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Primary mucosal melanoma

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Primary mucosal melanomas are rare, biologically aggressive neoplasms. The distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites is 55.4%, 18.0%, 23.8%, and 2.8%, respectively. The median age at presentation is the seventh decade, and women are given the diagnosis more frequently than men. Unfortunately, most afflicted individuals harbor micrometastatic disease and experience a course characterized by multiple local recurrences before the clinical development of distant disease. Approximately a third of patients have nodal involvement at presentation, and the overall 5-year survival is only 25%. Despite aggressive surgical resection and a multitude of adjuvant treatments, the prognosis remains grave. Early detection, which is difficult because of the occult anatomic locations in which these tumors occur, allows the best hope for cure.

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Epidemiology

Mucosal melanoma remains a rare disease, accounting for 0.03% of all new cancer diagnoses. According to the National Cancer Data Base Report on Cutaneous and Noncutaneous Melanoma, cutaneous melanoma comprises 91.2% of all melanoma, whereas ocular, mucosal, and unknown primaries account for 5.2%, 1.3%, and 2.2% of cases, respectively. Mucosal melanoma is most common in the head and neck (55.4% of cases), with female genital tract, anal/rectal, and urinary tract sites responsible for 18.0%,

Pathogenesis

The etiopathogenesis of mucosal melanomas is not yet fully elucidated. As neuroectodermal derivatives, melanocytes are known to migrate to the skin, retina, uveal tract, and other ectodermally derived mucosa. Melanocytes migrate much less frequently to endodermally derived mucosa, such as the nasopharynx, larynx, tracheobronchial tree, and esophagus.3 This explains the lower frequency of melanoma in these locations.

Although their function is not fully understood, the presence of melanocytes in

Diagnosis

Differentiating a primary mucosal melanoma from a metastasis of an unknown or regressed cutaneous tumor can be diagnostically challenging. Reliable clinical findings include the presence of a precursor lesion such as melanoma in situ in the mucosa.8 Unfortunately, these features are typically absent, given the delayed diagnosis and presence of secondary changes such as ulceration. When biopsying these lesions for pathologic diagnosis, it is imperative to include a rim of normal-appearing

Staging

In general, the growth of mucosal melanoma closely resembles the nodular pattern of its cutaneous counterpart. This characteristic, in part, explains the poor prognosis of these lesions, and several studies have corroborating data that link survival most closely with tumor thickness. Patients with lesions less than 2-mm thick have a significant survival advantage over those with lesions greater that 2 mm.13 Because of the typical delay in diagnosis, the vast majority of mucosal melanomas

Diagnostic workup

When a mucosal melanoma is diagnosed, there is frequently debate among clinicians concerning the extent of workup necessary to exclude metastatic melanoma, either as the source of the mucosal lesion or from the mucosal primary itself. Certainly, when a mucosal melanoma is detected, a total body skin examination is paramount to rule out a primary cutaneous melanoma that has metastasized. To evaluate the primary site, a computed axial tomography scan or magnetic resonance image may help determine

Head and neck

Primary mucosal melanomas of the head and neck comprise 55% of all mucosal melanomas.1 These tumors arise most frequently in the nasal cavity (55% of reported cases), followed by the oral cavity (40%).9, 15 As with most mucosal melanomas, those in the sinonasal region typically affect the elderly, with a mean age of onset of 70 years. Oral melanomas, on the other hand, tend to occur at a younger age than their sinonasal counterparts, with most afflicted individuals younger than 40 years.18 The

Differential diagnosis of pigmented oral lesions

Mucosal melanomas in the oral cavity can be confused with several benign lesions. Melanosis is an extremely common benign pigmentation of the attached gingiva, especially among African Americans. Based on its location, bilaterality, and symmetry, melanosis may be differentiated clinically from malignancy. Oral nevi are only present in 0.1% of the general population. Intramucosal nevi account for 55%, blue nevi for 36%, and junctional nevi for 3%. Because some investigators have suggested that

Larynx/pharynx

Primary mucosal melanoma of the larynx and pharynx is exceedingly rare. Only 10 cases of laryngeal melanomas have been reported. Most laryngeal melanomas occur in the supraglottic region.18 The 5-year survival for patients with pharyngeal melanoma is only 13%.10, 11, 26

Esophagus

Approximately 200 cases of esophageal mucosal melanoma have been described. Dysphagia, weight loss, and hematemesis are common presenting symptoms. The origin of these tumors is thought to be related to the embryologic migration of melanocytes down the upper two thirds of the esophagus.31 As the majority of patients present with disseminated disease, radical resections with nodal dissections have not improved the average survival time of 7.5 months.16, 20

Female genital tract

Primary mucosal melanomas of the female genital tract account for 18% of all mucosal melanomas and 3% of melanomas diagnosed in women.1 Usually affecting postmenopausal women between 60 and 70 years of age, approximately 500 cases have been reported to date. Vulvar melanomas, which are the second most common vulvar malignancy, greatly outnumber vaginal melanomas. Primary cervical and uterine melanomas are much more rare, with only 15 case reports in the literature. Presenting symptoms are

Anal/rectal

Primary mucosal melanomas of the anorectum account for 24% of all mucosal melanomas and less than 1% of malignant tumors of this site.1 Presenting symptoms include pain, rectal bleeding, and the presence of a large ulcerated, polypoid mass. Up to 30% of lesions may be amelanotic and, thus, unrecognized until an advanced mass develops.20 Most anorectal mucosal melanomas are believed to arise from the transitional zone of the anal canal, where melanocytes are present in the highest numbers.20

Urinary tract

Accounting for only 3% of all mucosal melanomas, melanomas of the urethral mucosa are an extremely rare entity. To date, 25 cases in male patients and 40 cases in female patients have been reported.44 Of all genitourinary sites, the penis is most commonly affected, but the vast majority of these cases are cutaneous.

Among male patients, the most common presenting symptoms include hematuria, dysuria, and the presence of a black lesion. The distal urethra is the most frequent site, followed by the

Conclusion

Primary mucosal melanomas are exceedingly rare and biologically aggressive malignancies. Unlike cutaneous melanomas, the occult locations in which mucosal melanomas occur preclude sun exposure as a predisposing risk factor. The relatively inaccessible and various locations in which these tumors arise also make consistent early screening difficult. Although the majority of patients present with clinically localized disease, the thickness and growth pattern of the primary tumors at diagnosis

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