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Mucosal Melanocytic Tumors
Mucosal Melanocytic Nevi
Melanocytic nevi rarely grow at mucosal sites. Mucosal nevi are most often found affecting the conjunctiva or oral mucosa. Conjunctival mucosal nevi are discussed in a separate chapter.
Oral mucosal melanocytic nevi are usually discovered during a routine intraoral exam. They are typically asymptomatic, presenting as well-defined brown macules, papules, patches, or plaques ( Fig. 24.1 ). There are limited data available on their incidence and distribution. For the oral mucosa an annual incidence of 4.35 cases per 10 million individuals has been reported for excised nevi. In another study oral melanocytic nevi accounted for 0.1% of nearly 90,000 oral biopsies over 19 years. Oral melanocytic nevi are mainly found in the hard palate and buccal mucosa, with a predilection for women.
Like cutaneous melanocytic nevi, they are clinically categorized as congenital and acquired and histopathologically classified by their microanatomic compartment of growth into junctional, compound, and submucosal nevi. There is a range of features from common “ordinary” to blue nevi, and rare nevi with spitzoid or other features. In the oral mucosa, the subepithelial (intrastromal) nevus with conventional features is the most common ( Figs. 24.2 and 24.3 ), followed by the blue nevus ( Fig. 24.4 ) and compound melanocytic nevus ( Fig. 24.5 ). Although oral mucosal melanoma may arise in association with a nevus, this is a rare event. Most oral mucosal melanocytic nevi are believed to be stable lesions with little risk for progression to melanoma. Most mucosal melanomas arise de novo. Similar diagnostic criteria apply for the distinction of an oral mucosal nevus from mucosal melanoma as for the distinction of an ordinary nevus from cutaneous melanoma. Mucosal nevi tend to be symmetric and circumscribed and show evidence of maturation.
Little has been published about melanocytic nevi at other mucosal sites. The type of melanocytic nevus, which can be seen anywhere, including visceral sites, is the blue nevus.
Mucosal Melanomas
Introduction
Most melanomas arise in cutaneous locations, but a small proportion (<2%) occur in mucosal sites, including mucosal epithelia of head and neck, anorectal region, female genital tract, urinary tract, and others. Melanocytes that give rise to mucosal melanomas may be located in the mucosal epithelium or in submucosal stroma. They are thought to have migrated to these locations during development.
Clinical Findings
Most mucosal melanomas occur in the head and neck region (31% to 55%), followed by the female genital tract (18% to 43%), anorectal region (16% to 24%), and urinary tract. Mucosal melanomas are more frequent in women and are diagnosed later (median age, approximately 70 years) than cutaneous melanomas (median age, approximately 55 years). Risk factors predisposing to the development of mucosal are not well established. This type of melanoma is not associated with exposure to ultraviolet radiation, and there does not appear to be a racial predilection its development.
Most mucosal melanomas tend to be large at the time of diagnosis. The prognosis is accordingly poor, with 5-year survival rates of approximately 25%. Several factors contribute to poor prognosis, including delayed diagnosis, more advanced stage at diagnosis, challenges facing complete surgical excision due to large size and/or difficult-to-access anatomic sites (e.g., head and neck), and the rich lymphovascular supply of mucosal surfaces that facilitates tumor dissemination. Involvement of lymph nodes, which is seen in greater than 20% of patients with mucosal melanoma, portends a more aggressive clinical course.
Histopathologic Features
Mucosal melanomas share some common histopathologic features. They usually display both intramucosal (in situ) and submucosal stromal growth (invasive melanoma). The in situ component often comprises atypical melanocytes arranged singly in a lentiginous pattern (mucosal lentiginous melanoma pattern), but in some cases it may be composed of nests of atypical melanocytes associated with pagetoid suprabasilar intraepithelial spread of melanocytes (superficial spreading melanoma pattern). Occasionally the tumor may consist entirely of an invasive nodular tumor (nodular melanoma pattern) without an associated in situ component. Furthermore, in some large tumors, a preexisting in situ component might be lost due to tumor ulceration. The invasive component may show sheetlike, solid, or nested growth patterns and may be composed of epithelioid and/or spindle cells and rarely small cells. They may be amelanotic or may contain variable amounts of melanin pigment. Multifocality and angioinvasion are frequent. Mucosal melanomas, like their cutaneous counterparts, are immunoreactive for melanocytic markers, including S100, HMB-45, MART1/Melan-A, tyrosinase, and Sox10.
Molecular Findings
Molecular genetic studies have revealed the KIT mutations and/or amplifications in a subset of mucosal melanomas (<25%), whereas BRAF mutations are seen in fewer than 10% of mucosal melanomas. This pattern is the inverse of that seen in cutaneous melanomas. KIT and BRAF inhibitors may be effective in the treatment of mucosal melanomas harboring these mutations. Recent whole-genome sequence analyses revealed that mucosal melanomas differ significantly from cutaneous melanoma, with a much lower mutation burden and dominance of structural genomic aberrations. Some mucosal melanomas have been found to carry GNAQ and SF3B1 mutations.
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