As with other anal canal tumors there is often a delay in diagnosis that results in advanced stage disease at the time of presentation. Because anorectal melanomas are rare, staging of the disease has previously been limited to local, regional, and distant disease . Most patients with such melanomas complain for bleeding, pain, or an anal mass. Digital examination provides information concerning size, fixation and ulceration of the tumor and proctosigmoidoscopy may be suggestive of anorectal melanoma when pigmentation is obvious. Anal canal melanomas present no specific clinical manifestations and due to their polypoid nature they are often misdiagnosed as a thrombosed hemorrhoid . Obviously, the inexperienced endoscopist should always have this rare pathology in mind in order to avoid misdiagnosing this lesion as a thrombosed hemorrhoid.
Endoluminal ultrasound is an established mode of evaluation of the tumor thickness and its' nodal status, but the diagnosis must always be based on the permanent sections due tendency of amelanotic types to masquerade as lymphoma, sarcoma or undifferentiated carcinoma . Immunohistochemistry may also be helpful in the diagnosis of anorectal melanomas; S 100 protein, HMB-45, Melan A, and MiTF (microphthalmia-transcription-factor) are useful immunohistochemical markers.
Metastases occur via lymphatic and hematogenous routes and it has been reported that 38% of patients have already metastatic disease at the time of diagnosis . Lymphatic spread to mesenteric nodes is more common than to inguinal nodes while lungs, liver and bones are the most frequent sites of distant metastases.
In the absence of any metastasis surgical therapy is indicated. Most series report no difference in survival in patients treated by wide local excision or abdominoperineal resection (APR) although the latter has proved more effective to control the local disease but, without clear improvement in survival [8, 9]. This is caused by the fact that most recurrences occur systemically regardless of the initial surgical procedure. However, a recent study suggests that sphincter-sparing local excision and adjuvant radiation is well tolerated and can effectively control local-regional disease while avoiding the functional morbidity of APR . The benefits of LE are clear and include quicker recovery from a less invasive procedure, minimal impact on bowel function, and no need for a stoma. Prophylactic lymph node resection is of no value whereas therapeutic lymph node dissection is indicated only in the presence of positive inguinal nodes.
Introducing sentinel lymph node mapping (SLNM) using different radioactive tracers and endoscopic ultrasonography in recent years has influenced the extent of surgical resection. Few case reports on the use of SLNM in anal melanoma have been reported . Although SLNM and biopsy in anal melanoma has not yet become a standard of care, it is technically feasible as reported in these case reports. SLNM seems to be helpful in preventing understaging patients who are pathologically node-positive but clinically node-negative. Long-term follow-up of the impact of the possible finding of micrometastases is needed.
In rare cases of anorectal melanomas which tend to block the anal orifice, palliative surgical treatment is indicated . In severely ill patients unable to tolerate any surgical procedure, intramural injections of natural interferon-beta and systemic administration of dacarbazine has been proposed with good results . No systemic therapy regimen for metastatic anal melanoma is considered standard of care. Treatment is based on drugs developed for advanced cutaneous melanoma and includes cisplatin, vinblastine, dacarbazine, INF, and interleukin-2, although given the clinical, biologic, and molecular differences, mucosal and cutaneous melanomas may be distinct disease entities . After temozolomide has shown efficacy comparable to dacarbazine in a randomized trial of cutaneous melanoma, a combination of temozolomide, cisplatin, and liposomal doxorubicin in one patient with metastatic anal melanoma was used with encouraging results .
The presence of perineural invasion (PNI) is an important prognostic factor and should be considered in future clinical trials . Notably, tumor thickness seems to be a strong predictive factor for the risk of local recurrences. Anorectal melanoma seems to be similar to cutaneous melanoma, for which tumor thickness is used to plan therapeutic procedures. Hence, for anorectal melanoma tumor thickness may also be used as a guideline, i.e. in early disease with a tumor thickness below 1 mm a local sphincter-saving excision with a 1-cm safety margin and in cases of tumor thickness between 1 and 4 mm a local sphincter-saving excision with a safety margin of 2 cm seems to be adequate . Tumors with thickness above 4 mm should be treated with APR to avoid local complications; even so, there will be a stoma and the risk of urinary and sexual dysfunction .
Nevertheless, despite sporadic promising reports, regardless of surgical approach, anorectal melanoma remains a highly lethal malignancy with overall 5-years survival rate less than 20% according to all reported series .
Regarding our case, there has been a long debate regarding the extent of resection, which was necessary to optimally treat the melanoma. APR procedure, based on the clinicopathological features of the tumor was preferred, although the benefits of LE are clear. The need for regional lymphadenectomy has been at the center of the debate. During APR, mesorectal lymph nodes are resected en bloc with the primary tumor. Although the patient's outcome was poor, we were able to identify risk factors associated with survival and prognosis. Clinical symptoms, PNI, tumor thickness and diameter, spindle cell histology, mural involvement and necrosis may ultimately impact outcome. Finally, we hypothesized that systemic dissemination is an early event in tumorigenesis and by the time the lesion is clinically apparent, micrometastases are well established.