ReviewPrimary mucosal melanoma
Section snippets
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
References (44)
- et al.
Mucosal melanomas
Surg Clin North Am
(2003) - et al.
Clinical radiobiology of malignant melanoma
Radiother Oncol
(1989) Oral mucosal pigment secondary to minocycline therapy
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
(2004)- et al.
Mucosal melanoma of the female genitalia: a clinicopathologic study of forty-three cases at Duke University Medical Center
Surgery
(1998) - et al.
Vulvar melanoma: a report of 20 cases and review of the literature
J Am Acad Dermatol
(2004) Malignant melanoma of the vulva and vagina in the United States
Am J Obstet Gynecol
(1994)- et al.
Vulvovaginal melanoma
Gynecol Oncol
(1989) - et al.
Vulvar melanoma: diffuse melanosis and metastasis to the placenta
J Am Acad Dermatol
(2004) - et al.
Malignant melanoma of the genitourinary tract
J Urol
(1984) - et al.
The national cancer data base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons commission on cancer and the American Cancer Society
Cancer
(1998)
Mucosal melanomas
The presence of melanocytes in the human larynx
Laryngoscope
The number of melanocytes in the human epidermis
Br J Med
Quantitative histologic investigation of the melanocyte system of the human epidermis: pigment cell biology
The morphology and quantitative distribution of dopa-positive melanocytes in the gingival epithelium of Caucasians
Oral Surg
The presence of melanocytes in the nasal cavity
Ann Otol
Mucosal malignant melanomas
Am J Surg
Malignant mucosal melanoma of the head and neck: review of the literature and report of 14 patients
Cancer
Malignant melanoma of the nasal cavity and paranasal sinuses
Arch Otolaryngol
Mucosal melanoma of the head and neck
Am J Surg
Distinct sets of genetic alterations in melanoma
N Engl J Med
Anorectal melanoma
Cancer
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2023, Melanoma Research
Funding sources: None.
Conflicts of interest: None declared.