Discussion
Malignant melanoma is an aggressive tumor that originates from melanocytes derived from neural crest cells in the basal layer of the epithelium. Malignant melanoma of the oral cavity mucosa is a distinctly rare entity with an incidence of 0.2-0.8% of all malignant melanoma, it was first described by Weber in 1859. 1.4.7 The common sites for intraoral melanoma are the palate and maxillary gingiva which account for 80–90 % of the cases, but any mucosal site may be involved.1.2 Tongue melanoma is extremely rare and makes up about 2.3% of all oro-nasal melanoma.5.7There are about 30 cases of tongue melanoma reported in English literature. Most cases of oral and tongue melanoma occur between the fourth and the seventh decade of life and have a predominance for the male gender with a male to female ratio of 2.8:1.6. 13.14 However there is no gender difference regarding some studies.4.15.16 It is diagnosed approximately a decade earlier in males than in females.10 It affects races differently and Japanese are especially more susceptible to OMM that can point to genetic or environmental susceptibility that is not identified yet.4.10 We presented a young woman with a history of primary tongue melanoma two years ago who presented with recurrence of tongue melanoma while being on maintenance imatinibR treatment.
The etiology of OMM is unknown. According to the literature some environmental factors and habits like alcohol consumption, cigarette smoking, denture irritation, and trauma may have some effect on its occurrence. But the majority of them are believed to be De nova. 10.15Mucosal melanosis was related to oral malignant melanoma in 66% of cases, pre-present in 36.2%, and synchronous in 29.8% of patients according to Takagi and colleagues report.4.7.17 Many genes are involved in the occurrence of melanoma, including CDKN2A (p16), CDK4 (chromosome 12q15), RB1, CD- KN2A (p19), and PTEN/MMAC1 that can be targeted for systemic therapy.13 Our patient has no risk factors relating to the etiology of mucosal melanoma, which is in favor of the current belief that most oral mucosal melanomas emerge De novo.
OMM can present as an asymptomatic pigmented macular or nodular lesion in the oral mucosal membrane and some cases without any pigmentation as an amelanotic lesion. The surface may be smooth and intact or ulcerated.16.18   Satellite foci may siege the primary tumor.2.13 By the way, as they are asymptomatic and most people don’t inspect their oral cavity precisely, even pigmented variants usually are diagnosed late at an advanced stage when they become painful, hemorrhagic, and ulcerative. The clinical manifestation of OMM may differ broadly and is intersected according to Tanaka et al study into pigmented nodular type, pigmented macular type, pigmented mixed type, non-pigmented nodular type, and non-pigmented mixed type. 13.19 Signs and symptoms of OMM contain bleeding, ill-fitting dentures, pain, increment mobility of teeth, and deferment healing of extraction sockets.2
OMM has a dismal prognosis that is somehow related to late diagnosis and advanced stage of the disease. So, any suspected lesion in the oral cavity should be biopsied and sent for histopathologic examination. Excisional biopsy with 1-2 mm margin for small lesions and incisional biopsy from the bulkiest or more suspected part of the large lesion is obligatory .2OMM can be diagnosed by hematoxylin and eosin staining. However, immunohistochemically markers, such as HMB45 and Melan-A, would be used for confirming the diagnosis.14
The most significant histopathologic finding is the proliferation of neoplastic melanocytes with nuclear changes. They can form in different phenotypes such as epithelioid, spindle, or fusiform, which are arranged in asymmetric shape architectures. There is a conquest of cells with a plentiful eosinophilic, clear cytoplasm, and melanin granules in the dermo-epidermal junction. They depict high mitotic activity and sometimes have Necrosis and ulcerations.3.19
According to Greene et al in 1953, the lesions with the following criteria are regarded as primary malignant melanoma of the oral cavity: 1) histological and clinical verification of malignant melanoma; 2) the existence of junctional activity, and 3) the incapacity to denote any other primary site. 12.16 So according to this criterion, our patient was considered as primary tongue melanoma at first presentation two years before the recent complaint.
There are several staging systems for malignant mucosal melanoma based on the TNM staging system, micro invasion, histopathologic pattern, and so on that neither of them is commonly utilized. Ballantyne explained a three-level staging system for classifying mucosal melanomas in 1970, which continues to be widely used. Stage I is the presence of the primary tumor (T anyN0M0) without lymph node involvement or distant metastasis, that itself spitted into three levels; level I is pure in situ melanoma with either lack of invasion or with micro invasion, in level II lamina propria is involved, level III is permeation into the deep skeletal tissue. Stage II is regional lymph node involvement (T anyN1M0) and stage III is tumor distant metastasis (Tany N anyM1).2.13.19.20
The American Joint Committee on Cancer (AJCC) staging system (8th edition,2018) for OMM begins with stage III as the most limited form of the disease (T3, N0). Stage IV is divided into three parts, IV A consists of (T3N1) or (T4a, N0 or N1), Stage IV B (T4b, N0 or N1), and stage IV C (any T, any N with metastasis). table.1.