|Ahead of print publication
Primary malignant melanoma of mandibular gingiva: A rare case report
Neha Verma, Adit Srivastava
Department of Oral Medicine and Radiology, Faculty of Dental Sciences, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
|Date of Submission||22-Aug-2019|
|Date of Decision||07-Dec-2019|
|Date of Acceptance||09-Feb-2020|
|Date of Web Publication||05-Nov-2020|
Department of Oral Medicine and Radiology, Faculty of Dental Sciences, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Oral malignant melanomas are rare neoplasms of the oral cavity which present significant diagnostic ambiguity. The etiology is unclear though the stimulation of melanoblasts by genetic, epigenetic, and traumatic causes that have been proposed in etiopathogenesis. Clinically, it presents as a pigmented swelling or growth which remains asymptomatic until it advances to later stages. It is highly invasive and metastasizes quickly; hence, it has a very poor prognosis with a survival rate of only 7%. Early diagnosis of the neoplasm and thorough investigation is not only necessary for prompt treatment but also necessary for a favorable prognosis.
Keywords: Malignant melanoma, oral malignant lesions, oral mucosal melanoma, pigmented lesion
| > Introduction|| |
Melanoma is a malignant tumor of the melanocytes. Melanocytes are pigment-producing cells found in the basal layer of the epidermis. They are derived from the neural crest cells and produce a pigment called melanin, which imparts color to the skin. Melanomas are aggressive and invade and metastasize quickly leading to poor prognosis and survival rate. They usually have a cutaneous manifestation but may involve mucosal regions as well., The most common sites for mucosal involvement are nasal and paranasal sinuses, oral cavity, and the nasopharynx.
Oral melanomas have a rare incidence and constitute only 0.2%–8% of all melanomas. The mucosa of the maxilla especially anterior gingiva is a prevalent site for the development of oral melanomas. Oral melanomas usually involve keratinizing mucosa of the palate and alveolar gingiva more as compared to nonkeratinizing mucosa. They have been differentiated into five types: pigmented nodular type, pigmented macular type, pigmented mixed type, nonpigmented nodular type, and nonpigmented mixed type. As most of the oral melanomas are asymptomatic, they are difficult to diagnose until there is ulceration or hemorrhage.
This report presents a case of oral malignant melanoma in the mandibular posterior gingiva which is an unusual site of its occurrence.
| > Case Report|| |
A 44-year-old male has been reported to the department with a chief complaint of discomfort due to swelling in the right lower back gum region for 1 month. The swelling was painless and progressive with no associated discharge. There was no history of other systemic diseases. On intraoral examination, blackish-blue pigmented, proliferative growth, measuring 2 cm × 2 cm, was seen extending from the right retromolar trigone to the right mandibular first molar, involving right gingivobuccal sulcus [Figure 1]. The borders were demarcated from the surrounding mucosa, irregular and raised. On palpation, growth was firm, fibrotic, and nontender with no associated bleeding. Orthopantomogram did not show any loss of bone or tooth displacement in the involved region [Figure 2]. Based on clinical and radiographic findings, the differential diagnosis of mucosal nevi, melanoacanthoma, and oral melanoma was derived. Routine blood investigations were normal. On histopathological examination, pleomorphic tumor cells with moderately eosinophilic to vacuolated cytoplasm, perivascular nucleus, and prominent eosinophilic nucleoli were seen. Melanin pigment was evident in tumor cells [Figure 3]. Immunohistochemical analysis showed tumor cells to be positive for melan-A. Histopathological and immunohistochemical examinations were consistent with the diagnosis of oral malignant melanoma. A positron-emission tomography scan was advised which was negative for any other primaries in the body. The patient was referred to the regional cancer center where he underwent segmental mandibulectomy and radiotherapy. The patient responded well to the treatment and no recurrence has been reported so far.
|Figure 1: Pigmented, proliferative growth seen in the right mandibular posterior region|
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|Figure 3: Micropictograph showing pleomorphic tumor cells with moderately eosinophilic to vacuolated cytoplasm, perivascular nucleus prominent eosinophilic nuclei, and melanin pigment|
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| > Discussion|| |
Oral malignant melanoma is a rare metastatic tumor of the oral cavity. It constitutes 0.2%–0.5% of the entire oral malignancies and 25% of all the head and neck melanomas. The incidence of oral melanomas is 2.3 per million population with a higher prevalence rate seen in the Asian population., The etiology of oral mucosal melanoma remains unclear; however, the mutation of the tumor-suppressor genes, oncogenes, and DNA repair genes has been postulated in its etiopathogenesis. The alteration of various cellular pathways, namely c-kit/stem cell factor pathway, endothelin receptor type B/endothelin pathway, Wnt/β-catenin pathway, and atypical expression of the cell-adhesion molecules, has also been suspected to play a major role in tumor initiation and progression. An immunohistochemical study conducted by Hsieh et al. on 35 cases of primary oral melanomas showed an association of advanced histological grade of melanoma, a higher rate of vascular invasion by them, and metastasis to other organs with the absence of RAS and ERK1 and presence of BRAF and ERK2. A better survival rate has been reported where there is an expression of bcl-2, whereas the loss of p16 was associated with poor prognosis tumor progression. Furthermore, the alteration of p53 has been associated with undifferentiated malignant cells.
Primary oral malignant melanoma was first reported by Weber in 1859; thereafter, many cases were identified based on clinical appearance. It was only in 1953 that Greene et al. proposed three-point criteria for diagnosing oral melanomas: (i) demonstration of malignant melanoma in the oral mucosa, (ii) presence of the so-called “junctional activity” (i.e., melanocytes arranged along the basal layer of the surface epithelium) in the lesion, and (iii) inability to show malignant melanoma at any other primary site. However, this criterion was later found to be inadequate, as melanomas can metastasize and involve the junctional epithelium.
Mucosal melanomas show three distinctive components: the central part shows a nodular component, a pigmented deep brownish-black plaque component which could be flat or slightly elevated, and a macular component which has a light brown pigment. Histologically, they can be differentiated into three patterns:
- In situ pattern – tumor is limited to epithelial–connective tissue interface
- Invasive or nodular pattern – tumor extends to deeper connective tissue
- Combined pattern – in situ and nodular patterns occur simultaneously.
Oral melanoma is mostly asymptomatic frequently presenting as a pigmented patch or a rapidly growing mass. In later stages, it can show rapid expansion, leading to bleeding or ulceration and mobility of the associated teeth. Oral melanomas show a radial growth pattern before invading the deeper tissues where they show a vertical growth pattern. Smith et al. studied 46 cases of oral melanomas and reported only one case of oral melanoma having a mandibular posterior gingival involvement, whereas maxillary gingiva was frequently involved in the rest of the patients. In our case as well, there was the involvement of the posterior mandibular gingiva which is a rare site of its occurrence.
Differential diagnosis of oral melanoma includes amalgam tattoo which is preceded by amalgam restoration, melanotic macule, melanotic nevus, melanoacanthoma, posttraumatic or racial pigmentation, systemic disease such as Peutz–Jeghers syndrome and Addison disease, drug-induced pigmentation, vascular malformations, epulis, pyogenic granuloma, irritation fibroma, peripheral giant cell granuloma, peripheral ossifying fibroma, Kaposi sarcoma, and metastatic nonpigmented lesions. Several cases in which oral melanomas were preceded by oral melanosis have been reported in the literature. Oral melanomas can be differentiated from other lesions by dermoscopy and immunohistochemical analysis. Melanoma cells have shown 88%–94% sensitivity to S-100 protein, MART-1 (melan-A), and gp100 (HMB-45). An analysis encompassing S-100, tyrosinase, and HMB-45 has been suggested for accurate identification of melanoma cases.,
Oral malignant melanoma is highly aggressive due to which it has a poor prognosis with a 5-year survival rate of only 7%. Recurrence in oral mucosal melanomas is a frequent finding, although in our case, no recurrence has been reported so far.
| > Conclusion|| |
Oral melanomas pose a diagnostic challenge to the clinicians due to their asymptomatic nature and variant clinical presentation. Pigmented lesions in the oral cavity should be suspected of melanomas. A histopathological and immunohistochemical examination is recommended for its adequate identification. Early diagnosis is the only approach for better prognosis and survival in oral mucosal melanomas.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Liu Y, Sheikh MS. Melanoma: Molecular pathogenesis and therapeutic management. Mol Cell Pharmacol 2014;6:228.
Boulaadas M, Benazzou S, Mourtada F, Sefiani S, Nazih N, Essakalli L, et al
. Primary oral malignant melanoma. J Craniofac Surg 2007;18:1059-61.
Ebenezer J. Malignant melanoma of the oral cavity. Indian J Dent Res 2006;17:94-6.
] [Full text]
Zito PM, Mazzoni T. Cancer, oral melanoma. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2019.
Padhye A, D'souza J. Oral malignant melanoma: A silent killer? J Indian Soc Periodontol 2011;15:425-8.
] [Full text]
Manigandan T, Sagar GV, Amudhan A, Hemalatha VT, Babu NA. Oral malignant melanoma: A case report with review of literature. Contemp Clin Dent 2014;5:415-8.
] [Full text]
Feller L, Khammissa RA, Lemmer J. A review of the aetiopathogenesis and clinical and histopathological features of oral mucosal melanoma. ScientificWorldJournal 2017;2017:9189812.
Warszawik-Hendzel O, Słowińska M, Olszewska M, Rudnicka L. Melanoma of the oral cavity: Pathogenesis, dermoscopy, clinical features, staging and management. J Dermatol Case Rep 2014;8:60-6.
Hsieh R, Nico MM, Coutinho-Camillo CM, Buim ME, Sangueza M, Lourenço SV. The CDKN2A and MAP kinase pathways: Molecular roads to primary oral mucosal melanoma. Am J Dermatopathol 2013;35:167-75.
Prasad ML, Patel SG, Shah JP, Hoshaw-Woodard S, Busam KJ. Prognostic significance of regulators of cell cycle and apoptosis, p16 (INK4a), p53, and bcl-2 in primary mucosal melanomas of the head and neck. Head Neck Pathol 2012;6:184-90.
Greene GW, Haynes JW, Dozier M, Blumberg JM, Bernier JL. Primary malignant melanoma of the oral mucosa. Oral Surg Oral Med Oral Pathol 1953;6:1435-43.
Meleti M, Leemans CR, Mooi WJ, Vescovi P, van der Waal I. Oral malignant melanoma: A review of the literature. Oral Oncol 2007;43:116-21.
Tlholoe MM, Khammissa RA, Bouckaert M, Altini M, Lemmer J, Feller L. Oral mucosal melanoma: Some pathobiological considerations and an illustrative report of a case. Head Neck Pathol 2015;9:127-34.
Femiano F, Lanza A, Buonaiuto C, Gombos F, Di Spirito F, Cirillo N. Oral malignant melanoma: A review of the literature. J Oral Pathol Med 2008;37:383-8.
Smith MH, Bhattacharyya I, Cohen DM, Islam NM, Fitzpatrick SG, Montague LJ, et al
. Melanoma of the oral cavity: An analysis of 46 new cases with emphasis on clinical and histopathologic characteristics. Head Neck Pathol 2016;10:298-305.
Rajendran R, Sivapathasundaram B. Benign and malignant tumors of the oral cavity. In: Shafer WG, Hine MK, Levy BM, editors. Shafer's Text Book of Oral Pathology. India: Elsevier; 2009. p. 120-7.
[Figure 1], [Figure 2], [Figure 3]