Article published online: 2021-08-24

THIEME
812 A
 Large
Case Oral Melanoma  Warin et al.
Report

A Large Oral Melanoma: A Case Report of a Rare but

Aggressive Malignancy
Kritsasith Warin1,   Poramaporn Klanrit2  Nutdanai Pattanajakr3

1 Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, Address for correspondence Kritsasith Warin, DDS, FRCDT,
Thammasat University, Pathum Thani, Thailand Division of Oral and Maxillofacial Surgery, Faculty of Dentistry,
2 Department of Oral Biomedical Sciences, Research Group of Thammasat University, Pathum Thani 12121, Thailand
Chronic Inflammatory Oral Diseases and Systemic Diseases (e-mail: [email protected]).
Associated with Oral Health, Faculty of Dentistry, Khon Kaen
University, Khon Kaen, Thailand
3 Oral and Maxillofacial Surgery Clinic, Udon Thani Hospital,
Udon Thani, Thailand

 Eur J Dent 2021;15:812–816.

Abstract A variety of black-pigmented lesions of the oral cavity can be found, ranging from
harmless benign lesions such as melanotic macule, smoker’s melanosis,
amalgam/graphite tattoos, and pigmented nevus to a life-threatening oral malignant
melanoma. Oral melanoma is a rare and aggressive malignant tumor that originates
from melanocytes’ proliferation and accounts for only 0.5% of all oral malignancies.
The etiology is unknown. Most oral melanomas are present at the palate and the upper
Keywords alveolar ridge, whereas occurrences at the buccal mucosa, the lower alveolar ridge,
► melanoma and the lip are rare, with only a few reports in the literature. The diagnosis is confirmed
► oral cavity by a biopsy. The prognosis is poor, with a 5-year survival rate of ~20%. In this report,
► pathology we present a case of large oral melanoma at the right buccal mucosa involving the
► immunohisto- right lower alveolar ridge and lip commissure, which are relatively unusual locations
chemistry for oral melanoma. In addition, immunohistochemical markers used for diagnostic,
► palliative care therapeutic, and prognostic decision-making of oral melanoma are also discussed.

Introduction brown, dark blue, or black macule, sometimes with ery-

thema or ulceration.1 Histologically, melanomas comprise
Melanoma is a malignant neoplasm comprising abnormal medium-to-large cells that may be polyhedral, fusiform,
melanocytes, which originates from neural crest cells. Oral round, spindle, pleomorphic, epithelioid, microcytic, or var-
melanoma is a rare neoplasm that represents ~2% of all mel- ious shapes.7 Immunohistochemically, melanomas variously
anomas and 0.5% of all oral malignancies, occurring much express S-100 protein and melanocytic markers, includ-
less frequently than its cutaneous relatives.1-3 Most oral ing HMB-45, melanoma antigen recognized by T-cells 1, or
melanoma studies report a wide range of ages and are more melanoma antigen A (MART-1/Melan-A), tyrosinase, and
common in males than females.4,5 The most regular site of microphthalmia-associated transcription factor (MITF).3,7 The
occurrence is the palate, followed by the upper alveolar ridge. prognosis for patients with oral melanoma is poor. These
Other oral sites are the lower alveolar ridge, tongue, buccal patients’ poor outcomes may be partly a result of a delay in
mucosa, upper and lower lip.2,5,6 diagnosis.8
Varied clinical features of oral melanoma have been This article presented a case of large oral melanoma at the
reported. The most common presentation is an asymptomatic right buccal mucosa involving the right lower alveolar ridge

published online DOI https://doi.org/ © 2021. European Journal of Dentistry.

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 A Large Oral Melanoma  Warin et al. 813

and lip commissure in a 69-year-old female who preferred

to obtain palliative care rather than surgery or other alterna-
tive treatments, including radiotherapy, chemotherapy, and
immunotherapy.

Case Report
A 69-year-old Thai female patient presented to the oral and
maxillofacial clinic to evaluate an asymptomatic black lesion
at her right buccal mucosa. The patient reported that the Fig. 2 Computed tomography scan revealed a heterogeneous,
enhancing mass with central hypodensity involving the right lower
lesion had been present for 4 months with a gradual increase
alveolar ridge with the destruction of the right mandible and bulging
in size. Extraoral examination revealed no cervical lymph- in a subcutaneous, right buccal region. The total size of the lesion
adenopathy and no facial paresthesia. Intraoral examination was ~4.7 × 2.4 × 1.9 cm.
showed asymptomatic scattered black patches, exhibiting flat,
irregular, nodular, and ulcerative surfaces, at the right buccal
with melanin pigments in basal and some suprabasal cell lay-
mucosa extending posteriorly to the right alveolar ridge and
ers of the epithelium. These pleomorphic cells are strongly
anteriorly to the lip commissure. The size of the lesion was
positive for S-100, HMB-45, and Melan-A. An early invasion
~5 × 3 cm (►Fig.  1). An incisional biopsy was performed at
of atypical melanocytes containing melanin pigments into
the buccal mucosal lesion, which showed a prominent nodu-
the superficial lamina propria was seen. The pathological
lar surface, and a computed tomography (CT) scan was taken.
diagnosis of oral melanoma with a superficial invasion was
The CT scan revealed a heterogeneous, enhancing mass
confirmed (►Fig.  3). Another panel of immunohistochemi-
with central hypodensity involving the right lower alveolar
cal staining further demonstrated the expression of BRAF
ridge with the destruction of the right mandible and bulging
(V600E) and CD117 (c-kit) of atypical cells at the superficially
in a subcutaneous, right buccal region. The lesion’s total size
invasive and in situ components (►Fig. 4).
was ~4.7 × 2.4 × 1.9 cm (►Fig. 2). Histopathological findings
Although the pathological diagnosis of an incisional
demonstrated several atypical, pleomorphic melanocytes
biopsy from the right buccal mucosa showed a superficial
invasion of oral melanoma, the bone invasion of the lesion
at the right mandible demonstrated by a CT scan indicated
an advanced stage of oral melanoma. On the follow-up day,
we informed the patient about the diagnosis and treatment
options, including surgical treatment and/or chemoradio-
therapy. She denied radical surgery and preferred alternative
medical treatment. Therefore, she was referred to be treated
by the oncologist for radiation therapy and/or systemic che-
motherapy. Later, with the pandemic of coronavirus disease
2019 (COVID-19), the patient subsequently chose palliative
care, in which some of the appointments were delivered by
telemedicine instead of previously planned radiation therapy
with chemotherapy. She received morphine for analgesia,
metoclopramide for antiemetic, and diazepam or lorazepam
for adjuvant therapy. After 4 months of follow-up, she contin-
ued to refuse radiotherapy and systemic chemotherapy. Her
caregiver informed us that the patient was satisfied with this
mode of treatment.

Discussion
Oral melanoma is a rare neoplasm and very aggressive
tumor of melanocytic origin, accounting for only 0.5% of all
oral malignancies. It frequently involves the hard palate and
upper alveolar ridge but rarely occurs in the buccal mucosa,
lower alveolar ridge, and lip.2,6 The pathogenesis of oral
mucosal melanomas has not yet confirmed whether muco-
sal melanocytes’ dysfunction is the main cause. Most stud-
Fig. 1 Clinical appearance. Asymptomatic scattered black patches
exhibiting flat, irregular, nodular, and ulcerative surfaces, at the right
ies have reported that the lesion occurs more frequently in
buccal mucosa extending posteriorly to the right alveolar ridge and males than females, with an average age of 53.4,6 The exact
anteriorly to the lip commissure. The size of the lesion was ~5 × 3 cm. etiology of oral melanoma is unknown. However, smoking

European Journal of Dentistry  Vol. 15  No. 4/2021  © 2021. European Journal of Dentistry.
814 A Large Oral Melanoma  Warin et al.

Clinically, oral melanoma demonstrates as a slow-growing,

asymptomatic, brown, purple, or black pigmentation with
irregular borders and may appear as a rapidly expanding
mass with or without ulceration.1,10 The clinical differential
diagnosis should exclude oral melanoma from normal vari-
ations11and other benign, harmless black lesions such as
melanotic macule, smoker’s melanosis, amalgam and graph-
ite tattoos, and pigmented nevus.12 In this case report, we
encountered a large oral melanoma at the buccal mucosa,
involving the lower alveolar ridge and lip commissure. A CT
scan highlighted an invasion of a lesion into the right man-
dible. According to previous studies, oral melanomas of the
buccal mucosa, lower alveolar ridge, and lip, which are infre-
quent locations, have been found in only 4 to 7% of all oral
melanomas.2,4 Another learning point of this case was that an
incisional biopsy’s pathological result revealed only a super-
ficial invasion of oral melanoma. Even though we carefully
selected the darkest and the most raised region of the lesion
at the buccal mucosa for the incisional biopsy, this area was
not representative of the true infiltrative and destructive
nature of this lesion as represented by a CT scan that showed
a large destructive area in the right mandible. However,
clinical features consisting of the “ABCD” warning signs (A:
asymmetry; B: border irregularities; C: color variegation;
D: diameter >6 mm)3 and radiographic presentations of this
case, in conjunction with histopathological features, offered
a diagnosis of oral melanoma.
The histopathology of oral malignant melanoma is similar
to cutaneous melanoma, with an initial phase characterized
by a “radial growth phase” followed by an invasion of the
Fig. 3 Histopathologic features. (A, B) Hematoxylin and eosin underlying tissues known as the “vertical growth phase.” The
stained section demonstrated several atypical, pleomorphic melano- malignant tumor cells of oral malignant melanoma exhibit a
cytes with melanin pigments in basal and some suprabasal cell layers
wide variety of forms, including spindle cells, plasmacytoid
of the epithelium. A pagetoid spread of some melanocytes to the
superficial layer of epithelium is observed (A: ×100, B: ×200). (C, D) cells, clear cells, small round blue cells, and epithelioid cells,
S-100 (C: ×100, D: ×200). (E, F) HMB-45 (E: ×100, F: ×200). (G, H) organized into sheets, organoid/alveolar, or desmoplastic for-
Melan-A (G: ×100, H: ×200). mation.13 The general histopathologic appearance of this case
demonstrated atypical melanocytes with melanin pigments,
horizontally spreading in the basal and suprabasal cell layers,
along with a superficial invasion of these atypical cells into
the superficial lamina propria.
Immunohistochemical study, positive staining for
S-100 protein, MART-1 or Melan-A, tyrosinase, and
HMB-45 strongly confirm the diagnosis of melanoma.2,3 In
this case, the pathological diagnosis was confirmed by the
expression of S-100 protein, Melan-A, and HMB-45 by tumor
cells, as shown in ►Fig.  3. Besides, it has been suggested
that MITF serves as a useful immunohistochemical marker
in diagnosing melanoma. Furthermore, studies show that
Fig. 4  The hematoxylin and eosin-stained section and immunohisto- MITF has high sensitivity and specificity for metastatic mel-
chemical study of BRAF (V600E) and CD117 (c-kit) at the superficially anoma, and positivity has been reported in S-100 negative
invasive area (A–C) and in situ component of an incisional biopsy melanoma,14,15 indicating that MITF may be another optional
specimen (D–F). (A, D) Hematoxylin and eosin (×400). (B, E) BRAF immunohistochemical marker to confirm the diagnosis of
(V600E) (×400). (C, F) CD117 (c-kit) (×400).
oral melanoma. The mutational analysis for BRAF and KIT
mutations, which are primarily found in an advanced stage
and chronic irritation caused by ill-fitting dentures, as well of melanoma, is another beneficial molecular test for ther-
as swallowing and inhaling environmental carcinogens at apeutic decision making for the most appropriate targeted
elevated internal body temperature, have been proposed to therapy in treating melanoma to improve patient survival
play a role in the development of malignant lesions.3,9 rate.16 In this case, we did not perform the mutational

European Journal of Dentistry  Vol. 15  No. 4/2021  © 2021. European Journal of Dentistry.
 A Large Oral Melanoma  Warin et al. 815

analysis of BRAF and KIT but found that BRAF (V600E) and to prevent tumor extension and reduce the risk of metastasis,
CD117 (c-kit) protein aberrantly expressed in our case by an leading to the improved prognosis of patients.
immunohistochemical study (►Fig. 4).
Ethical Approval
The 5-year survival rate for patients with oral melanoma
This study was ethically approved by the institutional eth-
remains poor and has been reported to be 13 to 38%.17,18 The
ics committee because of its retrospective nature. All the
poor outcome of these patients may be, in part, the result of
procedures performed were part of the routine care.
a delay in diagnosis. Widespread metastases are the leading
cause of death in patients with oral melanoma. Oral mela- Funding
noma metastases develop in regional lymph nodes or distant None.
organs such as the brain and breast.19-21 Since the mucosal
surfaces of the oral cavity are not regularly self-examined, Conflict of Interest
and these surfaces are not visible to others, the lesion may None declared.
remain asymptomatic and continue to grow overlooked for
some period of time. References
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European Journal of Dentistry  Vol. 15  No. 4/2021  © 2021. European Journal of Dentistry.