continuous efforts by researchers and constant addition of literature minimized the aura of one of the deadliest disease , that is , oral malignant melanoma ( omm ) . as a result , the new innovative approaches came to existence and this became the first step to successful treatment against this disease .
the disease is known since decades , but proper management is affected due to insufficient understanding regarding its pathophysiology and marked variation in its clinical findings .
the mucosal melanoma was discussed first , by weber in germany , and later on , the valuable information of head and neck mucosal melanoma was reported by lincoln in 1885 . in late 19 century , further studies were carried out , that focused to minimize the mortality and enhance public awareness towards the disease .
hence , an early detection and timely treatment is a key factor for its better prognosis . unlike omm
, there is a marked variation in the etiology and incidence rate of generalized cutaneous melanomas .
the continuous global environmental changes result in over - exposure to ultraviolet ( uv ) radiation .
furthermore , the growing trends of sunbeds or tanning beds increased the risk of this disease .
a sunbed is a device , which emits uv radiation ( typically 97% uva and 3% uvb ,  3% ) to produce a cosmetic tan .
today the worldwide incidence of newly diagnosed melanomas range between 3% and 8% . around 50% of mucosal melanomas
affect the head and neck region , almost representing approximately 9% of all malignant head and neck tumors .
comparatively , mucosal melanomas show an aggressive biological behavior resulting in a 5 years survival rate of < 25% .
the etiology of mucosal melanoma differs from its cutaneous counterpart , as there is no direct role of uv radiation .
primary causes are : ill - fitting dentures , betel nuts , tobacco , formaldehyde , amalgam tattoo , nevi at traumatic regions , racial pigmentation , etc .
some literatures explain that during embryologic development , melanocytes migrate from the neural crest to epithelial lining , which later show reactive changes by cytotoxic stimulant in the basal epithelial layer . though dendritic cells , derived from neural crest , produces the melanocytes but the exact mechanism of proliferation of these cells in melanoma
particularly , mucosal melanomas are asymptomatic in their initial phase , resulting in late diagnosis , thus allowing them to invade the deeper regions .
the clinical characteristics include , dark brown / black in color , asymmetrical margins , and irregular surface , etc .
, hence , the pigmented lesions of oral cavity ; which does not possess clinical specificity need to be carefully evaluated for possibility of omm .
differential diagnosis include : smoke related melanosis , drug pigments , physiologic or racial pigmentation , melanotic macule , kaposi 's sarcoma , nevus or melanoacanthoma , chronic leukemic , etc .
pigmentation is not the only criteria , as around 15% of the melanomas are nonpigmented .
the omm has distinct gender variation with majority of them showing male predominance . among the oral melanomas ; hard palate and maxillary gingiva
, we report a case of omm , in a 45-year - old female patient , who is conscious about the discoloration and growing bulk over mandibular anterior mucosa .
a 42-year - old indian female with average height and moderate built reported to the dental office , complaining of blackish discoloration on the lower jaw since 6 months and difficulty while eating ; especially with the lower front teeth .
intraoral examination revealed nontender and painless bluish - black growth with rough and irregular surface extending over the gingiva of 3544 regions , which revealed no findings of ulceration and bleeding [ figure 1 ] .
there was major involvement over the labial aspect of mandibular gingiva followed by anteroposterior extension into the vestibule and oral aspect of lip mucosa ; but with minimal extension of the lesion on lingual aspect .
the patient noticed a small blackish patch approximately 1 cm  1 cm which gradually increased to present size with associated mobility of teeth .
the overall general examination of the neck , back , extremities , and chest was insignificant except for nevi .
submandibular lymph nodes were enlarged but nontender approximately 1.5 cm  1.5 cm in dimension .
after evaluating hematological parameters , an incisional biopsy was performed under local anesthesia , for a confirmatory diagnosis . clinical photograph showing bluish - black irregularly spreading growth extending from mandibular left second premolar to right first premolar in microscopic examination , the h and e stained section revealed in situ melanotic pigments [ figure 2 ] .
the section showed large cells with pleomorphic vesicular nucleus and brown pigment , few abnormal mitoses , and altered nucleocytoplasmic ratio invading into the connective tissue in the form of sheets , cords , and islands [ figure 3 ] .
the tissue was also immunohistochemically stained for human melanoma black-45 , a specific marker for melanocytes that also revealed cytoplasmic positivity of malignant melanocytes for the antibody [ figures 4 and 5 ] . after confirming the diagnosis as malignant melanoma , segmental resection , and bone grafting
follow - up , patient reported with some other problems such as difficulty in eating and speech .
the intraoral examination revealed uneven healing of resected part and further development of the bluish - black patch on left posterior mandible . due to severe trismus and discomfort
wide excision of the growth and node biopsy was done and the patient is being recalled for follow - ups every 6 months .
h and e stained section reveals malignant melanocytes with hyperchromatic nuclei ; infiltrating the connective tissue as sheets ( h and e , 10 ) h and e stained section reveals pigmented cells with abnormal mitosis ( h and e , 10 ) immunohistochemistry stained slide shows positive expression ( ihc , 10 ) immunohistochemistry stained slide shows cytoplasmic positivity by the melanocytes ( ihc , 40 )
the oral mucosal melanoma is a rare entity with incidence rates of < 1% of all melanomas and among head neck tumors
, the head and neck mucosal melanomas accounted for 0.8% of all melanomas and 8% of head and neck melanomas .
they reviewed 2.5 million individuals in denmark over a 30 years period and found that omm mostly occur between the fourth and seventh decades of life , with a mean age of 5557 years .
melanocytes are dendritic cells that have migrated as neuroectodermal derivatives in the ectodermally derived mucosa .
some studies also suggest familial inheritance specially , along with dysplastic nevus syndrome where ; p16 and differences in dna repair impairments contributes to carcinogenesis of malignant melanoma . in such circumstances ,
the damaged dna , activates the proto - oncogenes or inactivates the tumor suppressor genes .
majority of patients show history of preexisting oral pigmentation before the diagnosis of oral melanoma .
moreover , common primary sites include ; the nasal cavity , paranasal sinuses and in the oral cavity ; most commonly in the maxillary alveolar ridge and hard palate , whereas it is rarely seen on the mandibular gingiva .
so far some studies have documented , relationship between free radicals , and melanoma cells , resulting into increased levels of reactive oxygen species .
this is due to the metal binding properties of melanin and loss of structural integrity of melanosomes . at present
it is accepted that , omm is very aggressive tumor and various factors contribute to its aggressiveness , such as late detection , poor resectability , and early metastasis .
this not only limits the 5 years survival rate up to 1025% , but also affects prognosis .
melanoma is notoriously resistant to chemotherapy , but the other approaches can be carried out during its treatment . according to oncosurgeons ; treatment of choice for malignant melanoma is surgery .
stage 1 , melanomas are excised along with 1 mm margins and t2an0m0 ( stage 1b ) needs sentinel lymph node biopsy .
stage 2 cases are treated with wide excision and node biposy , whereas for stage 3 it needs wide excision with 2 mm margins and node dissection and the radiation or chemotherapy is given post - operatively .
stage 4 is really the challenge , it is treated with surgery and chemotherapy ; interferons ( ifns ) , interleukins ( ils ) , vaccines , and different biochemotherapeutic agents serves as adjuncts .
today 's new technology has opened new hopes . as a result , biotherapies including ifns and il-2 provide intriguing avenues for further evaluation and treatment .
the mechanism of clinically effective il-2 therapy may be the direct action of il-2 on a biologically distinct subset of melanoma cells , leading to up - regulation of tumor suppressor il-24 .
hence , to avoid future complications the suspected oral pigmentations should be planned for biopsy . moreover , in some extent ; criteria given by green et al .
may be helpful to clinicians , that suggests ; demonstration of melanoma in the oral mucosa , presence of junctional activity and inability to demonstrate extra oral primary melanoma .
further , some studies have classified the disease for prediction of its prognosis , that is , stage 1 : when the lesion is confined locally , stage 2 : have positive metastasis and stage 3 : with hematogenous spread . in the later stage ; distant metastases may be found in a variety of sites , including the lungs , bones , liver , brain , and skin .
a detailed case history , thorough clinical examination , and suspicious eye to the irregular intraoral pigments can help the clinician for early diagnosis . sometimes patients ignore the symptoms that may reflect indirectly on health care provision and result in a poor prognosis .
any physiologic pigmentation to hormones , medication or pigmentations other than amalgam tattoo should be biopsied .
the treatment promoted by thorough oral examination and biopsy should be well planned to improve patient prognosis and avoid chances of recurrence .
 according to the world health organization , oral malignant melanoma ( omm ) is a rare disease , accounting for only 0.8% of all melanomas , 8% of head and neck melanomas , and up to 0.5% of all oral malignancies . 
 omm presents as a pigmented lesion with asymmetrical borders , irregular surface characteristics , and a distinct color . 
 melanoma - associated pigmented lesion of the oral cavity does not possess clinical specificity and frequently divert the clinical diagnosis ; hence , differential diagnosis becomes mandatory . 
 furthermore , the unpredictable pathophysiological behavior and delayed detection , contributes for poor prognosis of the disease . as a result , 
 the 5 years survival rate is only 1025% . 
 commonly omm is seen in maxillary gingiva of males 
 . however , we report a rare case of a middle - aged female having pigmentations and growth over mandibular gingiva . 
INTRODUCTION
CASE REPORT
DISCUSSION
CONCLUSION