Malignant Melanoma: A Case Report With Literature Review

Malignant Melanoma: A Case Report With Literature Review

Prakash Gadodia*, Ritesh Wadhwani**, Akshay Dhobley**, Namrata Patil**,
Vinod Kumar Patil***, Vinita Murgod***
*Professor & Head, **Reader, ***Lecturer, Department of Oral Pathology, SDDC, Parbhani, Maharashtra, India
Abstracts: Primary malignant melanoma of the oral cavity is a rare and aggressive neoplasm. They tend to
metastasize or locally invade tissue more readily than other malignant tumours in the oral region. Prognosis of oral
melanoma is comparatively poor and so an early diagnosis and follow-up is critical. Here we report a case of oral
melanoma, pigmented macular type, in maxillary anterior gingival region in a 60 year old female patient. [Gadodia P
NJIRM 2016; 7(1):120-124]
Key Words: Melanoma, neoplasm.
Author for correspondence: Dr. Prakash Gadodia, Professor & Head, Department of Oral Pathology, SDDC, Parbhani,
Maharashtra, India. Email: [email protected]
Introduction: Oral Malignant melanoma is a potentially trauma such as denture irritation , use of tobacco and
aggressive tumour of melanocytic origin and was first prolonged exposure to formaldehyde and alcohol.8
described by Weber in 1859.1,2 It accounts for 0.2% to Many genes are implicated in the development of
8% of all the melanomas and 0.5% of all the malignant melanoma, including CDKN2A (p16), CDK4 (chromosome
3
neoplasms of the oral cavity. It is more commonly seen 12q15), RB1, CD- KN2A (p19) and PTEN/MMAC1.9
in Japanese population than in other groups. In Japan, Delayed detection may be the reason for the poor
oral melanomas account for 11-12.4% of all melanomas. prognosis of oral malignant melanomas with the 5-year
This percentage is higher than the 0.2-8% reported in survival rate being between 15% to 38%. Early
the United States and Europe.4 In the East, mucosal recognition and immediate treatment may greatly
malignant melanoma seems to be more common than improve the prognosis.10
the West.5 The most common locations in oral cavity are
the palate and maxillary gingiva. Metastatic melanoma Case Report: A 60 yrs old female patient reported to the
most frequently affects the mandible, tongue, and department with chief complaint of mild pain and
buccal mucosa. Oral melanomas seem to be more swelling in upper left front region of jaw since 2 months.
aggressive and they spread and metastasize more (Fig.1) She gave history of trauma to upper teeth 2
rapidly than other oral cancers or cutaneous months back, few days after which she noticed small
melanomas.4 Most cases of oral melanoma occur gingival growth that region, which was surgically
between the fourth and the seventh decade of life, with removed but it reappeared in 4 days . The patient gave
an average of 55-57 years and having a predilection for history of pigmentation in the same area since last 40
the male gender with a male to female ratio of 2.8:1.6 years, and had hyperthyroidism since last 10 years. The
The clinical presentation of this condition may vary habit of tobacco quid chewing and paan chewing since
widely which is divided into following five types: 15 years. Intraoral examination revealed, gingival
Pigmented nodular type, pigmented macular type, growth 1 x 1.5 cm in the labial aspect of 22,23. (Fig.2)
pigmented mixed type, non-pigmented nodular type The inter-dental papilla was swollen and covered the
and non-pigmented mixed type.7 The clinical coloration labial aspect of involved teeth partially. The growth was
has a wide range, which can appear as black, grey, sessile and appeared to arise from the inter-dental
purple and reddish. The tumours are asymmetric, papilla of 22 and 23 and the attached gingiva. Black
irregular in outline and occasionally multiple. The pigmentation was seen on the gingivae from 11 to 24
symptoms of the oral mucosal melanoma include: labial as well as palatal aspect. (Fig.2, 3) Intra oral
bleeding, pain (it often appears late) and presence of periapical radiograph did not reveal any abnormality
melanotic pigmentation.4 Non pigmented forms of (Fig.4). Based on the clinical appearance, it was
malignant melanoma often cannot be distinguished provisionally diagnosed as Nevus transforming to Oral
clinically from other benign or malignant oral tumours Melanoma, oral melanotic macule. Incisional biopsy was
which can only be diagnosed through biopsy and performed after the routine hematologic investigations
immunohistochemistry.7 Its aetiology is unknown, were within normal limits. (Fig.5) Three small pieces of
although sometimes it is placed on pre-existing long- gross tissue were received for histopathological
term melanosis involving 33 to 55% of the mucosal examination soft in consistency and brownish black
melanomas of the head and neck , other possible colored. (Fig.6) Hematoxylin & Eosin stained sections of
etiological factors for this neoplasia are: mechanical these tissues revealed a parakeratinised stratified
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 Malignant Melanoma: A Case Report With Literature Review
squamous epithelium with atypical melanocytes Fig.4 showing the IOPAR in the affected region with no
throughout the epithelium and also invading in the distinct findings
underlying connective tissue stroma. These features
suggested the diagnosis of Oral Melanoma. (Fig.7,8,9)
Immunohistochemical staining with HMB45 showed
positive results and thus the diagnosis was
confirmed.(Fig 10)

Fig.1 showing the clinical photograph of the frontal

profile of the patient

Fig.5 showing the affected region being biopsied

Fig.2 showing pigmentation in relation to enlarged

gingivae in left maxillary anterior region

Fig.6 showing the excised gross specimen

Fig.3 showing pigmentation in relation to the palatal

aspect of enlarged gingivae in left maxillary anterior
region
Fig.7 showing H&E stained section showing
pigmentation throughout the epithelium (low power,
10X)

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 Malignant Melanoma: A Case Report With Literature Review
Fig.8 showing H&E stained section with parakeratinised difficult to diagnose. Oral Melanoma has an initial
stratified squamous epithelium with melanocytic phase characterized by radial growth followed by a
pigmentation (low power, 10X) phase of invasion of the underlying tissues (the so-called
“vertical growth phase”).11 A simple TNM clinical
staging, recognizing three stages, has shown to be of
prognostic value. A recent histopathological
microstaging for Stage I subclassifies it into three
levels:12

Stage I: Primary tumour present only (Tany N0M0)

Level I: pure in situ melanoma without evidence of
invasion or in situ melanoma with “micro-invasion”
Level II: invasion up to the lamina propria
Level III: deep skeletal tissue invasion into skeletal
muscle, bone, or cartilage
Fig.9 showing atypical, spindle shaped, malignant
Stage II: Tumour metastatic to regional lymph nodes
melanocytes (high power, 40X)
(Tany N1M0)

Stage III: Tumour metastatic to distant sites (Tany Nany

M1)

The traditional histologic staging for cutaneous

melanoma (e.g., Clark level) cannot be applied to the
mucosa because the mucosa lacks histologic land marks
analogous to papillary and reticular dermis. Breslow
thickness, the single most important histologic
prognostic factor in localized cutaneous melanoma, has
Fig. 10 showing HMB 45 positivity (scanner view) not been found to be useful in head and neck malignant
melanoma.13 Greene et al suggested the following
criteria for a lesion to be considered as primary
malignant melanoma of the oral cavity: 1)
demonstration of malignant melanoma both
histologically and clinically; 2) the presence of junctional
activity; and 3) the inability to demonstrate any other
primary site. Based on these criteria, this case could be
considered as a primary oral malignant melanoma.14
Malignant cells of Oral Melanoma shows presence of
atypical melanocytes showing wide range of shapes,
including spindle, plasmocytoid, clear cell, and
epithelioid ones with considerable pleomorphism with
Discussion: Oral malignant melanomas are extremely large, irregular hyperchromatic nuclei, and prominent
rare lesions, accounting for approximately 2% of all nucleoli, and have readily detectable mitotic activity.
melanomas with a male preponderance. The initial
symptom and sign of oral melanoma is generally a In most instances, the cells of melanoma contain
pigmented growth or swelling showing a smooth, intact melanin granules, but they may demonstrate no
or ulcerated overlying mucosa. Satellite foci may melanin production (amelanotic melanoma) which may
surround the primary tumour. Uniformly brown or black mimic poorly differentiated carcinoma. The melanocytes
or variation of colour, with black, brown, grey, purple, may be arranged irregularly at the epithelial connective
and red shades, or depigmentations may be seen. Some tissue interface or may be distributed in aggregates.
of these tumours are amelanotic which are rare, and are Oral Melanoma can be histologically sub-classified into

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 Malignant Melanoma: A Case Report With Literature Review
(1) in-situ melanoma, which is limited to the epithelium lymph nodes.1 Excision of the primary lesion is preferred
and the epithelial-connective tissue interface; (2) using an intraoral approach involving at least 1.5 cm of
melanomas with an invasive pattern, in which the healthy tissue. Neck dissection should be carried out for
neoplasm extends into the connective tissue; (3) cases with preoperatively confirmed lymph node
melanomas with a combined pattern of invasive metastases and the choice of the neck dissection
melanoma with in situ component.11 modality should be determined by the extent and the
level of the nodes.19
Differential diagnosis for oral melanoma includes oral
melanotic macule, smoking-associated melanosis, Surgery can be combined with radiotherapy,
melanoplakia, pituitary-based Cushing’s syndrome, post chemotherapy, or immunotherapy even though the
inflammatory pigmentation, melanoacanthoma, effectiveness of such therapies is mostly unknown.
melanocytic nevi of the oral mucosa, blue nevi, spitz Other irradiation modalities such as intraoral mould
nevi, Addison’s disease, Peutz-Jeghers syndrome, (60Co, 192Ir, or 198Au), intraoral electron beam or
amalgam tattoo, Kaposi’s sarcoma, physiologic interstitial brachytherapy have also been used with
pigmentation and many other conditions sharing variable results.12 Dacarbazine, platinum analogs,
macroscopic characteristics with oral melanoma.15 For nitrosoureas, microtubular toxins, dimethyl triazeno
distinguishing melanomas from other tumours imidazole carboxamide (DTIC), nimustine hydrochloride,
immunohistochemical stains should be used for or vincristine have been used as adjuvant therapy or
accurate diagnosis which includes S-100 protein, gp100 postoperative chemotherapy. IFN-α2b, IL-2, BCG, anti-
(HMB-45) and Mart-1 (Melan-A), these can also be Fas antibody, IL2, and cytokines have also shown varied
useful in identification of micrometastases in lymph results.1The prognosis of Oral Melanoma is poor. A
nodes. Tyrosinase, microphthalmia transcription factor tumour thickness greater than 5 mm, presence of
in adjunct can also be used as to confirm the diagnosis. vascular invasion, necrosis, polymorphous tumour cell
The Antibody HMB-45 reacts with the melanosomal morphology and the inability to properly resect the
glycoprotein gp 100, showing a positive staining in lesions with negative margins have been associated with
active early melanosome formation and showing poor survival in patients with primary Oral melanoma.
epithelioid lesions intensely immunoreactive for HMB- Gingival melanoma has a better 5-year survival rate than
45. It is considered as more specific but less sensitive palatal melanoma.20
than the S- 100 protein, an acidic calcium binding
protein, which is a very sensitive marker for nevus and Conclusion: Primary oral mucosal melanomas are
melanoma cells, and even spindled lesions appear exceedingly rare and biologically aggressive
intensely immunoreactive for S-100 protein.16 malignancies. Oral Melanomas clinically mimic many
other pigmented lesions of the oral cavity and thus is
Melan-A is considered to be specific for melanoma cell overlooked or clinically misinterpreted as a benign
lines, as a product of the MART-1 gene it is a pigmented process until it is well advanced. Thus
melanocytic differentiation marker which is recognized immediate treatment should be instituted to facilitate
on melanomas as an antigenic target of T lymphocytes.17 its early diagnosis, as a prerequisite for timely treatment
Ki-67 is commonly used as an adjunct in distinguishing and better prognosis of this rare pathology.
benign nevi from melanoma.18 Fine needle aspiration or
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