Rare and Extensive Malignant Melanoma of the Oral Cavity: Report of Two Cases
Identifieur interne : 001D82 ( Pmc/Corpus ); précédent : 001D81; suivant : 001D83Rare and Extensive Malignant Melanoma of the Oral Cavity: Report of Two Cases
Auteurs : Parviz Deyhimi ; Sayed Mohammad Razavi ; Shirin Shahnaseri ; Saeedeh Khalesi ; Solmaz Homayoni ; Payam TavakoliSource :
- Journal of Dentistry [ 2345-6485 ] ; 2017.
Abstract
Primary oral melanomas are uncommon malignant neoplasm of melanocytes origin. The most common site of oral melanoma is maxillary gingiva and hard palate. Oral mucosal melanoma exhibit a pathobiological behavior and clinical features different from cutaneous melanomas. Oral melanomas are often clinically silent which may consequently result in delayed diagnosis; thus, making the prognosis extremely poor.
This case report presents clinical, histopathological and immunohistochemical features of two cases of advanced oral melanoma, one pigmented or melanotic melanoma in a 46-year-old female and another amelanotic melanoma in a 59-year-old male patient, with chief complaint of swelling in oral mucosa.
Most oral melanomas are usually asymptomatic lesions with quick growing. Thus, the most cases are detected in late stage of diagnosis. Early diagnosis with careful examination by dentists, and early biopsy of pigmented and suspicious non-pigmented lesions would have an imperative role in more survival rate and better prognosis.
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PubMed: 29034279
PubMed Central: 5634364
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Rare and Extensive Malignant Melanoma of the Oral Cavity: Report of Two Cases
</title><author><name sortKey="Deyhimi, Parviz" sort="Deyhimi, Parviz" uniqKey="Deyhimi P" first="Parviz" last="Deyhimi">Parviz Deyhimi</name><affiliation><nlm:aff id="aff1">Dental Research Center, Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</nlm:aff></affiliation></author><author><name sortKey="Razavi, Sayed Mohammad" sort="Razavi, Sayed Mohammad" uniqKey="Razavi S" first="Sayed Mohammad" last="Razavi">Sayed Mohammad Razavi</name><affiliation><nlm:aff id="aff2">Dental Implant Research Center, Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</nlm:aff></affiliation></author><author><name sortKey="Shahnaseri, Shirin" sort="Shahnaseri, Shirin" uniqKey="Shahnaseri S" first="Shirin" last="Shahnaseri">Shirin Shahnaseri</name><affiliation><nlm:aff id="aff3">Dental Research Center, Dept. of Oral and Maxillofacial Surgery, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</nlm:aff></affiliation></author><author><name sortKey="Khalesi, Saeedeh" sort="Khalesi, Saeedeh" uniqKey="Khalesi S" first="Saeedeh" last="Khalesi">Saeedeh Khalesi</name><affiliation><nlm:aff id="aff2">Dental Implant Research Center, Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</nlm:aff></affiliation></author><author><name sortKey="Homayoni, Solmaz" sort="Homayoni, Solmaz" uniqKey="Homayoni S" first="Solmaz" last="Homayoni">Solmaz Homayoni</name><affiliation><nlm:aff id="aff4">Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Shahrekord University of Medical Sciences, Shahrekord, Iran.</nlm:aff></affiliation></author><author><name sortKey="Tavakoli, Payam" sort="Tavakoli, Payam" uniqKey="Tavakoli P" first="Payam" last="Tavakoli">Payam Tavakoli</name><affiliation><nlm:aff id="aff5">Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Islamic Azad University of Isfahan (Khorasgan), Isfahan, Iran.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29034279</idno><idno type="pmc">5634364</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634364</idno><idno type="RBID">PMC:5634364</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">001D82</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D82</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Rare and Extensive Malignant Melanoma of the Oral Cavity: Report of Two Cases
</title><author><name sortKey="Deyhimi, Parviz" sort="Deyhimi, Parviz" uniqKey="Deyhimi P" first="Parviz" last="Deyhimi">Parviz Deyhimi</name><affiliation><nlm:aff id="aff1">Dental Research Center, Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</nlm:aff></affiliation></author><author><name sortKey="Razavi, Sayed Mohammad" sort="Razavi, Sayed Mohammad" uniqKey="Razavi S" first="Sayed Mohammad" last="Razavi">Sayed Mohammad Razavi</name><affiliation><nlm:aff id="aff2">Dental Implant Research Center, Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</nlm:aff></affiliation></author><author><name sortKey="Shahnaseri, Shirin" sort="Shahnaseri, Shirin" uniqKey="Shahnaseri S" first="Shirin" last="Shahnaseri">Shirin Shahnaseri</name><affiliation><nlm:aff id="aff3">Dental Research Center, Dept. of Oral and Maxillofacial Surgery, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</nlm:aff></affiliation></author><author><name sortKey="Khalesi, Saeedeh" sort="Khalesi, Saeedeh" uniqKey="Khalesi S" first="Saeedeh" last="Khalesi">Saeedeh Khalesi</name><affiliation><nlm:aff id="aff2">Dental Implant Research Center, Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</nlm:aff></affiliation></author><author><name sortKey="Homayoni, Solmaz" sort="Homayoni, Solmaz" uniqKey="Homayoni S" first="Solmaz" last="Homayoni">Solmaz Homayoni</name><affiliation><nlm:aff id="aff4">Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Shahrekord University of Medical Sciences, Shahrekord, Iran.</nlm:aff></affiliation></author><author><name sortKey="Tavakoli, Payam" sort="Tavakoli, Payam" uniqKey="Tavakoli P" first="Payam" last="Tavakoli">Payam Tavakoli</name><affiliation><nlm:aff id="aff5">Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Islamic Azad University of Isfahan (Khorasgan), Isfahan, Iran.</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Dentistry</title><idno type="ISSN">2345-6485</idno><idno type="eISSN">2345-6418</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Primary oral melanomas are uncommon malignant neoplasm of melanocytes origin. The most common site of oral melanoma is maxillary gingiva and hard palate. Oral mucosal melanoma exhibit a pathobiological behavior and clinical features different from cutaneous melanomas. Oral melanomas are often clinically silent which may consequently result in delayed diagnosis; thus, making the prognosis extremely poor.
</p><p>This case report presents clinical, histopathological and immunohistochemical features of two cases of advanced oral melanoma, one pigmented or melanotic melanoma in a 46-year-old female and another amelanotic melanoma in a 59-year-old male patient, with chief complaint of swelling in oral mucosa.
</p><p>Most oral melanomas are usually asymptomatic lesions with quick growing. Thus, the most cases are detected in late stage of diagnosis. Early diagnosis with careful examination by dentists, and early biopsy of pigmented and suspicious non-pigmented lesions would have an imperative role in more survival rate and better prognosis.
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Jafari</name></author><author><name sortKey="Khalesi, S" uniqKey="Khalesi S">S Khalesi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="case-report"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Dent (Shiraz)</journal-id><journal-id journal-id-type="iso-abbrev">J Dent (Shiraz)</journal-id><journal-title-group><journal-title>Journal of Dentistry</journal-title></journal-title-group><issn pub-type="ppub">2345-6485</issn><issn pub-type="epub">2345-6418</issn><publisher><publisher-name>Journal of Dentistry Shiraz University of Medical Sciences</publisher-name><publisher-loc>Iran</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29034279</article-id><article-id pub-id-type="pmc">5634364</article-id><article-id pub-id-type="publisher-id">JDS-18-3</article-id><article-categories><subj-group subj-group-type="heading"><subject>Case Reports</subject></subj-group></article-categories><title-group><article-title>Rare and Extensive Malignant Melanoma of the Oral Cavity: Report of Two Cases
</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Deyhimi</surname><given-names>Parviz</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Razavi</surname><given-names>Sayed Mohammad</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Shahnaseri</surname><given-names>Shirin</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Khalesi</surname><given-names>Saeedeh</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Homayoni</surname><given-names>Solmaz</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Tavakoli</surname><given-names>Payam</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Dental Research Center, Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</aff><aff id="aff2"><label>2</label>Dental Implant Research Center, Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</aff><aff id="aff3"><label>3</label>Dental Research Center, Dept. of Oral and Maxillofacial Surgery, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.</aff><aff id="aff4"><label>4</label>Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Shahrekord University of Medical Sciences, Shahrekord, Iran.</aff><aff id="aff5"><label>5</label>Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Islamic Azad University of Isfahan (Khorasgan), Isfahan, Iran.</aff><author-notes><corresp id="cor1"><bold>Correspondence: </bold>Khalesi S.
Dental Materials Research Center, Dept. of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.
<bold> Tel:</bold>+98-3137922879</corresp><corresp id="cor2">E-mail : <email>s_khalesi@dnt.mui.ac.ir</email></corresp></author-notes><pub-date pub-type="ppub"><month>9</month><year>2017</year></pub-date><volume>18</volume><issue>3</issue><fpage>227</fpage><lpage>233</lpage><history><date date-type="rev-recd"><month>8</month><year>2017</year></date><date date-type="accepted"><month>8</month><year>2017</year></date><date date-type="received"><month>8</month><year>2017</year></date></history><permissions><copyright-statement>Copyright: © Journal of Dentistry Shiraz University of Medical Sciences</copyright-statement><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Primary oral melanomas are uncommon malignant neoplasm of melanocytes origin. The most common site of oral melanoma is maxillary gingiva and hard palate. Oral mucosal melanoma exhibit a pathobiological behavior and clinical features different from cutaneous melanomas. Oral melanomas are often clinically silent which may consequently result in delayed diagnosis; thus, making the prognosis extremely poor.
</p><p>This case report presents clinical, histopathological and immunohistochemical features of two cases of advanced oral melanoma, one pigmented or melanotic melanoma in a 46-year-old female and another amelanotic melanoma in a 59-year-old male patient, with chief complaint of swelling in oral mucosa.
</p><p>Most oral melanomas are usually asymptomatic lesions with quick growing. Thus, the most cases are detected in late stage of diagnosis. Early diagnosis with careful examination by dentists, and early biopsy of pigmented and suspicious non-pigmented lesions would have an imperative role in more survival rate and better prognosis.
</p></abstract><kwd-group><kwd>Oral manifestations </kwd><kwd> Melanoma </kwd><kwd> Neoplasms</kwd></kwd-group></article-meta></front><body><sec sec-type="Introduction" id="sec1-1"><title>Introduction</title><p>Cutaneous and mucosal melanomas are arising from malignant transformation of melanocytes.[<xref rid="ref1" ref-type="bibr">1</xref>] Mucosal melanoma (MM) is a rare form of melanoma with an aggressive clinico-pathological behavior and poor prognosis with a 5-year survival rate of <25%.[<xref rid="ref2" ref-type="bibr">2</xref>] Mucosal melanomas (MMs) are most often found in the upper aerodigestive tract (mouth, pharynx, larynx, nasal cavity, paranasal sinuses, and salivary glands), the genitourinary tract and the anorectal region.[<xref rid="ref3" ref-type="bibr">3</xref>] Approximately 55% of all MMs begin in the head and neck region.[<xref rid="ref4" ref-type="bibr">4</xref>] Furthermore, 70% of MMs of the head and neck are located in the nasal cavity and paranasal sinuses, but only 25% occurred in oral mucosa.[<xref rid="ref5" ref-type="bibr">5</xref>-<xref rid="ref6" ref-type="bibr">6</xref>] The incidence of primary oral melanoma (OMs) is varying broadly between 0.2-0.8% of all melanoma and 1.3% of all cancers and 0.5% of all oral malignant neoplasms.[<xref rid="ref7" ref-type="bibr">7</xref>-<xref rid="ref8" ref-type="bibr">8</xref>] The mucosal melanoma of oral cavity has a higher prevalence in African-American, Japanese and Indians of Asia. There is more frequent finding of melanin pigmentation in oral mucosa of these populations.[<xref rid="ref9" ref-type="bibr">9</xref>] Primary malignant melanoma of the oral cavity is a rare type of melanoma.[<xref rid="ref10" ref-type="bibr">10</xref>] In contrast to cutaneous melanoma, MMs have unknown etiology, because the affected sites of the lesion are not exposed to solar radiation.[<xref rid="ref6" ref-type="bibr">6</xref>-<xref rid="ref7" ref-type="bibr">7</xref>,<xref rid="ref11" ref-type="bibr">11</xref>] However, some studies presented a few causes for OMs such as ill-fitting dentures, tobacco use in any form, amalgam tattoo, nevus, and racial pigmentation.[<xref rid="ref12" ref-type="bibr">12</xref>] Although most OMs appear de novo, more than one-third of these neoplasms arise from benign melanotic oral lesions.[<xref rid="ref13" ref-type="bibr">13</xref>]</p><p>The most common location of oral melanomas is the maxillary gingiva, hard palate, and alveolar ridge; only 20% of theses lesions are observed in the mandibular mucosa.[<xref rid="ref7" ref-type="bibr">7</xref>-<xref rid="ref8" ref-type="bibr">8</xref>] These neoplasms usually occurs in the age range of 7-95.[<xref rid="ref8" ref-type="bibr">8</xref>] In some studies, no gender distribution was observed,[<xref rid="ref7" ref-type="bibr">7</xref>-<xref rid="ref8" ref-type="bibr">8</xref>] but in some other studies a slight male preponderance was reported.[<xref rid="ref13" ref-type="bibr">13</xref>-<xref rid="ref14" ref-type="bibr">14</xref>] Oral melanomas are usually asymptomatic with irregular shape and dark brown to block color. The lesion is often detected by significant swelling, tooth mobility, ulceration, or hemorrhage of the overlying epithelium.[<xref rid="ref8" ref-type="bibr">8</xref>,<xref rid="ref12" ref-type="bibr">12</xref>] However, a few cases of OM are painless, white, mucosa-colored, or red mass in clinical feature that contribute to late diagnosis, delay in starting treatment and decreasing the chance of survival.[<xref rid="ref8" ref-type="bibr">8</xref>,<xref rid="ref13" ref-type="bibr">13</xref>] Only 2.3% of all MMs are amelanotic melanoma. Amelanotic melanoma is extremely rare in oral cavity.[<xref rid="ref15" ref-type="bibr">15</xref>] Immunohistochemical staining with antibodies against certain melanocytic differentiation antigens is always required for confirmation the diagnosis of amelanotic melanoma.[<xref rid="ref15" ref-type="bibr">15</xref>] Based on clinical features, OMs can be divided into five types including the pigmented nodular type, the non-pigmented nodular type, the pigmented macular type, the pigmented mixed type and the non-pigmented mixed type.[<xref rid="ref15" ref-type="bibr">15</xref>] The non-pigmented nodular type is an amelanotic nodular tumor that has not a radial growth phase, while the non-pigmented mixed type is an amelanotic nodular tumor that is surrounded by a radial growth phase.[<xref rid="ref15" ref-type="bibr">15</xref>-<xref rid="ref16" ref-type="bibr">16</xref>] Most OMs have aggressive biological behavior and show high incidence of metastasis, recurrence and death. However, amelanotic melanomas have a poor prognosis than pigmented melanoma.[<xref rid="ref17" ref-type="bibr">17</xref>]</p><p>This report presents clinical, histopathological, and immunohistochemical features of two cases with an advanced oral melanoma; one pigmented melanoma in a 46-year-old female patient and another oral amelanotic melanoma in a 59-year-old male patient.
</p></sec><sec id="sec1-2"><title>Case 1</title><p>A 46-year-old female patient referred to the Department of Oral and Maxillofacial Surgery at Dental School of Isfahan University of Medical Sciences with the complaint of swelling and bleeding in the right anterior region of mandibular mucosa. The swelling was present during last 12 months, and the lesion size was increased in this period. Patient’s medical and familial history was not significant. No history of trauma and tobacco or alcohol consumption was reported. Furthermore, hematological parameters were normal. She has used dentures since 5 years ago, but now, she could not use her mandibular partial denture.
</p><p>In extraoral examination, the patient had lymphadenopathy and the regional lymph nodes were palpable. In intraoral examination, we observed non-tender, painless, gray to black,
broad based sessile tumor-like exophytic lesion with rough and irregular ulceration surface, with rubbery consistency, and 2 × 1.5×2cm dimension in anterior mandibular mucosa between
right and left canine teeth. The lesion extended over the gingiva of distal part of right canine tooth to posterior mandibular region, which revealed findings of ulceration and bleeding.
There was major involvement over the labial aspect of mandibular gingiva followed by anterior-posterior extension into the vestibule and oral aspect of lip mucosa (<xref ref-type="fig" rid="JDS-18-227-g001.tif">Figure 1a</xref>).
The canine teeth adjacent the lesion was vital. Panoramic radiography showed the shadow of the lesion with irregular outline on mandibular bone (<xref ref-type="fig" rid="JDS-18-227-g001.tif">Figure 1b</xref>). Clinical differential
diagnosis was giant cell tumor and squamous cell carcinoma.
</p><p>For the patient, excisional biopsy was done. In microscope examination, hematoxylin/eosin (H&E) stained sections showed the malignant cellular proliferation of
epitheloid and spindle shaped pleomorphic cells in connective tissue that was covered by stratified squamous epithelium. Junctional activity was also observed from epithelium
into connective tissue (<xref ref-type="fig" rid="JDS-18-227-g001.tif">Figure 1c</xref>). The nuclei were vesicular, pleomorphic, hyperchromatic with few abnormal mitoses, and contained one
or more amphophilic nucleoli. Furthermore, brown pigments were observed in some cells (<xref ref-type="fig" rid="JDS-18-227-g001.tif">Figure 1d</xref>). Immunohistochemical staining for S100,
Melan-A (Mart1), and HMB45 were strongly and diffusely positive that was confirming the diagnosis of malignant melanoma (<xref ref-type="fig" rid="JDS-18-227-g001.tif">Figure 1e, 1f</xref>). </p><fig id="JDS-18-227-g001.tif" position="float"><label>Figure1</label><caption><p><bold>a:</bold> Clinical image showing irregular lesion on mandibular alveolar mucosa in surgery procedure, <bold>b:</bold> Panoramic image showing the shadow of the lesion with irregular outline on mandibular bone,
<bold>c:</bold> There is a junctional activity from epithelium into connective tissue in histopathological view (H & E staining, original magnification ×100), <bold>d:</bold> The cells and nuclei were markedly pleomorphic and amphophilic
nucleoli and varied in number and size with melanin pigment (H & E staining, original magnification × 400), <bold>e:</bold> Tumor cell showing positive staining HMB-45 (Immunohistochemical staining, original magnification ×100),
<bold>f:</bold> Melan-A (Immunohistochemical staining, original magnification ×400).
</p></caption><graphic xlink:href="JDS-18-227-g001"></graphic></fig><p>Conventional tomography (CT) of head and neck revealed the metastatic lesions in anterior and posterior aspect of right mandibular gland (right mandibular aspect: level 1). After this result of CT, lateral and inferior tongue margins, mouth floor, submandibular salivary gland, and submandibular lymph nodes were resected under general anesthesia. The patient was referred to the Department of Oncology for further treatment. During radiotherapy and chemotherapy follow-up period, patient reported some other problems such as difficulty in eating and speech and severe trismus. The intraoral examination showed white lesions and ulcers.
</p><p>Five months after diagnosis, pulmonary metastasis has been detected. Because of headache, the patient was referred for magnetic resonance imaging (MRI). MRI showed irregular lesions in deep while matter, centrum semi-ovale and right frontal lobe and left temporal lobes that indicated brain metastasis. In addition, 9 months after diagnosis, multiple metastatic lesions were detected in liver by ultra sonographic examination. Unfortunately, the patient passed away one year after diagnosis.
</p></sec><sec id="sec1-3"><title>Case 2</title><p>A 59-year-old male patient was admitted to the Department of Oral and Maxillofacial Pathology at Dental School of Isfahan University of Medical Sciences with complaint of a
painful mass and ulcer on the anterior maxillary gingiva. According to the patient, the mass has grown three months ago. The non-healing ulcer in this edentulous patient made
him stop wearing his complete dentures last month. He had not any systemic disease or other medical problems.
</p><p>In extraoral examination, the patient did not have lymphadenopathy and the regional lymph nodes were not palpable or tender. Intraoral physical examination revealed a
dark purple lesion with erosive surface and irregular borders, measuring 3×2×2cm in dimension on the left maxillary alveolar mucosa (<xref ref-type="fig" rid="JDS-18-227-g002.tif">Figure 2a</xref>).
Panoramic radiograph showed a slight erosion of anterior maxillary alveolar process. An incisional biopsy was performed under local anesthesia for final diagnosis. Histopathological
examination showed the proliferation of polygonal, epitheloid, spindle or bizarre cells with pleomorphism and nuclear hyperchromatism and tumoral giant cells in connective tissue that
was covered by surface epithelium (<xref ref-type="fig" rid="JDS-18-227-g002.tif">Figure 2b and 2c</xref>). Furthermore, excessive mitotic figures were observed. These atypical cells were arranged as large
sheets rendering pseudoalveolar or storiform pattern. According to this feature, histological differential diagnoses included amelanotic melanoma, spindle cell malignancies of mesenchymal
tissues, and undifferentiated carcinoma. Immunohistochemistry was used to establish the final diagnosis. The tumor cells were strongly positive for vimentin, S100, Melan-A, but were
negative for pan-cytokeratin, epithelial membrane antigen (EMA), E-cadherin and desmin (<xref ref-type="fig" rid="JDS-18-227-g002.tif">Figures 2d, 2e, 2f</xref>). Based on the histopathological and immunohistochemical
findings, the lesion was diagnosed as amelanotic melanoma. The patient was referred to oral and maxillofacial surgeon and oncologist for further treatment. Chest X-ray revealed diffuse metastasis
to lungs. As the patient did not keep his appointment with dental school, no additional follow-up information is available.
</p><fig id="JDS-18-227-g002.tif" position="float"><label>Figure2</label><caption><p><bold>a:</bold> A tumor-like, erosive surface and amelanotic pink lesion on the left anterior buccal aspect of edentulous ridge of maxilla, <bold>b:</bold> Photomicrograph showing invasion
of malignant spindle and polygonal cells with nuclear hyperchromatic in the connective tissue (H & E staining, original magnification ×40), <bold>c:</bold> Tumoral giant cells,
<bold>d:</bold> Tumor cell showing positive staining Melan-A (Mart-1), <bold>e:</bold> S100, <bold>f:</bold> Vimentin (Immunohistochemical staining, original magnification ×100).
</p></caption><graphic xlink:href="JDS-18-227-g002"></graphic></fig></sec><sec sec-type="Discussion" id="sec1-4"><title>Discussion</title><p>Melanocytes originate from neural crest precursor cell during development. These cells migrate into dorsolateral pathway and differentiate into mature melanocytes that are located in the basal and parabasal layers of skin and various mucous membranes.[<xref rid="ref6" ref-type="bibr">6</xref>,<xref rid="ref10" ref-type="bibr">10</xref>,<xref rid="ref18" ref-type="bibr">18</xref>] Melanocytes can produce melatonin and serotonin. Thus, these cells have an important role in homeostasis of skin and mucosa both under physiological conditions and have a protective function against the damage effects of sun exposure.[<xref rid="ref10" ref-type="bibr">10</xref>,<xref rid="ref19" ref-type="bibr">19</xref>] However, the main functions of mature melanocytes have not been identified.[<xref rid="ref6" ref-type="bibr">6</xref>] Melanoma cells are the malignant transformed melanocytes that are round, spindle, and polygonal cells with hyperchromatic nuclei. These cells are devoid of dendritic processes and have clonal expansion ability.[<xref rid="ref10" ref-type="bibr">10</xref>] These features lead to the ability of deep invasion to the superficial epithelium and connective tissue, metastasis to regional lymph nodes and distant metastasis.[<xref rid="ref6" ref-type="bibr">6</xref>]</p><p>Primary OM is usually asymptomatic, so these features lead to the delay in diagnosis. Thus, most of OMs are in advanced stage at the time of diagnosis. Frequent symptoms such as denture problem, ulceration, bleeding, growth, teeth mobility and paresthesia may be observed, similar to clinical features of our patients.[<xref rid="ref7" ref-type="bibr">7</xref>] Clinically, most lesions are brown, black, grey, purple, red or rarely depigmented.[<xref rid="ref10" ref-type="bibr">10</xref>] Clinical differential diagnosis of malignant melanoma consist of oral melanotic macule, smoking-associated melanosis, drug- induced melanosis (such as minocycline and antimalarial drugs), melanoacanthoma, post-inflammatory pigmentation, nevus, amalgam tattoo, physiologic pigmentation, Kaposi’s sarcoma.[<xref rid="ref10" ref-type="bibr">10</xref>] Although some of these lesions are diagnosed based on medical history and clinical research, histological examination of all focal pigmented lesions is necessary to establish a definitive and early diagnosis.[<xref rid="ref8" ref-type="bibr">8</xref>]</p><p>The most common location of OMs is maxillary mucosa.[<xref rid="ref10" ref-type="bibr">10</xref>] However, the current case is one of rare cases in which the lesion was located in the mandibular mucosa. The highest incidence of oral melanoma was reported to be in the fifth decade of life, ranging from 40 to 70.[<xref rid="ref10" ref-type="bibr">10</xref>] Furthermore, in most studies, male predilection has been reported in mucosal melanomas.[<xref rid="ref10" ref-type="bibr">10</xref>,<xref rid="ref16" ref-type="bibr">16</xref>] Even in some studies, men were affected 3.5 times more than women were.[<xref rid="ref10" ref-type="bibr">10</xref>] The age of our patients was in accordance with the above-mentioned studies. The gender of first presented case of this study was different from reported predominant predilection. Most OMs appear de novo, although some risk factors including chronic irritation (prosthetic micro-trauma) and tobacco use have been introduced.[<xref rid="ref7" ref-type="bibr">7</xref>,<xref rid="ref16" ref-type="bibr">16</xref>] In present study, use of denture may be one of the predisposing factors.
</p><p>Histopathologically, MMs can show three patterns including <italic>in situ</italic> pattern (15%) in which the neoplasm is limited to the epithelium and the epithelial-connective tissue interface (junctional), an invasive pattern or nodular pattern (30%) in which the neoplasm is found within the underlying connective tissue, and a combined pattern (55%) which is invasive melanoma with an <italic>in situ</italic> component that is typical in most advanced lesion.[<xref rid="ref6" ref-type="bibr">6</xref>,<xref rid="ref10" ref-type="bibr">10</xref>] The histopathological examination of the first case showed the advanced lesion with invasive and <italic>in situ</italic> components. Criteria for diagnosis of primary OM were including intraepithelial (junctional) activity, evidence of malignant melanoma in the oral mucosa, and lack of any extraoral primary melanoma.[<xref rid="ref8" ref-type="bibr">8</xref>,<xref rid="ref19" ref-type="bibr">19</xref>] Besides, if the melanin pigmentation is observed in histopathological examination, the diagnosis is clear.[<xref rid="ref18" ref-type="bibr">18</xref>] In these cases, the use of immunohistochemical staining is essential for definitive diagnosis. Various expression of S100 protein, Mart1/ Melan-A, MITF, Tyrosinase and HMB45 are present in oral melanoma.[<xref rid="ref8" ref-type="bibr">8</xref>] In one of our cases, intraepidermal (junctional) activity and melanin pigmentation in histopathological features and positive result of immunohistochemical staining for specific melanocyte antigens in tumor cells was approved primary OMs. However, when the lesion is amelanotic as it was in another presented case, many tumors can be considered in differential diagnosis. The histopathological differential diagnosis includes spindle cell malignant tumors (such as leiomyosarcomas, spindle cell carcinoma, malignant peripheral nerve sheath tumor, undifferentiated pleomorphic sarcoma, angiosarcoma, synovial sarcoma), epitheloid malignant tumors (such as epithelioid sarcoma), round cell tumors (such as lymphomas, neuroendocrine tumors, rhabdomyosarcoma, plasmacytoma), clear cell malignant tumors (such as mucoepidermoid carcinoma, renal cell carcinoma), and metastatic lesions.[<xref rid="ref8" ref-type="bibr">8</xref>] In our second case, the diagnosis of amelanotic melanoma was confirmed by positive presence of Melan-A and S100. Furthermore, melanoma is negative for cytokeratins, EMA, desmin and positive for vimentin, consistent with our immunohistochemical findings.[<xref rid="ref20" ref-type="bibr">20</xref>]</p><p>Most studies have reported that OMs are very aggressive neoplasm and many factors are related to its invasion including late diagnosis, poor resectability, and early metastasis.[<xref rid="ref12" ref-type="bibr">12</xref>-<xref rid="ref15" ref-type="bibr">15</xref>] Older age, extent of oral primary tumor, poor resectability, non-pigmented (amelanotic) lesions and regional lymph node involvement have direct relation with poorer prognosis.[<xref rid="ref8" ref-type="bibr">8</xref>] Moreover, other factors associated with poor prognosis are a high mitotic rate of the atypical melanocytes, and vascular or neural invasion.[<xref rid="ref6" ref-type="bibr">6</xref>] Determining the stage of melanoma is imperative for treatment planning as presented in <xref ref-type="table" rid="T1">Table 1</xref>.[<xref rid="ref10" ref-type="bibr">10</xref>] Lymphatic metastasis at the time of diagnosis is the best prognostic factor for OMs.[<xref rid="ref21" ref-type="bibr">21</xref>] The first presented case had involvement of the regional lymph nodes and metastatic lesions to lung, brain, and liver. Thus, the patient at the time of diagnosis was in stage II, after 4 months of the diagnosis was in stage III, and had poor prognosis.
</p><table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Melanoma staging[<xref rid="ref10" ref-type="bibr">10</xref>]
</p></caption><table frame="hsides" rules="groups" width="100%"><tbody><tr><td style=" color:#000000;background-color:#BFBFBF;border:none;border-bottom:solid windowtext 1.0pt;" align="left" colspan="1" rowspan="3" valign="middle">Stage I (N0M0) Primary tumor present only</td><td style=" color:#000000;background-color:#BFBFBF;" align="left" colspan="1" rowspan="1" valign="top">Level I: <italic>in situ</italic> melanoma without invasion or <italic>in situ</italic> melanoma with microinvasion</td></tr><tr><td style=" color:#000000;background-color:#BFBFBF;" align="left" colspan="1" rowspan="1" valign="top">Level II: invasion up to the lamina propria</td></tr><tr><td style=" color:#000000;background-color:#BFBFBF;border:none;border-bottom:solid windowtext 1.0pt;" align="left" colspan="1" rowspan="1" valign="top">Level III: deep skeletal tissue invading in to the skeletal muscle, bone, or cartilage</td></tr></tbody></table><table-wrap-foot><p>Stage II: Tumor metastatic to regional lymph nodes (N1M0)</p><p>Stage III: Tumor metastatic to distant locations (M1)</p></table-wrap-foot></table-wrap><p>The most effective treatment for MMs is surgical resection.[<xref rid="ref16" ref-type="bibr">16</xref>] The primary lesion should be excised with 1.5 cm of surrounding healthy tissue. However, new treatment protocols for OMs consist of surgical resection, neck dissection for lymph node metastasis, cryotherapy, chemotherapy, radiotherapy and immunotherapy or combination of these modalities.[<xref rid="ref7" ref-type="bibr">7</xref>] This topic showed that the lesions with color change and abrupt enlargement should particularly be biopsied for histopathological evaluation and early diagnosis.[<xref rid="ref22" ref-type="bibr">22</xref>]</p></sec><sec sec-type="Conclusion" id="sec1-5"><title>Conclusion</title><p>Because the most OMs are usually asymptomatic with quick growing, they are detected in late stage of diagnosis. Careful oral examination by clinicians and early biopsy of pigmented and suspicious non-pigmented lesions, have an imperative role in more survival rate and better prognosis.
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