Anal Melanoma and Basal Cell Cancer of the Perianal Region

Introduction

Anorectal melanoma is a rare disease with a poor prognosis. It can be found anywhere in the anal canal or distal rectum and can spread anywhere in the body. Standard chemotherapy and radiation options are not effective, and thus surgery is the primary treatment. Debate is ongoing about whether the treatment of choice is local excision or radical resection.

Epidemiology and Risk Factors

Anorectal melanoma represents approximately 0.5% of all anal malignancies and accounts for 0.3% of all melanomas, making it the second most common site for mucosal-based melanoma after the head and neck. However, mucosal melanomas represent only 1.2% of all melanomas, with cutaneous melanoma accounting for the majority. The average age at diagnosis of anorectal melanomas is approximately 60 to 70 years, with males presenting at a slightly younger age. Females are more commonly affected than males with a ratio of 1.7:1. It is estimated that 1 in 1.7 million Americans will be diagnosed with anorectal melanoma. Unlike in cutaneous melanomas, exposure to ultraviolet-B radiation and a Caucasian background are not risk factors. A review from 1999 reported an indirect link to human immunodeficiency virus disease. This link was inferred mainly from a spike in the disease in the 1980s and 1990s in young males from San Francisco. These intriguing results have not been followed up.

Pathophysiology

Anal melanoma develops from the melanocytes found in the anal transition zone. Mutations in KIT are more commonly seen in mucosal than in cutaneous melanoma, which might play a role in future adjuvant therapies.

The disease is most commonly seen in the anal canal at or below the dentate line. However, up to 35% of tumors are found in the distal rectal mucosa. Rectal lesions tend to be more advanced than their anal counterparts. Anorectal melanoma is aggressive and penetrates the muscularis in 79% of cases. Approximately 20% of patients present with lymphatic involvement and 7% to 25% present with metastases. Disseminated disease develops in 90% of patients with nodal disease. The most common site of metastatic involvement is the liver. Other common sites include the lungs, bone, and brain.

Clinical Presentation and Diagnosis

The most common symptom associated with anorectal melanoma is bleeding. An anal mass, tenesmus, and pain are other frequent sequelae. Melanomas are often misdiagnosed as hemorrhoids because they share the same symptom profile. The rate of missed diagnosis is 55%, which can lead to a delay in treatment. Approximatey 25% of melanomas are amelanotic, which also contributes to the difficulty in diagnosis. Anorectal melanoma is rarely found incidentally in hemorrhoidectomy specimens. Workup includes a biopsy of the tumor along with a colonoscopy and computed tomography scans of the brain, chest, abdomen, and pelvis. Magnetic resonance imaging scans of the pelvis and positron emission tomography scans can be helpful but are not routinely necessary.

TNM staging for anorectal melanoma has not been developed, given its rarity. The following simple staging system has been used since the 1970s: stage I, local disease; stage II, regional lymph node spread; and stage III, disseminated disease. A recent article has suggested that this system should be amended to a four-stage system (stage I, local disease not in the muscularis; stage II, local disease into the muscularis; stage III, regional lymph node spread; and stage IV, disseminated spread) because patients with deeper local disease have been found to have a worse prognosis.

Surgery

Management of the Primary Tumor

The surgical management of anorectal melanoma often occurs in the context of widely metastatic disease. Lymph node metastases may involve the mesenteric, pelvic/iliac, and inguinal nodes, and distant metastasis occurs in 90% of affected patients. The variable biological drainage and the potential for synchronous involvement of multiple nodal regions has led to a shift in the classic paradigm for the surgical management of anorectal melanoma.

Historically, it was believed that patients with anorectal melanoma were optimally managed with a radical abdominoperineal resection (APR). This approach has never been prospectively studied. Therefore, as a result of the high morbidity of this procedure (including a permanent colostomy, infection, hernia, and sexual and urinary dysfunction) and the lack of documented survival benefit, a focus on wide local excision (WLE) has increased. Multiple single-center retrospective review studies and a review of 17 of these case series were unable to find a survival benefit for patients who underwent an APR compared with those who had a WLE. According to a recent Surveillance, Epidemiology, and End Results (SEER) database review of 143 patients undergoing curative surgery, 60% presented with localized disease, 19% with concurrent regional lymph node metastasis, and 21% with synchronous distant metastasis. The 5-year survival rate was 26.7%, 9.8%, and 0%, respectively. No survival advantage was observed for patients treated with WLE compared with APR. The authors concluded that the extent of surgical resection does not correlate with survival. Lymph node status at presentation is significant for its prognostic value.

With regard to local control, most groups have identified equivalent rates of local recurrence between patients managed with WLE and APR ( Table 14-1 ). Although some authors have found an increased rate of local recurrence in patients treated with WLE, disease-free survival is mostly affected by systemic metastasis. Although APR has a role for large and/or circumferential tumors, when technically feasible, WLE is generally recommended.

TABLE 14-1

Clinical Series of Anorectal Melanoma

Author	Year	No. of Patients	Treatment	Results	Comments
Ballo et al	2002	23	WLE + RTx, 23	5-yr overall survival, 31%; DSS, 36%; DFS, 37%; 5-yr local control, 74%; 5-yr regional control, 84%	WLE + RTx well tolerated and controlled local-regional disease while avoiding the morbidity of an APR
Pessaux et al	2004	30	WLE, 21; APR, 9	5-yr overall survival: WLE, 16%; APR, 33% ( P = NS)	WLE is recommended if a negative resection margin can be obtained
Droesch et al	2005	301 (review of 14 studies)	WLE, 129; APR, 172	Local recurrence: WLE, 47%; APR, 23% Median survival: WLE, 21 mo; APR, 17 mo	No stage-specific survival advantage for APR; WLE should be considered the initial choice of treatment
Yeh et al	2006	46	WLE, 27; APR, 19	Local recurrence: WLE, 26%; APR, 24% 5-year DSS: WLE, 35%; APR, 34%	Local excision should be offered when technically feasible
Ramakrishnan	2008	8	WLE, 5; APR, 3	Median overall survival (mo): WLE, 12; APR, 10 Local recurrence: WLE, 80%; APR, 0%	WLE with adjuvant radiation therapy for small, superficial tumors; APR for locally advanced disease or salvage for recurrence
Kiran et al	2010	109 (SEER database)	WLE, 60; RR, 49	Median survival: WLE, 28 mo; RR, 17 mo ( P = .3) Survival for RR with localized disease similar to patients who underwent WLE	Survival is similar after WLE or RR irrespective of whether patients have localized or regional stage of disease
Che et al	2011	56	WLE, 20; APR, 36	Local recurrence: WLE, 69%; APR, 16% Median survival: WLE, 21 mo; APR, 22 mo	Surgical method of treatment does not affect prognosis; depth of invasion is an independent prognostic factor influencing survival