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| Year : 2008 | Volume
: 19
| Issue : 1 | Page : 47-51 |
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| Malignant melanoma of the oral cavity: A review of literature |
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MS Hashemi Pour
Department of Oral Medicine, Faculty of Dentistry, Kerman University of Medical Sciences, Kerman, Iran
Click here for correspondence address and email
| Date of Submission | 20-May-2007 |
| Date of Decision | 11-Jun-2007 |
| Date of Acceptance | 12-Jun-2007 |
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 Abstract | | |
Oral malignant melanoma is a rare aggressive neoplasm of the middle age. This malignancy commonly affects male subjects and is more frequently seen at the level of the hard palate and gingiva. At present, the clinicopathological classification of oral melanoma is not yet clearly outlined; consequently, the skin form is often taken as a reference. In many cases (up to 30%), the diagnosis of melanoma is made on lesions, which have evolved from the pre-existing pigmented lesions. The poor prognosis of oral melanomas requires that pigmented lesions of undetermined origin be routinely biopsied. The surgical approach, combined with the chemotherapeutic one, is the first choice treatment. The purpose of this study is to review literature that has been published about malignant melanoma of the oral cavity.
Materials and Methods: Thirty-eight published articles and 8 textbooks related to oral malignant melanoma and been published in the last two decades are reviewed.
Conclusion: The review of literature in the field of malignant melanoma of the oral cavity show that this malignancy might be different from cutaneous malignant melanomas, and new criteria for diagnosis and therapy should be considered for this disease. Physicians and dentists who treat problems of the oral cavity should be aware of the need for early diagnosis of oral melanomas and performing biopsies of doubtful pigmented lesions. Keywords: Malignant oral, melanoma
How to cite this article:
Hashemi Pour M S. Malignant melanoma of the oral cavity: A review of literature. Indian J Dent Res 2008;19:47-51 |
Melanocytes in skin provide a protective function against the harmful effects of sun exposure. The function of melanocytes in mucosa is unknown. In oral mucosa, melanocytes are located along the tips and peripheries of the rete pegs. Melanocytes in single tissue sections are found in the gingiva with a ratio of 1 melanocyte to 15 keratinocytes. Melanocytes, nevus cells, and melanoma cells differ markedly in their cytologic appearance, organization, and biologic characteristics. Nevus cells lack cytologic atypia, pleomorphism, and rarely have mitotic activity. Melanoma cells retain some features of nevus cells, such as lack of dandritic processes, round to spindled shape, and loss of contact inhibition. These malignant cells possess considerable pleomorphism, with large, irregular hyperchromatic nuclei, prominent nucleoli, and have readily detectable mitotic activities. [1]
The incidence of melanoma has been steadily increasing in the past several decades. This increased frequency of newly diagnosed melanomas has been observed worldwide and is of the order of 3-8% in a year. This increase in the incidence of melanoma has been sustained over time. In the United States in 1935, the lifetime risk of an invasive melanoma developing was only 1 in 500; in 1960, 1 in 600; in 1992, 1 in 105; in 1996, 1 in 88, and the lifetime risk would be 1 in 75 by the year 2000. [2]
Melanoma could infrequently arise from mucosal surfaces. The most common sites are the mucosal surfaces of the head and neck (typically involving the nasal and oral cavity), vulva, and anorectal mucosa. [2],[3] Head and neck mucosal melanomas are much less common than their cutaneous counterparts and probably represent less than 1-8% of all melanomas. [3],[4],[5],[6],[7],[8],[9],[10],[11]
| Epidemiology | |  |
Oral melanoma is rare, and incidence rates of oral melanoma are not available. They are, however, estimated to represent 1-2% of all oral malignancies [1],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18] and accounting for about 0.2-8% of all melanomas. [19],[20] It is frequent in countries like Japan, Uganda, and India. [3],[6],[10],[11],[14],[21] Among the Japanese, oral melanoma accounts for 11-14% of all cases of melanomas. [4],[6],[10] In Australia, primary malignant melanoma of the oral mucosa is rare. [8] In the East, mucosal malignant melanoma seems to be more common than the West. [10]
Primary oral melanomas are extremely rare in the United States and account for less than 2% of all melanomas. At 1.2 cases per 10 million people per year, the annual incidence of oral melanoma is very low. [22]
Recent and major investigations in Africa showed oropharyngeal melanoma as 1.7% of all melanomas in Sudan and oral melanomas as 0.9% of all melanomas of Nigeria. It was suggested that mouth is a common site for melanoma in Uganda, with a frequency of 8% in 125 melanomas. This proportion was reduced to 4.6% in a similar study with a slightly larger sample. [14],[17]
In a study by Jackson and Simpson, primary malignant melanoma of the mouth represented less than 2% of all malignant melanomas. [23]
Robertson et al . and Reddy et al . showed that primary malignant melanoma of the oral cavity comprises 0.4-1.3% of all malignant melanomas. [9],[10] Van der Wall showed that only 2.5% of all melanomas were oral primaries. [8] Subsequent studies confirm the predominance of oral melanoma in American, Caribbean, African, and Indian population. Indian studies show between 20.41% and 34.4% of all melanomas at mucosal surface, and up to 16% of these tumors are intraoral. [10]
Oral melanoma is excessively uncommon at any site in prepubertal children of all races. [14],[18] This malignancy is a lesion of the adulthood, rarely occurring under the age of 20 years. In different studies, the highest incidence of malignant melanoma is in the fifth decades of life (40-70 years). [3],[4],[5],[6],[8],[9],[15],[16],[18],[23],[24],[25],[26] Barker et al. showed that the average age of patients with mucosal melanoma was 56 years, and the age range was 22-83 years. [27]
Males appear to be more often affected than females. [1],[3],[7],[8],[9],[10],[12],[14],[15],[16],[23],[25],[27],[28],[29]
From different studies, the male-to-female ratio ranges between 1/1 and 2/1. [3],[8],[9],[15],[16],[30]
Barker et al. showed that the gender distribution was 37 male to 13 female (ratio = 2.8). [27] As per a study in Netherlands, oral malignant melanomas appeared to be slightly more common in men. [8] In their review of literature, Hicks and Flaitz reported a male predilection and an age range of 22-83 years, with a mean age of 56 years. [1]
In addition, Hashemi Pour reported a male prediction (male-to-female ratio, 2/1) and age range between 56 and 77 years. The mean age of patients was 69.2 years. [31]
Morris and Horn found that malignant melanomas are 4.4 times more common in Whites than in Negroes. Reports of cases of oral melanomas in Blacks are infrequent. [14]
Primary melanoma occurs most frequently in the hard palate and maxillary gingiva; other oral sites are mandible, tongue, buccal mucosa, and upper and lower lip. [1],[3],[4],[5],[7],[8],[9],[10],[12],[15],[17],[21],[23],[25],[27],[29],[30],[32],[33]
The ethnic groups most commonly affected by oral melanomas are Japanese, Black Africans, Native Americans, and Hispanics. [34]
| Etiology | | |
In contrast to well-established etiologic factors participating in the evolution of cutaneous melanoma, such factors are either not a consideration (sun exposure, tendency to tan) or have not been studied extensively (familial history, syndromes, cytogenetic defects) with mucosal melanomas of the oral cavity. Probably the major reason for this lack of understanding regarding mucosal melanomas is the rarity of this malignancy. [1],[12],[27],[35]
No etiologic factors have been identified for oral melanomas. Risk factors have also remained elusive. There appear to be no geographic differences and possibly only slight ethnic and gender differences. [7]
Like their cutaneous counterparts, primary oral melanomas are believed to arise either from nevus, pre-existing pigmented areas or de novo (30% cases). [1],[2],[3],[5],[6],[8],[12],[15],[18],[23],[36]
Some oral melanomas are believed to originate from junctional nevis. Despite such observations, risk factors such as fair complexion and light hair, a tendency to sunburn, a history of painful or blistering sunburn in childhood, an indoor occupation with outdoor recreational habits, a personal history of melanoma, and a personal history of dysplastic or congenital nevus (xeroderma pigmentosum and basal cell nevus syndrome) have no role in the etiology of oral melanomas. Rarely, oral melanomas arise from pre-existing Hutchinson's malignant lentigo, which is believed to occur occasionally in the oral mucosa. [5],[6]
In the mouth, mechanical traumas including injury from ill-fitting prostheses and infection have been cited as possible causative factors, but there is no proof of their etiological role. [2],[14]
It is conceivable that oral habits and self-medication may be of etiological significance in some Indian and African groups. [2,14] Probably, racial pigmentation bears a negative relationship to melanoma. [9]
| Clinical Features | | |
Clinically, the tumors are classified into five types: 1 - pigmented nodular, 2 - nonpigmented nodular, 3 - pigmented macular, 4 - pigmented mixed, and 5 - nonpigmented mixed type. [37] Melanoma of the oral cavity may occur with or without a radial growth phase. [2] The clinical coloration of oral melanomas has a wide range, which can appear as black, gray, purple, or even reddish. While some lesions are uniform in color, others exhibit marked variation. The lesions are asymmetric, irregular in outline, and occasionally multiple. The surface architecture of oral melanomas ranges from macular to ulcerated and nodular. [4],[5],[7],[15]
Some of these tumors are amelanotic. Amelanotic oral malignant melanoma (AOMM) is a rare tumor, which is difficult to diagnose. [38] In two different studies, less than 10% of oral melanomas were described as amelanotic. [1],[27] Another unusual feature is the pseudocarcinomatous hyperplasia. This feature has been reported previously in association with melanotic lesions, such as Spitz nevi. [39]
Few symptoms are found early in the malignancy. The patient's attention may be drawn to the lesion by the presence of a swelling or mass, especially in a pigmented area, possible interference with the fit of dentures, hemorrhage, and loosening of teeth. Pain is an uncommon symptom of malignant melanoma, generally found in the advanced stages. [3],[5],[8],[23],[25],[27] The tumor causes extensive destruction of the underlying bone in 78% of cases. [5]
| Histological Features | | |
Histologically, the presence of atypical melanocytes (usually larger than normal melanocytes and having varying degrees of nuclear pleomorphism and hyperchromatism) in the epithelial and connective tissue junction, high density of melanocytes, and atypical cells in the biopsy of melanotic lesions of the oral mucosa are suspicious for oral malignant melanoma. [6],[40]
In most instances, the cells of melanoma contain melanin granules, but they may demonstrate no melanin production (amelanotic melanoma). Lack of production may cause diagnostic confusion at light microscopic level because melanoma can mimic a variety of undifferentiated tumors. Immunohistochemical studies showing S-100 protein, MART-1, and HMB-45 reactivity of the lesional cells are beneficial in distinguishing such melanomas from other malignancies. [6]
| Diagnosis | | |
Diagnosis of oral mucosal melanomas may be difficult for several reasons, including small biopsy size, unrepresentative sampling, biopsy of late-stage lesions, lack of clinical data, and lack of recognition of early in situ lesions by both clinician and pathologist. [7] Because of frequent delay in diagnosis, the tumors are often diagnosed after they grow deeper than the average cutaneous melanoma. [24]
Tanaka et al . showed that pRb2/p130 may be inversely correlated with the malignancy of oral malignant melanoma, but further study is needed. [41]
CT and MRI studies should be undertaken to explore regional metastases to the submandibular and cervical lymph nodes. Incisional biopsy is the method of choice for diagnosis. [4] The finding of a melanotic oral lesion in a patient presents the difficulty in deciding whether or not to do biopsy. The relatively high incidence of malignant versus benign melanotic lesions suggests that melanotic lesions of the oral mucosa should be assessed with some care. [3]
| Differential Diagnosis | | |
Differential diagnosis includes oral melanotic macule, smoking-associated melanosis, medication-induced melanosis (antimalarial drugs and Minocycline), melanoplakia, pituitary-based Cushing's syndrome, postinflammatory pigmentation, melanoacanthoma, melanocytic nevi of the oral mucosa, blue nevi, nevi of Spitz, Addison's disease, Peutz-Jeghers syndrome More Details, amalgam tattoo, Kaposi's sarcoma, physiologic pigmentation, pigmentation related with the use of heavy metals, and many other conditions sharing some macroscopic characteristics. [40],[42],[43]
Moreover, it is necessary that oral malignant melanoma should be under differential diagnosis than other malignant entities, such as poorly differentiated carcinoma and large cell anaplastic lymphoma. [40]
Amelanotic malignant melanoma without radial growth phase may be misdiagnosed as epulis or squamous cell carcinoma. [38]
| Management | | |
Surgery is the mainstay of treatment, but it is often difficult because of anatomic restraints. Although melanoma is classically not very radiosensitive, patients have occasionally had good response to radiation therapy, especially in early melanomas or in melanomas in situ . Other treatment modalities are similar to those used for cutaneous melanoma. Immunotherapy has been used, and chemotherapy has a low response rate. [4],[5],[6],[8],[9],[13],[17],[21],[24],[25],[26],[32],[35],[36]
Dacarbazine-DTIC and INF-alpha-2b have been described as chemotherapical and immunotherapical treatments associated in different combinations of BCG and recombinant interleukin-2 (rIL-2). [44]
| Prognosis and Survival | | |
Most oral melanomas are large at presentation and have a poorer prognosis than cutaneous melanoma. [3],[6],[7],[12],[13],[16],[17],[18],[25],[36],[45]
Cutaneous melanomas can be graded by Clark levels or the Breslow tumor thickness grading system. The former classification assesses the depth of invasion, whereas Breslow's system measures the thickness of the tumor from the surface of the epidermis to the greatest depth of the tumor. The risk for developing metastatic lesions from primary cutaneous melanomas increases with tumor thickness. The Breslow and Clark grading systems have not been validated as prognostic predictors in oral melanomas, probably owing to the rarity of this lesion. Additionally, in contrast to cutaneous melanomas, most oral melanomas are larger than 4 mm at the time of initial presentation. This factor, together with inadequate resection of margins and higher stage at initial diagnosis, may contribute to the discrepancy in patients' 5-year survival rates between cutaneous melanoma (80%) and oral melanomas (15%). [1] In general, the survival rates are poor and are worse for those with metastasis. [23]
Chaudhry et al . reported that the average duration of life from the point of diagnosis was about 18 months. Sampat and Sirsates reported that 79% of patients died within 5 years. [5] In addition, Vairaktaris et al. showed that the 5-year survival rate of intraoral melanoma does not exceed 5-9%. [46]
Factors that are significant in predicating worse disease-specific survival include high clinical stage at presentation, tumor thickness greater than 5 mm, presence of vascular invasion, absence of melanosis, and development of nodal and distant metastases. [5],[6],[8]
| Conclusion | | |
The review of literatures in the field of oral melanoma shows that oral malignant melanoma might be different from cutaneous malignant melanoma, and that new criteria for diagnosis and therapy should be considered for this disease.
Dentists and physicians who treat problems in the oral cavity should be aware of the need for early diagnosis of melanoma and performing biopsies of any pigmented lesion.
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Correspondence Address:
M S Hashemi Pour
Department of Oral Medicine, Faculty of Dentistry, Kerman University of Medical Sciences, Kerman
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0970-9290.38932
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