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.