The oral cavity is a rare location for the development of primary malignant melanoma. The most common primary lesion sites are the palate and gingiva. Melanoma of the tongue is specifically uncommon. A 66-year-old woman was referred to our clinic with a complaint of a huge, painless, black, discolored mass on the right side of the oral tongue for 7 years. There were no cutaneous lesions suggestive of malignant melanoma over the rest of her body. The biopsy of the tongue lesion revealed a histopathology consistent with primary malignant melanoma. Computed tomography of the neck showed no significant cervical lymphadenopathy. Chest radiograph, whole body bone scanning, and abdominal sonography revealed no definite distal metastatic lesions. She received composite resection of the tumor on the right side of the tongue and right functional neck dissection. The patient had an uneventful recovery and received regular follow-up examinations. She was free of disease for more than 2 years. The treatment principle for primary tongue melanoma is wide surgical excision. Early diagnosis will be promoted by careful oral examination and early biopsy of pigmented and non-pigmented masses. We reviewed the published reports in the English literature since 1970 and fewer than 30 cases of primary tongue melanoma were presented. We present a case report and a review of the relevant literature. (Chang Gung Med J 2002;25:764-68)

Key words: malignant melanoma, tongue.

Primary malignant melanoma of the oral cavity is a rare neoplasm. The incidence of oral cavity melanoma is about 0.2% to 8% of all malignant melanoma cases.(1) Primary lesions arising from oral mucosa occur most frequently on the maxillary gingiva and palate, with the lips following as the third most common in frequency. Melanoma of the tongue is specifically uncommon and represents less than 2% of all oro-nasal melanoma cases.(2) A review of the literature revealed fewer than 30 cases of primary malignant melanoma of the tongue had been reported and a tumor size of more than 6×5 cm was even more unusual as discovered in our review.

CASE REPORT

A 66-year-old woman was referred to our clinic with the complaint of a painless mass on the right side of the oral tongue. She had been aware of the dark discolored mass for 7 years; however, it gradually increased in size within the past 6 months. On examination, a black, pigmented and ulcerated mass measuring approximately 6×5 cm in size was found on the right side of the tongue with floor extension (Fig. 1). There were no cutaneous lesions suggestive of malignant melanoma over the rest of her body. The biopsy of the tongue lesion revealed a histopathology consistent with primary malignant melanoma. Computed tomography of the neck showed a right anterior lateral tongue mass with high intensity after contrast enhancement (Fig. 2). There was no significant cervical lymphadenopathy. Chest radiograph, whole body bone scanning and abdominal sonography revealed no definite distant metastatic lesions. She received a composite resection of the tumor on the right side of her tongue and right functional neck dissection. The histopathological findings revealed a malignant melanoma characterized by neoplastic proliferation of epithelioid to spindle melanocytes with melanin deposits and underlying skeletal muscle invasion. Scattered tumor cell nests were also present in the overlying squamous epithelium, suggesting that the tumor was a primary rather than a metastatic lesion (Fig. 3). The resection margin and base of the tumor were clear and no evidence of metastasis was found in the tissue of the functional neck dissection. The patient had an uneventful recovery and received regular follow-up examinations. She has been free of disease for more than 2 years, with no clinical or biochemical evidence of metastasis.

DISCUSSION

The mucosal membranes are rare sites for primary malignant melanoma. The presence of melanocytes in the mucosal membrane of respiratory, alimentary and urogenital tracts explains the occurrence of malignant melanoma in these sites.(3) Melanoma of the oral cavity mucosa is a distinctly rare occurrence with an incidence of 0.012/105 for combined primary and metastatic lesions to oral cavity.(2) The tumors are commonly found in patients older than 40 years and there are no significant differences between genders.(2,4,5) The oral cavity may be a site of predilection for melanomas in Japanese,(4,6) although it is very rare in the white populations.(7) We reviewed the reports in the English literature and fewer than 30 cases of primary malignant melanoma of the tongue were found. Men were more commonly affected than women in primary malignant melanoma of the tongue which was in contrast to skin melanoma where the incidence between genders was roughly equal.
Oral pigmentation preceded the development of malignant melanoma in about a third of the patients.(8) Takagi et al. reported that mucosal melanosis was associated in 66% of oral melanoma, pre-existing in 36.2% and concurrent in 29.8%.(6) There are many situations to be considered in the clinical differential diagnosis: Tattoos, melanotic macules, Laugier's disease, melanocytic nevus, drug intake, some vascular lesions, and oral pigmented lesions associated with endocrine disorders or different syndromes.(9) Our patient had had the oral dark pigmentation for 7 years, but she did not pay much attention to it. We suggested that a deep biopsy should be performed on any intra-oral pigmented lesions with the tendency of malignant transformation.
Oral melanomas may present as flat, painless, dark brown or black discoloration macules or nodules, sometimes with erythema or ulceration. As the disease progresses, bony erosion is common. A very important point in the management of malignant melanoma of the oral cavity is to exclude the possibility of it being a metastasis from a cutaneous melanoma. This is because metastasis plays a large role in determining the goals and method of treatment. In the histopathologic distinction, Billings et al. found that all metastatic lesions lacked evidence of junctional activity in the overlying mucosa and showed no epidermal migration. This is in contrast to primary lesions, in which 44 % and 38% had junctional activity and epidermal migration, respectively. A unique feature seen in the primary lesions (25%) was the presence of extensions of the melanotic pigment into the minor salivary glands.(10) However, these findings may be inconsistent, and the diagnosis of a primary oral mucosal melanoma requires the careful search for and exclusion of any suggested cutaneous or mucosal lesions.(11) For this patient, there was no history of melanoma-like lesion excision. We did not find any cutaneous lesions suggestive of malignant melanoma over her body, extremities, head or neck; there were not any pigmented lesions in the nasal cavity, pharynx and larynx. The histopathological findings revealed scattered tumor cell nests that were also present in the overlying squamous epithelium, suggesting that the tumor was a primary rather than a metastatic lesion. Physical examination and histopathologic findings suggested the diagnosis of primary melanoma.
The immunohistochemical profile of oral malignant melanoma was similar to that of cutaneous melanoma, with the exception that no oral malignant melanoma was positive for cytokeratin.(12) HMB-45 are regarded as showing greater specificity for melanoma than S-100 protein.(13) The immunoperoxidase stains of our patient showed positive finding in S-100 protein and HMB-45 stains.
Surgery is believed to be the most effective treatment for melanoma.(1) Wide resection with a surgical margin 2 to 5 cm is necessary for cutaneous melanoma, but is difficult to achieve for oral melanoma because of anatomical reasons. Our patient received a composite resection of the tumor on the right side of the tongue and right functional neck dissection. The histopathological findings revealed no evidence of metastasis and the resection margin was clear. A series of studies showed no evidence of distal metastasis. The role of radiotherapy is controversial because many authors believe melanoma to be a radioresistant neoplasm, and it is frequently used for palliation. Radiotherapy and chemotherapy play an important role in the primary management of unresectable diseases. Because the resection margin was clear and no loco-regional recurrence or distant metastasis have been found till now, our patient do not received any radiation therapy or chemotherapy. In recent years, immunological therapies have been used. The most widely used cytokines are interferons and interleukin-2. However, immunotherapy has not improved survival or local regional control rates in patients with mucosal melanoma.(14)
In general, the prognosis for patients with oral malignant melanoma is poorer than that for patients with cutaneous lesions. The 5-year survival rates were 6.6% to 20%.(5,6,15) Several factors may contribute to this poor prognosis including lack of symptoms early in the disease, difficulty in achieving wide radical excision because of anatomic limitations, and rich blood supply that may facilitate hematogenous spread.(2)
Early diagnosis will be promoted by careful oral examination and early biopsy of pigmented and non-pigmented masses. Early diagnosis and treatment will improve the prognosis of patients with oral malignant melanoma.

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From the Department of Otolaryngology, 1Department of Pathology, Chang Gung Memorial Hospital, Kaoshung; Chang Gung University, Taoyuan.
Received: Oct. 29, 2001; Accepted: Feb. 28, 2002
Address for reprints: Dr. Chih-Ying Su, Department of Otolaryngology, Chang Gung Memorial Hospital. 123, Ta-Pei Road, Niaosung 833, Kaoshung, Taiwan, R.O.C. Tel.: 886-7-7317123 ext. 2533; Fax: 886-7-7318762; E-mail: usgniy@cgmh.org.tw