000 Blackwell Oxford, International IJD 0011-9059 2002 41 UK Science Science, Journal Ltd 2001 of Dermatology

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Primary malignant melanoma of the oral cavity: case report

Malignant melanoma Bongiorno and Aric of the oral cavity

Maria Rita Bongiorno, MD, and Mario Aric, MD

From the Department of Dermatology, University of Palermo, Italy Correspondence Maria Rita Bongiorno, MD Department of Dermatology University of Palermo Via del Vespro 131, 90123 Palermo Italy. E-mail: ISTDERM@UNIPA.IT

An 80-year-old-female patient had a pigmented lesion on: the hard palate, the soft palate, the alveolar mucosa and the vestibolar mucosa of the maxillary gingiva. Pigmented macules and patchs had been persistent and asymptomatic for many years (Fig. 1). The lesion exhibited irregularities of pigmentation, border and surface contour. About 1 year later the patient had noticed an extension of the pigmented macules and plaques; there was also the appearance of nodules of the maxillary gingiva accompanied by swelling. Loosening of teeth as a result of extensive destruction of bone was further noted (Fig. 2). The histological examination showed a downward streaming in the dermis of the tumor cells and a disintegration and ulceration of the epidermis (Fig. 3). An increased number of large round or polygonal cells resembling atypical epithelioid cells were found on the submucosa. The atypical cells had enlarged, pleomorphic nuclei with prominent and sometimes multiple nucleoli. Mitoses were observed at various tissue levels (Fig. 4). Abundant pigmented melanin was present in the tumor cells (Fig. 5). Many cells had ne, dusty melanin particles. The tumor cells showed great variations in size. Immunohistochemical staining, with S100 protein and HMB45 antibodies, stained many of the spindleshaped cells, indicating that they were melanocytic cells. An inammatory inltrate of lymphocytes was seen in a band beneath the invading tumor cells.

Discussion An 80-year-old female patient had a pigmented lesion on: the hard palate, the soft palate, the alveolar mucosa and the vestibolar mucosa of the maxillary gingiva. There was also the appearance of nodules of the maxillary gingiva accompanied by swelling and loosening of teeth.

The melanin-containing tumor was largely composed of epithelioid cells in irregularly branching formations. The atypical cells had enlarged, pleomorphic nuclei with prominent and sometimes multiple nucleoli. Immunohistochemical staining, with S100 protein and HMB45 antibodies, stained many of the spindleshaped cells.

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Figure 1 Pigmented macules and patchs with irregularities of pigmentation, border and surface contour
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Figure 2 About one year: nodules of the maxillary gingiva accompanied by swelling and loosening of teeth
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Figure 3 An increased number of large round or polygonal cells resembling atypical epithelioid cells were found on the submucosa, the epidermis is atrophic (200)

The 5-year survival rate for patients with malignant melanomas of the oral mucosal is only 5% with a median survival of 12 years after diagnosis. The prognosis for patients with oral melanoma is extremely poor and it has received little attention. All pigmented lesions of the oral cavity should be viewed very carefully. For patients with these unusual variants of melanoma, early diagnosis, due to a routine mucosal examination, is the key to proper treatment and an improved survival rate. Mucosal melanomas are rare, comprising less than 1% of all melanomas.1,2 They are usually asymtomatic and occur in the mouth, esophagus3, gall bladder,4 urethra5, anus, vulva6 and vagina.7 For this reason mucosal melanomas are generally detected late and thus have a very poor prognosis. Oral cavity melanomas occur most frequently between the age 40 and 70 years. For this particular type of melanoma the frequency drops off dramatically after the age of 70 years.8 The 5-year survival rate for patients with malignant melanomas of the oral mucosa is only 5%. Prevalence by sex also
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varies, depending on geographic location. In England the ratio is 2.5 females to 1 male, most studies support equal sexual predilection or a slightly higher incidence in men. In most cases, oral melanomas in adults occur almost three times more frequently in men than women.8 The distribution of malignant melanomas within the oral cavity has a decided predilection for the palate and maxillary gingiva.9,10 Malignant melanomas may present two clinical patterns:1 a macular area precedes the rapid appearance and enlargement of a pigmented lesion, or2 the tumor is preceded by a macular, palpable and pigmented lesion for a period of time, which may vary from a few months to several years, whereas some lesions exhibit a clinically detectable and prolonged in situ growth phase. Whereas others same to lack this property and exhibit only invasive characteristics.11 Due to its rarity the origin of oral melanomas and the risk factors are largely unknown. Certain races may be more commonly affected: the Japanese12, black Africans13, native Americans14 and Hispanics.15 A clearer correlation exists between melanomas of the oral mucosa and pre-existing pigmentation. Asymptomatic oral pigmentation, at the site of oral melanoma, is noted before diagnosis in approximately one third of patients.16 Mucosal melanomas involving the oral cavity are not well understood or characterized. This is due to the fact that this subtype of melanoma accounts for less than 1% of all cases. Mucosal melanomas tend to be present at a higher stage, are more aggressive17 and are in a vertical growth phase of disease. A definitive precursor lesion of oral mucosal melanoma has not been identified. Dysplastic nevus syndrome is known to be associated with an increased risk of cutaneous melanoma, and with an increased incidence of primary ocular melanoma however, mucosal atypical melanocytic hyperplasia may represent a proliferative phase before overt tumorigenesis occurs.18,19 The prognosis for patients with oral melanoma is extremely poor and it has received little attention. All pigmented lesions of the oral cavity should be viewed very carefully. Changes in color of the oral mucosa may result from a variety of causes of exogenous origin (amalgam tattoos, carbon, ink, antimalarials, gold, arsenic, mercury, silver, copper, etc.) and of endogenous origin (trauma, bleeding diatheses, Addisons disease, PeutzJeghers syndrome, hemochromatosis, nevi, oral melanocitic macule, Kaposis sarcoma, melanoma, etc.). Whereas some primary oral melanomas exhibit a clinically detectable and prolonged in situ growth phase, other mucosal melanomas seem to exhibit only an invasive phase. All oral pigmented lesions that are not clinically diagnostic should be biopsied, because mucosal melanomas have a far more aggressive and more rapid lifeconsuming biologic course. The appearance of pigmentation in the oral cavity preceding invasive malignant melanoma underscores the necessity of routine oral examinations and prompt diagnosis.
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Figure 4 Mitoses were observed at various tissue levels (400)

The prognostic factors of mucosal melanomas, which indicate dangerous limits, are deep invasion or thickness of the melanoma at the time of diagnosis. Oral melanomas are also more refractory to therapeutic modalities due to the anatomic restriction of site and the large size of the tumor when first discovered.20 The poor prognosis includes a delayed development of symptoms and a substantial delay in the diagnosis.21 The 5-year survival rate for patients with malignant melanomas of the oral mucosal is only 5% with a median survival of 12 years after diagnosis. For patients with these unusual variants of melanoma, early diagnosis, due to a routine mucosal examination, is the key to proper treatment and an improved survival rate.2 References
1 Batsakis JG, Suarez P. Mucosal melanomas: a review. Adv Anat Pathol 2000; 7: 167 180. 2 Rogers RS, Gibson LE. Mucosal, genital, and unusual clinical variants of melanoma. Mayo Clin Proc 1997; 72: 362 366. 3 Gollub MJ, Prowda JC. Primary melanoma of the esophagus: radiologic and clinical findings in six patienta. Radiology 1999; 213: 97 100. 4 Heath DI, Womack C. Primary malignant melanoma of the gall bladder. J Clin Pathol 1988; 41: 1073 1077. 5 Oliva E, Quinn TR, Amin MB, et al. Primary malignant melanoma of the urethra: a clinicopathologic analysis of 15 cases. Am J Surg Pathol 2000; 24: 785 796. 6 Ragnarsson-Olding BK, Kanter-Lewensohn LR, Lagerlof B, et al. Malignant melanoma of the vulva in a nationwide, 25 year study of 219 Swedish females: clinical observations and histopathologic features. Cancer 1999; 86: 1273 1284. 7 DeMatos P, Tyler D, Seigler HF. Mucosal melanoma of the female genitalia: a clinicopathologic study of forty-three cases at Duke University Medical Center. Surgery 1998; 124: 38 48.
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Figure 5 Abundant pigmented melanin was present in the tumor

cells (250)
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8 Rapini RP, Golitz LE, Greer RO, et al. Primary malignant melanoma of the oral cavity: a review of 177 cases. Cancer 1985; 55: 1543 1551. 9 Fejerskov O, Nybroe L. Primary malignant melanoma of the hard palate. J Oral Surg 1973; 31: 53 55. 10 Jackson D, Simpson HE. Primary malignant melanoma of the oral cavity. Oral Surg 1975; 39: 553 559. 11 Barker BF, Carpenter WM, Daniels TE., et al. Oral mucosal melanomas: the WESTOP Banff workshop proceedings. Western Soc Teachers Oral Pathol Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 83: 672 679. 12 Umeda M, Shimada K. Primary malignant melanoma of the oral cavity its histologic classification and treatment. Br J Oral Maxillofac Surg 1994; 32: 39 47. 13 Broomhall C, Lewis MG. Malignant melanoma of the oral cavity in Uganda. Africans Br J Surg 1967; 54: 581 584. 14 Black WC, Wiggins C. Melanoma in southwestern American Indians. Cancer, 1984; 55: 2899 2902. 15 Black WC, Goldham RT, Wiggins C. Melanoma within a

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southwestern Hispanic population. Arch Dermatol 1987; 7: 13311334. Chaudhry AP, Hampel A, Gorlin RJ. Primary malignant melanoma of oral cavity: a review of 105 cases. Cancer 1958; 11: 923 928. Eisen D. Voorhees JJ Oral melanoma and journal pigmented lesions of the oral cavity. J Am Acad Dermatol; 24: 527 537, 1991. Hicks MJ, Flaitz CM. Oral mucosal melanoma: epidemiology and pathobiology. Oral Oncol 2000; 36: 152 169. Tremblay JF, OBrien EA, Chauvin PJ. Melanoma in situ of oral mucosa in an adolescent with dysplastic nevus syndrome. J Am Acad Dermatol 2000; 42: 844 846. Batsakis JG, Suarez P. Mucosal melanomas: a review. Adv Anat Pathol 2000; 7: 167 180. Eisen D, Voorhees JJ. Oral melanoma and journal pigmented lesions of the oral cavity. J Am Acad Dermatol 1991; 24: 527 537.

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International Journal of Dermatology 2002, 41, 178181