eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa

Oral Malignant Melanoma

Author: Bobby Collins II, DDS, MS, Associate Professor of Oral and Maxillofacial Pathology, Department of Diagnostic Sciences, University of Pittsburgh School of Dental Medicine
Coauthor(s): E Leon Barnes Jr, MD, Professor of Pathology and Professor of Otolaryngology, University of Pittsburgh School of Medicine; John Abernethy, MD, Winston-Salem, North Carolina
Contributor Information and Disclosures

Updated: Mar 21, 2008

Introduction

Background

Pigmented entities are relatively common in the oral mucosa and arise from intrinsic and extrinsic sources. Conditions such as melanotic macules, nevi, 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.

The following related eMedicine articles may be helpful:

• Nevi of Ota and Ito
• Nevi, Melanocytic
• Smoker's Melanosis
• Disorders of Oral Pigmentation
• Addison Disease
• Peutz-Jeghers Syndrome

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 explainable or 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 (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 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, 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 authorities¹ 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 al¹ 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 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).

Frequency

United States

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.

A critical review of the literature by Hicks and Flaitz² found that the vast majority of melanomas occur on the skin (91.2%), ocular melanomas account for 5.3%, unknown primary lesions account for 2.2%, and melanomas of the mucous membrane account for 1.3%.

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

In contrast to the incidence of cutaneous melanoma, which continues to rise, the incidence of oral melanoma has remained stable for more than 30 years.

International

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.³ 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.

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. However, 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 recognition, diagnosis, and treatment, that being assured surgical removal, greatly improves the prognosis.
• In one large study (1074 mucosal melanomas), when lymph node status was known, 30% of patients with mucosal melanomas had positive nodes. When lymph node metastasis occurs, the prognosis worsens precipitously. For instance, the 5-year survival rate in patients with positive nodes is 16.4% as opposed to 38.7% in patients with negative nodes.

Race

• Oral melanoma reportedly occurs more commonly in the Japanese than in other groups. This observation is based on a review of frequently cited historical literature. Oral malignant melanoma, although rare in whites, is still a major cause for concern.
• A separate categorization of "oral mucosal melanoma" in the cancer surveillance data reported in the United States and by the World Health Organization would be useful in clarifying race and gender prevalence. Until it is, statistics will continue to be derived from case reports and review articles that reflect the observation and opinion of those authors.

Sex

• A male predilection exists, with a male-to-female ratio of almost 2:1. Oral melanoma is diagnosed approximately a decade earlier in males than in females.
• This ratio is contrasted with the roughly equal gender distribution of cutaneous melanoma. In Japan, data suggest an equal or slight male predilection.

Age

Oral malignant melanoma is largely a disease of those older than 40 years, and it is rare in patients younger than 20 years.

• The average patient age at diagnosis is 56 years.
• Oral malignant melanoma is commonly diagnosed in men aged 51-60 years, whereas it is commonly diagnosed in women aged 61-70 years.

Clinical

History

• Oral melanomas arise silently, with few symptoms until progression has occurred.
• Most people do not inspect their oral cavity closely, and melanomas are allowed to progress until significant swelling, tooth mobility, or bleeding causes them to seek care.
• Pigmented lesions 1.0 mm to 1.0 cm or larger are found.
• Reports of previously existing pigmented lesions are common. These lesions may represent unrecognized melanomas in the radial growth phase.
• Amelanotic melanoma accounts for 5-35% of oral melanomas.
  • This melanoma appears in the oral cavity as a white, mucosa-colored, or red mass.
  • The lack of pigmentation contributes to clinical and histologic misdiagnosis. However, the presence of a lymphocytic infiltrate is helpful histopathologically.

Physical

• Because oral malignant melanomas are often clinically silent, they can be confused with a number of asymptomatic, benign, pigmented lesions.
• Oral melanomas are largely macular, but nodular and even pedunculated lesions occur.
• Pain, ulceration, and bleeding are rare in oral melanoma until late in the disease.
• The pigmentation varies from dark brown to blue-black; however, mucosa-colored and white lesions are occasionally noted, and erythema is observed when the lesions are inflamed.
• The palate and maxillary gingiva are involved in approximately 80% of patients, but buccal mucosa, mandibular gingiva, and tongue lesions are also identified.
  • The oral mucosa is primarily involved in less than 1% of melanomas.
  • Metastatic melanoma most frequently affects the mandible, tongue, and buccal mucosa.
• Features of long-standing lesions include elevation, color variegation, ulceration, and satellite lesions that may have the appearance of physiologic pigmentation.
• A neck mass may be present, indicating regional metastasis; however, this is rare unless the primary tumor is extensive.

Causes

• The cause of oral melanoma or melanoma of any mucosal surface remains unknown, and the incidence has remained stable for more than 25 years. In contrast, cutaneous lesions are linked directly to fair-skinned and blue-eyed persons with a history of blistering sunburns, and incidence has increased dramatically (approximately 4-6% per year) over the same period.
• The predilection for occurrence in the palate remains a mystery.
  • No link has been established with denture wearing, chemical or physical trauma, or tobacco use.
  • Melanocytic lesions, such as blue nevi, are more common on the palate.
  • Oral blue nevi are not reported to undergo malignant transformation.

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