Vol. 116 No.

4 October 2013

Oral malignant melanoma: systematic review of literature and

report of two cases
Muralee Mohan, MDS, DNB, Vihang Y. Sukhadia, MDS, Deepak Pai, MDS, and Smitha Bhat, MDS,
Mangalore, India
A. B. SHETTY MEMORIAL INSTITUTE OF DENTAL SCIENCES
Objective. Oral malignant melanoma (OMM) is a rare tumor of the oral cavity with very poor prognosis despite the
implementation of an aggressive treatment. This paper aims to shed some light on current evidence for management of OMM.
Study Design. We report 2 cases of OMM treated at our institute and a review of the literature in an endeavor to establish
current understanding on various aspects of OMM.
Results. Both patients in our study are showing good local control with aggressive multimodal treatment. Long-term follow-up
is needed to rule out distant metastasis.
Conclusions. Because late diagnosis and advanced disease at the time of diagnosis are the only sure predictors of outcome,
thorough clinical and pathologic workup of any suspected melanotic lesion should be carried out to diagnose OMM. Early
diagnosis and aggressive multimodal treatment are the only means available to surgeons to provide better outcome to patients
with OMM. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:e247-e254)

Pigmented lesions in the oral cavity may be classified

as melanotic or nonmelanotic lesions. Melanotic lesions are more common than nonmelanotic ones. Melanocytes may be found in the oral mucosa but may not
be noticeable because of their low level of pigment
production. However, when they are active in pigment
production or proliferation, they may be responsible for
several oral pigmentations ranging from focal to diffuse
and physiologic to malignant neoplasm.
Diffuse pigmentations are mostly systemic-related,
drug-induced, or caused by exogenous pigments,
whereas most focal pigmentations are brought about by
overproduction of melanin. Although most pigmented
lesions are benign, it is necessary to distinguish the
origin of pigmentation for melanocytic lesions which
may be a malignant tumor, so-called oral malignant
melanoma (OMM). This justifies that melanocytic lesions should not be ignored and that a definite diagnosis
must be established in all cases.
Melanomas are malignant neoplasms arising from
melanocytes, originating from the neural crest cells.
Melanocytes are primarily present in the basal portion
of the epidermis at the dermo-epidermal junction. Primary malignant melanoma has been described in virtually all sites and organ systems where neural crest
cells migrate. One of the unusual sites is the upper
aerodigestive tract.
Department of Oral and Maxillofacial Surgery, A. B. Shetty Memorial Institute of Dental Sciences, Mangalore, India.
Received for publication Apr 3, 2011; returned for revision Oct 30,
2011; accepted for publication Nov 9, 2011.
2013 Elsevier Inc. All rights reserved.
2212-4403/$ - see front matter
doi:10.1016/j.oooo.2011.11.034

Primary mucosal melanoma of the head and neck is

a rare entity, occurring much less frequently than its
cutaneous relatives. It constitutes 1% of all melanomas and 10% of head and neck melanomas.1 Its
incidence is thought to be stable, contrary to its cutaneous counterpart, which has been rapidly increasing.2
Some authors think that oral malignant melanoma has
radial growth phase and appears to be similar to acral
lentiginous melanoma of the skin, whereas others think
that oral malignant melanoma is a separate entity from
its cutaneous counterpart and should be classified separately.3
Surgery remains the main treatment modality, with
added radiotherapy and/or chemotherapy to prevent
recurrence and metastasis. Despite aggressive resection
and multimodal treatment, prognosis of OMM remains
very poor.3 Also, because of the rarity of this tumor,
there is lack of definite proof regarding etiology, pathogenesis, treatment protocol, and prognostic factors for
OMM. This paper reports 2 cases of OMM treated at
A. B. Shetty Memorial Institute of Dental Sciences,
Mangalore, and a review of literature in an endeavor to
establish current understanding on various aspects of
OMM.

CASE REPORTS
Case 1
A 60-year-old woman reported to our department with
complaint of swelling in the palate for 3 months. It was
insidious in onset and growing in size. It was not associated
with any pain, ulceration, or bleeding. The patient had a
history of breast carcinoma 8 years prior, for which she had
undergone surgery followed by radiotherapy, detailed records
which were not available. There was no recurrence noted at
the time of thorough physical examination. On examination,

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ORAL AND MAXILLOFACIAL SURGERY

Mohan et al.

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e248

Fig. 1. Case 1. A, Typical clinical presentation of oral malignant melanoma. B, Resected specimen showing adequate clearance
margins. C, Postresection view showing split thickness graft stabilized with surgical splint.

a single 3 3 cm smooth-surfaced swelling was noted in the

middle of the palate with slightly darker pigmentation around
it. Blackish discoloration of anterior alveolar mucosa was also
present. Lesion was nontender and firm to hard in consistency. Incisional biopsy was performed and was reported as
malignant melanoma with fibrous hyperplasia. A thorough
physical examination was undertaken to detect any skin lesion and in the absence of that, the oral lesion was labeled as
primary malignant melanoma. Systemic examination was carried out with chest x-ray, ultrasonography of the abdomen,
and computerized tomography (CT) scan of the cervical area
to rule out any metastatic lesion. After a thorough work-up,
the patient was scheduled for surgery and low-level maxillectomy was performed with 2 cm gross soft tissue margin all
around the lesion. The defect was closed with split-thickness
skin graft, and a temporary obturator was placed intraoperatively (Figure 1).
The histopathology report showed atypical cells which
resembled melanocytes infiltrating into connective tissue and
migrating upward into superficial layers of epithelium. The
atypical melanocytes were epitheloid in the superficial region
and spindle shaped in the deeper regions of connective tissue
(Figure 2). The tumor cells showed hyperchromatism, pleomorphism, multinucleation, increased nuclear-cytoplasmic
ratio, and atypical mitoses. Resected margins were free from
tumor cells.
Two months later, the patient reported with neck swelling
on the right side. The primary lesion had healed well and
showed no evidence of recurrence, with 100% take-up of skin
graft. Fine-needle aspiration cytology of the neck swelling
revealed it to be metastatic lymphadenopathy. CT scan was
done which revealed bilateral submandibular lymph node
enlargement. Modified radical neck dissection was performed
on both sides and the patient recovered well with no postoperative sequelae. Histopathologic examination revealed only
one positive lymph node in the right side specimen at level II
lymph node. Patient was given adjuvant radiotherapy after the
surgery. At the time of writing this paper the patient was
disease-free with no locoregional recurrence or metastasis for
almost 20 months. The patient is under regular follow-up at
6-month intervals.

Fig. 2. Histopathologic section of case 1.

Case 2
A 40-year-old female patient reported to our department
with chief complaint of blackish discoloration/patch in maxillary anterior gingivae for 4 months which was rapidly growing in size. The patient consulted a local hospital, where she
was advised to undergo incisional biopsy for diagnostic purpose. But she declined and visited our department for personal reasons. On examination, an elevated black to brown
patch of approximately 5 3 cm was noted involving maxillary attached gingivae extending from right central incisor to
left second premolar area. Superoinferiorly it was involving
the whole of gingivae extending up to the mucogingival
junction (Figure 3). The lesion was firm in consistency and
tender on palpation. It was also extending onto the palate
where a black to brown discoloration of approximately 4 3
cm was present in the anterior half of the palate on the left
side which was crossing midline in incisive papillae region
(Figure 3). Small brown spots were also noted on the right
side of palate. The lesion was asymmetric with irregular
borders along with color variegation present, and it was
enlarging in size. These are characteristic features of malignant melanoma along with the fact that lesion was also
elevated. Therefore, keeping OMM as provisional diagnosis,
thorough physical examination, oropharyngeal examination,
and chest radiography were done to rule out any metastatic

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CASE REPORT
Mohan et al. e249

Fig. 3. Case 2. A, Clinical presentation. B, Palatal view.

Fig. 4. Case 2. A, B, Resected specimen. C, Postresection view showing amniotic membrane dressing.
lesion. No clinically palpable lymphnodes were detected on
neck examination. CT scan showed no gross bony invasion,
and cervical lymph node involvement was ruled out.
Excision of the lesion was performed under general anesthesia with Le Fort I level maxillectomy and adequate soft
tissue margin of 1.5 cm all around the lesion (Figure 4).
Bilateral buccal pad of fat was mobilized to cover the maxillary sinus and the entire area of defect was covered with
amniotic membrane (Figure 4). The postoperative period was
uneventful, and the patient was discharged on postoperative
day 8 with a temporary obturator.
Histopathologic examination revealed stratified squamous
parakeratinized epithelium with long and narrow rete ridges.
Ovoid and spindle-shaped tumor cells were seen at junction as
well as infiltrating into underlying connective tissue (Figure 5).
Increased junctional activity was noted along with pleomorphism of tumor cells. Numerous large melanophages were seen
in the vicinity, along with dense chronic inflammatory cells
mainly in the form of plasma cells and lymphocytes. Margins of
the specimen were free from the tumor cells.
At 1 month follow-up, the surgical site had healed well and
no local or regional recurrence was noted, and the patient was
referred for adjuvant chemoradiotherapy. At the time of this
writing, the patient had been closely followed for 1 year with
appointments every 3 months for local examination and chest
radiography to rule out metastasis.

DISCUSSION
Pigmented lesions of melanocytic origin is a rare occurrence in the oral cavity, and they can span a spec-

Fig. 5. Histopathologic section of case 2.

trum ranging from innocuous lesions, such as oral

melanotic macule, and various benign nevi to lifethreatening malignant melanoma of oral mucosa.
Therefore, meticulous clinical and pathologic examination must be made of any suspicious lesion to avert the
progress of a malignant melanoma.
OMM is an extremely rare and very aggressive tumor of melanocytic origin. Apart from oral mucosa
malignant melanoma can affect mucous membranes of
nose and paranasal sinuses, pharynx, and conjunctiva.
As a group, mucosal melanomas invade and spread

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e250 Mohan et al.

more quickly and metastatize more frequently, and are

therefore associated with much poorer prognosis than
cutaneous melanomas.
After conjunctiva, oral cavity and sinonasal tract are
the second most common affected sites in the head and
neck region.4 In the oronasal region approximately
one-half of melanomas occur in the oral cavity (48%)
and the remaining portions are located in the nasal
cavity (44%) and sinuses (8%).2,3 OMM accounts for
only 0.5% of all oral malignancies,5 and oral melanoma
represents 0.2%-8.0% of all melanomas.5 OMM usually occurs in the fourth to sixth decades of life and is
extremely rare before 30 years of age.6 Some studies
have shown a male predilection of 2:1, whereas other
studies show no sex predilection.3,7 OMM is known to
occur more frequently in Japanese, African, and North
American Indian populations than in European populations.8-13 Most commonly involved intraoral site is
palate and maxillary alveolar gingiva.7,9,13,14 and they
are labeled as high-risk sites for OMM.5 Other sites less
frequently affected include the labial and buccal mucosa, tongue, and floor of mouth.5
Etiology of OMM is essentially unknown. Unlike
cutaneous melanoma, no definite risk factors for OMM
have been defined, and tobacco use as well as chronic
irritation from ill-fitting dentures has been mentioned as
possible risk factors.12 Also, a possible role of ingested
and inhaled environmental carcinogens at higher internal body temperature has been suggested.15 Most
OMMs are thought to arise de novo from apparently
normal mucosa. But it has been shown that one-third of
patients have a history of preexisting oral pigmentation
for several months or even years before diagnosis of
malignant melanoma.12 Some of these flat precursor
lesions actually consist of atypical melanocytes and
represent radial growth phase of malignant melanoma,
whereas others represent benign proliferation of melanocytes. Exact mechanism for transformation of benign
melanocytic nevus to melanoma is not known, but
expressions of some melanoma-associated antigens
have been implicated.3 p53 protein alterations have
been identified in two-thirds of OMMs, and a recent
study demonstrates loss of heterozygosity at 12p13 and
loss of p27KIP1 protein expression contributing to melanoma progression.3
The most common presenting symptom is a pigmented swelling. Hemorrhage and ulceration are usually late findings when the lesion has entered vertical
growth phase.3,5 OMM can be uniformly brown or
black, or variable pigmentation may be present which
ranges as black, brown, gray, purple, red, and/or white.
The lesions are asymmetric, irregular in outline, and
occasionally multiple, which represents satellite lesions.5 Umeda et al. noted that on close examination

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October 2013

typical OMM usually presents with 3 distinct components: a nodular component usually affecting the center; a flat or slightly elevated, deep brownish-black
pigmented plaque component; and a nonelevated light
brown macular component.16 Approximately 10% of
cases are known to be amelanotic in nature, lacking
macular component, thus posing a difficulty in diagnosis.17 Induration is usually absent in cases with prolonged radial growth phase or with minimal invasion.
Other presenting signs and symptoms include bleeding,
ill-fitting dentures, pain, increased mobility of teeth,
and delayed healing of extraction sockets.5
Tanaka et al.18 identified 5 types of OMM based on
clinical appearance: pigmented nodular type, nonpigmented nodular type, pigmented macular type, pigmented mixed type, and nonpigmented mixed type.
Mucosal melanoma can be primary or metastatic. It
is therefore very important to rule out any other primary
malignant melanoma elsewhere in the body. Green et
al. gave criteria for diagnosis of primary OMM as
follows19:
1. Demonstration of clinical and microscopic tumor in
the oral mucosa.
2. Presence of junctional activity in the oral mucosa.
3. Inability to show any other primary site.
Both of our patients fulfilled all of these criteria.
Diagnosis of OMM can be made based on clinical
presentation of the pigmented lesion with the so-called
ABCD checklist (asymmetry, border irregularities,
color variegation, and diameter 6 mm) that is commonly used for cutaneous melanomas. Deferential diagnosis includes melanoma, melanotic macule, oral
pigmented nevus, smokers melanosis, amalgam tattoo,
and Kaposis sarcoma.5
It has often been suggested that cutting into an
OMM, either for incisional biopsy or other invasive
procedures, may lead to seeding of tumor cell into
adjacent tissue or even into bloodstream or lymphatics,
leading to dissemination of tumor cells and increased
rate of metastasis. Umeda et al.16 in his study concluded that 5-year survival rate of patients who underwent some surgical procedures, such as incision, biopsy, or tooth extraction, before definitive surgery was
poor (25.9%) compared with those who did not undergo such procedures (91.7%). Similar results were
shown by Rampen et al. and Austin et al.20 However,
many authors believe that biopsy of an undiagnosed
lesion, pigmented or nonpigmented, occurring in high
risk sites for OMM should be done, because benefits
gained by a definite diagnosis of OMM far more outweigh the risk of distant metastasis which is not yet
fully established.21-23 According to Batsakis,24 there is
no evidence that a preliminary biopsy of the primary

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Volume 116, Number 4

lesion increases the risk of metastatic dissemination or

unfavourably affects prognosis. Excisional biopsy of
small lesion should be performed and incisional biopsy
from the thickest and darkest area is recommended for
larger lesions.25
Apart from biopsy, radiologic examination through
CT, magnetic resonance imaging, or positron-emission
tomography could be useful for evaluation of primary
tumor invasion and regional or distant metastases. Robert Marx et al. recommends a chest radiograph as the
primary diagnostic tool for metastatic workup and on
every 6-month follow-up after surgery to assess for
distant metastasis, because lungs and liver are the most
commonly affected organs with OMM metastases.26 In
both of our patients, CT scan was done to assess the
primary lesion and its invasion of bone along with
assessment of neck for regional spread. Case 1 showed
bony invasion of palate, and both patient had no regional involvement of neck nodes.
No definite classification for OMM exists, in contrast
to cutaneous melanoma which is divided into clinically
and pathologically well defined varieties. In the past it
was thought that OMM represented a mucosal counterpart of acral lentiginous melanoma, based on similar
histopathologic findings, but it was observed that OMM
has a very different biologic growth pattern and very
poor prognosis. Therefore, it was thought that clear
distinction should be made between cutaneous melanomas and OMM. During the Workshop on OMM, convened at the Western Society of Teachers of Oral
Pathology annual meeting in 1995, the authors agreed
on the fact that oral lesions should be considered separately from cutaneous melanomas until definitive information on cause and natural history of OMM is
forthcoming. In situ OMM, invasive OMM, invasive
melanoma with in situ component, and atypical melanocytic proliferation are the preferred descriptive terms.5
TNM staging for cutaneous melanoma does not provide specific guidelines for OMM. A simple clinical
staging system for head and neck mucosal melanomas
is commonly used and has been shown to be of prognostic value. Prasad et al.27 has proposed histopathologic microstaging for stage I tumor (Table I).
Microscopically, two patterns have emerged for the
mucosal melanomas: an in situ pattern in which the
neoplasm is limited to the epithelial-connective tissue
interface; and an invasive pattern in which the neoplasm was found within the supporting connective tissue. Also, a combined pattern of invasive melanoma
with in situ component is typical of most advanced
lesions. Varied types of neoplastic cells, including spindled, plsmacytoid, and epitheloid, are seen in invasive
melanoma. They are usually arranged in either sheetlike, organoid/alveolar, neurotropic, or desmoplastic

CASE REPORT
Mohan et al. e251

Table I. Clinical staging system for oral malignant melanoma with histopathologic microstaging for stage I
Stage I

Stage II
Stage III

Primary tumor present only (Tany N0 M0)

Level I: pure in situ melanoma without evidence of
invasion or in situ melanoma with
microinvasion
Level II: invasion up to the lamina propria
Level III: deep skeletal tissue invasion into skeletal
muscle, bone, or cartilage
Tumor metastatic to regional lymphnodes (Tany
N1 M0)
Tumor metastatic to distant sites (Tany Nany M1)

Table II. Breslow scale for the measurement of tumor

thickness of oral malignant melanoma
Thickness (mm)

Risk of recurrence

0.76
0.76-1.50
1.50-3.99
4.00

Low risk
Low to intermediate risk
Intermediate to high risk
High risk

pattern. Approximately 10% of cases are amelanotic,

for which diagnosis requires immunohistochemical
staining. Various markers commonly used are S-100
protein, HMB45, and Melan-A.3
Measurement of tumor thickness should also be included in the report, because it is shown to be a strong
predictor of prognosis.28 Breslow measurement for tumor thickness is usually used, in which tumor thickness
is determined with the use of a micrometer in the ocular
of a microscope (Table II).26
Usually, OMM tends to present at a more advanced
stage compared with cutaneous melanomas, with 70%
of stage I and 83% of stage II tumors presenting with a
thickness 4 mm, leading to poor prognosis.29
Most authors think that the mainstay of treatment for
OMM is surgery with wide clear margins; however, most
of the time proximity of vital structures makes this objective difficult. Also, most OMM presents at a more advanced stage, when the tumor has entered vertical growth
phase with deep invasion of surrounding tissue and bone,
requiring extensive resection to achieve clear margins. For
the most common site, the palate, surgery usually consist
of a type of maxillectomy with 3-5-cm margins and sometimes it is necessary to extend the excision to the soft
palate and tonsillar pillar, and into the pterygomaxillary
space. No particular guidelines for the surgical treatment
of OMM exist, and treatment of most patients is left to the
discretion of the individual surgeon. Umeda and Shimada29 suggested a protocol for management of OMM
which refers to the extent of margins:
1. Excision of the primary lesion, preferably using an
intraoral approach and involving at least 1.5 cm of
healthy tissue.

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e252 Mohan et al.

2. Excision of any lymph node metastasis (stage II).

3. Consider chemotherapy.
Tanaka et al.30 reported that primary lesion was controlled in 92.3% of cases with surgery, whereas in a
nonsurgery group treated with radiotherapy, only 53%
cases had controlled primary lesion. This clearly correlates with the traditional opinion of surgery being the
treatment of choice, with radiotherapy and chemotherapy having only adjunctive roles. During the 1995
Workshop on OMM, it was concluded that there is
currently no compelling new information that would
suggest that another approach would be better. Moreover, they also advised that serious consideration
should be given to combination therapy in primary
patient care, because of the high recurrence rate associated with OMM.5
Another area of controversy in OMM is regarding
the issue of prophylactic neck dissection. Various authors have reported lymph node metastasis in primary
OMM at approximately 25%-50%.3,30,31 According to
Shah et al., regional metastases at the time of presentation do not affect the survival of patients with OMM,
whereas other authors think that it carries a negative
prognostic value.29,32 According to most authors, neck
dissection should be reserved for cases with preoperatively confirmed lymph node metastasis, and the choice
of the neck dissection modality should be guided by the
extent and the level of nodes. There is no proof that
prophylactic neck dissection improves survival.30,33
Both of our patients were treated with surgical resection of palate with 1.5-cm macroscopic margin all
around the lesion which is as per the guidelines given
by Umeda and Shimada et al.29 The patient of case 1
developed neck node involvement after 2 months,
though local recurrence was not present. According to
Snow et al., lymph node metastases rarely develop
without local recurrence after initial treatment of primary lesion. But this was not the case in our patient;
even Tanaka et al reported good loco-regional control
with surgery alone or surgery combined with other
treatments.30 Bilateral neck dissection was performed
in this patient.
Very few studies are done on the effect of primary
radiotherapy for OMM, and it does not show any apparent advantage over surgery based on survival rate
and local control.30 Postoperative radiotherapy is recommended in cases with positive surgical margins or a
strong likelihood of local or regional recurrence.4 Various studies have shown that postoperative radiotherapy was useful for increasing local control,34-36 but it
does not seem to improve survival rate.3 It has been
suggested that local failure is a harbinger of distant
metastases in mucosal melanoma, because the majority

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October 2013

of patients who die of distant metastases have also local

or regional recurrent disease. Therefore, efforts to improve loco-regional control by adding postoperative
radiotherapy might also result in higher survival rates.
Another role of radiotherapy is in advanced disease,
where it is used as a primary treatment modality for
palliation. Radiotherapy is the most effective treatment
modality for unresectable disease.37
Role of adjuvant chemotherapy in management of
OMM does not seem to influence survival.3 Umeda and
Shimeda et al.29 reported that adjuvant chemotherapy
with dimethyl triazeno imidazole carboximide, nimustine hydrochloride, vincristine, and biologic response
modifier OK-432 was effective for OMM and shows
improved survival rate. Another recent retrospective
study showed that adjuvant chemotherapy decreased
the relapse rates of both local and distant metastasis
disease.38 But further studies are necessary to assess the
definitive role of adjuvant chemotherapy in OMM.
Most of patients die owing to distant metastases to
lungs, brain, liver, and bones despite good locoregional
control. Because many patients dies of disseminated
disease, it makes sense to add a systemic therapy when
treating advanced OMM. Systemic immunotherapy
with interleukin-2 and other cytokines has not shown
very encouraging results, and further research is required to develop some sort of definitive targeted systemic therapy.3
There is no disagreement regarding prognosis of
OMM, and a majority of reported case series attest to
that. OMM carries a quite poor prognosis compared
with its cutaneous counterpart. The average survival
rate after diagnosis has varied from 13% to 20% in
various case series, and mean survival for OMM is 28
months.39 Various prognostic factors have been put
forward for OMM, but to date only clinical staging at
presentation has been affirmed by all as the most important factor determining outcome. Other independent
risk factors are thickness of the tumor (5 mm), cervical lymph node metastases, anatomic site (palate being poorer than gingiva), and presence or absence of
ulceration.3 The reasons for poor prognosis are not
known with certainty, but various probable reasons are
put forward, the most important of them being late
diagnosis of OMM due to nonspecific symptoms. Others include anatomic location, because mucosal tumors
can easily invade the deeper structures, such as bone.
Also, there is high vascularity of oral mucous membrane, which along with earlier bone invasion can contribute to the high incidence of distant metastases.31
Also because of anatomic location, sometimes it is
difficult to achieve clear margins during resection. Positive surgical margins are seen in 43% of OMM4 and
have been shown to be associated with poor outcome.

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Volume 116, Number 4

CONCLUSION
Malignant melanoma is a rare tumor of the oral cavity,
with very poor prognosis. Local, regional, and distant
metastases occur in OMM despite the implementation
of aggressive multimodal treatment. Because late diagnosis with advanced disease at the time of diagnosis is
the only sure predictor of outcome, thorough clinical
and pathologic work-up of any suspected melanotic
lesion should be carried out to diagnose OMM in its
early stages. Early diagnosis and aggressive multimodal treatment are the only means available to surgeons to provide better outcome to a patient with
OMM. There is also need for pooling of data from
various centers to analyze key determinants of outcome
and thereby establish a treatment policy.
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Reprint requests:
Vihang Y. Sukhadia, MDS
Surgical Fellow
Dr. Jeysekharan Centre for Cleft Care
K P Road
Nagercoil 629 003
Tamilnadu
India
vihangsukhadia@gmail.com