Squamous Cell Carcinoma of the Anal Margin

William M. Mendenhall, MD
Professor of Radiation Oncology
University of Florida College of Medicine
Gainesville, Florida, USA

Squamous cell carcinoma of the anal margin is defined as a lesion originating between the anal verge and the outer limit of the perianal skin, which is defined as 5 cm from the anal verge in any direction. These lesions represent about one fourth to one third of all squamous cell carcinomas of the anus and should be distinguished from squamous cell carcinoma of the anal canal, which has a different natural history and a less favorable prognosis. Patients with anal margin carcinomas are usually 60 years to 70 years of age; range actually is quite wide (25 to 90 years). Although some authors have observed a slight female preponderance, others have reported that the disease is more likely to occur in men.

Presenting symptoms usually include bleeding, pain, and a palpable mass. Less frequently, patients may complain of a change of bowel habits, discharge, and pruritus ani. Median duration of symptoms is approximately 6 months with a range of 2 months to 60 months. Chronic fistulae and condylomata are observed in approximately 15% of patients. An erroneous diagnosis is made at first visit in less than one third of patients compared with slightly over half of those presenting with squamous cell carcinoma of the anal canal. The vast majority of tumors tend to be well differentiated or moderately differentiated keratinizing squamous cell carcinomas; fewer than 10% of anal margin carcinomas are poorly differentiated.

The primary cancer usually starts as a slow-growing nodule that remains localized to the perianal skin until late in the course of the disease, when it may extend into the anal canal. The lesion usually is ulcerated and may have a significant palpable subcutaneous component. The sphincter muscle usually is not invaded. The distribution of primary tumor size varies depending on referral patterns. Approximately 15% of patients have T1 lesions, 50% have T2 lesions, approximately one third have T3 lesions, and the remainder have T4 lesions.

The first-echelon lymph node drainage for the anal margin is the medial inguinal lymph nodes, although the iliac nodes occasionally may be involved. The incidence of inguinal lymph node involvement is approximately 15% to 25% and is related to the size and histological differentiation of the primary cancer. The risk of positive inguinal nodes is less than 10% for carcinomas smaller than 2 cm in diameter, approximately 20% to 25% for those ranging from 2 cm to 5 cm diameter, and over 50% for those that are 5 cm or larger in size. Distant metastases at presentation are rare.

The cancers are staged according to either the American Joint Committee on Cancer (AJCC) staging system or the International Union Against Cancer (UICC). The AJCC staging system for the primary tumor is as follows: T1, tumor 2 cm or less in greatest diameter; T2, tumor greater than 2 cm but no more than 5 cm in diameter; T3, tumor more than 5 cm in greatest diameter; T4, tumor invades deep extradermal structures such as skeletal muscle, bone, cartilage, or nerve. The regional lymph nodes are staged as either N0 if no regional lymph node metastases are present or N1 if regional lymph node metastases are present.

Pretreatment evaluation of the patient should take into account the patterns of the disease spread and include a chest radiograph and computed tomography (CT) of the abdomen and pelvis. CT is obtained to evaluate the presence and extent of lymph node metastases, to exclude the unlikely possibility of liver metastases, and to complement the physical examination of the primary malignancy.

The goal of treatment is to cure the patient while preserving anal function, thus avoiding a permanent colostomy. Traditionally, the treatment consisted of either local excision or, in advanced cases, abdominoperineal resection. In recent years, a few centers have reported promising results with radiation therapy alone or radiation therapy combined with concomitant chemotherapy. Currently, early lesions that may be successfully treated with local excision are managed surgically. A skin graft may be necessary if the surgical defect cannot be closed primarily or healed by secondary intention. An abdominoperineal resection is not indicated unless the lesion has been treated with radiation therapy or radiation and chemotherapy, and recurred after treatment.

Patients with lesions that are not suitable for a limited surgical excision undergo radiation therapy. Superficial, well-differentiated T1 and early T2 cancers may be irradiated through a perineal field using either 60Co or electron beam. The inguinal lymph nodes should be electively irradiated for patients with T2 cancers and probably for those with poorly differentiated T1 lesions. The pelvic lymph nodes also are irradiated, in addition to the inguinal lymph nodes, for patients with advanced T3 and T4 primary cancers. The dose-fractionation schedule for the primary lesion is approximately 60 Gy in 33 fractions in a continuous course.If elective regional node irradiation is indicated, the dose to the clinically negative nodes is 45 Gy in 25 fractions over 5 weeks. Clinically positive nodes are treated to essentially the same dose that the primary lesion receives. Patients with T1 and T2 cancers are treated with radiation therapy alone. Those with T3 and T4 lesions receive concomitant chemotherapy, using a schedule that is essentially the same as the protocol employed for patients treated for squamous cell carcinoma of the anal canal. This consists of 2 cycles of fluorouracil and mitomycin or, in some instances, fluorouracil and cisplatin.

The probability of local control is related to T stage and is > 80% for T1 and T2 cancers and 50% to 70% for T3 and T4 malignancies. The probability of severe complications, which depends on T stage and whether adjuvant chemotherapy is employed, is less than 5% for T1 and T2 cancers and 5% to 10% for more advanced lesions.

Published October 2000