Search Results (28)

Mucosal melanomas (MMs) are under-researched tumors with a poor prognosis that arise from melanocytes found in the mucous membranes at different anatomical locations throughout the body. MMs are an uncommon yet highly aggressive tumor that typically develops on mucosal surfaces, predominantly in the head and neck region. MM of the head and neck occurs in 8–10% of all head and neck melanomas. It most commonly affects the mucosa of the nasal cavity and paranasal sinuses (75%), followed by the oral cavity mucosa (25%). A family history and the presence of mucosal nevi are associated with the occurrence of MM. Inhaled and dietary carcinogens are also linked to the development of sinonasal melanoma, much like other malignancies of the nasal cavity. Overexpression of the C-KIT gene is found in more than 80% of all primary mucosal melanomas, with somatic mutations in 10–30% of cases. The presence of these genetic alterations is also reflected in recent clinical studies of specific gene inhibitors that have proven efficiency in the systemic therapy of melanoma. There are various treatment modalities for MM. Surgical therapy involves en bloc surgical resection with a macroscopically visible and palpable mucosal margin of 1.5–2 cm. Partial resection of the maxilla may be considered if it ensures adequate tumor-free margine. Because of its rarity, outcome data for locally advanced head and neck MM is limited and primarily derived from retrospective studies with small case numbers. This review aims to update and summarize findings from clinical trials, prospective observational studies, and retrospective studies, while also exploring future directions for multimodal treatment approaches in this area. Full article

Malignant melanoma of the tongue is a rare and highly aggressive neoplasm, constituting less than 2% of oral melanomas. Due to its rarity and atypical clinical presentation, diagnosis and management pose significant challenges. This study provides a scoping review of research on melanoma of the tongue to determine the available data on the epidemiology, clinical features, histopathological characteristics, treatment strategies, and outcomes of this malignancy. Our literature search identified papers published from 1941 to 2024, and 47 individual cases were analyzed. The mean age at diagnosis was 58.6 years, with a male predominance (58.1%). Lesions were most frequently located on the body and lateral borders of the tongue. A high percentage (38.5%) presented with distant metastases at diagnosis, commonly involving the lungs and brain. Histopathological examination highlighted spindle cell morphology in many cases, with immunohistochemical markers such as HMB-45 and S-100 proving essential for diagnosis. Wide local excision with or without neck dissection was the primary treatment, though recurrence rates remained high (20.5%). Despite aggressive management, overall outcomes were poor, reflecting the melanoma’s advanced stage at diagnosis in most cases. This scoping review underscores the need for heightened clinical suspicion, particularly for pigmented or ulcerative lesions of the tongue. Early diagnosis, multidisciplinary management, and further research into the genetic and molecular mechanisms underlying tongue melanoma are crucial to improve outcomes for this rare and aggressive disease. Full article

Mucosal melanoma of the head and neck (HNMM) is a rare but highly aggressive malignancy, often diagnosed at an advanced stage with poor prognosis. This review discusses current treatment strategies, emphasizing the role of radiotherapy in managing this challenging disease. A comprehensive analysis of 33 studies provides updated information on techniques and outcomes, highlighting the consistent benefit of adjuvant radiation in improving local control. Advances in conformal techniques, such as intensity-modulated radiotherapy (IMRT), have significantly reduced toxicity rates. Preliminary data on proton and carbon ion therapies suggest the potential for further enhancement of the therapeutic ratio, despite limited availability. Although recent studies report 3-year local control rates as high as 90%, overall survival within the same time frame remains well below 50–60%, underscoring the need for continued improvement in systemic therapies to address the persistent issue of distant metastases. Full article

Canine malignant melanoma (CMM) is highly aggressive and mostly located in the oral cavity. CMM is the predominant type of canine oral malignancy and shows striking homologies with human mucosal melanoma. In comparative oncology, canine oral melanomas (COMs), as spontaneous tumor models, have the potential to acquire a unique value as a translational model of rare human melanoma subtypes. This review aims to provide a comprehensive summary of targeted therapies for canine malignant melanoma and to enrich the field of comparative oncology. Following the PRISMA guidelines, a comprehensive literature search was conducted across databases for studies from 1976 to April 2024. Studies were selected based on their relevance to targeted treatments. A total of 30 studies met the inclusion criteria. Based on the treatment approaches, the studies were further categorized into immunotherapies, small molecule signaling inhibitors, indirect kinase inhibitors, and other alternative strategies. Some treatments have been shown to result in stable disease or partial response, accounting for 29% (monoclonal antibody) and 76.5% (micro-RNA therapies) in clinical trials. Moreover, in vitro experiments of small molecule inhibitors, including cell signaling inhibitors and indirect kinase inhibitors, have shown the potential to be an effective treatment option for the development of therapeutic strategies in canine malignant melanoma. The observed response in in vitro experiments of CMM (particularly the oral and certain cutaneous subtypes) to drugs used in the treatment of human melanoma underlines the resemblance to human melanoma, therefore supporting the notion that CMM may be a valuable model for understanding rare human melanoma subtypes and exploring potential therapeutic avenues in preclinical trials. Finally, this literature review serves as a valuable resource for the development of therapeutic strategies for CMM and highlights the potential for translating these findings to human cancer treatment. Full article

Oral melanoma (OM) is the most common malignant oral tumour among dogs and shares similarities with human mucosal melanoma (HMM), validating the role of canine species as an immunocompetent model for cancer research. In both humans and dogs, the prognosis is poor and radiotherapy (RT) represents a cornerstone in the management of this tumour, either as an adjuvant or a palliative treatment. In this study, by means of RNA-seq, the effect of RT weekly fractionated in 9 Gray (Gy), up to a total dose of 36 Gy (4 weeks), was evaluated in eight dogs affected by OM. Furthermore, possible transcriptomic differences in blood and biopsies that might be associated with a longer overall survival (OS) were investigated. The immune response, glycosylation, cell adhesion, and cell cycle were the most affected pathways by RT, while tumour microenvironment (TME) composition and canonical and non-canonical WNT pathways appeared to be modulated in association with OS. Taking these results as a whole, this study improved our understanding of the local and systemic effect of RT, reinforcing the pivotal role of anti-tumour immunity in the control of canine oral melanoma (COM). Full article

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. Full article

Canine oral melanoma is the most prevalent malignant tumor in dogs and has a poor prognosis due to its high aggressiveness and high metastasis and recurrence rates. More research is needed into its treatment and to understand its pathogenic factors. In this study, we isolated a canine oral mucosal melanoma (COMM) cell line designated as COMM6605, which has now been stably passaged for more than 100 generations, with a successful monoclonal assay and a cell multiplication time of 22.2 h. G-banded karyotype analysis of the COMM6605 cell line revealed an abnormal chromosome count ranging from 45 to 74, with the identification of a double-armed chromosome as the characteristic marker chromosome of this cell line. The oral intralingual and dorsal subcutaneous implantation models of BALB/c-nu mice were successfully established; Melan-A (MLANA), S100 beta protein (S100β), PNL2, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2) were stably expressed positively in the canine oral tumor sections, tumor cell lines, and tumor sections of tumor-bearing mice. Sublines COMM6605-Luc-EGFP and COMM6605-Cherry were established through lentiviral transfection, with COMM6605-Luc-EGFP co-expressing firefly luciferase (Luc) and enhanced green fluorescent protein (EGFP) and COMM6605-Cherry expressing the Cherry fluorescent protein gene. The COMM6605-Luc-EGFP fluorescent cell subline was injected via the tail vein and caused lung and lymph node metastasis, as detected by mouse live imaging, which can be used as an animal model to simulate the latter steps of hematogenous spread during tumor metastasis. The canine oral melanoma cell line COMM6605 and two sublines isolated and characterized in this study can offer a valuable model for studying mucosal melanoma. Full article

Canine melanoma is a malignant and aggressive neoplasm showing clinical, histological, and molecular features similar to the human counterpart. In human medicine, epidermal growth factor receptors (EGFRs) have already been suggested as prognostic markers and potential therapeutic targets in cutaneous melanoma. The aim of this study was to evaluate the expression of HER-2 and HER-3 in canine melanomas by immunohistochemistry and correlate their expression to the clinicopathological parameters of the examined tumors. Thirty-seven canine melanoma samples were recruited. Data regarding signalment and clinical parameters were also collected. The population was composed of 18 cutaneous, 16 oral/mucosal, and three digital/foot pad melanomas. Histopathological investigations were carried out to analyze histological type, ulceration, and mitotic count. On each sample, immunohistochemistry was performed using an anti-Melan-A or anti-Melanoma antigen, i.e., anti-HER-2 and anti-HER-3 antibodies. HER-2 and HER-3 positivity were classified using already established scoring criteria and a statistical analysis was carried out. The results highlighted that HER-2 expression was observed in 48.6% of the samples and HER-3 expression in 18.9%. The highest HER 2 score (3+) was recorded in 16.2% of the samples, while the coexpression of the two receptors was detected in 13.5% of the samples. A statistically significant association (p < 0.05) was observed between the expression of HER-2 and HER-3 and the presence of ulceration in oromucosal tumors. This work confirms the expression of HER-2 and HER-3 in canine melanomas and suggests a putative association with negative prognostic parameters. Further studies are necessary to strengthen these data by increasing the samples size and combining pathological examinations with molecular biology in the investigation of EGFR family receptors. Full article

Background: Melanoma cancer represents the most lethal type of skin cancer originating from the malignant transformation of melanocyte cells. Almost 50% of melanomas show the activation of BRAF mutations. The identification and characterization of BRAF mutations led to the development of specific drugs that radically changed the therapeutic approach to melanoma. Methods: We conducted a narrative review of the literature according to a written protocol before conducting the study. This article is based on previously conducted studies. We identified articles by searching electronic databases (Medline, Google Scholar and PubMed). We used a combination of “melanoma”, “Braf-Mek inhibitors”, “ targeted therapy” and “oral side effects”. Results: Eighteen studies were reported in this article showing the relationship between the use of targeted therapy in melanoma cancer and the development of oral side effects, such as mucositis, hyperkeratosis and cellular proliferation. Conclusion: Targeted therapy plays an important role in the treatment of melanoma cancer, showing a notable increase in response rate, prolonged progression-free survival and overall survival in BRAF-mutated melanoma patients. Oral side effects represent a common finding over the course of treatment. However, these adverse effects can be easily managed in a multidisciplinary approach involving collaboration between medical oncologists and dental doctors. Full article

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies, have initiated a new era in the treatment of malignant melanoma. ICIs can be used in various settings, including first-line, adjuvant, and neo-adjuvant therapy. In the scope of this review, we examined clinical studies utilizing ICIs in the context of treating oral mucosal melanoma, a rare disease, albeit with an extremely poor prognosis, with a specific focus on unraveling the intricate web of resistance mechanisms. The absence of a comprehensive review focusing on ICIs in oral mucosal melanoma is notable. Therefore, this review seeks to address this deficiency by offering a novel and thorough analysis of the current status, potential resistance mechanisms, and future prospects of applying ICIs specifically to oral malignant melanoma. Clarifying and thoroughly understanding these mechanisms will facilitate the advancement of effective therapeutic approaches and enhance the prospects for patients suffering from oral mucosal melanoma. Full article

Nevi are pigmented lesions of bluish-black colour that may occasionally occur in the oral cavity. Out of several oral melanocytic nevi (OMN), blue nevi are significant as some variants are diagnostically challenging due to histopathological overlap with malignant melanoma. The aim of the present report was to present the clinico-pathologic characteristics of 8 new cases of intraoral common blue nevi and 22 OMN. A literature review-based comparison of the clinico-pathological characteristics of intraoral blue nevi with intramucosal nevi is presented. Analysis of the clinico-pathologic characteristics of eight common blue nevi revealed that they are generally small lesions of less than 1 cm in size and are of bluish-black colouration. These lesions were commonly identified in adults (88%), with a female predilection. The hard palate was the most common site of occurrence. These findings could be collaborated with the findings observed in the literature review. It was also revealed that a common blue nevus was the second most common lesion among all OMN. The intraoral common blue nevi included in the present series did not show recurrences or undergo malignant transformation after being followed up for up to 15 years. Unlike a common blue nevus, the literature reveals that a cellular blue nevus or its atypical variant is more diagnostically challenging, while a diagnosis of an epithelioid blue nevus should be followed up with investigations to exclude Carney complex. In conclusion, this case series and literature review reveal that OMN, including intraoral common blue nevi, are small indolent lesions with extremely low malignant transformation potential. A significantly smaller size, well-defined margins and lack of variegations in colour are all features that could be used as clues to differentiate intraoral common blue nevi from mucosal malignant melanoma. However, the diagnosis needs to be confirmed with histopathology. Full article

Oral mucosal melanoma (OMM) is the most common oral cancer in dogs and is very aggressive in this species; its risk factors and etiology are yet to be determined. This study aimed to unravel the risk factors for the development of OMM in dogs and to investigate the possible presence of papillomaviruses as an etiological factor. A case-control study was conducted in 15 dogs with OMM and 15 paired controls whose owners answered an epidemiological questionnaire. Oral swabs from the same dogs were subjected to 16S rRNA sequencing for microbiome analyses. In addition, DNA fragments of OMM had their DNA extracted and amplified by polymerase chain reaction in an attempt to detect canine papillomaviruses. The gingiva was the most frequent anatomical site (47%) of OMM, and most tumors were stage III when diagnosed. Most dogs bearing OMM and the controls had grade 3 periodontal disease, and this factor, along with tartar treatment and tooth brushing, did not differ between cases and controls. Most dogs with OMM and most controls had contact with smokers; there was no statistically significant difference. Canine papillomaviruses were not detected among OMM cases. Tannerella forsythia and Porphyromonas gingivalis were significantly increased in case dogs compared to the controls. As these bacteria are reportedly involved in the pathogenesis of periodontal disease and esophageal cancer in humans, we suggest that they might be risk factors for the development of canine OMM. The limitations of this study include the low number of dogs, and therefore, further studies on canine OMM with larger numbers of animals are encouraged. Full article

Canine melanocytic neoplasms have a highly variable biological behavior ranging from benign cutaneous melanocytomas to malignant oral melanomas that readily metastasize to lymph nodes and internal organs. This review focuses on the diagnosis and prognosis of canine melanocytic neoplasms. While pigmented melanocytic neoplasms can be diagnosed with fine-needle aspirates, an accurate prognosis requires surgical biopsy. However, differentiating amelanotic spindloid melanomas from soft tissue sarcomas is challenging and often requires immunohistochemical labeling with a diagnostic cocktail that contains antibodies against Melan-A, PNL-2, TRP-1, and TRP-2 as the current gold standard. For questionable cases, RNA expression analysis for TYR, CD34, and CALD can further differentiate these two entities. The diagnosis of amelanotic melanomas will be aided by submitting overlying and/or lateral flanking epithelium to identify junctional activity. Wide excision of lateral flanking epithelium is essential, as lentiginous spread is common for malignant mucosal melanomas. Combining histologic features (nuclear atypia, mitotic count, degree of pigmentation, level of infiltration, vascular invasion; tumor thickness and ulceration) with the Ki67 index provides the most detailed prognostic assessment. Sentinel lymph nodes should be evaluated in cases of suspected malignant melanomas using serial sectioning of the node combined with immunohistochemical labeling for Melan-A and PNL-2. Full article

Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted. Full article