The terminology used by pathologists when reporting premalignant lesions of the anus and perineum is often confusing to the treating clinicians.

The terms squamous cell carcinoma in situ (CIS), anal intraepithelial neoplasia (AIN), anal dysplasia, squamous intraepithelial lesion (SIL), and Bowen’s disease may all be used to refer to the same histopathology.

AIN (a cytologic diagnosis) and dysplasia have both historically been broken into AIN I, II, and III and low-, moderate-, and high-grade dysplasia. However, as with other pathological staging systems, the intra- and interobserver variability is too high with this many categories. Therefore, when referring to anal canal, perianal, and skin lesions of the buttock, the tissue should be classified histologically, as either normal, low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), or invasive cancer as is done in the AJCC Staging Manual.

Lymphatic drainage above the dentate line occurs via the superior rectal lymphatics to the inferior mesenteric lymph nodes and laterally to the internal iliac nodes. Below the dentate line, drainage is primarily to the inguinal nodes but may also involve the inferior or superior rectal lymph nodes.

The HPV is a necessary but not sufficient cause for the development of anal SCC and SIL. HPV is a DNA papovavirus with an 8 kb genome and is the most common viral sexually transmitted infection.

Although most patients clear the virus with only 1 % of the patients developing genital warts with low oncogenic potential (HPV serotypes 6 and 11), an estimated 10–46 % of patients develop subclinical infections that may harbor malignant potential (HPV serotypes 16, 18, 31, 33, 35).

Transmission is not prevented by condoms as the virus pools at the base of the penis and scrotum. Thus, abstinence is the only effective means of prevention. In women, the virus may pool and extend from the vagina to the anus.

Anoreceptive intercourse may be associated with the development of intra-anal disease, but the presence of condylomata or dysplasia within the anus does not indicate that anoreceptive intercourse has occurred.

Fortunately, the angiogenic changes associated with the development of anal HSIL are also visible with the aid of acetic acid and Lugol’s solution in the perianal skin, anus, and distal rectum through an operative microscope, colposcope, or loupes in the office or operating room (Fig. 20.2a–d). Targeted destruction is safe and may result in the same decrease in anal cancer incidence as was seen with cervical cancer when cervical Pap smears and targeted destruction were introduced for cervical disease.

The cost-effectiveness of anal cytology screening system to prevent anal cancer has been demonstrated using an economic model in both HIV-positive and HIV-negative men who have sex with men (MSM).

Although the association of MSM and anal cancer is clear, the association of HIV with the development and progression of anal cancer has been hard to separate from other confounding factors. Initial studies accumulating anal cancer rates from the pre-HAART (highly active antiretroviral therapy) era failed to show a correlation presumably because patients succumbed to complications of the HIV.

HPV is an indolent infection that leads to cancer in a minority of patients who generally suffer from a long-term infection. Thus, as might be expected, more recent studies reporting anal cancer rates in patients who are now surviving longer with effective HAART suggest an association with HIV and anal cancer. Supporting this association is the observed rise in anal cancer and dysplasia rates seen in HIV-positive MSM and HIV-positive heterosexual men and women who do not report anoreceptive intercourse.

Data is accumulating that suggests that as men and women live longer in the HAART era, the indolent HPV infection results in an increased risk for the development of anal cancer, and this effect is the most significant in the most immunocompromised patients.

The incidence of anal SCC has been increasing in frequency in over the last 30 years in the United States, Europe, and South America.

The distinction between Bowen’s disease and HSIL is unclear and appears to have more to do with the pathologist’s training and histopathologic versus cytopathologic terminology, than any biologic difference.

Bowen’s disease is anal SCC in situ, AIN II and III, and HSIL.

The term Bowen’s disease is applied to SCC in situ in both keratinizing and nonkeratinizing tissues. Thus, we feel the term is archaic and confusing, and should be abandoned in favor of HSIL. Throughout this chapter, we use the term HSIL to refer to what has previously been termed Bowen’s disease.

HSIL is commonly found as an incidental histologic finding after surgery for an unrelated problem, often hemorrhoids. The lesion is clinically unapparent, but histologic assessment of the specimen reveals HSIL (Fig. 20.3). Alternatively, patients may present with complaints of perianal burning, pruritus, or pain. Physical examination may reveal scaly, discrete, erythematous, or pigmented lesions (Fig. 20.4).

The natural history of HSIL is poorly defined.

As we are as yet unable to identify those patients that progress, the authors favor treatment of HSIL.

The preferred treatment is controversial and should be tailored to the given patient. An older recommendation for the unsuspected lesion found after hemorrhoidectomy is to return the patient to the operating room for random biopsies taken at 1 cm intervals starting at the dentate line and around the anus in a clocklike fashion.

A less radical approach involves taking patients to the operating room to perform high resolution anoscopy (HRA) with the aid of an operating microscope, acetic acid, and Lugol’s solution. The lesions are visualized and targeted for electrocautery destruction. Like cervical disease, the HSIL is visible because of its characteristic vascular pattern identifying the at-risk tissue for selective destruction (Fig. 20.2). This technique minimizes the morbidity of the procedure and saves the normal anal mucosa and perianal skin that would otherwise be sacrificed. Postoperative pain is significant as with any perianal procedure. HSIL identified with HRA may also simply be locally excised taking care to stay close to the lesion margin directly visualized with the operative microscope. The deep margin is kept equally close as wide local excision seems of limited benefit and increases morbidity. The resulting minimal defects heal in secondarily. High-risk patients, the immunocompromised, and patients practicing anoreceptive intercourse should be followed with Pap smears at yearly and 3 yearly intervals for the immunocompromised and immunocompetent, respectively.

Other therapeutic modalities include topical 5-fluorouracil (5-FU) cream, imiquimod, photodynamic therapy, radiation therapy, laser therapy, and combinations of the above. The reports are generally small series with limited follow-up, but there may be anecdotal success with each approach, and the options may be kept in mind for challenging cases.

SCC arises from both the perianal skin and the anal canal.

The distinction between the two locations has become more important as they are increasingly considered different entities with separate treatments and prognosis. Immunohistochemical studies of squamous cell tumors from the anal margin and anal canal demonstrate differences in expression of cadherin, cytokeratins, and p53 confirming that these tumors are of distinct histogenetic origin.

Perianal lesions are completely visible and fall within a 5 cm radius of the anal opening when gentle traction is placed on the buttocks.