it develops most of the time on the skin ; however , other parts of the body could be involved , including the oral cavities . oral malignant melanoma ( omm ) , unlike cutaneous melanoma , is considered a rare lesion with an incidence of 0.4 - 1.8% of all melanomas and 0.5% of all oral malignancies .
the etiology of omm is still not defined , contrarily to cutaneous melanoma for which sunlight and genetic background are considered etiologic factors .
the most frequently affected oral sites are the palate and the maxillary gingiva ; other less frequently affected sites include the labial and buccal mucosa as well as the tongue .
black africans , japanese , and native americans are more commonly affected than the european population .
histologically , melanomas are characterized by proliferation of malignant melanocytes arranged along the basal layer , having the potential for tissue invasion and metastasis .
these cells show a considerable pleomorphism , with a wide range of shapes , such as round to spindled , plasmacytoid , clear cell and epithelioid , and have a solid , alveolar , organoid or pagetoid pattern .
necrosis , lack of an inflammatory reaction , and not always detectable mitotic activity are other histological features of this disease .
the purpose of this report is to describe a case of omm and to emphasize the importance of histological examination .
an 80-year - old woman was referred to our clinic for evaluation and treatment of a pigmented oral lesion .
intraoral examination showed multiple lesions represented by macules and nodules on the hard and soft palate , superior alveolar mucosa and gingiva ( fig .
a biopsy , which included the free and attached gingiva and alveolar mucosa was performed and submitted to histopathological analysis .
2a , b ) showed sheets and nests of melanocytes , some with round , plasmacytoid or epithelioid morphology in the superficial corium extending to the deep tissues .
some of them presented round nuclei of various sizes , occupying nearly the entire cell cytoplasm and prominent nucleoli .
3d ) and negative for ae1/ae3 ( not shown ) , confirming the diagnosis of melanoma .
the patient refused a complete workup examination ( i.e. ct scan , mri , etc . ) as well as any type of treatment and died 11 months later .
we presented a case of omm which was initially misdiagnosed as a probable racial pigmentation elsewhere 2 years earlier .
this diagnosis was made by taking only the clinical aspect into account and without performing histological analyses . acquired and small congenital nevi show a high frequency of braf mutations . in cutaneous melanoma ,
nevertheless , there is no report in the literature about the potential malignant transformation rate of oral melanocytic nevi or other pigmented lesions . in our case
, we can not establish if the melanoma arose de novo or from a preexistent benign pigmented lesion or precursor , since a biopsy was not carried out .
therefore , all suspicious lesions presenting an asymmetric , irregular form , with variation in color and diameter should be investigated in order to obtain a definitive diagnosis .
the differential diagnosis for pigmented lesions includes tattoos , oral melanotic macule , racial pigmentation , nevi , melanoacanthoma , melanoma and systemic diseases such as polyostotic fibrous dysplasia , neurofibromatosis , multiple endocrine neoplasia syndrome , peutz - jeghers syndrome , and addison 's disease .
initially , omm appears as an asymptomatic lesion characterized by a flat macule , or a slightly elevated lesion that may later become elevated and develop signs and symptoms such as swelling , ulceration , bleeding , pain and tooth mobility . according to the literature ,
swelling is considered the main reason for consultation , followed by bleeding , ill - fitting dentures , pain , increased mobility of teeth and delayed healing of extraction sockets .
omm occurs in adults of all ages , but it is most common in the elderly .
when studying 187 cases , showed an average age of 67.5 years , and an unusual case of a 9-year - old patient was described by loreno et al . .
there is no agreement in the literature concerning the ratio of the patients ' gender , having no sex predilection or presenting a slight predilection for men or sometimes for women .
histologically , the tumor cells show a considerable pleomorphism , with a wide range of shapes and patterns that could mimic other tumors such as lymphomas , poorly differentiated carcinomas , neuroendocrine carcinomas , sarcomas , and germ - cell tumors .
in addition , more rarely , the melanomas may be nonpigmented , causing difficulties in clinical diagnosis and are typically diagnosed at a later stage .
therefore , the use of immunohistochemical staining is an important tool to help distinguish melanomas from other malignancies .
the helpful markers of melanoma diagnosis are s-100 , hmb-45 , melan - a , and tyrosinase . for this case , we used s-100 , hmb-45 and melan - a .
s-100 is very sensitive ( around 97 - 100% ) but not very specific ( 75 - 87% ) .
some carcinomas , sarcomas ( such as rhabdomyosarcomas , leiomyosarcomas , and peripheral nerve sheath tumors ) , and langerhans cell histiocytosis can be positive for s-100 .
hmb-45 recognizes a type i membrane - bound melanosomal protein called pmel17 or gp100 protein .
the analysis of hmb-45 and ki-67 antibodies can be useful for distinguishing primary cutaneous melanomas from some nevi .
ki-67 is a marker of tumor cell proliferation , which is commonly used as a complement to distinguish benign nevi from melanoma . with less than 5% of positive cells ,
the lesion is considered as benign nevi , while with 13 - 30% of positive cells , it is considered as malignant melanoma . in our case
the multi - cytokeratin ( ae1/ae3 ) antibody is reported to be characteristic of epidermal cells .
many predictors of prognostics have been proposed in the literature on omm such as age , clinical stage , depth of invasion and vascular invasion . however , because of the rarity of this disease , consensus criteria have not yet been established . according to the microstaging classification by prasad et al .
, which is based on the invasion of the tissue within the mucosa , level i is defined as melanoma in situ , level ii as melanoma invading up to the lamina propria and level iii as melanoma with deep tissue invasion .
our case was classified as level iii because the malignant melanocytes reached the periosteum . however , there was no invasion of blood vessels and nerve fibers .
melanoma has an initial phase named radial or horizontal growth , which is characterized by a laterally spreading growth of malignant melanocytes only within the epithelium , representing the in situ stage .
later , in the vertical growth phase , there is an invasion of the underlying tissues .
omm is normally diagnosed in the vertical growth pattern , which may explain its very poor prognosis . in this case , the patient refused any type of treatment and died 11 months after the diagnosis .
it has been shown that early identification of the melanoma and its treatment by radical surgery comprise the most important treatment strategy .
an association with adjuvant radiation can also be performed . in cases of metastatic diseases ,
chemotherapy should be considered with the aim of improving the survival of patients with head and neck melanoma . due to the deadly behaviour of omm , showing a poor prognosis with a 5-year survival rate of 15% , all focally pigmented lesions and most diffusely pigmented lesions require a biopsy for diagnosis .
 oral malignant melanoma ( omm ) is rare , representing less than 0.5% of all oral malignancies . 
 the most affected sites are the palate and the maxillary gingiva . 
 histological examination is important to establish the diagnosis of any suspicious pigmented lesion in the oral cavity , mainly if a precise clinical diagnosis is not possible . 
 we present one case of omm that was initially diagnosed as a racial pigmentation elsewhere 2 years earlier . 
 clinical examination showed multiple macules and nodules located on the hard and soft palate , gingiva and superior alveolar mucosa . 
 these lesions were painless and presented a color variation going from dark blue to black . 
 histological analysis showed sheets and nests of atypical melanocytes displaying a range of shapes such as plasmacytoid , epithelioid , and round cells , located in the superficial corium extending to the deep tissues . 
 a few tumor cells contained variable amounts of melanin . 
 there was no invasion of blood vessels or nerve fibers . 
 immunohistochemical analysis revealed that the neoplastic cells were positive for hmb-45 , melan - a , s-100 and negative for ae1/ae3 , confirming the diagnosis of melanoma . 
 the ki-67 labeling index was around 25% . 
 the patient refused any treatment and died 11 months later . 
Introduction
Case Report
Discussion
Statement of Ethics
Disclosure Statement