Primary Oral Melanoma Research Articles

Establishment of Primary Cell Cultures from Canine Oral Melanomas via Fine-Needle Aspiration: A Novel Tool for Tumorigenesis and Cancer Progression Studies.

Oral melanomas are the most common oral malignancies in dogs and are characterized by an aggressive nature, invasiveness, and poor prognosis. With biological and genetic similarities to human oral melanomas, they serve as a valuable spontaneous comparative model. Primary cell cultures are widely used in human medicine and, more recently, in veterinary medicine to study tumorigenesis, cancer progression, and innovative therapeutic approaches. This study aims to establish two- and three-dimensional primary cell lines from oral canine melanomas using fine-needle aspiration as a minimally invasive sampling method. For this study, samples were collected from six dogs, represented by four primary oral melanomas and five lymph nodal metastases. The cells were digested to obtain single-cell suspensions, seeded in flasks, or processed with Matrigel® to form organoids. The cell cultures were characterized through flow cytometry using antibodies against Melan-A, PNL2, and Sox-10. This technique offers a minimally invasive means to obtain cell samples, particularly beneficial for patients that are ineligible for surgical procedures, and enables the establishment of in vitro models crucial for comparative studies in mucosal melanoma oncology. To the best of our knowledge, this is the first work establishing neoplastic primary cell cultures via fine-needle aspiration in dogs.

Investigation of oncolytic effect of recombinant Newcastle disease virus in primary and metastatic oral melanoma

Malignant melanoma is aggressive cancer with a high rate of local invasiveness and metastasis. Currently, the treatment options for patients with advanced-stage and metastatic oral melanoma are limited. A promising treatment option is oncolytic viral therapy. This study aimed to evaluate novel therapies for malignant melanoma using a canine model. Oral melanoma, which frequently occurs in dogs is used as a model for human melanoma, was isolated and cultured and used for the evaluation of the tumor lytic effect induced by viral infection. We constructed a recombinant Newcastle disease virus (rNDV) that promotes the extracellular release of IFNγ from the virus-infected melanoma. The expression of oncolytic and apoptosis-related genes, the immune response by lymphocytes, and IFNγ expression were evaluated in virus-infected melanoma cells. The results showed that the rate of rNDV infection varied according to the isolated melanoma cells and the oncolytic effect differed between melanoma cells owing to the infectivity of the virus. The oncolytic effect tended to be greater for the IFNγ-expressing virus than for the GFP-expressing prototype virus. Additionally, lymphocytes co-cultured with the virus showed induced expression of Th1 cytokines. Therefore, recombinant NDV expressing IFNγ is expected to induce cellular immunity and oncolytic activity. This oncolytic treatment shows promise as a therapeutic approach for melanoma treatment once evaluated using clinical samples from humans.

Oral melanoma: a multicenter study of 69 patients from Japan.

The purpose of this multicenter retrospective study was to investigate the demographic characteristics and treatment outcomes of patients with mucosal malignant melanoma (MM) of the oral cavity. This was a multicenter study involving 8 Japanese universities. The medical records of 69 patients who were diagnosed with primary oral MM between January 2000 and December 2020 were retrospectively analyzed. Overall survival (OS) and prognostic factors for OS were analyzed statistically. There were 40 (58.0%) males and 29 (42.0%) females, and their mean (range) age was 69.8 ± 14.6 (22-96) years old. The most common primary site was the palate (30 patients, 43.5%). Stage IVA was the most common disease stage (36 patients, 52.2%). Radical therapy was performed in 55 patients (79.7%). The 2-year and 5-year OS rates of the 69 patients were 64.6% and 42.5%, respectively. The 2-year and 5-year OS rates of the stage III patients were 85.9% and 72.5%, respectively, and those of the stage IVA patients were 56.3% and 26.0%, respectively. The 1-year OS rate of the stage IVB/IVC patients was 26.7%. The 2-year and 5-year OS rates of the radical therapy group were 74.1% and 50.5%, respectively, whereas the 2-year OS rate of the non-radical therapy group was 26.0%. An advanced T classification was the only identified prognostic factor for OS (hazard ratio: 6.312, 95% confidence interval: 1.133-38.522, p < 0.05). Early detection and radical treatment are essential for improving the prognosis of oral MM patients. Early detection and adequate radical therapy leads to the better prognosis of oral MM patients.

Actionable Mutation Profile of Sun-Protected Melanomas in South America.

Melanomas that arise in sun-protected sites, including acral and oral mucosal melanomas, are likely under the control of unique, specific mechanisms that lead to mutagenesis through various pathways. In this study, we examined somatic mutations in tumors by targeted sequencing using a custom Ion Ampliseq Panel, comprising hotspots of 14 genes that are frequently mutated in solid tumors. Tumor DNA was extracted from 9 formalin fixation, paraffin-embedded sun-protected melanomas (4 primary oral mucosal melanomas and 5 acral lentiginous melanomas), and we identified mutations in the NRAS , PIK3CA , EGFR , HRAS , ERBB2 , and ROS1 genes. This study reveals new actionable mutations that are potential targets in the treatment of photo-protected melanomas. Additional studies on more of these melanoma subtypes could confirm our findings and identify new mutations.

Accurate Delineation of Mucosal Lesions in Treatment-Planning Computed Tomography Using Iodine Paste Markers for Oral Mucosal Melanoma

This technical report introduces the utility of iodine paste markers using endodontic materials for the accurate contouring of mucosal lesions of oral mucosal melanoma, which are difficult to delineate on imaging during the planning of carbon-ion radiation therapy (CIRT). The patient had a primary oral mucosal melanoma located in the palatal mucosa without palatal or maxillary bone invasion. A dental root canal filling material, which is a calcium hydroxide/iodoform nonhardenable paste, was used as a marker. We first performed treatment-planning computed tomography (CT) without an iodine paste marker for mucosal lesions. Subsequently, we placed an iodine paste marker on the palatal mucosal lesion to accurately delineate the mucosal lesions of the palate. Finally, we obtained a reference CT image with an iodine paste marker. Computed tomography without the marker was fused to the reference CT with markers during treatment planning, and the gross tumor volume was contoured. Thereafter, CIRT was delivered without markers. During CIRT, expected acute mucositis was observed in the area of the planning target volume, including melanosis, in accordance with the dose distribution. The use of iodine paste markers for localized mucosal lesions, which are difficult to delineate on CT and magnetic resonance imaging, may be useful for accurately contouring gross tumor volumes on treatment-planning CT.

Palatal Malignant Melanoma: A Case Report of an Unusual Site and Histologic Presentation

Malignant melanoma is a potentially aggressive tumor of melanocytic origin. Primary oral malignant melanoma is a rare neoplasm, accounting for 0.5% of all oral malignancies. We report a case of 44yr old male patient who presented with a painful pigmented nodule involving the palate and histologically showing a spindle cell type of Melanoma.

Oral Mucosal Melanoma.

Primary oral mucosal melanoma (OMM) is a rare neoplasm accounting for the 0.2% to 0.8% of all melanomas. The aim of the present manuscript is (1) to describe 2 cases of primary OMM treated at our department, and (2) to perform a systematic literature review on primary OMM occurrence and treatment. Two cases of primary OMM were described. A systematic review is presented in order to assess the treatment options, recurrence, metastasis development, and survival rate of primary OMM. Two patients were referred for the development of a lesion of the hard palate and the maxillary gingival mucosa, respectively. An incisional biopsy was performed in both patients, followed by extensive surgical resection after a thorough consideration of patient history and systemic involvement. The literature search retrieved 447 primary OMM cases. In the 30% of cases, distant metastases were already present at the time of diagnosis. The management of primary OMM most frequently involved surgical treatment and adjuvant radiotherapy. Primary OMM still represents a challenge for the clinician, as the diagnosis is often performed when metastases have already developed. The prognosis is generally poor, thus highlighting the need for further investigations to improve early diagnosis.

A Rare Case of Primary Oral Malignant Melanoma of Mandibular Gingiva with an Update on Clinical Staging.

A Rare Case of Primary Oral Malignant Melanoma of Mandibular Gingiva with an Update on Clinical Staging.

PRIMARY ORAL MELANOMA: A CASE REPORT WITH IMMUNOHISTOCHEMICAL FINDINGS

Melanoma is a potentially aggressive and rare malign neoplasm of melanocytic origin. Only 1% occur in oral mucosa, and it is more aggressive compared with the cutaneous counterpart. The tumor occurs more frequently in the hard palate and gingiva. The aim of this study is to report a case of primary oral melanoma in a 70-year-old female patient. Multiple asymptomatic pigmented lesions were observed in the upper vestibular gingiva and hard palate. An incisional biopsy was performed. Microscopic findings revealed proliferation of pleomorphic epithelioid and plasmacytoid cells positive by immunohistochemistry for S-100 protein, HMB-45, Melan-A, and Ki-67 (80%) confirming the diagnostic of oral melanoma. The patient was forwarded to a head and neck surgeon service for treatment. This study showed the importance of histopathologic and immunohistochemical evaluation to determine the morphologic aspects of oral melanoma to establish the final diagnosis.

Does BCL-2 Play Role in the Pathogenesis of Primary Oral Mucosal Melanoma?

Primary Oral Mucosal Melanoma represents 0.2 to 8% of all melanomas and 0.5% of all oral malignant neoplasia. The etiology still unknown, however, it has been suggested that head and neck mucosal melanomas change their genetic and metabolic pathways through intracellular cascades, which are associated with its etiopathogenesis mechanisms. The BCL2 protein is an integral part of the cell membrane, and it is also found in the cell nucleus, mitochondria, and endoplasmic reticulum. It is overexpressed in several malignant neoplasms, including cutaneouse ocular melanomas. Among all evaluated cases, we found positive immunostaining of BCL-2 in 26/34 (76.47%) and they had a membrane and cytoplasmic pattern, and the intensity was variable. According to our results and the findings of the literature, it can be suggested that BCL-2 has an important role in melanoma pathogenesis, including Primary Oral Mucosal Melanoma and also melanoma metastases. It seems that BCL-2 could be an adjunct marker for POMM and also a target for treatment development. New researches involving BCL-2 and a larger primary oral mucosal melanoma cohort could corroborate the present study

METABOLIC-RELATED AND STEM CELL MARKERS IN A SERIES OF PRIMARY ORAL MUCOSAL MELANOMAS AND ORAL NEVI

Primary oral mucosal melanomas (POMM) are rare and aggressive neoplasms arising in the melanocytes from the epithelial lining of the oral cavity, and currently few prognostic markers are described. Objective: In this study, we investigated the expression of glucose transporter 1 (GLUT1), antimitochondrial antibody (AMT), and stem cell markers (CD44) in a series of 3 POMM and 3 oral nevi. Methods: Immunostainings of GLUT1, CD44, and AMT were quantitatively assessed by digital analyses. Results: POMM showed a proliferation of epithelioid or fusiform variable-pigmented melanocytes. GLUT1, CD44, and AMT were negative in all nevi and strongly expressed in the melanomas. Conclusion: Our results suggest that overexpression of mitochondrial and stem cells markers can help confirm the diagnosis of melanomas and they can be associated with the aggressive behavior of these rare tumors.

Genome-wide analysis of canine oral malignant melanoma metastasis-associated gene expression

Oral malignant melanoma (OMM) is the most common canine melanocytic neoplasm. Overlap between the somatic mutation profiles of canine OMM and human mucosal melanomas suggest a shared UV-independent molecular aetiology. In common with human mucosal melanomas, most canine OMM metastasise. There is no reliable means of predicting canine OMM metastasis, and systemic therapies for metastatic disease are largely palliative. Herein, we employed exon microarrays for comparative expression profiling of FFPE biopsies of 18 primary canine OMM that metastasised and 10 primary OMM that did not metastasise. Genes displaying metastasis-associated expression may be targets for anti-metastasis treatments, and biomarkers of OMM metastasis. Reduced expression of CXCL12 in the metastasising OMMs implies that the CXCR4/CXCL12 axis may be involved in OMM metastasis. Increased expression of APOBEC3A in the metastasising OMMs may indicate APOBEC3A-induced double-strand DNA breaks and pro-metastatic hypermutation. DNA double strand breakage triggers the DNA damage response network and two Fanconi anaemia DNA repair pathway members showed elevated expression in the metastasising OMMs. Cross-validation was employed to test a Linear Discriminant Analysis classifier based upon the RT-qPCR-measured expression levels of CXCL12, APOBEC3A and RPL29. Classification accuracies of 94% (metastasising OMMs) and 86% (non-metastasising OMMs) were estimated.

CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway.

Mutations on KIT and downstream genes of MAPK pathway that overstimulate cellular proliferation have been associated with primary oral and sinonasal melanomas (POSNM), but there is limited information that allows the use of personalized therapy. Thus, the aim of the present study was to determine a possible association between the C-KIT immunohistochemical expression with the presence of somatic driver mutations in NRAS, BRAF, KIT, MITF and PTEN on POSNM. A retrospective study included 62 tumour samples of an oncological reference centre in Mexico City (17-year period). Immunohistochemistry stain of C-KIT was carried out. Genomic DNA was obtained and used to assess hotspot mutations of KIT, NRAS, BRAF, MITF and PTEN through qPCR. Chi-square, Fisher's exact and the Mann-Whitney U tests were applied when necessary. The significance was set at P<0.05. Sixty-two cases were included, 74% were positive for C-KIT immunoexpression, all exhibited moderate/strong intensity. Ten (16.1%) samples harboured at least one mutation, 6.4% and 6.6% for NRASQ 61R and BRAFV 600E , respectively, followed by KITK624E (3.2%). No KITL 576P , MITF or PTEN mutations were identified. No significant correlation was observed between mutations and immunostaining (rs=-0.057, P=0.765). Regardless of the high immunoexpression of C-KIT, there was no association with the MAPK mutations among POSNM samples. Thus, C-KIT immunohistochemistry is not a reliable tool to detect POSNM candidates for biological therapy.

Oral Malignant Melanoma: a Case Report

Malignant melanoma is a potentially aggressive tumor of melanocytic origin. Primary oral malignant melanoma (OMM) has a low prevalence, accounting for about 0.5% of all oral malignancies. This report is of an 80-year-old man who attended the stomatology clinic, reporting an increase in the volume of the lower lip since 6 months prior. Intraoral examination revealed a 2.5-cm pedunculated lesion, whitish in color, of friable surface in the right lower lip, and surrounded by irregular areas of brownish black pigmentation. The diagnostic hypothesis was squamous cell carcinoma and OMM. Incisional biopsy rendered a histopathologic diagnosis of malignant neoplasm of uncertain histogenesis. Immunohistochemically, the tumor cells were positive for S-100 protein and melan A and negative for CKAE1/AE3, p63, and CD31, yielding a diagnosis of OMM. The patient underwent lip shave surgery with tumor-free margins, and follow-up showed no signs of recurrence. Pigmented lesions in the oral cavity require great attention.

Malignant oral melanoma: how to spot it and how it is managed

Abstract: Primary oral melanoma (POM) is a rare malignancy affecting primarily the hard palate and maxillary gingivae. Oral melanoma has a poor prognosis due to the frequent delay in diagnosis, the tendency of the tissues to be invaded locally and the potential to metastasize. This article aims to summarize the key clinical features of different types of oral pigmentation that are likely to be encountered by a general dental practitioner (GDP) and to highlight those that should prompt an urgent referral for investigation. CPD/Clinical Relevance: The aim of this article is to increase awareness of the varying and sometimes atypical features of oral melanoma.

An Unusual and Rare Case of Primary Oral Malignant Melanoma Involving the Mandible in a Young Female

Background: Primary oral malignant melanomas (POMM) are rare and have been estimated to represent 1.6% of all oral malignancies and 0.2-8% of all melanomas. Most cases of melanomas involve palate and maxillary gingiva (80%) and about 20% involve mandible. The purpose of this article is to report a very unusual and rare case of melanoma in a young female involving mandible causing extreme destruction of bone. Methods and Findings: A 23 year-old female presented with a painful swelling over right mandible since 3 months. The growth extended from right preauricular region to submandibular region, was nodular and bluish black in colour and bled on touching. It caused displacement of mandibular premolars and molars. A provisional diagnosis of malignant osteolytic tumor was made. The patient underwent right hemimandibulectomy. Intraoperatively, the tumor was seen involving the entire mandibular body. On gross examination, right hemimandibulectomy specimen was received in pieces measuring 12 × 9.5 × 5.2 cm containing seven teeth. The tumor had perforated the lingual cortical plate. Cut surface was friable and black in colour. Microscopy showed a biphasic high grade neoplasm comprising of round to spindled tumor cells exhibiting marked nuclear pleomorphism and brisk mitosis, laden with granular brownish pigment melanin. The findings were consistent with the diagnosis of pigmented malignant melanoma and confirmed on immunohistochemistry as the tumor expressed vimentin and HMB45 and was negative for CK, EMA and p40. Conclusion: Involvement of mandibular bone by melanoma is rare. However, when they involve the bone, they are indistinguishable from other lytic malignant tumors or osteomyelitis. The present case emphasizes the need to learn the unusual location, the possible presentation of oral melanoma and inclusion of this rare tumor in the differential diagnosis of lytic bone tumors.

A preliminary immunohistochemical study of signal transducer and activator of transcription (STAT) proteins in primary oral malignant melanoma

Primary oral malignant melanoma (POMM) is a rare type of malignancy with a very poor prognosis, the molecular pathogenesis of which remains elusive. The aim of this study was to assess the expression status of signal transducer and activator of transcription (STAT) proteins in POMM. Six POMMs were included in the study. Total protein levels of STAT1, STAT3, and STAT5a, as well as the tyrosine phosphorylated (activated) form of STAT3 (pSTAT3), were assessed immunohistochemically. Immunohistochemical evaluation of total STAT3 revealed diffuse and strong cytoplasmic and nuclear expression in the majority of tumor cells of all cases, whereas activated pSTAT3 had mostly mild nuclear expression in 5%-40% of malignant melanocytes in all cases. Evaluation of STAT1 and STAT5a identified mainly mild cytoplasmic expression in the absence of nuclear localization. The identification of aberrant STAT3 expression and activation in oral malignant melanocytes supports a possible role of this molecule in POMM. In contrast, STAT5a has only limited cytoplasmic expression, mitigating against its involvement in POMM. Also, STAT1's low levels may have implications for POMM sensitivity to interferon-based therapeutic strategies, considering the role of this molecule in cutaneous melanoma immunotherapy.

Head and Neck: Primary oral mucosal melanoma

Head and Neck: Primary oral mucosal melanoma

NRAS and BRAF mutation frequency in primary oral mucosal melanoma

NRAS and BRAF mutation frequency in primary oral mucosal melanoma

Primary oral malignant melanoma metastasis to the brain and breast: A case report and literature review.

Primary oral malignant melanoma is a rare tumor, which is estimated to comprise 0.2–8.0% of all melanoma cases. This type of cancer is fairly uncommon, its prognosis is dismal, and it frequently exhibits a biologically aggressive behavior. The common location of primary oral malignant melanoma is the hard palate and maxillary alveolus. In ~85% of cases, the melanoma will metastasize to the liver, lung, bone and brain early in the course of the disease. The present study reports the case of a 50-year-old premenopausal woman who presented with primary oral malignant spindle cell melanoma (T3bN2aM0) and underwent complete surgical resection followed by an adjuvant course of radiation therapy. After 1 year, the patient presented with sudden onset slurred speech, and upon examination, was found to have left-sided hemiparesis and a hard left breast mass. Workup confirmed breast and brain metastasis. The patient developed lung metastasis 4 weeks later and was referred for palliative care.