Background:

Pigmented entities are relatively common in the oral mucosa and arise from intrinsic and extrinsic sources. Conditions such as melanotic macules, smoker’s melanosis, amalgam and graphite tattoos, racial pigmentation, and vascular blood-related pigments occur with some frequency. Addison disease and Peutz-Jeghers syndrome also appear in perioral and oral locations as pigmented macules. Oral pigmentations may range from light brown to blue-black, red, or purple. The color depends on the source of the pigment and the depth of the pigment from which the color is derived. Melanin is brown, yet it imparts a blue, green, or brown color to the eye. This effect is due to the physical properties of light absorption and reflection described by the Tyndall light phenomenon or effect. Oral conditions with increased melanin pigmentation are common; however, melanocytic hyperplasias are rare. Clinicians must visually inspect the oral cavity, obtain good clinical histories, and be willing to perform a biopsy in any condition that is not readily diagnosed. Patients with oral malignant melanoma often recall having an existing oral pigmentation months to years before diagnosis, and the condition may even have elicited prior comment from physicians or dentists.

Pathophysiology:

Oral melanomas are uncommon, 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 constantly is exposed. Although benign, intraoral melanocytic proliferations (nevi) occur and are potential sources of some oral melanomas; the sequence of events is poorly understood in the oral cavity. Currently, most oral melanomas are thought to arise de novo.

Although rare, tumor 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 (Elder et al) have stated that these different growth patterns require cellular alteration or transformation to progress to the next, more biologically aggressive phase. Radial growth phase–melanomas do not tend to invade the underlying reticular dermis, but they are associated with metastasis. Vertical growth phase–melanomas, though 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. However, phase progression is not absolute because most benign melanocytic lesions do not evolve into melanoma. Melanoma development requires a 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 oral mucosal melanomas.

Rates of occurrence:

  • U.S. Surveillance data are not available for oral melanoma alone. Data for oral melanoma are included in the combined statistics for oral cancer. In a review of the large studies, melanoma of the oral cavity is reported to account for 0.2-8% of melanomas and approximately 1.6% of all malignancies of the head and neck. In some studies, primary lesions of the lip and nasal cavity also are included in the statistics, thereby increasing the incidence.

  • The oral mucosa is primarily involved in fewer than 1% of melanomas, and the most common locations are the palate and maxillary gingiva. Metastatic melanoma most frequently affects the mandible, tongue, and buccal mucosa.

    In contrast to the incidence of cutaneous melanoma, the incidence of oral melanoma has remained stable for more than 25 years.

  • Internationally, oral melanoma is more common in the Japanese than in other groups. In Japan, oral melanomas account for 11-12.4% of all melanomas, and males may be affected slightly more often than females. This percentage is higher than the 0.2-8% reported in the United States and Europe. Because cutaneous melanoma is less common in more darkly pigmented races, people of these races have a greater relative incidence of oral mucosal melanoma.

    The prevalence of oral melanoma in the Japanese population is somewhat controversial. Authorities state that, as with cutaneous melanoma, oral mucosal melanomas are more common in whites than in other groups.

Mortality/Morbidity:

Oral melanoma often is overlooked or clinically misinterpreted as a benign pigmented process until it is well advanced. Radial and vertical extension is common at the time of diagnosis. The anatomic complexity and lymphatic drainage of the region dictate the need for aggressive surgical procedures.

  • The prognosis is poor, with a 5-year survival rate generally in the range of 10-25%. The median survival is less than 2 years. As a result of the absence of corresponding histologic landmarks in the oral mucosa (ie, papillary and reticular dermis), Clark levels of cutaneous melanoma are not applicable to those of the oral cavity. Conversely, tumor thickness or volume may be a reliable prognostic indicator.
  • The relative rarity of mucosal melanomas has dictated that tumor staging be based on the broader experience with cutaneous melanoma. Oral melanomas seem uniformly more aggressive and spread and metastasize more rapidly than other oral cancers or cutaneous melanomas. Early recogn