Vol. 116 No. 4 October 2013

Oral malignant melanoma: systematic review of literature andreport of two casesMuralee Mohan, MDS, DNB, Vihang Y. Sukhadia, MDS, Deepak Pai, MDS, and Smitha Bhat, MDS,Mangalore, IndiaA. 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 theimplementation 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 establishcurrent understanding on various aspects of OMM.Results. Both patients in our study are showing good local control with aggressive multimodal treatment. Long-term follow-upis 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. Earlydiagnosis 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 classifiedas melanotic or nonmelanotic lesions. Melanotic le-sions are more common than nonmelanotic ones. Me-lanocytes may be found in the oral mucosa but may notbe noticeable because of their low level of pigmentproduction. However, when they are active in pigmentproduction or proliferation, they may be responsible forseveral oral pigmentations ranging from focal to diffuseand physiologic to malignant neoplasm.

Diffuse pigmentations are mostly systemic-related,drug-induced, or caused by exogenous pigments,whereas most focal pigmentations are brought about byoverproduction of melanin. Although most pigmentedlesions are benign, it is necessary to distinguish theorigin of pigmentation for melanocytic lesions whichmay be a malignant tumor, so-called oral malignantmelanoma (OMM). This justifies that melanocytic le-sions should not be ignored and that a definite diagnosismust be established in all cases.

Melanomas are malignant neoplasms arising frommelanocytes, originating from the neural crest cells.Melanocytes are primarily present in the basal portionof the epidermis at the dermo-epidermal junction. Pri-mary malignant melanoma has been described in vir-tually all sites and organ systems where neural crestcells migrate. One of the unusual sites is the upperaerodigestive tract.

Department of Oral and Maxillofacial Surgery, A. B. Shetty Memo-rial 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 isa rare entity, occurring much less frequently than itscutaneous relatives. It constitutes �1% of all melano-mas and �10% of head and neck melanomas.1 Itsincidence is thought to be stable, contrary to its cuta-neous counterpart, which has been rapidly increasing.2

Some authors think that oral malignant melanoma hasradial growth phase and appears to be similar to acrallentiginous melanoma of the skin, whereas others thinkthat oral malignant melanoma is a separate entity fromits cutaneous counterpart and should be classified sep-arately.3

Surgery remains the main treatment modality, withadded radiotherapy and/or chemotherapy to preventrecurrence and metastasis. Despite aggressive resectionand multimodal treatment, prognosis of OMM remainsvery poor.3 Also, because of the rarity of this tumor,there is lack of definite proof regarding etiology, patho-genesis, treatment protocol, and prognostic factors forOMM. This paper reports 2 cases of OMM treated atA. B. Shetty Memorial Institute of Dental Sciences,Mangalore, and a review of literature in an endeavor toestablish current understanding on various aspects ofOMM.

CASE REPORTSCase 1

A 60-year-old woman reported to our department withcomplaint of swelling in the palate for 3 months. It wasinsidious in onset and growing in size. It was not associatedwith any pain, ulceration, or bleeding. The patient had ahistory of breast carcinoma 8 years prior, for which she hadundergone surgery followed by radiotherapy, detailed recordswhich were not available. There was no recurrence noted at

the time of thorough physical examination. On examination,

e247

stabili

ORAL AND MAXILLOFACIAL SURGERY OOOOe248 Mohan et al. October 2013

a single 3 � 3 cm smooth-surfaced swelling was noted in themiddle of the palate with slightly darker pigmentation aroundit. Blackish discoloration of anterior alveolar mucosa was alsopresent. Lesion was nontender and firm to hard in consis-tency. Incisional biopsy was performed and was reported asmalignant melanoma with fibrous hyperplasia. A thoroughphysical examination was undertaken to detect any skin le-sion and in the absence of that, the oral lesion was labeled asprimary malignant melanoma. Systemic examination was car-ried out with chest x-ray, ultrasonography of the abdomen,and computerized tomography (CT) scan of the cervical areato rule out any metastatic lesion. After a thorough work-up,the patient was scheduled for surgery and low-level maxil-lectomy was performed with 2 cm gross soft tissue margin allaround the lesion. The defect was closed with split-thicknessskin graft, and a temporary obturator was placed intraopera-tively (Figure 1).

The histopathology report showed atypical cells whichresembled melanocytes infiltrating into connective tissue andmigrating upward into superficial layers of epithelium. Theatypical melanocytes were epitheloid in the superficial regionand spindle shaped in the deeper regions of connective tissue(Figure 2). The tumor cells showed hyperchromatism, pleo-morphism, multinucleation, increased nuclear-cytoplasmicratio, and atypical mitoses. Resected margins were free fromtumor cells.

Two months later, the patient reported with neck swellingon the right side. The primary lesion had healed well andshowed no evidence of recurrence, with 100% take-up of skingraft. Fine-needle aspiration cytology of the neck swellingrevealed it to be metastatic lymphadenopathy. CT scan wasdone which revealed bilateral submandibular lymph nodeenlargement. Modified radical neck dissection was performedon both sides and the patient recovered well with no postop-erative sequelae. Histopathologic examination revealed onlyone positive lymph node in the right side specimen at level IIlymph node. Patient was given adjuvant radiotherapy after thesurgery. At the time of writing this paper the patient wasdisease-free with no locoregional recurrence or metastasis foralmost 20 months. The patient is under regular follow-up at

Fig. 1. Case 1. A, Typical clinical presentation of oral maligmargins. C, Postresection view showing split thickness graft

6-month intervals.

Case 2A 40-year-old female patient reported to our department

with chief complaint of blackish discoloration/patch in max-illary anterior gingivae for 4 months which was rapidly grow-ing in size. The patient consulted a local hospital, where shewas advised to undergo incisional biopsy for diagnostic pur-pose. But she declined and visited our department for per-sonal reasons. On examination, an elevated black to brownpatch of approximately 5 � 3 cm was noted involving max-illary attached gingivae extending from right central incisor toleft second premolar area. Superoinferiorly it was involvingthe whole of gingivae extending up to the mucogingivaljunction (Figure 3). The lesion was firm in consistency andtender on palpation. It was also extending onto the palatewhere a black to brown discoloration of approximately 4 � 3cm was present in the anterior half of the palate on the leftside which was crossing midline in incisive papillae region(Figure 3). Small brown spots were also noted on the rightside of palate. The lesion was asymmetric with irregularborders along with color variegation present, and it wasenlarging in size. These are characteristic features of malig-nant melanoma along with the fact that lesion was alsoelevated. Therefore, keeping OMM as provisional diagnosis,thorough physical examination, oropharyngeal examination,

Fig. 2. Histopathologic section of case 1.

elanoma. B, Resected specimen showing adequate clearancezed with surgical splint.

nant m

and chest radiography were done to rule out any metastatic

iew sh

OOOO CASE REPORTVolume 116, Number 4 Mohan et al. e249

lesion. No clinically palpable lymphnodes were detected onneck examination. CT scan showed no gross bony invasion,and cervical lymph node involvement was ruled out.

Excision of the lesion was performed under general anes-thesia with Le Fort I level maxillectomy and adequate softtissue margin of 1.5 cm all around the lesion (Figure 4).Bilateral buccal pad of fat was mobilized to cover the max-illary sinus and the entire area of defect was covered withamniotic membrane (Figure 4). The postoperative period wasuneventful, and the patient was discharged on postoperativeday 8 with a temporary obturator.

Histopathologic examination revealed stratified squamousparakeratinized epithelium with long and narrow rete ridges.Ovoid and spindle-shaped tumor cells were seen at junction aswell as infiltrating into underlying connective tissue (Figure 5).Increased junctional activity was noted along with pleomor-phism of tumor cells. Numerous large melanophages were seenin the vicinity, along with dense chronic inflammatory cellsmainly in the form of plasma cells and lymphocytes. Margins ofthe specimen were free from the tumor cells.

At 1 month follow-up, the surgical site had healed well andno local or regional recurrence was noted, and the patient wasreferred for adjuvant chemoradiotherapy. At the time of thiswriting, the patient had been closely followed for 1 year withappointments every 3 months for local examination and chestradiography to rule out metastasis.

DISCUSSIONPigmented lesions of melanocytic origin is a rare oc-

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

Fig. 4. Case 2. A, B, Resected specimen. C, Postresection v

currence in the oral cavity, and they can span a spec-

trum ranging from innocuous lesions, such as oralmelanotic macule, and various benign nevi to life-threatening malignant melanoma of oral mucosa.Therefore, meticulous clinical and pathologic examina-tion must be made of any suspicious lesion to avert theprogress of a malignant melanoma.

OMM is an extremely rare and very aggressive tu-mor of melanocytic origin. Apart from oral mucosamalignant melanoma can affect mucous membranes ofnose and paranasal sinuses, pharynx, and conjunctiva.

owing amniotic membrane dressing.

Fig. 5. Histopathologic section of case 2.

As a group, mucosal melanomas invade and spread

ORAL AND MAXILLOFACIAL SURGERY OOOOe250 Mohan et al. October 2013

more quickly and metastatize more frequently, and aretherefore associated with much poorer prognosis thancutaneous melanomas.

After conjunctiva, oral cavity and sinonasal tract arethe second most common affected sites in the head andneck region.4 In the oronasal region approximatelyone-half of melanomas occur in the oral cavity (48%)and the remaining portions are located in the nasalcavity (44%) and sinuses (8%).2,3 OMM accounts foronly 0.5% of all oral malignancies,5 and oral melanomarepresents 0.2%-8.0% of all melanomas.5 OMM usu-ally occurs in the fourth to sixth decades of life and isextremely rare before 30 years of age.6 Some studieshave shown a male predilection of 2:1, whereas otherstudies show no sex predilection.3,7 OMM is known tooccur more frequently in Japanese, African, and NorthAmerican Indian populations than in European popula-tions.8-13 Most commonly involved intraoral site ispalate and maxillary alveolar gingiva.7,9,13,14 and theyare labeled as high-risk sites for OMM.5 Other sites lessfrequently affected include the labial and buccal mu-cosa, tongue, and floor of mouth.5

Etiology of OMM is essentially unknown. Unlikecutaneous melanoma, no definite risk factors for OMMhave been defined, and tobacco use as well as chronicirritation from ill-fitting dentures has been mentioned aspossible risk factors.12 Also, a possible role of ingestedand inhaled environmental carcinogens at higher inter-nal body temperature has been suggested.15 MostOMMs are thought to arise de novo from apparentlynormal mucosa. But it has been shown that one-third ofpatients have a history of preexisting oral pigmentationfor several months or even years before diagnosis ofmalignant melanoma.12 Some of these flat precursorlesions actually consist of atypical melanocytes andrepresent radial growth phase of malignant melanoma,whereas others represent benign proliferation of mela-nocytes. Exact mechanism for transformation of benignmelanocytic nevus to melanoma is not known, butexpressions of some melanoma-associated antigenshave been implicated.3 p53 protein alterations havebeen identified in two-thirds of OMMs, and a recentstudy demonstrates loss of heterozygosity at 12p13 andloss of p27KIP1 protein expression contributing to mel-anoma progression.3

The most common presenting symptom is a pig-mented swelling. Hemorrhage and ulceration are usu-ally late findings when the lesion has entered verticalgrowth phase.3,5 OMM can be uniformly brown orblack, or variable pigmentation may be present whichranges as black, brown, gray, purple, red, and/or white.The lesions are asymmetric, irregular in outline, andoccasionally multiple, which represents satellite le-

sions.5 Umeda et al. noted that on close examination

typical OMM usually presents with 3 distinct compo-nents: a nodular component usually affecting the cen-ter; a flat or slightly elevated, deep brownish-blackpigmented plaque component; and a nonelevated lightbrown macular component.16 Approximately 10% ofcases are known to be amelanotic in nature, lackingmacular component, thus posing a difficulty in diagno-sis.17 Induration is usually absent in cases with pro-longed 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 onclinical appearance: pigmented nodular type, nonpig-mented nodular type, pigmented macular type, pig-mented mixed type, and nonpigmented mixed type.

Mucosal melanoma can be primary or metastatic. Itis therefore very important to rule out any other primarymalignant melanoma elsewhere in the body. Green etal. gave criteria for diagnosis of primary OMM asfollows19:

1. Demonstration of clinical and microscopic tumor inthe 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-calledABCD checklist (asymmetry, border irregularities,color variegation, and diameter �6 mm) that is com-monly used for cutaneous melanomas. Deferential di-agnosis includes melanoma, melanotic macule, oralpigmented nevus, smoker’s melanosis, amalgam tattoo,and Kaposi’s sarcoma.5

It has often been suggested that cutting into anOMM, either for incisional biopsy or other invasiveprocedures, may lead to seeding of tumor cell intoadjacent tissue or even into bloodstream or lymphatics,leading to dissemination of tumor cells and increasedrate of metastasis. Umeda et al.16 in his study con-cluded that 5-year survival rate of patients who under-went some surgical procedures, such as incision, bi-opsy, or tooth extraction, before definitive surgery waspoor (25.9%) compared with those who did not un-dergo such procedures (91.7%). Similar results wereshown by Rampen et al. and Austin et al.20 However,many authors believe that biopsy of an undiagnosedlesion, pigmented or nonpigmented, occurring in highrisk sites for OMM should be done, because benefitsgained by a definite diagnosis of OMM far more out-weigh the risk of distant metastasis which is not yetfully established.21-23 According to Batsakis,24 “there is

no evidence that a preliminary biopsy of the primary

OOOO CASE REPORTVolume 116, Number 4 Mohan et al. e251

lesion increases the risk of metastatic dissemination orunfavourably affects prognosis.” Excisional biopsy ofsmall lesion should be performed and incisional biopsyfrom the thickest and darkest area is recommended forlarger lesions.25

Apart from biopsy, radiologic examination throughCT, magnetic resonance imaging, or positron-emissiontomography could be useful for evaluation of primarytumor invasion and regional or distant metastases. Rob-ert Marx et al. recommends a chest radiograph as theprimary diagnostic tool for metastatic workup and onevery 6-month follow-up after surgery to assess fordistant metastasis, because lungs and liver are the mostcommonly affected organs with OMM metastases.26 Inboth of our patients, CT scan was done to assess theprimary lesion and its invasion of bone along withassessment of neck for regional spread. Case 1 showedbony invasion of palate, and both patient had no re-gional involvement of neck nodes.

No definite classification for OMM exists, in contrastto cutaneous melanoma which is divided into clinicallyand pathologically well defined varieties. In the past itwas thought that OMM represented a mucosal counter-part of acral lentiginous melanoma, based on similarhistopathologic findings, but it was observed that OMMhas a very different biologic growth pattern and verypoor prognosis. Therefore, it was thought that cleardistinction should be made between cutaneous melano-mas and OMM. During the Workshop on OMM, con-vened at the Western Society of Teachers of OralPathology annual meeting in 1995, the authors agreedon the fact that oral lesions should be considered sep-arately from cutaneous melanomas until definitive in-formation on cause and natural history of OMM isforthcoming. In situ OMM, invasive OMM, invasivemelanoma with in situ component, and atypical melano-cytic proliferation are the preferred descriptive terms.5

TNM staging for cutaneous melanoma does not pro-vide specific guidelines for OMM. A simple clinicalstaging system for head and neck mucosal melanomasis commonly used and has been shown to be of prog-nostic value. Prasad et al.27 has proposed histopatho-logic microstaging for stage I tumor (Table I).

Microscopically, two patterns have emerged for themucosal melanomas: an in situ pattern in which theneoplasm is limited to the epithelial-connective tissueinterface; and an invasive pattern in which the neo-plasm was found within the supporting connective tis-sue. Also, a combined pattern of invasive melanomawith in situ component is typical of most advancedlesions. Varied types of neoplastic cells, including spin-dled, plsmacytoid, and epitheloid, are seen in invasivemelanoma. They are usually arranged in either sheet-

like, organoid/alveolar, neurotropic, or desmoplastic

pattern. Approximately 10% of cases are amelanotic,for which diagnosis requires immunohistochemicalstaining. Various markers commonly used are S-100protein, HMB45, and Melan-A.3

Measurement of tumor thickness should also be in-cluded in the report, because it is shown to be a strongpredictor of prognosis.28 Breslow measurement for tu-mor thickness is usually used, in which tumor thicknessis determined with the use of a micrometer in the ocularof a microscope (Table II).26

Usually, OMM tends to present at a more advancedstage compared with cutaneous melanomas, with 70%of stage I and 83% of stage II tumors presenting with athickness �4 mm, leading to poor prognosis.29

Most authors think that the mainstay of treatment forOMM is surgery with wide clear margins; however, mostof the time proximity of vital structures makes this objec-tive difficult. Also, most OMM presents at a more ad-vanced stage, when the tumor has entered vertical growthphase with deep invasion of surrounding tissue and bone,requiring extensive resection to achieve clear margins. Forthe most common site, the palate, surgery usually consistof a type of maxillectomy with 3-5-cm margins and some-times it is necessary to extend the excision to the softpalate and tonsillar pillar, and into the pterygomaxillaryspace. No particular guidelines for the surgical treatmentof OMM exist, and treatment of most patients is left to thediscretion of the individual surgeon. Umeda and Shi-mada29 suggested a protocol for management of OMMwhich refers to the extent of margins:

1. Excision of the primary lesion, preferably using anintraoral approach and involving at least 1.5 cm of

Table I. Clinical staging system for oral malignant mel-anoma with histopathologic microstaging for stage IStage I Primary tumor present only (Tany N0 M0)

Level I: pure in situ melanoma without evidence ofinvasion or in situ melanoma with“microinvasion”

Level II: invasion up to the lamina propriaLevel III: deep skeletal tissue invasion into skeletal

muscle, bone, or cartilageStage II Tumor metastatic to regional lymphnodes (Tany

N1 M0)Stage III Tumor metastatic to distant sites (Tany Nany M1)

Table II. Breslow scale for the measurement of tumorthickness of oral malignant melanomaThickness (mm) Risk of recurrence

�0.76 Low risk0.76-1.50 Low to intermediate risk1.50-3.99 Intermediate to high risk�4.00 High risk

healthy tissue.

ORAL AND MAXILLOFACIAL SURGERY OOOOe252 Mohan et al. October 2013

2. Excision of any lymph node metastasis (stage II).3. Consider chemotherapy.

Tanaka et al.30 reported that primary lesion was con-trolled in 92.3% of cases with surgery, whereas in anonsurgery group treated with radiotherapy, only 53%cases had controlled primary lesion. This clearly cor-relates with the traditional opinion of surgery being thetreatment of choice, with radiotherapy and chemother-apy having only adjunctive roles. During the 1995Workshop on OMM, it was concluded that there iscurrently no compelling new information that wouldsuggest that another approach would be better. More-over, they also advised that serious considerationshould be given to combination therapy in primarypatient care, because of the high recurrence rate asso-ciated with OMM.5

Another area of controversy in OMM is regardingthe issue of prophylactic neck dissection. Various au-thors have reported lymph node metastasis in primaryOMM at approximately 25%-50%.3,30,31 According toShah et al., regional metastases at the time of presen-tation do not affect the survival of patients with OMM,whereas other authors think that it carries a negativeprognostic value.29,32 According to most authors, neckdissection should be reserved for cases with preopera-tively confirmed lymph node metastasis, and the choiceof the neck dissection modality should be guided by theextent and the level of nodes. There is no proof thatprophylactic neck dissection improves survival.30,33

Both of our patients were treated with surgical re-section of palate with 1.5-cm macroscopic margin allaround the lesion which is as per the guidelines givenby Umeda and Shimada et al.29 The patient of case 1developed neck node involvement after 2 months,though local recurrence was not present. According toSnow et al., lymph node metastases rarely developwithout local recurrence after initial treatment of pri-mary lesion. But this was not the case in our patient;even Tanaka et al reported good loco-regional controlwith surgery alone or surgery combined with othertreatments.30 Bilateral neck dissection was performedin this patient.

Very few studies are done on the effect of primaryradiotherapy for OMM, and it does not show any ap-parent advantage over surgery based on survival rateand local control.30 Postoperative radiotherapy is rec-ommended in cases with positive surgical margins or astrong likelihood of local or regional recurrence.4 Var-ious studies have shown that postoperative radiother-apy was useful for increasing local control,34-36 but itdoes not seem to improve survival rate.3 It has beensuggested that local failure is a harbinger of distant

metastases in mucosal melanoma, because the majority

of patients who die of distant metastases have also localor regional recurrent disease. Therefore, efforts to im-prove loco-regional control by adding postoperativeradiotherapy might also result in higher survival rates.Another role of radiotherapy is in advanced disease,where it is used as a primary treatment modality forpalliation. Radiotherapy is the most effective treatmentmodality for unresectable disease.37

Role of adjuvant chemotherapy in management ofOMM does not seem to influence survival.3 Umeda andShimeda et al.29 reported that adjuvant chemotherapywith dimethyl triazeno imidazole carboximide, nimus-tine hydrochloride, vincristine, and biologic responsemodifier OK-432 was effective for OMM and showsimproved survival rate. Another recent retrospectivestudy showed that adjuvant chemotherapy decreasedthe relapse rates of both local and distant metastasisdisease.38 But further studies are necessary to assess thedefinitive role of adjuvant chemotherapy in OMM.

Most of patients die owing to distant metastases tolungs, brain, liver, and bones despite good locoregionalcontrol. Because many patients dies of disseminateddisease, it makes sense to add a systemic therapy whentreating advanced OMM. Systemic immunotherapywith interleukin-2 and other cytokines has not shownvery encouraging results, and further research is re-quired to develop some sort of definitive targeted sys-temic therapy.3

There is no disagreement regarding prognosis ofOMM, and a majority of reported case series attest tothat. OMM carries a quite poor prognosis comparedwith its cutaneous counterpart. The average survivalrate after diagnosis has varied from 13% to 20% invarious case series, and mean survival for OMM is 28months.39 Various prognostic factors have been putforward for OMM, but to date only clinical staging atpresentation has been affirmed by all as the most im-portant factor determining outcome. Other independentrisk factors are thickness of the tumor (�5 mm), cer-vical lymph node metastases, anatomic site (palate be-ing poorer than gingiva), and presence or absence ofulceration.3 The reasons for poor prognosis are notknown with certainty, but various probable reasons areput forward, the most important of them being latediagnosis of OMM due to nonspecific symptoms. Oth-ers include anatomic location, because mucosal tumorscan easily invade the deeper structures, such as bone.Also, there is high vascularity of oral mucous mem-brane, which along with earlier bone invasion can con-tribute to the high incidence of distant metastases.31

Also because of anatomic location, sometimes it isdifficult to achieve clear margins during resection. Pos-itive surgical margins are seen in �43% of OMM4 and

have been shown to be associated with poor outcome.

OOOO CASE REPORTVolume 116, Number 4 Mohan et al. e253

CONCLUSIONMalignant melanoma is a rare tumor of the oral cavity,with very poor prognosis. Local, regional, and distantmetastases occur in OMM despite the implementationof aggressive multimodal treatment. Because late diag-nosis with advanced disease at the time of diagnosis isthe only sure predictor of outcome, thorough clinicaland pathologic work-up of any suspected melanoticlesion should be carried out to diagnose OMM in itsearly stages. Early diagnosis and aggressive multi-modal treatment are the only means available to sur-geons to provide better outcome to a patient withOMM. There is also need for pooling of data fromvarious centers to analyze key determinants of outcomeand thereby establish a treatment policy.

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Reprint requests:

Vihang Y. Sukhadia, MDSSurgical FellowDr. Jeysekharan Centre for Cleft CareK P RoadNagercoil—629 003TamilnaduIndia

vihangsukhadia@gmail.com