery as a first line treatment and resulted in a significant decrease in patient morbidity from this disease.