Malignancies of the anus, anal canal, and perianal skin include epidermoid carcinoma, malignant melanoma, squamous cell carcinoma, adenocarcinoma, and basal cell carcinoma. From 2006 to 2010, the number of new cases of anal cancer was 1.7 per 100,000 men and women per year. The number of deaths was 0.2 per 100,000 men and women per year. This chapter focuses on perianal intraepithelial squamous cell carcinoma and perianal intraepithelial adenocarcinoma. These conditions present subtly, and affected patients may present with other diagnoses after protracted medical therapy has failed to relieve their symptoms. Prompt diagnosis requires awareness of these conditions and a high index of suspicion.
The symptoms produced by neoplasms of the perianal and anal skin frequently mimic those of more common benign inflammatory conditions. Patients may be asymptomatic or may report pruritus, burning, pain, bleeding, drainage, or a sensation of a mass. Failure to investigate these common symptoms may result in a delay in the diagnosis of a malignant tumor. Performing a biopsy of all nonhealing lesions, atypical rashes, or perianal growths is important, with subsequent cytologic and histologic examination by a skilled pathologist.
High-Grade Squamous Intraepithelial Lesion (Formerly Bowen Disease)
When Bowen first described this entity in 1913, he designated it as a “precancerous dermatosis.” Now the term “Bowen disease” is synonymous with “squamous cell carcinoma in situ,” “high-grade anal intraepithelial neoplasia,” and “high-grade squamous intraepithelial lesion” (HSIL). In this chapter, to consolidate terminology and eliminate confusion, these entities will all be referred to as HSIL.
HSIL of the perianal skin and anal canal is a rare, slow-growing, intraepithelial squamous cell carcinoma that occurs most often in patients in their fourth to fifth decade of life. These lesions are commonly caused by human papilloma virus (HPV) infection, specifically with serotypes HPV-6, -11, -16, and -18. Risk factors include medical immunosuppression (e.g., in patients who have undergone a kidney transplant), human immunodeficiency virus (HIV) seropositivity, cigarette smoking, and anal receptive intercourse. Prevention strategies include vaccination against these HPV strains.
Grossly, HSIL appears as discrete, erythematous, occasionally pigmented, noninfiltrating, scaly or crusted plaques. HSIL is sometimes identified incidentally on histopathologic examination of specimens removed in the treatment of other perianal and anal diseases. Biopsies of all nonhealing perianal lesions should be performed. Histologic features of HSIL show multinucleated giant cells with some vacuolization, giving a “halo” effect. The distinction between low- and high-grade anal intraepithelial neoplasm (AIN) is based on the percentage of epithelial cells replaced by abnormal basaloid cells; low-grade AIN has less than 50% replacement, and high-grade AIN has greater than 50% replacement. Although more common in women, the incidence of low-grade squamous intraepithelial lesions and HSIL is increasing in both sexes; the group most at risk is HIV-positive men who have sex with men (MSM). Although low-grade lesions may regress or progress to high-grade lesions, HSIL rarely regresses regardless of appropriate treatment and control of HIV and HPV.
The relationship between HSIL and concomitant systemic and cutaneous cancers has been controversial. However, it is now generally accepted that, unlike with Paget disease, HSIL is not directly associated with other malignancies.
Screening programs for the general population are not cost-effective because of the rarity of the disease. However, in certain high-risk groups such as MSM, annual screening and screening every 2 to 3 years have been shown to have benefits in life expectancy and cost-effectiveness, respectively.
Inspection and biopsy of gross lesions underestimate the local extent of disease. Traditionally, mapping of the perianal region is carried out using full-thickness punch biopsies around a superimposed clock face at the 3-, 6-, 9-, and 12-o’ clock positions to plan resection margins ( Fig. 13-1 ). Subsequent wide local excision (WLE) of areas of positive HSIL with 1-cm margins has been used. However, this method has led to significant morbidity, including pain, chronic wounds, anal stricture, and the necessity of advancement or rotational skin flaps to cover tissue defects. Healing by secondary intention is an alternative. Unfortunately, WLE is associated with a rate of persistent disease as high as 63% at 1 year and local recurrence rates as high as 34% over the same period.