What is the pathophysiology of oral malignant melanoma?

Updated: Jan 31, 2020
  • Author: Elizabeth Ann Bilodeau, DMD, MD, MSEd; Chief Editor: Jeff Burgess, DDS, MSD  more...
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Oral melanomas are uncommon (1.2 cases per 10 million population per year in the United States), and, similar to their cutaneous counterparts, they are thought to arise primarily from melanocytes in the basal layer of the squamous mucosa. Melanocytic density has a regional variation. Facial skin has the greatest number of melanocytes. In the oral mucosa, melanocytes are observed in a ratio of about 1 melanocyte to 10 basal cells.

In contrast to cutaneous melanomas, which are etiologically linked to sun exposure, risk factors for mucosal melanomas are unknown. These melanomas have no apparent relationship to chemical, thermal, or physical events (eg, smoking; alcohol intake; poor oral hygiene; irritation from teeth, dentures, or other oral appliances) to which the oral mucosa is constantly exposed. Although benign, intraoral melanocytic proliferations (nevi) occur and are potential sources of some oral melanomas (see the following image); the sequence of events is poorly understood in the oral cavity. Currently, most oral melanomas are thought to arise de novo.

Photo from a male Japanese patient with extensive, Photo from a male Japanese patient with extensive, black-pigmented and irregularly bordered macule in the maxillary labial mucosa and midline facial gingiva, (teeth 8 and 9). (The patient's fingers are depicted.) The diagnosis is oral melanoma. Courtesy Dr Bob Goode, Tufts University.

Although rare, malignant transformation of nevi to melanoma involves the clonal expansion of cells that acquire a selective growth advantage. This transformation of melanocytes in an existing nevus, or of single melanocytes in the basal cell layer, must occur before the altered cells proliferate in any dimension.

In cutaneous melanomas, well-known differences exist in the biologic behaviors of the radial growth phase–melanoma (flat or macular), vertical growth phase–melanoma (mass, nodule, elevation), and vertical growth phase–melanoma with metastasis. Some authorities have stated that these different growth patterns require cellular alteration or transformation to progress to the next, more biologically aggressive phase. [1] Radial growth phase–melanomas do not tend to invade the underlying reticular dermis, but they are associated with metastasis. Vertical growth phase–melanomas, although invasive, must achieve some competence before subsequent metastasis can occur.

Elder et al have described this progression and state that differences in each phase are qualitative. [1] However, phase progression is not absolute, because most benign melanocytic lesions do not evolve into melanoma. Melanoma development requires a cytogenetic or biochemical alteration in the precursor cells undergoing clonal expansion. This alteration triggers accelerated growth and invasive potential, but not necessarily progression from horizontal to vertical growth phases.

The oral mucosa has an underlying lamina propria, not a papillary and reticular dermis with easily discernible boundaries as observed in skin. This architectural difference obviates the use of Clark levels for describing mucosal melanomas. The term melanoma in situ, once reserved for a cutaneous melanoma that had not breached the basement membrane zone, is now used for mucosal lesions confined to the epithelium (although some authorities prefer the term melanocytic intraepithelial neoplasia for both the cutaneous and mucosal lesions). See Staging.

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