J Oral Pathol Med (2008) 37: 383–388
doi: 10.1111/j.1600-0714.2008.00660.x
REVIEW ARTICLE
Oral malignant melanoma: a review of the literature
Felice Femiano, Alessandro Lanza, Curzio Buonaiuto, Fernando Gombos, Federica Di Spirito, Nicola Cirillo
Stomatology Clinic, School of Medicine and Surgery, University of Naples 11, Naples, Italy
Primary oral melanoma (POM) is an uncommon malig-
nant tumor that originates from the proliferation of
melanocytes. Such tumors can be present at any location
in the oral cavity; however, it affects more frequently the
hard palate and the maxillary alveolar mucosa. POM is
usually asymptomatic in the early stages and it presents
normally as a pigmented patch or as a mass with a rapid
growth rate. In the advanced stages, it can show ulcera-
tion, swelling, bleeding, rapid enlargement and loosening
of teeth. Melanoma of the mouth is rare, most commonly
occurring in the upper jaw of patients more than
65 years. Because of a frequent delay in diagnosis, the
tumors are often diagnosed when they are deeper than
the average cutaneous melanoma. The prognosis is ex-
tremely poor, especially in advanced stages. Therefore,
pigmented lesions of undetermined origin should be
routinely subjected to a biopsy examination. In this study,
we aimed to present a review on primary malignancy.
J Oral Pathol Med (2008) 37: 383–388
Keywords: mucosal melanoma; oral melanoma; pigmented
lesions
Introduction
A melanoma is a malignant tumor comprising melano-
cytes, which are cells derived from the neural crest that
constitute the melanin pigment in the basal layer of
epithelium. Although most melanomas arise in the skin,
they may also arise from mucosal surfaces or at other
sites wherein neural crest cells migrate (1, 2).
Primary oral melanoma (POM) is a rare neoplasm
(accounting for approximately 2% of all melanomas)
and is known to share some clinical features with its
cutaneous counterpart.
As a result, there is a paucity of data elucidating its
etiopathogenesis and predictive factors. Altogether,
primary mucosal melanomas behave more aggressively
and have a poorer prognosis than their cutaneous
Correspondence: Dr Femiano Felice, Via Francesco Girardi 2,
S. Antimo, Naples 80029, Italy. Tel: +39 81 8304248, Fax: +39 81
5665477, E-mail: femiano@libero.it
Accepted for publication December 17, 2007
ª 2008 The Authors. Journal compilation ª 2008 Blackwell Munksgaard Æ All rights reserved
www.blackwellmunksgaard.com/jopm
counterparts. Because of the unusual anatomic locations
in which they occur they are easily mistaken for other
diseases in far more common conditions, and because of
the lack of early signs and symptoms mucosal melano-
mas are always diagnosed at advanced stages. Their
5-year survival rate is 15–38% (2, 3).
Pigmented lesion of the oral cavity should be viewed
with suspicion because it does not possess clinical
specificity. It must be differentiated from other forms
of pigmented oral disease, including drug, disease- or
smoking-associated melanosis, oral melanotic macule,
Kaposi’s sarcoma, physiologic or racial pigmentation,
melanocytic nevus and melanoacanthoma (4, 5).
The most common oral cavity sites of POM are the
palate and the maxillary gingiva. POM is slightly more
common in men and is generally not diagnosed before
40 years. The peak age for diagnosis of mucosal
melanoma is between 65 and 79 years, on average one
to two decades later than cutaneous melanoma (6, 7).
Pathophysiology
Despite the existence of POM being known for a long
time, the etiology of this neoplasm is still obscure. As
neuroectodermal derivatives, melanocytes are known
to migrate to the skin, retina, uveal tract and other
ectodermally derived mucosae. Melanocytes migrate
much less frequently to endodermally derived mucosae,
such as the nasopharynx, larynx, tracheobronchial tree
and esophagus. This explains the lower frequency of
melanoma in these locations. Although their function is
not fully understood, the presence of melanocytes in the
mucous membranes is well established (1, 6).
Melanocytes have also been documented in the deep
stroma of oral mucosa. Because mucosal melanomas
are frequently found at mucocutaneous junctions, they
were once believed to arise only as extensions of
melanocytic hyperplasia from adjacent skin. Indeed,
some mucosal melanomas do evolve in this manner.
However, there are now several cases describing
primary melanocytic junctional activity solely within
the mucosal epithelium.
The incidence of melanoma on skin has been reported
to be higher in patients of darker races, such as the
Orientals, Hispanics and Africans (8).
 Oral melanoma
Femiano et al.
384
Ethnicity and sun exposure appear to play a major
role in the development of cutaneous melanoma. Ultra-
violet-B light is believed to be the most important factor
during sun exposure. According to epidemiologic data,
those with blond hair, blue eyes and those who tend to
burn or freckle easily after sun exposure are at the
highest risk. Mucosal melanoma, on the other hand, has
no association with sun exposure. Cigarette smoking,
denture irritation and alcohol are some of the risk
factors, but the correlation is unsubstantiated and risk
factors remain obscure (9).
Clinical and histologic features
Primary oral melanoma is initially asymptomatic and
usually not noticed by the patients, which contribute to
the delay in diagnosis.
Most POMs appear as new lesions from apparently
normal mucosa, whereas about 30–50% are preceded by
oral pigmentations for several months or even years.
Some of these flat pre-melanoma lesions include the so-
called mucosal melanosis [i.e., a junctional proliferation
of melanocytes, with or without cytological atypia,
resulting in a macular hyperpigmentation (pre-invasive
macular phase of melanoma)] and a variety of melan-
ocytic nevi (5, 10).
Nevi are histologically benign proliferations of nevus
cells either in the epithelium or in the subepithelial
stroma. They are categorized as hamartomas rather
than true neoplasms. Nevi of the oral cavity are usually
called mucosal melanocytic nevi or intramucosal nevi.
On the basis of the histologic location of nevus cells,
oral nevi can be classified into three categories. The first
category includes junctional nevus that is when nevus
cells are limited to the basal cell layer of the epithelium.
In the second category, compound nevus is used if the
cells are found in the epithelium and the subepithelial
connective tissue. The third category, subepithelial
nevus, is when nests of nevus cells are entirely in the
subepithelial connective tissue. Although rare, malig-
nant transformation of nevi to melanoma involves the
clonal expansion of cells that acquire a selective growth
advantage. This transformation of melanocytes, in an
existing nevus or of a single melanocyte in the basal cell
layer, must occur before the altered cells proliferate in
any dimension (10, 11).
In cutaneous melanomas, well-known differences
exist in the biologic behavior of the radial growth-phase
melanoma (flat or macular), vertical growth-phase
melanoma (mass, nodule and elevation) and vertical
growth-phase melanoma with metastasis (12). Elder
et al. have reported that these different growth patterns
require cellular alteration or transformation to progress
to the next, more biologically aggressive, phase. If this is
consistent with the biologic behavior of cutaneous
melanoma, the natural history of POMs gives evidence
for a more anomalous and unpredictable behavior.
Indeed, radial growth-phase melanomas of the oral
cavity do not tend to invade the underlying reticular
corion, but they are associated with metastasis. Vertical
growth-phase melanomas, although invasive, must
J Oral Pathol Med
achieve some competence before subsequent metastasis
can occur.
Besides, they have described this progression and
state that differences in each phase are qualitative.
However, phase progression is not absolute because
most benign melanocytic lesions do not evolve into
melanoma. Melanoma development requires a biochem-
ical alteration in the precursor cells undergoing clonal
expansion. This alteration triggers off an accelerated
growth and invasive potential, but not necessarily
progress from the horizontal to the vertical growth
phase (13).
Malignant melanoma of the skin has been divided
into four types: (i) lentigo maligna melanoma (LMM),
(ii) superficial spreading melanoma (SSM), (iii) nodular
melanoma (NM), and (iv) acral-lentiginous melanoma
(ALM).
Lentigo maligna melanoma, also denominated as
melanoma in situ, frequently occurs in sun-exposed
areas. Its radial growth phase can be present for up to
25 years, having the best prognosis of the other three
types. SSM is the most usual type, commonly found as a
slightly elevated pigmented patch lesion with a regular
outline. NM is usually an elevated lesion with vertical
growth only; thus, it metastasizes early and shows very
poor prognosis. ALM is the most common melanoma in
dark-skinned people. This type can occur on the palms,
soles and nail beds (subungual). Like NM, ALM is
extremely aggressive, with rapid progression from the
horizontal to the vertical growth phase.
In spite of this, the classification of oral melanoma
(OM) is still controversial because of its different
behavior (14, 15).
Many POMs have a histologic similarity with LMM
in its radial growth phase. However, once invasion
begins, oral lesions are very aggressive and can metas-
tasize similar to the vertical growth phase of SSM.
Some investigators reported that POM-like palmar,
plantar and subungual melanomas, which are aggressive
types of skin melanomas, should be classified as ALM
(16–18).
Clinical features vary, but the most common presen-
tation is that of an asymptomatic brown, dark blue or
black macule, sometimes with erythema or ulceration.
Small lesions can easily be confused with benign
conditions such as reactive denture hyperplasia caused
by an ill-fitting upper denture, amalgam tattoos. Thus,
they can enlarge, and local or distant metastases can
occur until identification is completed. A more advanced
disease may take on nodular or irregular surface
characteristics. They may exhibit asymmetric and irreg-
ular borders just like cutaneous melanomas. In the
mouth, bony erosion is common.
Melanomas may be difficult to distinguish on a
clinical basis from solitary oral melanotic macules’,
labial lentigines, foreign bodies or racial pigmentation.
Amelanotic lesions may simulate pyogenic granulomas
(19–21).
Oral melanoma is related to pre-existing radial growth
phase through the epithelium identifying macular
melanosis’ in about one-third of the cases, and such

an oral pigmentation (melanoplakia) can be a normal
finding in most pigmented races (22).
Some of the pre-existing hyperpigmentation in OM
cases appears histologically benign, without significant
cytological atypia, whereas in other cases they appear to
represent melanoma in situ from the beginning. Small
biopsy specimens may result in an erroneous benign
diagnosis. In some cases, the macular pigmentation or
melanoma in situ may persist for years before deeper
invasion, as with lentigo maligna (melanoma in situ of
sun-damaged skin).
Melanocytic nevi are believed to be precursors of
melanomas in the mouth in only a small minority of
cases. Because oral nevi are rare and their biologic
behavior may be uncertain, routine prophylactic exci-
sion has been recommended. When oral nevi appear,
they are most commonly found on the palate: the most
common site for OM as well (11, 15, 23).
Oral melanotic macules (increased melanotic pigmen-
tation in the basal and occasionally in the immediately
suprabasal keratinocytes), melanoacanthoma or mela-
noacanthosis (probably reactive proliferation of both
keratinocytes and melanocytes) and oral melanocytic
nevi can represent oral lesions preceding OM.
Like melanomas of the skin, invasive OM can exhibit
epithelioid or spindled nuclei, and they may be pig-
mented or amelanotic.
The surface architecture of mucosal melanomas
ranges from macular (melanomas in situ) to ulcerated
and nodular (invasive melanomas and invasive with
in situ component).
It requires the utmost attention and suspicions of
these irregular or heterogeneous macules (even those less
than 1 cm in greatest dimension) occur in high-risk sites
(palate and gingiva) potentially representing as in situ
melanomas (24, 25).
The mucosal melanomas can show two principal
patterns: an in situ pattern in which the neoplasm is
limited to the epithelium and the epithelial–connective
tissue interface (junctional), and an invasive pattern in
which the neoplasm is found within the supporting
connective tissue. A combined pattern of invasive
melanoma with in situ component is typical for most
advanced lesions. Approximately 15% of cases are
represented by in situ mucosal lesions, 30% are invasive
lesions and 55% are lesions having a combined pattern.
Because of the differences in clinical features, histo-
logic characteristics and prognosis, OM is not easily
classified into the existing cutaneous melanoma catego-
ries (nodular, superficial spreading, lentigo maligna and
ALM) (26–29).
At present, OMs should continue to be separated
from cutaneous lesions and that they should be simply
subclassified into in situ and invasive types.
The 1995 WESTOP Banff Workshop recommended
that OM should be classified separately from cutaneous
lesions and terminology should include descriptive terms
such as melanoma in situ and invasive melanoma.
In association with these categories, two further types
were considered. One type is described as invasive
melanoma with an in situ component (mixed in situ and
Oral melanoma
Femiano et al.
385
invasive oral mucosal melanomas) and the other type is
defined as an atypical melanocytic proliferation (bor-
derline lesion) to identify lesions that may have origi-
nated from an in situ melanoma.
The surface architecture of mucosal melanomas
ranges from macular (in situ melanomas) to ulcerated
and nodular (invasive melanomas and invasive with
in situ component) (30).
Microscopically, melanomas in situ show an increase
in atypical melanocytes. Although these atypical mela-
nocytes have angular and hyperchromatic nuclei, mitoses
tend to be sparse. The melanocytes may form aggregates
or may be irregularly distributed in a junctional location.
The melanocytes present in invasive melanomas show a
variety of cell types including epithelioid, spindle and
plasmacytoid. They typically have large, vescicular
nuclei with prominent nucleoli; mitoses may be present
but usually not in large numbers. They are usually
aggregated into sheets or alveolar groups and less
commonly neurotropic or desmoplastic configurations
are seen.
About 10% of cases are amelanotic. More than 95%
of lesions are anti S-100 antigen positive and more
specific markers include HMB45, Melan-A and anti-
tyrosinase (24, 31).
Diagnosis
Pigmented melanoma is usually easy to diagnose
clinically, as there is often a variation in color from
red to black to brown, asymmetry and an irregular
outline, but amelanotic lesions have also been reported.
Unfortunately, OMs usually remain asymptomatic with
recognition of the lesion occurring when there is a
breakdown of the overlying epithelium or hemorrhage
(32, 33).
As with non-melanoma skin cancers, biopsy is indi-
cated for all suspicious pigmented lesions. According
to the American Academy of Dermatology (AAD)
Guidelines, whenever possible, the lesion should be
excised with narrow margins for diagnostic purposes.
An incisional biopsy technique is appropriate when
suspicion for melanoma is low, when the lesion is large
or it is impractical to perform a complete excision (33).
Greene et al. proposed three criteria for the diagnosis
of POM:
• demonstration of malignant melanoma in the oral
mucosa;
• presence of the so-called junctional activity’ (i.e.
melanocytes arranged along the basal layer of the
surface epithelium) in the lesion;
• inability to show malignant melanoma at any other
primary site (34).
However, the presence of junctional activity’ is now
known to be an unreliable indicator and that the lesion
is a primary one because melanoma metastases may
similarly involve the epithelial junction. Cytological
examination and brushed samples were negative in all
the cases with a proven histologic diagnosis of POM
(35).
J Oral Pathol Med
 Oral melanoma
Femiano et al.
386
It should be borne in mind that in cutaneous
melanoma, fine needle aspiration or exfoliative cytology
of primary pigmented lesions is contraindicated.
Differential diagnosis has to be considered for the
following pathologies and conditions: amalgam tattoo,
Kaposi’s sarcoma, vascular blood-related pigments, oral
melanotic macule, physiologic pigmentation, Peutz–
Jeghers syndrome, Addison disease, and drug-induced
pigmentation.
The amalgam tattoo is frequently found in persons
who have had amalgam for dental restorations. When
the amalgam is removed with a high-speed dental
handpiece, amalgam particles can be embedded in
the oral mucosa. Kaposi sarcoma is often observed in
the mouths of patients with AIDS, and it is a red-to-
violaceous, vascular proliferation caused by human
herpesvirus 8. Ecchymosis and petechiae are common
in the junctional area of the hard and soft palates.
Melanin pigmentation is a common feature of the oral
mucosa. This pigmentation is observed diffusely as
racial pigmentation, which can be patchy, and focally as
melanotic macules and nevi. The relative constancy of
the brown color, without variegation, indicates its
benign status. Melanotic macules are common on the
lip, but they are also found in the oral cavity. Patients
with Peutz–Jeghers syndrome have pigmented lesions of
the oral mucosa with intestinal polyposis, and a family
history can typically be elucidated.
In Addison patients, the oral pigmentations are
caused by activity of melanocyte-stimulating hormone:
ACTH via MC1 receptors (36).
Medication-induced pigment may be more localized
and blotchy. Azidothymidine is often the culprit (33,
37).
Staging
Determination of the melanoma stage is important for
planning appropriate treatment and assessing prognosis.
Prognosis of cutaneous melanoma is based on Clark’s
level of tumor invasion relative to the layers of the skin
interested. In relationship to this, cutaneous melanoma
is classified into five levels in Table 1.
Classification is not a valuable prognostic determi-
nant for oral cavity tumors. As there are no muscle
bundles and a true dermis in the oral cavity, we cannot
apply Clark’s classification to these tumors (38).
In general, the growth of mucosal melanoma closely
resembles the nodular pattern of its cutaneous counter-
part. This characteristic, in part, explains the poor
Table 1 Classification of tumor based on Clark’s level
Level I All tumor cells are confined to the epidermis,
above the basement membrane (in situ)
Level II Tumor invades into the papillary dermis, past
the basement membrane
Level III Tumor fills the papillary dermis and extends
to the interface between the papillary and
the reticular dermis
Level IV Tumor invades the reticular dermis
Level V Tumor invasion of subcutaneous tissue
J Oral Pathol Med
Table 2 Clinical staging system for POM with histopathological
microstaging for stage I
Stage I Primary tumor present only (N0M0)
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
Stage II Tumor metastatic to regional lymph nodes (N1M0)
Stage III Tumor metastatic to distant sites (M1)
prognosis of these lesions, and several studies have
corroborating data that link survival most closely with
tumor thickness. Patients with lesions of less than 2 mm
thick have a significant survival advantage compared
with those with lesions of greater than 2 mm.
The American Joint Committee on Cancer (AJCC)
does not have published guidelines for the staging of
oral malignant melanomas.
A simple TNM classification of malignant tumors
(TNM) clinical staging system for oral mucosal
melanoma recognizes three stages, and this system
has been shown to be of prognostic value. A recent
histopathological microstaging for stage I subclassifies
itself into three levels (Table 2) (19, 34, 39, 40).
Prognosis and therapy
Medical therapy is not often beneficial with OM. Drug
therapy (dacarbazine), therapeutic radiation and immu-
notherapy are used in the treatment of cutaneous
melanoma, but they are of questionable benefit to
patients with OM. Dacarbazine is not effective in the
treatment of OM; however, dacarbazine administration
in conjunction with interleukin-2 (IL-2) may have
therapeutic value (41–43).
Other immunotherapeutic drugs that are occasionally
used include interferon and cimetidine, which, when
used together, are believed to activate killer T cells and
inhibit suppressor T cells, resulting in a reduction in the
size of the melanoma.
Surgery remains the preferred treatment. Recently,
surgical excision with a course of IL-2 as adjunctive
therapy to prevent or limit recurrence has been proposed,
but there are only few data in the literature. The
prognosis for patients with oral malignant melanoma is
relatively dismal, but early recognition and treatment
greatly improve the prognosis (19, 44). Unfortunately,
late discovery and diagnosis often indicate the existence
of an extensive tumor with metastasis. After surgical
ablation, recurrence and metastasis are frequent events,
and most patients die because of the disease in 2 years.
Tumor vaccines are being widely used as adjuvant
therapy for melanoma. Vaccines have potential for
preventing recurrence and prolonging survival when
patient has been rendered clinically tumor free by
standard means, such as surgery, but is known to be at
high risk of recurrence (45, 46).
A review of the literature indicates the 5-year survival
rate to be within a broad range of 4.5–48%, but a large
cluster occurs at 10–25% (35).

The best option for survival is the prevention of
metastasis by surgically excising any recurrent tumor.
Systemic chemotherapy is used in patients with
advanced stage II or III melanoma in which response
to therapy is associated with prolonged survival. The
main objective of therapy for patients with metastatic
malignant melanoma is palliation. It is generally agreed
upon that melanomas are not radiosensitive. Irradiation
therapy is used occasionally as a primary modality in the
older population and in medically compromised pa-
tients. However, a few patients with OMs have been
reported to have a good response to X-ray that can
achieve temporary shrinkage of tumor size without a
lasting cure (47).
Conclusions
Primary mucosal melanomas are exceedingly rare and
biologically aggressive malignancies. The natural history
of melanoma in situ within the oral cavity is not known
for certain, but it is considered to be a lesion which will
evolve into invasive melanoma over time. If diagnosis of
melanoma is early, essentially during melanoma in situ
stage, it is potentially curable.
Intraoral malignant melanomas are easy to diagnose
clinically, as they are pigmented and have an irregular
shape and outline. These lesions usually remain asymp-
tomatic and may be detected only when there is an
ulceration of the overlying epithelium and⁄or hemor-
rhage.
We wish to emphasize how essential it is to maintain a
high index of suspicion for any pigmented lesion within
the oral cavity, but especially for those occurring in
high-risk sites such as the palate and the maxillary
gingiva. Practitioners in these fields must maintain a low
threshold for performing biopsies of suggestive lesions
in these occult anatomic locations.
References
1. Boulaadas M, Benazzou S, Mourtada F, Sefiani S, Nazih
N, Essakalli L, Kzadri M. Primary oral malignant
melanoma. J Craniofac Surg 2007; 18: 1059–61.
2. Ebenezer J. Malignant melanoma of the oral cavity. Indian
J Dent Res 2006; 17: 94–6.
3. Doval DC, Rao CR, Saitha KS, et al. Magliant melanoma
of the oral cavity: report of 14 cases from a regional cancer
centre. Eur J Surg Oncol 1996; 22: 245–9.
4. Satter EK. Pigmented squamous cell carcinoma. Am J
Dermatopathol 2007; 29: 486–9.
5. Hatch CL. Pigmented lesions of the oral cavity. Dent Clin
North Am 2005; 49: 185–201.
6. Uratani AM, da Cruz Perez DE, Vargas PA, Jorge J,
Lopes MA. Oral melanoma: review of the literature. Braz
J Oral Sci 2004; 3: 428–32.
7. Tanaka N, Mimura M, Ogi K, Amagasa T. Primary
malignant melanoma of the oral cavity: assessment of
outcome from the clinical records of 35 patients. Int J Oral
Maxillofac Surg 2004; 33: 761–5.
8. Hicks MJ, Flaitz CM. Oral mucosal melanoma: epide-
miology and pathobiology. Oral Oncol 2000; 36: 152–69.
9. Freedman DM, Sigurdson A, Doody MM, Rao RS, Linet
MS. Risk of melanoma in relation to smoking, alcohol
Oral melanoma
Femiano et al.
387
intake, and other factors in a large occupational cohort.
Cancer Causes Control 2003; 14: 847–57.
10. Kahn MA, Weathers DR, Hoffman JG. Transformation
of a benign oral pigmentation to primary oral melanoma.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;
100: 454–9.
11. Contreras E, Carlos R. Oral melanoacanthosis (melanoa-
chantoma): report of a case and review of the literature.
Med Oral Patol Oral Cir Bucal 2005; 10: 9–11.
12. Mendenhall WM, Amdur RJ, Hinerman RW, Werning
JW, Villaret DB, Mendenhall NP. Head and neck mucosal
melanoma. Am J Clin Oncol 2005; 28: 626–30.
13. Elder DE, Clark WH Jr, Elenitsas R, Guerry D IV,
Halpern AC. The early and intermediate precursor lesions
of tumor progression in the melanocytic system: common
acquired nevi and atypical (dysplastic) nevi. Semin Diagn
Pathol 1993; 10: 18–35.
14. Forastiere AA, Trotti A, Pfister DG, Grandis JR. Head
and neck cancer: recent advances and new standards of
care. J Clin Orthod 2006; 10: 2603–5.
15. Kroumpouzos G, Frank EW, Albertini JG, et al. Lentigo
maligna with spread onto oral mucosa. Arch Dermatol
2002; 138: 1216–20.
16. Kessler HP, Pollock K. Oral and maxillofacial pathology
case of the month: malignant melanoma. Tex Dent J 2007;
124: 314.
17. Symvoulakis EK, Kyrmizakis DE, Drivas EI, et al. Oral
mucosal melanoma: a malignant trap. Head Face Med
2006; 2: 7.
18. Sivakumar G, Sivapathasundharam B, Karthiga KS.
Malignant melanoma of the oral cavity: case reports and
review of literature. Indian J Dent Res 2004; 15: 70–3.
19. 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.
20. Manganaro AM, Hammond HL, Dalton MJ, Williams
TP. Oral melanoma: case reports and review of the
literature. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 1995; 80: 670–6.
21. Tanaka N, Mimura M, Kimijima Y, Amagasa T. Clinical
investigation of amelanotic malignant melanoma in the
oral region. J Oral Maxillofac Surg 2004; 62: 933–7.
22. Andrews BT, Trask DK. Oral melanoacanthoma: a case
report, a review of the literature, and a new treatment
option. Ann Otol Rhinol Laryngol 2005; 114: 677–80.
23. Magliocca KR, Rand MK, Su LD, Helman JI. Mela-
noma-in-situ of the oral cavity. Oral Oncol Extra 2006; 42:
46–8.
24. Rapini RP. Oral melanoma: diagnosis and treatment.
Semin Cutan Med Surg 1997; 16: 320–2.
25. Lopez Ortega K, Soares de Araujo N, Bitu de Souza F,
Magalhaes MH. Primary malignant melanoma of the oral
cavity: a case report. Int J Dermatol 2004; 43: 750–2.
26. Rapini RP, Golitz LE, Greer RO, Krekorian EA, Poulson
T. Primary malignant melanoma of the oral cavity: a
review of 177 cases. Cancer 1985; 55: 1543–51.
27. Tanaka N, Amagasa T, Iwaki H, et al. Oral malignant
melanoma in Japan. Oral Surg Oral Med Oral Pathol
1994; 78: 81–90.
28. Barrett AW, Bennett JH, Speight PM. A clinicopatholog-
ical and immunohistochemical analysis of primary oral
mucosal melanoma. Oral Oncol Eur J Cancer 1995; 31B:
100–5.
29. Ohashi K, Kasuga T, Tanaka N, Enomoto S, Horiuchi J,
Okada N. Malignant melanomas of the oral cavity:
heterogeneity of pathological and clinical features. Virch-
ows Arch A Pathol Anat 1992; 420: 43–50.
J Oral Pathol Med
 Oral melanoma
Femiano et al.
388
30. Barker BF, Carpenter WM, Daniels TE, et al. Oral
mucosal melanomas: the WESTOP Banff workshop pro-
ceedings. Western society of teachers of oral pathology.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;
83: 672–9.
31. McGovern VJ, Cochran AJ, Van der Esch EP, Little JH,
MacLennan R. The classification of malignant melanoma,
its histological reporting and registration: a revision of the
1972 Sydney classification. Pathology 1986; 18: 12–21.
32. Rowland HN, Schnetler JF. Primary malignant melanoma
arising in the dorsum of the tongue. Br J Oral Maxillofac
Surg 2003; 41: 197–8.
33. Patrick RJ, Fenske NA, Messina JL. Primary mucosal
melanoma. J Am Acad Dermatol 2007; 56: 828–34.
34. 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.
35. Gonzales-Garcia R, Naval-Gias L, Martos PL, et al.
Melanoma of the oral mucosa. Clinical cases and review of
literature. Med Oral Patol Oral Cir Bucal 2005; 10: 264–71.
36. Dell’Ermo A, Gaeta G, Femiano F. Oral pigmented
lesions as a sign of Addison disease. J Stomatol Invest
2007; 1: 68–71.
37. Kauzman A, Pavone M, Blanas N, Bradley G. Pigmented
lesions of the oral cavity: review, differential diagnosis,
and case presentations. J Can Dent Assoc 2004; 70: 682–3.
38. Clark WH Jr, From L, Bernardino EA, Mihm MC. The
histogenesis and biologic behavior of primary human
malignant melanomas of the skin. Cancer Res 1969; 29:
705–26.
J Oral Pathol Med
39. Balch CM, Buzaid AC, Soong SJ, et al. New TNM
melanoma staging system: linking biology and natural
history to clinical outcomes. Semin Surg Oncol 2003; 21:
43–52.
40. Prasad ML, Patel SG, Huvos AG, Shah JP, Busam KJ.
Primary mucosal melanoma of the head and neck: a
proposal for microstaging localized, stage I (lymph node-
negative) tumors. Cancer 2004; 100: 1657–64.
41. Chidzonga MM, Mahomva L, Marimo C, Makunike-
Mutasa R. Primary malignant melanoma of the oral
mucosa. J Oral Maxillofac Surg 2007; 65: 1117–20.
42. Umeda M, Komatsubara H, Shibuya Y, Yokoo S,
Komori T. Premalignant melanocytic dysplasia and
malignant melanoma of the oral mucosa. Oral Oncol
2002; 38: 714–22.
43. Kowalski LP, Sanabria A. Elective neck dissection in oral
carcinoma: a critical review of the evidence. Acta Otorh-
inolaryngol Ital 2007; 27: 113–7.
44. Gonzalez-Garcia R, Naval-Gias L, Martos PL, et al.
Melanoma of the oral mucosa. Clinical cases and review of
the literature. Med Oral Patol Oral Cir Bucal 2005; 10:
264–71.
45. Temam S, Mamelle G, Marandas P, et al. Postoperative
radiotherapy for primary mucosal melanoma of the head
and neck. Cancer 2005; 103: 313–9.
46. Rapidis AD, Apostolidis C, Vilos G, Valsamis S. Primary
malignant melanoma of the oral mucosa. J Oral Maxillo-
fac Surg 2003; 61: 1132–9.
47. Ulusal BG, Karatas O, Yildiz AC, Oztan Y. Primary
malignant melanoma of the maxillary gingiva. Dermatol
Surg 2003; 29: 304–7.