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de Arruda JAA, Drumond VZ, Tenório JR, Abreu LG, Silva TA, Mesquita RA, de Andrade BAB. Oral Melanoma in Older Adults: Epidemiology, Molecular Landscape, and Treatment Strategies. Pigment Cell Melanoma Res 2025; 38:e70017. [PMID: 40229937 DOI: 10.1111/pcmr.70017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 02/28/2025] [Accepted: 04/02/2025] [Indexed: 04/16/2025]
Abstract
Oral melanoma is an aggressive neoplasm arising from melanocytes in the mucosal epithelium, accounting for 0.2%-0.8% of all melanomas. Unlike cutaneous melanoma, it is not associated with UV exposure, and its pathogenesis involves complex genetic and molecular alterations. This neoplasm predominantly affects older adults (≥ 60 years). Clinically, lesions often present as macular or nodular with an exophytic growth pattern, sometimes ulcerated, and exhibit varied pigmentation. Diagnosis is further complicated by non-pigmented (amelanotic) variants that can resemble other oral pigmentations. Wide surgical excision remains the mainstay treatment, often combined with chemotherapy; however, recurrence and distant metastasis remain high. While immunotherapy has shown promise in other melanoma subtypes, its efficacy in oral melanoma remains uncertain. Treatment in older adults is particularly challenging due to comorbidities and treatment-related morbidity. This review summarizes the epidemiology, clinical features, and current treatment strategies for oral melanoma in older adults. Key advances in the molecular mechanisms underlying this neoplasm are also outlined. As a strategic approach, integrating oral melanoma screening into routine geriatric dental care, supported by diagnostic algorithms, may improve early detection, prognosis, and survival outcomes in this vulnerable population.
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Affiliation(s)
- José Alcides Almeida de Arruda
- Department of Oral Diagnosis and Pathology, School of Dentistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Victor Zanetti Drumond
- Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Jefferson R Tenório
- Department of Oral Diagnosis and Pathology, School of Dentistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Lucas Guimarães Abreu
- Department of Child and Adolescent Oral Health, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Tarcília Aparecida Silva
- Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Ricardo Alves Mesquita
- Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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2
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Vos TG, Googe PB, Blumberg JM. Melanoma In Situ of the Hard Palate. EAR, NOSE & THROAT JOURNAL 2025; 104:25S-28S. [PMID: 35822805 DOI: 10.1177/01455613221113793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Mucosal melanoma of the oral cavity is rare and highly aggressive, thought to represent less than 1% of melanomas. Within this subgroup, melanoma in situ has been rarely described. We describe the case of a 54-year-old male with history of tobacco use presented with extensive pigmented changes to the hard and soft palate. Biopsy demonstrated melanoma in situ. Mucosal surgical resection was performed with all peripheral epithelial margins involved and negative deep margins. After extensive multidisciplinary discussion, remaining mucosal margins were re-resected to the teeth and posteriorly onto the soft palate. Deep margins remained negative with melanoma in situ still present peripherally. The patient is routinely surveilled without evidence of recurrence. Oral cavity melanoma in situ has been rarely described. The treatment of choice is surgical excision, ranging from wide local excision to composite resections, with consideration given to medical adjuncts. This unique entity should be considered in pigmented oral abnormalities.
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Affiliation(s)
- Teresa G Vos
- Department of Otolaryngology/Head and Neck Surgery, Division of Head and Neck Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Paul B Googe
- Department of Dermatology, Division of Dermatopathology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jeffrey M Blumberg
- Department of Otolaryngology/Head and Neck Surgery, Division of Head and Neck Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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3
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Skudalski L, McMullan P, Grant-Kels JM. Melanoma in patients with skin of color. Clin Dermatol 2025; 43:48-55. [PMID: 39900308 DOI: 10.1016/j.clindermatol.2025.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2025]
Abstract
Cutaneous melanoma is far less common in skin of color patients than in non-Hispanic White individuals but carries a poorer prognosis. Melanomas in skin of color populations are more often identified on sun-protected locations such as acral surfaces, nail units, and mucous membranes, making them challenging to detect in early stages due to unfamiliar clinical and dermatoscopic features. Additionally, racial health care disparities compound the difficulty in diagnosis and ultimately contribute to poorer prognosis. We explore the epidemiology, clinical presentation, and health care disparities surrounding melanoma in skin of color individuals to increase awareness of the intricacies and nuances in identifying these malignancies.
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Affiliation(s)
- Lauren Skudalski
- Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut, USA
| | - Patrick McMullan
- Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut, USA
| | - Jane M Grant-Kels
- Department of Dermatology, University of Connecticut Health Center, Farmington, Connecticut, USA; Department of Dermatology, University of Florida College of Medicine, Gainesville, Florida, USA.
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4
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Abati S, Sandri GF, Finotello L, Polizzi E. Differential Diagnosis of Pigmented Lesions in the Oral Mucosa: A Clinical Based Overview and Narrative Review. Cancers (Basel) 2024; 16:2487. [PMID: 39001549 PMCID: PMC11240708 DOI: 10.3390/cancers16132487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/28/2024] [Accepted: 07/02/2024] [Indexed: 07/16/2024] Open
Abstract
This paper examines the clinical differentiation of pigmented lesions in the oral mucosa, which poses significant diagnostic challenges across dental and medical disciplines due to their spectrum from benign to potentially malignant conditions. Through a literature review and analysis of clinical cases, this study clarifies current diagnostic methodologies, with an emphasis on differential diagnosis, to provide a practical guide for clinicians. The classification of pigmented lesions, such as endogenous, focal melanocytic, and multifocal pigmentation, based on clinical and histological features, highlights the necessity for a structured and informed approach. A retrospective examination of cases from our oral medicine and pathology clinic, coupled with analysis of photographic and histological records, aids in classifying these lesions. This fosters a better understanding and promotes informed discussions among clinicians, ultimately aiming to enhance early and precise diagnosis, thus improving patient management and outcomes.
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Affiliation(s)
- Silvio Abati
- Clinical Unit of Oral Medicine and Pathology, Dental School, IRCCS San Raffaele Hospital and University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Giacomo Francesco Sandri
- Clinical Unit of Oral Medicine and Pathology, Dental School, IRCCS San Raffaele Hospital and University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Leonardo Finotello
- Clinical Unit of Oral Medicine and Pathology, Dental School, IRCCS San Raffaele Hospital and University Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Elisabetta Polizzi
- Center for Oral Hygiene and Prevention, Dental School, IRCCS San Raffaele Hospital and University Vita-Salute San Raffaele, 20132 Milan, Italy
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5
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Shahina KT, Madhu SK, Ravindran V, Kumar SS, Krishnan A, Balan BC. Mucosal Melanoma of Palate: A Case Report with Review of Literature. J Maxillofac Oral Surg 2024; 23:706-709. [PMID: 38911408 PMCID: PMC11190108 DOI: 10.1007/s12663-024-02180-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 03/25/2024] [Indexed: 06/25/2024] Open
Abstract
The World Health Organisation defines mucosal malignant melanoma as a malignant tumour of melanocytes or of melanocyte progenitors. Due to the lack of symptoms and unknown etiology, mucosal malignant melanoma may go undiagnosed. The surgeon can find it challenging to come up with a definitive treatment strategy because of its rarity and rapid spread. In this case study, a 57-year-old female patient with hyperpigmented gingiva and palate diagnosed pathologically and immunohistochemically as malignant melanoma underwent surgical excision and a modified radical neck dissection.
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Affiliation(s)
- K. T. Shahina
- Department of Oral and Maxillofacial Surgery, Government Dental College, Kozhikode, affiliated to Kerala University of Health Sciences, Kozhikode, Kerala 673008 India
| | - Sandeep K. Madhu
- Manipal College of Dental Sciences, Mangalore Affiliated to MAHE, Hampankatta, 575006 India
| | - V. Ravindran
- Department of Oral and Maxillofacial Surgery, Government Dental College, Kozhikode, affiliated to Kerala University of Health Sciences, Kozhikode, Kerala 673008 India
| | - Sreekanth S. Kumar
- Government Tertiary Cancer Centre, Kozhikode, affiliated to Kerala University of Health Sciences, Kozhikode, 673008 India
| | - Abcish Krishnan
- Department of Oral and Maxillofacial Surgery, Government Dental College, Kozhikode, affiliated to Kerala University of Health Sciences, Kozhikode, Kerala 673008 India
| | - Babin C. Balan
- Department of Oral and Maxillofacial Surgery, Government Dental College, Kozhikode, affiliated to Kerala University of Health Sciences, Kozhikode, Kerala 673008 India
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6
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Boutros A, Croce E, Ferrari M, Gili R, Massaro G, Marconcini R, Arecco L, Tanda ET, Spagnolo F. The treatment of advanced melanoma: Current approaches and new challenges. Crit Rev Oncol Hematol 2024; 196:104276. [PMID: 38295889 DOI: 10.1016/j.critrevonc.2024.104276] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 01/15/2024] [Accepted: 01/26/2024] [Indexed: 02/17/2024] Open
Abstract
In recent years, advances in melanoma treatment have renewed patient hope. This comprehensive review emphasizes the evolving treatment landscape, particularly highlighting first-line strategies and the interplay between immune-checkpoint inhibitors (ICIs) and targeted therapies. Ipilimumab plus nivolumab has achieved the best median overall survival, exceeding 70 months. However, the introduction of new ICIs, like relatlimab, has added complexity to first-line therapy decisions. Our aim is to guide clinicians in making personalized treatment decisions. Various features, including brain metastases, PD-L1 expression, BRAF mutation, performance status, and prior adjuvant therapy, significantly impact the direction of advanced melanoma treatment. We also provide the latest insights into the treatment of rare melanoma subtypes, such as uveal melanoma, where tebentafusp has shown promising improvements in overall survival for metastatic uveal melanoma patients. This review provides invaluable insights for clinicians, enabling informed treatment choices and deepening our understanding of the multifaceted challenges associated with advanced melanoma management.
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Affiliation(s)
- Andrea Boutros
- Skin Cancer Unit, U.O. Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Sciences (DiMI), School of Medicine, University of Genova, Genova, Italy.
| | - Elena Croce
- Skin Cancer Unit, U.O. Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Marco Ferrari
- Azienda Ospedaliero Universitaria Pisana, Medical Oncology Unit, Pisa, Italy
| | - Riccardo Gili
- Skin Cancer Unit, U.O. Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Sciences (DiMI), School of Medicine, University of Genova, Genova, Italy
| | - Giulia Massaro
- Unit of Medical Oncology, Careggi University-Hospital, 50134 Florence, Italy
| | - Riccardo Marconcini
- Azienda Ospedaliero Universitaria Pisana, Medical Oncology Unit, Pisa, Italy
| | - Luca Arecco
- Department of Internal Medicine and Medical Sciences (DiMI), School of Medicine, University of Genova, Genova, Italy; Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Enrica Teresa Tanda
- Skin Cancer Unit, U.O. Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Francesco Spagnolo
- Skin Cancer Unit, U.O. Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Surgical Sciences and Integrated Diagnostics (DISC), Plastic Surgery Division, University of Genova, Genova, Italy
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Heifetz-Li JJ, Smith MH, Roche A. Multifocal pigmented lesions in the maxilla. Oral Surg Oral Med Oral Pathol Oral Radiol 2024; 137:205-208. [PMID: 38171999 DOI: 10.1016/j.oooo.2023.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Revised: 11/11/2023] [Accepted: 11/20/2023] [Indexed: 01/05/2024]
Affiliation(s)
| | | | - Ansley Roche
- Division of Otolaryngology-Head & Neck Surgery, Yale School of Medicine, New Haven, CT, USA
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Usta SZ, Uchihashi T, Kodama S, Kurioka K, Inubushi T, Shimooka T, Sugauchi A, Seki S, Tanaka S. Current Status and Molecular Mechanisms of Resistance to Immunotherapy in Oral Malignant Melanoma. Int J Mol Sci 2023; 24:17282. [PMID: 38139110 PMCID: PMC10743423 DOI: 10.3390/ijms242417282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/19/2023] [Accepted: 11/28/2023] [Indexed: 12/24/2023] Open
Abstract
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.
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Affiliation(s)
- Sena Zeynep Usta
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita 565-0871, Osaka, Japan; (S.Z.U.); (S.K.); (K.K.); (T.S.); (A.S.); (S.S.); (S.T.)
| | - Toshihiro Uchihashi
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita 565-0871, Osaka, Japan; (S.Z.U.); (S.K.); (K.K.); (T.S.); (A.S.); (S.S.); (S.T.)
| | - Shingo Kodama
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita 565-0871, Osaka, Japan; (S.Z.U.); (S.K.); (K.K.); (T.S.); (A.S.); (S.S.); (S.T.)
| | - Kyoko Kurioka
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita 565-0871, Osaka, Japan; (S.Z.U.); (S.K.); (K.K.); (T.S.); (A.S.); (S.S.); (S.T.)
| | - Toshihiro Inubushi
- Department of Orthodontics & Dentofacial Orthopedics, Graduate School of Dentistry, Osaka University, Suita 565-0871, Osaka, Japan;
| | - Takuya Shimooka
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita 565-0871, Osaka, Japan; (S.Z.U.); (S.K.); (K.K.); (T.S.); (A.S.); (S.S.); (S.T.)
| | - Akinari Sugauchi
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita 565-0871, Osaka, Japan; (S.Z.U.); (S.K.); (K.K.); (T.S.); (A.S.); (S.S.); (S.T.)
- Unit of Dentistry, Osaka University Hospital, 2-15, Yamadaoka, Suita 565-0871, Osaka, Japan
| | - Soju Seki
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita 565-0871, Osaka, Japan; (S.Z.U.); (S.K.); (K.K.); (T.S.); (A.S.); (S.S.); (S.T.)
| | - Susumu Tanaka
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita 565-0871, Osaka, Japan; (S.Z.U.); (S.K.); (K.K.); (T.S.); (A.S.); (S.S.); (S.T.)
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9
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Yip HM, Cameron A, Sheppard K, Fasanmade A, Garg M. Oral mucosal melanoma in situ: a case report and review of the literature. Int J Oral Maxillofac Surg 2023; 52:1230-1234. [PMID: 37179134 DOI: 10.1016/j.ijom.2023.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 04/10/2023] [Accepted: 04/24/2023] [Indexed: 05/15/2023]
Abstract
Oral mucosal melanoma is a rare presentation of malignant melanoma with a 5-year survival rate of only 15%. Oral mucosal melanoma in situ (OMMIS) is its assumed precursor. This report describes one of only 20 documented cases of OMMIS and outlines how early clinical recognition resulted in prompt histopathological diagnosis and subsequent complete surgical excision. A literature review of existing reported cases, their management, and latest outcomes was also performed, highlighting this rare condition for consideration in the differential diagnosis of pigmented oral pathologies.
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Affiliation(s)
- H M Yip
- Department of Oral and Maxillofacial Surgery, John Radcliffe Hospital, Headington, Oxford, UK.
| | - A Cameron
- Department of Oral Surgery, Great Western Hospital, Swindon, UK
| | - K Sheppard
- Department of Pathology, John Radcliffe Hospital, Headington, Oxford, UK
| | - A Fasanmade
- Department of Oral and Maxillofacial Surgery, Churchill Hospital, Headington, Oxford, UK
| | - M Garg
- Department of Oral and Maxillofacial Surgery, Churchill Hospital, Headington, Oxford, UK
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10
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Rana HS, Dertinger JE, Clabeaux C, Makepeace N, Lewis J. Metastatic Melanoma to the Orbit With Dedifferentiation: A Case Report. Cureus 2023; 15:e41591. [PMID: 37559849 PMCID: PMC10408357 DOI: 10.7759/cureus.41591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2023] [Indexed: 08/11/2023] Open
Abstract
We present the first documented case of metastatic melanoma to the orbit with dedifferentiation. A patient with a history of melanoma of the lip and other poorly differentiated carcinomas presented with both a sub-brow and an intraorbital mass. Radiographically and intraoperatively, the sub-brow mass communicated with the intraorbital mass via perineural spread along the supraorbital nerve. Histopathology confirmed the diagnosis of melanoma based on the melanocytic markers, SOX-10 and Melan-A; dedifferentiation was demonstrated within the orbital tumor. Two weeks following surgical debulking, the intraorbital mass returned to its full size. Local radiotherapy and immunotherapy were performed, which initially led to a dramatic improvement; however, the patient succumbed to his systemic metastases six months later. Dedifferentiation serves as a prognostic indicator and should be considered in patients when histopathology does not lead to a definitive diagnosis.
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Affiliation(s)
- Harkaran S Rana
- Ophthalmology, Walter Reed National Military Medical Center, Bethesda, USA
| | - Jake E Dertinger
- Ophthalmology, California Health Sciences University College of Osteopathic Medicine, Clovis, USA
| | | | - Nicole Makepeace
- Ophthalmology, Walter Reed National Military Medical Center, Bethesda, USA
| | - Jason Lewis
- Ophthalmology, Walter Reed National Military Medical Center, Bethesda, USA
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11
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Chabrillac E, Even C, Costes-Martineau V, Fakhry N, Digue L, Moya-Plana A, Baujat B, Righini CA, De Gabory L, Verillaud B, Vergez S, Thariat J. [Rare cancers of the head and neck on behalf of the REFCOR, part 2]. Bull Cancer 2023:S0007-4551(23)00202-3. [PMID: 37169602 DOI: 10.1016/j.bulcan.2023.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 04/04/2023] [Accepted: 04/15/2023] [Indexed: 05/13/2023]
Abstract
Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology as well as their anatomical location when arising from the paranasal sinuses, salivary glands and ear. The management of these heterogeneous rare diseases of complex treatment has considerably been structured over the last 15 years, in particular via the French ENT Cancer Expertise Network (REFCOR) and international networks and registries (EURACAN, etc.). Structuration also favors research with identification of new entities and setting up of specific therapeutic trials. A first article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the REFCOR concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. This second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.
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Affiliation(s)
- Emilien Chabrillac
- Institut universitaire du cancer Toulouse-oncopole, département de chirurgie, 1, avenue Irène-Joliot-Curie, 31100 Toulouse, France
| | - Caroline Even
- Institut Gustave Roussy, département d'oncologie médicale, 114, rue Edouard-Vaillant, 94805 Villejuif, France
| | - Valérie Costes-Martineau
- CHU de Montpellier, département de biopathologie, 191, avenue du Doyen Gaston-Giraud, 34295 Montpellier, France
| | - Nicolas Fakhry
- Hôpital La Conception, département de chirurgie ORL et cervico-faciale, 147, boulevard Baille, 13005 Marseille, France
| | - Laurence Digue
- Hôpital Saint-André, département d'oncologie médicale, 1, rue Jean-Burguet, 33000 Bordeaux, France
| | - Antoine Moya-Plana
- Institut Gustave-Roussy, département de chirurgie ORL et cervico-faciale, 114, rue Edouard-Vaillant, 94805 Villejuif, France
| | - Bertrand Baujat
- Hôpital Tenon, département de chirurgie ORL et cervico-faciale, 4, rue de la Chine, 75020 Paris, France
| | - Christian-Adrien Righini
- CHU de Grenoble-Alpes, département de chirurgie ORL et cervico-faciale, 1, avenue du Maquis du Grésivaudan, 38700 La Tronche, France
| | - Ludovic De Gabory
- CHU de Pellegrin, département de chirurgie ORL et cervico-faciale, 1, Place Amélie-Raba-Léon, 33000 Bordeaux, France
| | - Benjamin Verillaud
- Hôpital Lariboisière, département de chirurgie ORL et cervico-faciale, 2, rue Ambroise-Paré, 75010 Paris, France
| | - Sébastien Vergez
- Institut Universitaire du Cancer Toulouse-Oncopole, CHU de Toulouse-Larrey, département de chirurgie ORL et cervico-faciale, 1, avenue Irène-Joliot-Curie, 31100 Toulouse, France
| | - Juliette Thariat
- Centre François-Baclesse, département de radiothérapie, 3, avenue du Général-Harris, 14000 Caen, France.
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12
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Kingsley C, Kourtidis A. Critical roles of adherens junctions in diseases of the oral mucosa. Tissue Barriers 2023; 11:2084320. [PMID: 35659464 PMCID: PMC10161952 DOI: 10.1080/21688370.2022.2084320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/18/2022] [Accepted: 05/26/2022] [Indexed: 10/18/2022] Open
Abstract
The oral cavity is directly exposed to a variety of environmental stimuli and contains a diverse microbiome that continuously interacts with the oral epithelium. Therefore, establishment and maintenance of the barrier function of the oral mucosa is of paramount importance for its function and for the body's overall health. The adherens junction is a cell-cell adhesion complex that is essential for epithelial barrier function. Although a considerable body of work has associated barrier disruption with oral diseases, the molecular underpinnings of these associations have not been equally investigated. This is critical, since adherens junction components also possess significant signaling roles in the cell, in addition to their architectural ones. Here, we summarize current knowledge involving adherens junction components in oral pathologies, such as cancer and oral pathogen-related diseases, while we also discuss gaps in the knowledge and opportunities for future investigation of the relationship between adherens junctions and oral diseases.
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Affiliation(s)
- Christina Kingsley
- Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA
| | - Antonis Kourtidis
- Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA
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13
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Kukde MM, Madurwar AU, Selokar DS, Noman O. A Case Report of Oral Malignant Melanoma: A Silent Killer. Cureus 2023; 15:e36671. [PMID: 37102023 PMCID: PMC10124672 DOI: 10.7759/cureus.36671] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 03/25/2023] [Indexed: 03/29/2023] Open
Abstract
Melanoma of the oral cavity is a rare malignant tumor that develops from a malignant melanocytic or de novo from melanocytes within the normal mucosa or skin and appears blue, black, or reddish-brown. Oral mucosal melanoma has a higher proclivity for metastasis and attacks tissue more aggressively than any other malignant tumor in the mouth. Intestinal melanoma of the head and neck is an uncommon type of cancer that should be counted among the deadliest. Malignant melanoma of the oral cavity accounts for only 0.2%-8.0% of all reported melanoma, although accounting for 1.3% of all malignancies. Because most melanotic mucosal lesions are painless at first, the diagnosis is sometimes delayed until the ulcer or growth causes symptoms. Early detection is critical for effective therapy and the only way to improve survival and prognosis in patients with oral malignant melanoma due to its poor prognosis. To avoid oral melanomas, every single colored lesion identified in the oral cavity should be treated with suspicion and adequate inquiry because a colored lesion might expand, and it should be referred for a biopsy to avoid poisoning. This article shows how the oral clinic is important in the diagnosis of oral ulcers and argues that early detection is necessary to enhance patient outcomes.
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Haimowitz S, Cohen DA, Dhanda A, Barron K, Povolotskiy R, Roden D. Mucosal Melanoma of the Oral Cavity: What is the Role of Elective Neck Dissection? Laryngoscope 2023; 133:317-326. [PMID: 35560997 PMCID: PMC10084066 DOI: 10.1002/lary.30152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 04/05/2022] [Indexed: 01/19/2023]
Abstract
OBJECTIVES Mucosal melanoma (MM) is a rare malignancy that can present in the head and neck (H&N). The Oral cavity is the second most common primary site in the H&N after sinonasal mucosa. This study investigates the impact of demographic and clinical factors on survival in oral cavity MM. Further, it investigates the outcomes and utility of elective neck dissections (END) in the management of oral MM. METHODS The National Cancer Database was used to evaluate 432 patients with oral cavity MM from 2004 to 2016. Kaplan-Meir and Cox regression analyses were used to determine variables associated with survival. RESULTS The mean age was 64.0 ± 16.0 years. Most patients were white (85.1%) and male (60.0%). Gingiva (37.6%) and hard palate (36.1%) were the most common primary subsites in the oral cavity. Five-year overall survival was 31.0%. Age (Hazards Ratio [95% Confidence Interval], 1.03 [1.01-1.06]), N-stage (1.94 [1.10-3.42]), M-stage (10.13 [3.33-30.86]), male sex (1.79 [1.06-3.03]), and African-American race (2.63 [1.14-6.11]) were significantly associated with worse survival. 199 patients (46.9%) underwent neck dissection including 118 with lymph node yield (LNY) ≥ 18. The rate of occult nodal positivity was 45.4% for LNY ≥ 18 and 28.3% for LNY ≥ 1. ENDs were not associated with improved outcomes. However, occult lymph node involvement was associated with worse overall survival (p = 0.004). CONCLUSIONS Oral cavity MM has a poor prognosis. Lymph node involvement, distant metastasis, age, race, and male sex are associated with worse outcomes. Performing an END did not improve survival. However, END may have a prognostic role and help select patients for treatment intensification. LEVEL OF EVIDENCE 4 Laryngoscope, 133:317-326, 2023.
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Affiliation(s)
- Sean Haimowitz
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
| | - David A Cohen
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
| | - Aatin Dhanda
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
| | - Kendyl Barron
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
| | - Roman Povolotskiy
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
| | - Dylan Roden
- Department of Otolaryngology - Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
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15
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Thawani R, Kim MS, Arastu A, Feng Z, West MT, Taflin NF, Thein KZ, Li R, Geltzeiler M, Lee N, Fuller CD, Grandis JR, Floudas CS, Heinrich MC, Hanna E, Chandra RA. The contemporary management of cancers of the sinonasal tract in adults. CA Cancer J Clin 2023; 73:72-112. [PMID: 35916666 PMCID: PMC9840681 DOI: 10.3322/caac.21752] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 05/21/2022] [Accepted: 06/27/2022] [Indexed: 01/25/2023] Open
Abstract
Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.
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Affiliation(s)
- Rajat Thawani
- Division of Hematology and Oncology, Knight Cancer Institute, Oregon Health and Science University
| | - Myung Sun Kim
- Division of Hematology and Oncology, Knight Cancer Institute, Oregon Health and Science University
| | - Asad Arastu
- Department of Internal Medicine, Oregon Health and Science University
| | - Zizhen Feng
- Division of Hematology and Oncology, Knight Cancer Institute, Oregon Health and Science University
| | - Malinda T. West
- Division of Hematology and Oncology, Knight Cancer Institute, Oregon Health and Science University
| | | | - Kyaw Zin Thein
- Division of Hematology and Oncology, Knight Cancer Institute, Oregon Health and Science University
| | - Ryan Li
- Department of Otolaryngology, Division of Head and Neck Surgery, Oregon Health and Science University
| | - Mathew Geltzeiler
- Department of Otolaryngology, Division of Head and Neck Surgery, Oregon Health and Science University
| | - Nancy Lee
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center
| | | | - Jennifer R. Grandis
- Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco
| | | | - Michael C. Heinrich
- Division of Hematology and Oncology, Knight Cancer Institute, Oregon Health and Science University
| | - Ehab Hanna
- Department of Head and Neck Surgery, MD Anderson Cancer Center
| | - Ravi A. Chandra
- Department of Radiation Medicine, Oregon Health and Science University
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16
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Zhang Y, Lin C, Liu Z, Sun Y, Chen M, Guo Y, Liu W, Zhang C, Chen W, Sun J, Xia R, Hu Y, Yang X, Li J, Zhang Z, Cao W, Sun S, Wang X, Ji T. Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies. Cell Metab 2022; 34:1999-2017.e10. [PMID: 36395769 DOI: 10.1016/j.cmet.2022.10.012] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 08/19/2022] [Accepted: 10/26/2022] [Indexed: 11/17/2022]
Abstract
Although nutrient-starvation therapies can elicit strong anti-tumor effects in multiple carcinomas, it has been convincingly demonstrated that cancer cells exploit the tumor microenvironment to thrive in nutrient-poor environments. Here, we reveal that cancer cells can co-opt nociceptive nerves to thrive in nutrient-poor environments. Initially examining the low-glucose environment of oral mucosa carcinomas, we discovered that cancer cells employ ROS-triggered activation of c-Jun to secrete nerve growth factor (NGF), which conditions nociceptive nerves for calcitonin gene-related peptide (CGRP) production. The neurogenic CGRP subsequently induces cytoprotective autophagy in cancer cells through Rap1-mediated disruption of the mTOR-Raptor interaction. Both anti-glycolysis and anti-angiogenesis-based nutrient-starvation therapies aggravate the vicious cycle of cancer cells and nociceptive nerves and therapeutically benefit from blocking neurogenic CGRP with an FDA-approved antimigraine drug. Our study sheds light on the role of the nociceptive nerve as a microenvironmental accomplice of cancer progression in nutrient-poor environments and upon nutrient-starvation therapies.
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Affiliation(s)
- Yu Zhang
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Chengzhong Lin
- College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China; The 2nd Dental Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Zheqi Liu
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Yiting Sun
- College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China; Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Mingtao Chen
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Yibo Guo
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Wei Liu
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Chenping Zhang
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Wantao Chen
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Jian Sun
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Ronghui Xia
- College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China; Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Yuhua Hu
- College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China; Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Xi Yang
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Jiang Li
- College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China; Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Zhiyuan Zhang
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Wei Cao
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Shuyang Sun
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China.
| | - Xu Wang
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China.
| | - Tong Ji
- Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China.
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Zahid E, Bhatti O, Zahid MA, Stubbs M. Overview of common oral lesions. MALAYSIAN FAMILY PHYSICIAN : THE OFFICIAL JOURNAL OF THE ACADEMY OF FAMILY PHYSICIANS OF MALAYSIA 2022; 17:9-21. [PMID: 36606178 PMCID: PMC9809440 DOI: 10.51866/rv.37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
This article summarises common oral lesions that clinicians may face in everyday practice by categorising them by clinical presentation: ulcerated lesions, white or mixed white-red lesions, lumps and bumps, and pigmented lesions. The pathologies covered include recurrent aphthous stomatitis, herpes simplex virus, oral squamous cell carcinoma, geographic tongue, oral candidosis, oral lichen planus, pre-malignant disorders, pyogenic granuloma, mucocele and squamous cell papilloma, oral melanoma, hairy tongue and amalgam tattoo. The objective of this review is to improve clinician knowledge and confidence in assessing and managing common oral lesions presenting in the primary care setting.
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Affiliation(s)
- Esha Zahid
- BHSc, MDent, LaTrobe University, Melbourne, Australia
| | - Osama Bhatti
- MBBS, FRACGP, Monash Health, Melbourne, Australia
| | | | - Michael Stubbs
- BDS, MDS, FRACDS, MRACDS, Epworth Freemasons Hospital, Melbourne, Australia
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18
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Chemotherapy in combination with anti-PD-1 agents as adjuvant therapy for high-risk oral mucosal melanoma. J Cancer Res Clin Oncol 2022; 149:2293-2300. [PMID: 36088610 DOI: 10.1007/s00432-022-04090-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 05/24/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND Adjuvant therapy plays a critical role in the treatment of oral mucosal melanoma (OMM). Anti-programmed cell death-1 (PD-1) agents are recommended as front-line therapy for metastatic melanoma, but their efficacy as adjuvant therapy for high-risk OMM remains unclear. PATIENTS AND METHODS A single-center, retrospective cohort study was conducted in 193 nodular-type oral mucosal melanoma (NOMM) patients who received chemotherapy alone or in combination with high-dose interferon-α2b (HDI) or anti-PD-1 agents as adjuvant therapy. Multivariate analysis was performed to identify significant prognostic factors for the 2-year overall survival (OS) and progression-free survival (PFS). RESULTS Tumor thickness, ulceration and invasion level were found to be independent prognostic factors for both 2-year OS and PFS, while T-stage was only associated with OS. The 2-year OS and PFS were 43.5% and 10.9% in patients who received only chemotherapy. In comparison, the 2-year OS was improved, albeit not significantly (47.4%; p > 0.05), and PFS was significantly improved (43.6%; p = 0.0028) in patients who received chemotherapy plus HDI; and both 2-year OS (71.0%; p = 0.0118) and PFS (53.6%; p = 0.0001) were significantly improved in patients received chemotherapy plus anti-PD-1. The serious adverse event (SAE) (p < 0.0001) and discontinued treatment due to SAE (p < 0.0001) were significantly lower in patients who received anti-PD-1 than in patients who received HDI. CONCLUSIONS Invasion level and tumor thickness are independent prognostic factors for NOMM. Chemotherapy plus anti-PD-1 agents seem to be the adjuvant therapy of choice for NOMM, as it is safer and more tolerable than HDI and, more importantly, it can significantly improve the OS and PFS.
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19
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Bansal SP, Dhanawade SS, Arvandekar AS, Mehta V, Desai RS. Oral Amelanotic Melanoma: A Systematic Review of Case Reports and Case Series. Head Neck Pathol 2022; 16:513-524. [PMID: 34309791 PMCID: PMC9187796 DOI: 10.1007/s12105-021-01366-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 07/14/2021] [Indexed: 12/16/2022]
Abstract
Oral amelanotic melanoma (OAM) is a rare, non-pigmented mucosal neoplasm representing less than 2% of all melanoma. The present study analyses the available data on OAM and describes its clinicopathological features, identifying potential prognostic factors. Online electronic databases such as PubMed-Medline, Embase, and Scopus were searched using appropriate keywords from the earliest available date till 31st March 2021 without restriction on language. Additional sources like Google Scholar, major journals, unpublished studies, conference proceedings, and cross-references were explored. 37 publications were included for quantitative synthesis, comprising 55 cases. The mean age of the patients was 59.56 years, and the lesions were more prevalent in males than in females. OAM's were most prevalent in the maxilla (67.2%) with ulceration, pinkish-red color, nodular mass, and pain. 2 patients (3.36%) were alive at their last follow-up, and 25 were dead (45.4%). Univariate survival analysis of clinical variables revealed that age older than 68 years (p = 0.003), mandibular gingiva (p = 0.007), round cells (p = 0.004), and surgical excision along with chemotherapy & radiation therapy (p = 0.001) were significantly associated with a lower survival rate. Oral Amelanotic Melanoma is a neoplasm with a poor prognosis, presenting a 6.25% possibility of survival after 5 years. Patients older than 68 years, lesions in the mandibular gingiva, round cells, and surgical excision along with chemotherapy and radiotherapy, presented the worst prognosis. However, they did not represent independent prognostic determinants for these patients.
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Affiliation(s)
- Shivani P. Bansal
- Department of Oral Pathology, Nair Hospital Dental College, Dr. A.L Nair Road Mumbai Central, Mumbai, 400008 India
| | - Sonal Sunil Dhanawade
- Department of Oral Pathology, Nair Hospital Dental College, Dr. A.L Nair Road Mumbai Central, Mumbai, 400008 India
| | - Ankita Satish Arvandekar
- Department of Oral Pathology, Nair Hospital Dental College, Dr. A.L Nair Road Mumbai Central, Mumbai, 400008 India
| | - Vini Mehta
- Department of Public Health Dentistry, Peoples College of Dental Sciences & Research Center, Bhopal, Madhya Pradesh 462037 India
| | - Rajiv S. Desai
- Department of Oral Pathology, Nair Hospital Dental College, Dr. A.L Nair Road Mumbai Central, Mumbai, 400008 India
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20
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Nenclares P, Harrington KJ. Management of Head and Neck Mucosal Melanoma. Oral Maxillofac Surg Clin North Am 2022; 34:299-314. [DOI: 10.1016/j.coms.2021.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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21
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Blue Nevus of the Hard Palate: The Importance of a Careful Examination in an Emergency Setting. Case Rep Dermatol Med 2022; 2022:6329334. [PMID: 35211347 PMCID: PMC8863491 DOI: 10.1155/2022/6329334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 01/28/2022] [Indexed: 12/02/2022] Open
Abstract
Oral common blue nevus is an asymptomatic, benign, rare, pigmented lesion and sometimes clinically indistinguishable from other pigmented lesions such as the cellular blue nevus or early-stage malignant melanoma. Since it shows clinical similarities with a malignant lesion and with cellular blue nevus that can itself suffer malignant transformation, the decisive diagnosis is crucial for adequate treatment, follow-up, and prognosis. Diagnosis confirmation is given by histological analysis, the reason why most oral pigmented lesions are excised. The following case presents an asymptomatic oral pigmented lesion of the hard palate discovered during observation in an emergency setting due to an abscess of dental origin. The lesion was fully excised, and histological examination reported a “common blue nevus.” In this case, we intend to present a rare lesion of the oral cavity and the importance of performing a routine oral examination when given a chance as a preventive approach.
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22
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Hovander D, Allen J, Oda D, Moshiri AS. PRAME immunohistochemistry is useful in the diagnosis of oral malignant melanoma. Oral Oncol 2022; 124:105500. [PMID: 34452831 DOI: 10.1016/j.oraloncology.2021.105500] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 08/14/2021] [Indexed: 01/11/2023]
Abstract
OBJECTIVES While the incidence of cutaneous melanoma has dramatically increased in recent years, oral malignant melanoma (OMM) remains a rare form of noncutaneous melanoma with poor survival. PRAME (PReferentially expressed Antigen in MElanoma) is reported to have diagnostic and some prognostic utility in cutaneous melanomas and some head and neck malignancies. We sought to explore the diagnostic utility of PRAME in OMM. METHODS A total of ten specimens from eight unique cases of OMM were identified from the Oral Pathology Biopsy Service (OPBS) at University of Washington School of Dentistry between 2005 and 2019. For all cases, standard histology and immunohistochemistry stains were performed, including a stain against PRAME. The diagnoses were reviewed and confirmed by two pathologists. Clinical and epidemiologic features were described. RESULTS Patient ages ranged from 55 to 82. The group consisted of five males and three females. All eight cases were located on the hard palate. Six cases represented invasive melanoma while two were early melanoma in situ. PRAME immunohistochemistry was successfully performed on seven of eight cases: six were positive (86%), one was negative (14%) and one case lacked sufficient tissue for staining. CONCLUSIONS Our results suggest that PRAME immunohistochemistry may be useful in the diagnosis of OMM, including early melanoma in situ. Further studies with clinical follow-up and a larger number of cases are needed to explore prognostic value as well as the ability to distinguish between benign, intermediate and malignant melanocytic proliferations of the oral cavity.
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Affiliation(s)
- Daniel Hovander
- University of Washington School of Dentistry, Seattle, WA 98195, USA
| | - Joshua Allen
- University of Washington School of Dentistry, Seattle, WA 98195, USA
| | - Dolphine Oda
- Department of Oral & Maxillofacial Surgery, University of Washington School of Dentistry, Seattle, WA 98195, USA
| | - Ata S Moshiri
- Division of Dermatology, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Laboratory Medicine and Pathology, Seattle, WA 98195, USA.
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23
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Moltajaei MH, Pourzare Mehrbani S, Motahari P, Rezapour R. Clinicopathological and prognostic value of Ki-67 expression in oral malignant melanoma: A systematic review and meta-analysis. J Dent Res Dent Clin Dent Prospects 2022; 16:140-146. [PMID: 36704188 PMCID: PMC9871167 DOI: 10.34172/joddd.2022.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 07/18/2022] [Indexed: 01/20/2023] Open
Abstract
Background. Ki-67 is one of the new biological markers with clinical value in the pathology and prognosis of oral melanoma. It is a nuclear protein involved in regulating cell proliferation. Some studies have suggested an association between Ki-67 and poor survival in patients with oral melanoma. This systematic review was undertaken to clarify this issue. Methods. Databases of PubMed, Scopus, and Web of Science were searched using relevant English keywords from 1988 to April 2022. STATA software version 16 and random models were used for meta-analysis. Results. Eleven articles were included in this systematic review, six of which were selected for meta-analysis. The mean expression of the Ki-67 index in patients with oral melanoma was estimated at 43.81% (28.66‒58.95 with 95% CI, I2=94.2, P<0.001). In addition, the results showed a significant relationship between Ki-67 expression and the prognosis of oral melanoma lesions. Increased expression of this marker weakens the prognosis and decreases the survival rate. Conclusion. High expression of Ki-67 may serve as a predictive biomarker for poor prognosis in patients with malignant oral melanoma. Therefore, classifying this malignancy by Ki-67 expression may be considered for therapy regimen selection and integrated management.
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Affiliation(s)
| | - Solmaz Pourzare Mehrbani
- Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Paria Motahari
- Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran,Corresponding author: Paria Motahari,
| | - Ramin Rezapour
- Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Kim WS, Vinayak A, Powers B. Comparative Review of Malignant Melanoma and Histologically Well-Differentiated Melanocytic Neoplasm in the Oral Cavity of Dogs. Vet Sci 2021; 8:vetsci8110261. [PMID: 34822634 PMCID: PMC8624997 DOI: 10.3390/vetsci8110261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 10/17/2021] [Accepted: 10/27/2021] [Indexed: 01/19/2023] Open
Abstract
Oral malignant melanoma (OMM) is the most common neoplasm of the canine oral cavity. It is characterized by its aggressive local disease as well as its high rate of lymphatic invasion and distant metastasis. OMM carries a poor prognosis, with most patients succumbing to the disease due to progression of the neoplasm. Histopathologically, OMM is characterized by significant nuclear atypia, a mitotic index of greater than 4/10 hpf, and evidence of vascular invasion or metastasis. Clinically, these lesions can become locally invasive, causing lysis of bones and severe inflammation of the surrounding soft tissue. With time, these lesions can spread to the regional lymph node and to the lungs and other organs. Prognosis can vary depending on the size of the primary tumor, regional node involvement, and distant metastatic disease; however, multiple studies report a relatively short median survival time ranging from less than 4 months to 8 months. Histologically well- differentiated melanocytic neoplasms (HWDMN) are a variant of OMM and sometimes referred to as canine oral melanocytic neoplasms of low malignant potential. Unlike OMM, patients with HWDMN have longer survival times. Histopathologically, HWDMNs have well-differentiated melanocytes with a low mitotic index of 3 or less per 10 hpf and minimal nuclear atypia. HWDMNs have better prognosis with a mean survival time of up to 34 months. This article is a comparative review of OMM and its less aggressive counterpart.
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Affiliation(s)
- Won Suk Kim
- Department of Surgical Oncology, VCA West Coast Specialty and Emergency Animal Hospital, 18300 Euclid Street, Fountain Valley, CA 92708, USA;
- Correspondence:
| | - Arathi Vinayak
- Department of Surgical Oncology, VCA West Coast Specialty and Emergency Animal Hospital, 18300 Euclid Street, Fountain Valley, CA 92708, USA;
| | - Barbara Powers
- Antech Diagnostics, 17620 Mt Hermann St, Fountain Valley, CA 92708, USA;
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Pandiar D, Ramani P, Krishnan RP, Sushanthi CL, Ramasubramanian A. Is cellularity alone sufficient to sub-grade malignant melanoma histologically as spindle cell/desmoplastic variant? Oral Oncol 2021; 121:105497. [PMID: 34418697 DOI: 10.1016/j.oraloncology.2021.105497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 08/11/2021] [Indexed: 10/20/2022]
Affiliation(s)
- Deepak Pandiar
- Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India
| | - Pratibha Ramani
- Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India.
| | - Reshma Poothakulath Krishnan
- Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India
| | - Casilda L Sushanthi
- Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India
| | - Abilasha Ramasubramanian
- Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India
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Tavares TS, Da Costa AAS, Aguiar MCF, Loyola AM, Barcelos NS, Abreu MHNG, Mesquita RA, Tarquínio SBC, De Moraes Ê, Vasconcelos ACU, Costa NL, Mendonça EF, Cardoso SV, Nonaka CFW, Andrade ADO, Johann ACBR, Michels AC, Libório-Kimura TN, Neto GOP, Caldeira PC. Differential diagnoses of solitary and multiple pigmented lesions of the oral mucosa: Evaluation of 905 specimens submitted to histopathological examination. Head Neck 2021; 43:3775-3787. [PMID: 34519124 DOI: 10.1002/hed.26872] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/29/2021] [Accepted: 08/31/2021] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND The aim was to analyze the frequency, clinical and demographic features of solitary and multiple/diffuse oral pigmented lesions submitted to histopathological examination, and to summarize the features that guide the clinical differential diagnosis. METHODS Clinical and demographic data were retrieved from biopsy records and descriptive statistics were performed. RESULTS Nine hundred and five (0.51%) oral pigmented lesions were retrieved among 177 356 specimens, being 95.9% solitary and 4.1% multiple/diffuse lesions. Regardless the overlapping clinical presentation, age, site, association with amalgam restoration, and a nodular appearance may help in the clinical differential diagnosis of solitary oral pigmentations. Patient's habits, site, and systemic signs and symptoms are helpful in the clinical differential diagnosis of multiple/diffuse lesions. CONCLUSIONS Oral pigmented lesions are a rare diagnosis in oral pathology and solitary lesions are more commonly submitted to biopsy. Some key features help in the differential diagnosis, though biopsy can be warranted in doubtful cases.
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Affiliation(s)
- Thalita Soares Tavares
- Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Maria Cássia Ferreira Aguiar
- Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Adriano Mota Loyola
- Area of Pathology, School of Dentistry, Universidade Federal de Uberlândia, Uberlândia, Brazil
| | - Natália Santos Barcelos
- Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Ricardo Alves Mesquita
- Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Êmile De Moraes
- Department of Semiology and Clinics, School of Dentistry, Universidade Federal de Pelotas, Pelotas, Brazil
| | | | - Nádia Lago Costa
- Department of Stomatology (Oral Medicine and Oral Pathology), School of Dentistry, Universidade Federal de Goiás, Goiânia, Brazil
| | - Elismauro Francisco Mendonça
- Department of Stomatology (Oral Medicine and Oral Pathology), School of Dentistry, Universidade Federal de Goiás, Goiânia, Brazil
| | - Sérgio Vitorino Cardoso
- Area of Pathology, School of Dentistry, Universidade Federal de Uberlândia, Uberlândia, Brazil
| | | | | | | | - Arieli Carini Michels
- Department of Dentistry, School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil
| | | | - Gerson Oliveira Paiva Neto
- Department of Pathology and Forensic Medicine, School of Medicine, Universidade Federal do Amazonas, Manaus, Brazil
| | - Patrícia Carlos Caldeira
- Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Warin K, Klanrit P, Pattanajakr N. A Large Oral Melanoma: A Case Report of a Rare but Aggressive Malignancy. Eur J Dent 2021; 15:812-816. [PMID: 34428837 PMCID: PMC8630955 DOI: 10.1055/s-0041-1731836] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
A variety of black-pigmented lesions of the oral cavity can be found, ranging from harmless benign lesions such as melanotic macule, smoker's melanosis, amalgam/graphite tattoos, and pigmented nevus to a life-threatening oral malignant melanoma. Oral melanoma is a rare and aggressive malignant tumor that originates from melanocytes' proliferation and accounts for only 0.5% of all oral malignancies. The etiology is unknown. Most oral melanomas are present at the palate and the upper alveolar ridge, whereas occurrences at the buccal mucosa, the lower alveolar ridge, and the lip are rare, with only a few reports in the literature. The diagnosis is confirmed by a biopsy. The prognosis is poor, with a 5-year survival rate of ~20%. In this report, we present a case of large oral melanoma at the right buccal mucosa involving the right lower alveolar ridge and lip commissure, which are relatively unusual locations for oral melanoma. In addition, immunohistochemical markers used for diagnostic, therapeutic, and prognostic decision-making of oral melanoma are also discussed.
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Affiliation(s)
- Kritsasith Warin
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, Thammasat University, Pathum Thani, Thailand
| | - Poramaporn Klanrit
- Department of Oral Biomedical Sciences, Research Group of Chronic Inflammatory Oral Diseases and Systemic Diseases Associated with Oral Health, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand
| | - Nutdanai Pattanajakr
- Oral and Maxillofacial Surgery Clinic, Udon Thani Hospital, Udon Thani, Thailand
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Ma Y, Xia R, Ma X, Judson-Torres RL, Zeng H. Mucosal Melanoma: Pathological Evolution, Pathway Dependency and Targeted Therapy. Front Oncol 2021; 11:702287. [PMID: 34350118 PMCID: PMC8327265 DOI: 10.3389/fonc.2021.702287] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 07/02/2021] [Indexed: 12/16/2022] Open
Abstract
Mucosal melanoma (MM) is a rare melanoma subtype that originates from melanocytes within sun-protected mucous membranes. Compared with cutaneous melanoma (CM), MM has worse prognosis and lacks effective treatment options. Moreover, the endogenous or exogenous risk factors that influence mucosal melanocyte transformation, as well as the identity of MM precursor lesions, are ambiguous. Consequently, there remains a lack of molecular markers that can be used for early diagnosis, and therefore better management, of MM. In this review, we first summarize the main functions of mucosal melanocytes. Then, using oral mucosal melanoma (OMM) as a model, we discuss the distinct pathologic stages from benign mucosal melanocytes to metastatic MM, mapping the possible evolutionary trajectories that correspond to MM initiation and progression. We highlight key areas of ambiguity during the genetic evolution of MM from its benign lesions, and the resolution of which could aid in the discovery of new biomarkers for MM detection and diagnosis. We outline the key pathways that are altered in MM, including the MAPK pathway, the PI3K/AKT pathway, cell cycle regulation, telomere maintenance, and the RNA maturation process, and discuss targeted therapy strategies for MM currently in use or under investigation.
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Affiliation(s)
- Yanni Ma
- Department of Oncology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.,Shanghai Institute of Precision Medicine, Shanghai, China
| | - Ronghui Xia
- Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xuhui Ma
- Department of Oral & Maxillofacial - Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Robert L Judson-Torres
- Department of Dermatology, University of Utah, Salt Lake City, UT, United States.,Huntsman Cancer Institute, Salt Lake City, UT, United States
| | - Hanlin Zeng
- Department of Oncology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.,Shanghai Institute of Precision Medicine, Shanghai, China
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30
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Xu QQ, Li QJ, Chen L, Su XY, Song JX, Du J, Chen L, Lu LX. A nomogram for predicting survival of head and neck mucosal melanoma. Cancer Cell Int 2021; 21:224. [PMID: 33865388 PMCID: PMC8052848 DOI: 10.1186/s12935-021-01927-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 04/07/2021] [Indexed: 01/21/2023] Open
Abstract
Objectives We aimed to understand the clinical characteristics and better predict the prognosis of patients with mucosal melanoma of the head and neck (MMHN) using a nomogram. Methods Three hundred patients with nometastatic MMHN were included. Multivariable Cox regression was performed to analyze independent prognostic factors for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS), and these factors were used to develop a nomogram. Concordance indexes (C-indexes), calibration plots, and receiver operating characteristic (ROC) analysis were performed to test the predictive performance of the nomogram in both the primary (n = 300) and validation cohorts (n = 182). Results The primary tumor site, T stage and N stage were independent risk factors for survival and were included in the nomogram to predict the 3- and 5-year OS, DFS, DMFS, and LRRFS in the primary cohort. The C-indexes (both > 0.700), well-fit calibration plots, and area under the ROC curve (both > 0.700) indicated the high diagnostic accuracy of the nomogram, in both the primary and validation cohorts. The patients were divided into three groups (high-risk, intermediate-risk, and low-risk groups) according to their nomogram scores. The survival curves of OS, DFS, DMFS, and LRRFS were well separated by the risk groups in both cohorts (all P < 0.001). Conclusions The nomogram can stratify MMHN patients into clinically meaningful taxonomies to provide individualized treatment.
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Affiliation(s)
- Qing-Qing Xu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Qing-Jie Li
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Liu Chen
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Xin-Yi Su
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Jing-Xia Song
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Juan Du
- Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430079, Hubei, China
| | - Lei Chen
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.
| | - Li-Xia Lu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.
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Palma SD, McConnell A, Verganti S, Starkey M. Review on Canine Oral Melanoma: An Undervalued Authentic Genetic Model of Human Oral Melanoma? Vet Pathol 2021; 58:881-889. [PMID: 33685309 DOI: 10.1177/0300985821996658] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Oral melanoma (OM) is a highly aggressive tumor of the oral cavity in humans and dogs. Here we review the phenotypic similarities between the disease in these 2 species as the basis for the view that canine OM is a good model for the corresponding human disease. Utility of the "canine model" has likely been hindered by a paucity of information about the extent of the molecular genetic similarities between human and canine OMs. Current knowledge of the somatic alterations that underpin human tumorigenesis and metastatic progression is relatively limited, primarily due to the rarity of the disease in humans and consequent lack of opportunity for large-scale molecular analysis. The molecular genetic comparisons between human and canine OMs that have been completed indicate some overlap between the somatic mutation profiles of canine OMs and a subset of human OMs. However, further comparative studies featuring, in particular, larger numbers of human OMs are required to provide substantive evidence that canine OMs share mechanisms of tumorigenesis with at least a subset of human OMs. Future molecular genetic investigations of both human and canine OMs should investigate how primary tumors develop a metastatic gene expression signature and the genetic and epigenetic alterations specific to metastatic sites. Such studies may identify genetic alterations and pathways specific to the metastatic disease which could be targetable by new drugs.
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Affiliation(s)
| | | | - Sara Verganti
- 170851Dick White Referrals, Station Farm, Cambridgeshire, UK
| | - Mike Starkey
- 11661Animal Health Trust, Newmarket, Suffolk, UK
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Dika E, Lambertini M, Pellegrini C, Veronesi G, Melotti B, Riefolo M, Sperandi F, Patrizi A, Ricci C, Mussi M, Fargnoli MC. Cutaneous and Mucosal Melanomas of Uncommon Sites: Where Do We Stand Now? J Clin Med 2021; 10:478. [PMID: 33525348 PMCID: PMC7866093 DOI: 10.3390/jcm10030478] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 01/18/2021] [Accepted: 01/24/2021] [Indexed: 12/13/2022] Open
Abstract
Melanomas arising at uncommon sites include a group of lesions related to unusual localizations in specific ethnic groups. The rarity of the disease often represents a limit to the participation of patients in specific trials. However, this peculiar genetic scenario has important therapeutic implications regarding new oncologic therapies. The aim of this article is to review the clinical features, somatic alterations and therapeutic options for melanomas of uncommon sites. They can be classified as cutaneous and mucosal lesions affecting the nail apparatus, palms/soles, oral mucosa, genital area and scalp. The prognosis may be worse compared to melanomas of other districts, and a prompt diagnosis may dramatically influence the outcome. Dermatologists and oncologists should therefore distinguish this melanoma subgroup in terms of surgical intervention and medical treatment. Due to the lack of mutations in genes usually found in cutaneous melanomas, the discovery of novel targets is required to develop new strategies and to change the prognosis of non-responders or wild-type patients.
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Affiliation(s)
- Emi Dika
- Dermatology, IRCCS Policlinico di Sant’Orsola, via Massarenti 9, 40138 Bologna, Italy; (M.L.); (G.V.); (A.P.); (M.M.)
- Dermatology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy
| | - Martina Lambertini
- Dermatology, IRCCS Policlinico di Sant’Orsola, via Massarenti 9, 40138 Bologna, Italy; (M.L.); (G.V.); (A.P.); (M.M.)
- Dermatology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy
| | - Cristina Pellegrini
- Dermatology, Department of Biotechnological and Applied Clinical Science, University of L’Aquila, 67100 L’Aquila, Italy; (C.P.); (M.C.F.)
| | - Giulia Veronesi
- Dermatology, IRCCS Policlinico di Sant’Orsola, via Massarenti 9, 40138 Bologna, Italy; (M.L.); (G.V.); (A.P.); (M.M.)
- Dermatology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy
| | - Barbara Melotti
- Division of Oncology, IRCCS di Policlinico Sant’Orsola, via Massarenti 9, 40138 Bologna, Italy; (B.M.); (F.S.)
| | - Mattia Riefolo
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (M.R.); (C.R.)
| | - Francesca Sperandi
- Division of Oncology, IRCCS di Policlinico Sant’Orsola, via Massarenti 9, 40138 Bologna, Italy; (B.M.); (F.S.)
| | - Annalisa Patrizi
- Dermatology, IRCCS Policlinico di Sant’Orsola, via Massarenti 9, 40138 Bologna, Italy; (M.L.); (G.V.); (A.P.); (M.M.)
- Dermatology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy
| | - Costantino Ricci
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (M.R.); (C.R.)
- Pathology Unit, Ospedale Maggiore, 40100 Bologna, Italy
| | - Martina Mussi
- Dermatology, IRCCS Policlinico di Sant’Orsola, via Massarenti 9, 40138 Bologna, Italy; (M.L.); (G.V.); (A.P.); (M.M.)
- Dermatology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy
| | - Maria Concetta Fargnoli
- Dermatology, Department of Biotechnological and Applied Clinical Science, University of L’Aquila, 67100 L’Aquila, Italy; (C.P.); (M.C.F.)
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Aloua R, Kaouani A, Kerdoud O, Salissou I, Slimani F. Melanoma of the oral cavity: A silent killer. Ann Med Surg (Lond) 2021; 62:182-185. [PMID: 33532067 PMCID: PMC7829076 DOI: 10.1016/j.amsu.2021.01.026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 01/12/2021] [Accepted: 01/12/2021] [Indexed: 02/03/2023] Open
Abstract
Melanoma of the mouth is a rare entity of cancer. It has a bad prognosis. We report two cases of mouth melanoma. In the first case, 68 years old man developed a mandibular gingival tumor. Head and neck MRI scans showed an aggressive tumor process in the mouth with bone extension and in the deep spaces. The patient was free of cervical lymph nodes. The second case is a 75-years-old male with heavy tobacco smoke. The man felt a burgeoning mass on the right palate. The neck palpation found a firm mobile non-tender mass at the left upper jugular region. The anatomopathological study of the biopsies assigned both cases to malignant melanoma. Because of the rarity and delays in diagnosis, case reports are an invaluable source of information.
Melanoma of the mouth is a rare entity of cancer with a bad prognosis. Tobacco and alcohol use are two of the most important risk factors for oral cavity and oropharyngeal cancers. Maxillofacial surgeons and physicians who treat oral lesions must be conscious of the need for early diagnosis of melanoma.
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Affiliation(s)
- Rachid Aloua
- Oral and Maxillofacial Surgery Department, CHU Ibn Rochd, B.P 2698, Casablanca, Morocco
| | - Amine Kaouani
- Oral and Maxillofacial Surgery Department, CHU Ibn Rochd, B.P 2698, Casablanca, Morocco
- Corresponding author.
| | - Ouassime Kerdoud
- Oral and Maxillofacial Surgery Department, CHU Ibn Rochd, B.P 2698, Casablanca, Morocco
| | - Iro Salissou
- Oral and Maxillofacial Surgery Department, CHU Ibn Rochd, B.P 2698, Casablanca, Morocco
| | - Faiçal Slimani
- Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, B.P 5696, Casablanca, Morocco
- Oral and Maxillofacial Surgery Department, CHU Ibn Rochd, B.P 2698, Casablanca, Morocco
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Keser G, Celik I, Pekiner F. Knowledge and awareness assessment of dental students about malignant melanoma. CLINICAL CANCER INVESTIGATION JOURNAL 2021. [DOI: 10.4103/ccij.ccij_74_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Cardoso DDM, Bastos DB, Dos Santos DM, Conrado-Neto S, Collado FU, Crivelini MM, Xavier-Júnior JCC, Biasoli ÉR, Miyahara GI, Bernabé DG. In situ melanoma of oral cavity: Diagnosis and treatment of a rare entity. Oral Oncol 2020; 115:105116. [PMID: 33341377 DOI: 10.1016/j.oraloncology.2020.105116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 11/22/2020] [Indexed: 12/20/2022]
Abstract
Oral melanoma is an extremely aggressive and rare tumor. Commonly, oral melanomas are diagnosed as invasive tumors, which considerably reduces the chances of cure. In situ oral melanomas being exceedingly rare, which makes its clinicopathological and prognostic characteristics poorly known. Herein, we report a case of 67-year-old non-white woman with a large black patch on the maxillary alveolar mucosa. A biopsy was made and microscopical analysis revealed moderate atypical junctional melanocytic. Tumor cells were positive for S100 (Polyclonal), Melan-A (Clone A103) and Melanosome (HMB-45). The diagnosis of in situ oral melanoma was made and the patient was treated surgically with partial maxillectomy and rehabilitated with obturator prosthesis. Although extremely rare in situ melanomas should be considered in the differential diagnosis of non-invasive pigmented lesions of the oral mucosa.
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Affiliation(s)
- Diovana de Melo Cardoso
- Oral Oncology Center, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil
| | - Daniela Brito Bastos
- Oral Oncology Center, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil
| | - Daniela Micheline Dos Santos
- Oral Oncology Center, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil; Department of Dental Materials and Prosthesis, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil
| | - Sebastião Conrado-Neto
- Oral Oncology Center, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil
| | - Francisco Urbano Collado
- Oral Oncology Center, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil
| | - Marcelo Macedo Crivelini
- Department of Diagnosis and Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil
| | - José Cândido Caldeira Xavier-Júnior
- Pathology Institute of Araçatuba, Araçatuba, São Paulo, Brazil; School of Medicine, Centro Universitário Católico Unisalesiano Auxilium, Araçatuba, São Paulo, Brazil
| | - Éder Ricardo Biasoli
- Oral Oncology Center, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil; Department of Diagnosis and Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil
| | - Glauco Issamu Miyahara
- Oral Oncology Center, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil; Department of Diagnosis and Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil
| | - Daniel Galera Bernabé
- Oral Oncology Center, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil; Department of Diagnosis and Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil.
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Aziz Z, Aboulouidad S, Bouihi ME, Hattab NM, Chehbouni M, Raji A. Oral amelanotic malignant melanoma: a case report. Pan Afr Med J 2020; 37:350. [PMID: 33738038 PMCID: PMC7934186 DOI: 10.11604/pamj.2020.37.350.27330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 12/10/2020] [Indexed: 11/11/2022] Open
Abstract
Amelanotic malignant melanoma is an extremely rare and aggressive oral tumor. Herein we report the case of a 42-year-old woman presented with a painful growth in anterior maxillary region. Intra-oral examination showed a non-pigmented exophytic mass occupying the anterior maxillary sector. Incisional biopsy with immunohistochemistry examination revealed a malignant melanoma as it strongly expressed melan A and S-100. Facial computed tomography showed extension to the maxillary bone and hard palate. After thoraco-abdominal computed tomography revealing absence of metastasis, tumor resection was performed respecting 2cm security margin. Oral localization of malignant melanoma is rare especially its amelanotic variant. Lack of pigmentation makes the diagnosis more difficult, usually resulting in treatment delay and making the prognosis even worse. Early detection by histological and immunochemistry examination combined to wide resection are the keys to improving the survival for patients with oral amelanotic melanoma.
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Affiliation(s)
- Zakaria Aziz
- Maxillofacial Surgery Department, University Hospital Center Mohammed VI, Marrakesh, Morocco
| | - Salma Aboulouidad
- Maxillofacial Surgery Department, University Hospital Center Mohammed VI, Marrakesh, Morocco
| | - Mohamed El Bouihi
- Maxillofacial Surgery Department, University Hospital Center Mohammed VI, Marrakesh, Morocco
| | - Nadia Mansouri Hattab
- Maxillofacial Surgery Department, University Hospital Center Mohammed VI, Marrakesh, Morocco
| | - Mohamed Chehbouni
- Department of Otorhinolaryngology, University Hospital Center Mohammed VI, Marrakesh, Morocco
| | - Abdelaziz Raji
- Department of Otorhinolaryngology, University Hospital Center Mohammed VI, Marrakesh, Morocco
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Leite AK, Kulcsar MAV, Matsuura D, Matos LL, Kowalski LP. Amelanotic melanoma presenting as a tongue tumor. Oral Oncol 2020; 114:105075. [PMID: 33187823 DOI: 10.1016/j.oraloncology.2020.105075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 10/14/2020] [Accepted: 10/18/2020] [Indexed: 11/15/2022]
Affiliation(s)
- Ana Kober Leite
- Head and Neck Surgery Department, Instituto do Câncer do Estado de São Paulo/Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
| | - Marco Aurélio V Kulcsar
- Head and Neck Surgery Department, Instituto do Câncer do Estado de São Paulo/Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
| | - Danielli Matsuura
- Head and Neck Surgery Department, Instituto do Câncer do Estado de São Paulo/Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
| | - Leandro Luongo Matos
- Head and Neck Surgery Department, Instituto do Câncer do Estado de São Paulo/Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
| | - Luiz Paulo Kowalski
- Head and Neck Surgery Department, Instituto do Câncer do Estado de São Paulo/Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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38
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Chandan SN, Shetty SK, Deepa BV. Primary Malignant Melanoma of Oral Mucosa - Report of Two Cases. Contemp Clin Dent 2020; 11:195-198. [PMID: 33110337 PMCID: PMC7583535 DOI: 10.4103/ccd.ccd_380_19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 11/09/2020] [Accepted: 04/17/2020] [Indexed: 02/03/2023] Open
Abstract
Primary malignant melanoma of oral mucosa is a rare and aggressive tumor. It is usually seen in the 5th and 6th decades of life. Its mainstay of treatment is surgery. It has a very poor prognosis, which is attributed to its late detection and distant metastasis. Dentists are often the first clinicians to come across these lesions and need to be able to identify them at the earliest for a better prognosis. In this article, we present two cases of extensive primary malignant melanoma of the oral cavity. Clinically, both the cases had a similar appearance of grayish-black pigmented nodular swelling on the buccal aspect and grayish-black discoloration on the palatal aspect. There were no significant radiological changes in both cases, indicating the superficial spread of the lesion. A positron emission tomography scan was performed in the second patient, which did not show any distant metastasis. Surgery was advised as a treatment for both the patients.
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Affiliation(s)
- S N Chandan
- Department of Oral and Maxillofacial Surgery, JSS Dental College and Hospital, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
| | - Sahith Kumar Shetty
- Department of Oral and Maxillofacial Surgery, JSS Dental College and Hospital, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
| | - B V Deepa
- Department of Oral and Maxillofacial Surgery, JSS Dental College and Hospital, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
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Koca RB, Ünsal G, Soluk Tekkeşin M, Kasnak G, Orhan K, Özcan İ, Fıratlı E. A review with an additional case: amelanotic malignant melanoma at mandibular gingiva. Int Cancer Conf J 2020; 9:175-181. [PMID: 32904143 DOI: 10.1007/s13691-020-00425-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 06/09/2020] [Indexed: 12/16/2022] Open
Abstract
The purpose of this review with an additional case is to evaluate the clinical, ultrasonographic and histopathological features of a rare case of Amelanotic Malignant Melanoma (AMM) at mandibular gingiva and to compare our case with other published AMMs at mandibular gingiva. A 52-year-old male patient with no systemic diseases was referred to our clinic with a soft tissue lesion at mandibular gingiva. Ultrasonographic examination was performed and a lesion with malignant features was observed. A periapical radiograph was taken to investigate bone destruction and biopsy was planned. Histopathological examination revealed AMM and a literature search was performed to congregate reports which were indexed in PubMed, ScienceDirect, and ResearchGate. Three AMM cases at mandibular gingiva were found. Doppler Ultrasound examination suggested bone destruction and a 1.8 cm × 0.6 cm soft tissue mass with well-defined borders and increased vascularity. Due to its hypervascularity, depth of invasion and destruction at the bone, the lesion was prediagnosed as a malignancy. Lack of melanin pigmentation caused the large immunohistochemical panel study. The tumour cells showed HMB45 and S100 positivity and they were negative with SMA, Desmin, CK1.3, and CK20. Routine ultrasound examination of all soft tissue lesions is very important for assessing features such as vascularity, bone destruction and depth of invasion to detect malignancy. Melanocytic-associated immunohistochemical markers are crucial for AMM diagnosis.
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Affiliation(s)
- Revan Birke Koca
- Faculty of Dentistry, Department of Periodontology, University of Kyrenia, Kyrenia, Cyprus
| | - Gürkan Ünsal
- Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Near East University, Nicosia, Cyprus
| | - Merva Soluk Tekkeşin
- Institute of Oncology, Department of Tumour Pathology, Istanbul University, Istanbul, Turkey
| | - Gökhan Kasnak
- Faculty of Dentistry, Department of Periodontology, Istanbul University, Istanbul, Turkey
| | - Kaan Orhan
- Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Ankara University, Ankara, Turkey
| | - İlknur Özcan
- Faculty of Dentistry, Department of Dentomaxillofacial Radiology, Istanbul University, Istanbul, Turkey
| | - Erhan Fıratlı
- Faculty of Dentistry, Department of Periodontology, Istanbul University, Istanbul, Turkey
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Rossi E, Schinzari G, Maiorano BA, Indellicati G, Di Stefani A, Pagliara MM, Fragomeni SM, De Luca EV, Sammarco MG, Garganese G, Galli J, Blasi MA, Paludetti G, Scambia G, Peris K, Tortora G. Efficacy of immune checkpoint inhibitors in different types of melanoma. Hum Vaccin Immunother 2020; 17:4-13. [PMID: 32663057 PMCID: PMC7872095 DOI: 10.1080/21645515.2020.1771986] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Immunotherapy can be used for cutaneous, mucosal, uveal and conjunctival melanoma. Nevertheless, we cannot expect the same benefit from checkpoint inhibitors for all the types of melanoma. The different biological features can explain the variable efficacy. The main results obtained with immune checkpoint inhibitors in the various types of melanoma were reviewed.
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Affiliation(s)
- Ernesto Rossi
- Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy
| | - Giovanni Schinzari
- Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy.,Medical Oncology, Università Cattolica del Sacro Cuore , Rome, Italy
| | | | - Giulia Indellicati
- Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy
| | - Alessandro Di Stefani
- Dermatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome - Italy
| | - Monica Maria Pagliara
- Ophtalmology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy
| | - Simona Maria Fragomeni
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy
| | | | - Maria Grazia Sammarco
- Ophtalmology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy
| | - Giorgia Garganese
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy.,Ginecology and Breast Care Center, Mater Olbia Hospital , Olbia, Italy
| | - Jacopo Galli
- Department of Head and Neck Surgery, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Maria Antonietta Blasi
- Ophtalmology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy.,Ophtalmology, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Gaetano Paludetti
- Department of Head and Neck Surgery, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Giovanni Scambia
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy.,Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Ketty Peris
- Dermatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome - Italy.,Institute of Dermatology, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Giampaolo Tortora
- Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Rome, Italy.,Medical Oncology, Università Cattolica del Sacro Cuore , Rome, Italy
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41
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FARP1 Facilitates Cell Proliferation Through Modulating MAPK Signaling Pathway in Cutaneous Melanoma. Am J Dermatopathol 2019; 41:908-913. [PMID: 31021836 DOI: 10.1097/dad.0000000000001426] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE The purpose of our study was to investigate the biological functions of FARP1 gene in cutaneous melanoma. METHODS The mRNA expression level of FARP1 in cutaneous melanoma was analyzed based on the data obtained from ONCOMINE and The Cancer Genome Atlas database. Kaplan-Meier analysis was conducted to explore the association between FARP1 expression and the overall survival time of patients with cutaneous melanoma. The mRNA expression of FARP1 in melanoma cells was determined by qRT-PCR. A-375 cell line with silenced FARP1 was constructed to explore its biological functions. Cell proliferation, migration, and invasion abilities were determined by CCK8 assay, wound-healing assay, and transwell assays, respectively. Western blot was performed to explore the protein expression of FARP1, pMEK, MEK, pERK, and ERK. RESULTS Our results showed that the expression level of FARP1 was upregulated in cutaneous melanoma tissues and cells. Kaplan-Meier analysis revealed that high expression of FARP1 is predictive of shorter overall survival time in patients with cutaneous melanoma. Through CCK8 assay, we found that knockdown of FARP1 in A-375 cells exhibited dramatically inhibitory effect on cell proliferation. The results of wound-healing and transwell assays revealed that the motility of A-375 cells was notably suppressed after silencing FARP1. Moreover, the relative expression levels of pMEK/MEK and pERK/ERK decreased remarkably in A-375 cells following being transfected with si-FARP1. CONCLUSIONS Our present results preliminary proofed that FARP1 possibly acts as a promoter in cutaneous melanoma development and possesses the potential to be a therapeutic target in patients with cutaneous melanoma.
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Bowlt Blacklock KL, Birand Z, Selmic LE, Nelissen P, Murphy S, Blackwood L, Bass J, McKay J, Fox R, Beaver S, Starkey M. Genome-wide analysis of canine oral malignant melanoma metastasis-associated gene expression. Sci Rep 2019; 9:6511. [PMID: 31019223 PMCID: PMC6482147 DOI: 10.1038/s41598-019-42839-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 04/04/2019] [Indexed: 12/12/2022] Open
Abstract
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.
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Affiliation(s)
| | - Z Birand
- Animal Health Trust, Newmarket, Suffolk, UK
| | - L E Selmic
- Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio, USA
| | - P Nelissen
- Dick White Referrals, Newmarket, Suffolk, UK
| | - S Murphy
- Animal Health Trust, Newmarket, Suffolk, UK
- The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
| | - L Blackwood
- Institute of Veterinary Science, University of Liverpool, Liverpool, UK
| | - J Bass
- Animal Health Trust, Newmarket, Suffolk, UK
- Finn Pathologists, Harleston, UK
| | - J McKay
- IDEXX Laboratories, Ltd, Wetherby, UK
| | - R Fox
- Finn Pathologists, Harleston, UK
| | - S Beaver
- Nationwide Laboratory Services, Poulton-le-Fylde, UK
| | - M Starkey
- Animal Health Trust, Newmarket, Suffolk, UK.
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43
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Malinoski H, Reddy R, Cohen DM, Bhattacharyya I, Islam MN, Bowers TL. Oral Melanomas: A Case Series of a Deadly Neoplasm. J Oral Maxillofac Surg 2019; 77:1832-1836. [PMID: 30998880 DOI: 10.1016/j.joms.2019.03.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 03/16/2019] [Accepted: 03/16/2019] [Indexed: 11/29/2022]
Abstract
PURPOSE To describe and discuss the demographic and clinical features of oral melanomas, which are relatively rare but deadly neoplasms, and list the criteria for their diagnosis to increase early detection. MATERIALS AND METHODS An institutional review board-approved retrospective search of oral melanomas was performed in the archives of the University of Florida Oral and Maxillofacial Pathology Biopsy Service (Gainesville, FL) from 2015 through 2018. Exclusion criteria included cases with inconclusive diagnosis, skin involvement, and missing clinical data or slide material. Of 7 patients with a diagnosis of melanoma of the head and neck region, 6 (87.5%) were found to be diagnosed with oral melanomas and met the inclusion criteria. RESULTS All 6 patients were at least 45 years (range, 45 to 87 yr). The male-to-female ratio was 4:2. Three patients were asymptomatic and 3 experienced symptoms, including pain, swelling, and tingling. Seven lesions were detected in these 6 patients. Three of these lesions were located on the maxillary gingiva, 2 were on the mandibular gingiva, and 2 involved the palate. Two lesions were diagnosed as spindle cell melanoma, 4 were diagnosed as melanoma, and 1 was diagnosed as a mucosal lentiginous melanoma. CONCLUSION Oral melanomas should be considered in the differential diagnosis of oral pigmented lesions, especially on the gingiva or palate, in middle-age and elderly patients. Oral melanomas have a male bias. In addition, supportive criteria enabling early diagnosis of oral melanomas is addressed.
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Affiliation(s)
- Holly Malinoski
- Resident, Department of Oral and Maxillofacial Surgery, University of Florida College of Dentistry, Gainesville, FL.
| | - Rekha Reddy
- Chief Resident, Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL
| | - Donald M Cohen
- Chair and Professor, Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL
| | - Indraneel Bhattacharyya
- Division Director and Professor, Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL
| | - Mohammed N Islam
- Clinical Professor, Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL
| | - Thomas L Bowers
- Clinical Assistant Professor, Department of Oral and Maxillofacial Surgery, University of Florida College of Dentistry, Gainesville, FL
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44
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Analysis of nicotinamide N-methyltransferase in oral malignant melanoma and potential prognostic significance. Melanoma Res 2019; 29:151-156. [DOI: 10.1097/cmr.0000000000000548] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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45
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Abstract
Black and brown-colored mucocutaneous lesions present a differential diagnostic challenge, with malignant melanoma being the primary clinical concern. The vast majority of pigmented lesions in the head and neck region are the result of benign, reactive factors such as post-inflammatory melanosis. However, it is not uncommon to discover a range of muco-cutaneous black and brown neoplasms in the oro-facial area. The majority of black/brown pigmented neoplasms are melanocytic in origin; these are neoplasms of neural crest derivation. Melanocytic nevi are a diverse group of benign neoplasms that are the result of specific oncogenic mutations. They are common on cutaneous surfaces but can manifest in mucosal sites. Currently, nevi are classified based on clinical and histological criteria. The most common cutaneous and oral mucosal nevus is the acquired melanocytic nevus; nevi do not pose an increased risk for the development of malignant melanoma. Emerging information on specific genetic differences supports the notion of biologically distinct nevi. This article will review the classic clinical and microscopic features of nevi commonly found in the head and neck region, and discuss emerging concepts in nevus pathogenesis and taxonomy. Melanoma is a malignant melanocytic neoplasm and is a result of cumulative genetic deregulation. The etiology of malignant melanoma (MM) is multifactorial and includes underlying genetic susceptibility, UV radiation, skin-type, and race. The majority of MM occurs on cutaneous surfaces and less commonly on mucosal and extra-cutaneous visceral organs. Regardless of location, MM exhibits clinical-pathological features that relate to horizontal or vertical tumor spread. Cutaneous and mucosal MM typically present as asymmetrical, irregularly bordered, large (> 0.5 cm), heterogeneous brown-black lesions with foci of erythema, atrophy or ulceration. As with melanocytic nevi, advances in melanomagenesis research have revealed primary oncogenic BRAF and NRAS mutations associated with cutaneous MM. Unlike their cutaneous counterparts, mucosal melanomas exhibit primary oncogenic alterations in c-KIT and other genes. This article will discuss the role of specific primary oncogenic and secondary/tertiary genetic defects in differential clinical presentation, anatomic distribution, future classification changes, and targeted therapy of melanoma. The clinical and microscopic features of mucosal melanomas and a summary of management guidelines will be discussed. Additionally, this article will cover the salient features of melanocytic neuroectodermal tumor of infancy, a neoplastic entity that can involve the oro-facial region, and the clinical-pathological features of selected, commonly occurring pigmented ectodermally-derived neoplasms that are often part of the clinical differential diagnosis of black-brown pigmented lesions.
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Affiliation(s)
- Easwar Natarajan
- Section of Oral and Maxillofacial Pathology, University of Connecticut Health Center, 263 Farmington Ave, MC-0925, Farmington, CT, 06030, USA.
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46
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Mayo Z, Seyedin S, Marquardt M, Mohiuddin I, Milhem M, Liu V, Pagedar N, Anderson C. Cutaneous malignant melanoma of the oral cavity following skin graft reconstruction: Case report. Head Neck 2019; 41:E26-E29. [PMID: 30537068 DOI: 10.1002/hed.25417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 09/06/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Malignant melanomas on skin graft recipient sites are rare, with few cases reported in the literature. METHODS We present a case report of a patient with recurrent cutaneous melanoma in the grafted anterolateral thigh flap of the tongue. RESULTS A patient underwent hemiglossectomy with free flap reconstruction for squamous cell carcinoma of the tongue. Five years later the patient was seen with a 1-cm nodule and surrounding erythroplakia at the recipient site of the graft. Analysis revealed cutaneous malignant melanoma. Patient then related a remote history of a suspected skin melanoma of the donor leg that had been treated with excision, with unknown histology. CONCLUSION This may be the first reported case of a cutaneous malignant melanoma in the oral cavity following an anterolateral thigh free flap reconstruction, emphasizing the importance of obtaining a comprehensive history of skin cancers and closely inspecting the donor site prior to graft harvesting.
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Affiliation(s)
- Zachary Mayo
- Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Steven Seyedin
- Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Michael Marquardt
- Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Imran Mohiuddin
- Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Mohammed Milhem
- Department of Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Vincent Liu
- Department of Dermatology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Nitin Pagedar
- Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Carryn Anderson
- Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
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47
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Jafarian AH, Mohamadian Roshan N, Gharib M, Moshirahmadi V, Tasbandi A, Ayatollahi AA, Ayatollahi H. Evaluation of Cyclooxygenase-2 Expression in Association with Clinical-Pathological Factors in Malignant Melanoma. IRANIAN JOURNAL OF PATHOLOGY 2019; 14:96-103. [PMID: 31528165 PMCID: PMC6679669 DOI: 10.30699/ijp.14.2.96] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 04/24/2018] [Indexed: 11/06/2022]
Abstract
Background and Objective The primary goal of this study is to develop a rigorous understanding of the correlation between COX-2 expression and malignant melanoma prognostic factors. Material and Methods In this cross-sectional study, we analyzed 60 cases of cutaneous malignant melanoma. The related stained slides were reviewed by two pathologists. The results were interpreted according to the COX2 staining index (SI), tumor thickness (Breslow, Clark), number of mitoses per 10 hpf, and melanoma types. Gender, lymph node involvement, metastasis, and survival were considered as evaluation factors as well. Results The expression of the COX-2 protein was evident in 98.4% of cases. A strong Staining Index(SI) was reported in 60% of all melanomas, moderate staining was detected in 20.8% and weak staining in 10%; 1.6% of studied cases showed no staining. Benign nevus specimens showed no staining for the COX-2 enzyme. Conclusion We have demonstrated that COX-2 is strongly expressed in the majority of malignant melanomas and that the SI score of COX-2 is related to the number of mitoses, tumor thickness (based on Clark level and Breslow), melanoma sub-type, lymph node involvement, and metastases; No association was noted between the anatomic site, gender, and survival. COX-2 can be applied as a prognostic factor in malignant melanoma and a promising candidate for future target therapies.
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Affiliation(s)
- Amir Hossein Jafarian
- Associate Professor of Pathology, Department Of Pathology, Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nema Mohamadian Roshan
- Associate Professor of Pathology, Department Of Pathology, Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Masoumeh Gharib
- Assistant Professor of Pathology, Department Of Pathology, Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vahid Moshirahmadi
- Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Aida Tasbandi
- Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Ali Ayatollahi
- Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Ayatollahi
- Associate Professor of Pathology, Department Of Pathology, Cancer Molecular Pathology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Segaoula Z, Primot A, Lepretre F, Hedan B, Bouchaert E, Minier K, Marescaux L, Serres F, Galiègue-Zouitina S, André C, Quesnel B, Thuru X, Tierny D. Isolation and characterization of two canine melanoma cell lines: new models for comparative oncology. BMC Cancer 2018; 18:1219. [PMID: 30514258 PMCID: PMC6280433 DOI: 10.1186/s12885-018-5114-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 11/20/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Metastatic melanoma is one of the most aggressive forms of cancer in humans. Among its types, mucosal melanomas represent one of the most highly metastatic and aggressive forms, with a very poor prognosis. Because they are rare in Caucasian individuals, unlike cutaneous melanomas, there has been fewer epidemiological, clinical and genetic evaluation of mucosal melanomas. Moreover, the lack of predictive models fully reproducing the pathogenesis and molecular alterations of mucosal melanoma makes its treatment challenging. Interestingly, dogs are frequently affected by melanomas of the oral cavity that are characterized, as their human counterparts, by focal infiltration, recurrence, and metastasis to regional lymph nodes, lungs and other organs. In dogs, some particular breeds are at high risk, suggesting a specific genetic background and strong genetic drivers. Altogether, the striking homologies in clinical presentation, histopathological features, and overall biology between human and canine mucosal melanomas make dogs invaluable natural models with which to investigate tumor development, including tumor ætiology, and develop tailored treatments. METHODS We developed and characterized two canine oral melanoma cell lines from tumors isolated from dog patients with distinct clinical profiles; with and without lung metastases. The cells were characterized using immunohistochemistry, pharmacology and genetic studies. RESULTS We have developed and immunohistochemically, genetically, and pharmacologically characterized. Two cell lines (Ocr_OCMM1X & Ocr_OCMM2X) were produced through mouse xenografts originating from two clinically contrasting melanomas of the oral cavity. Their exhaustive characterization showed two distinct biological and genetic profiles that are potentially linked to the stage of malignancy at the time of diagnosis and sample collection of each melanoma case. These cell lines thus constitute relevant tools with which to perform genetic and drug screening analyses for a better understanding of mucosal melanomas in dogs and humans. CONCLUSIONS The aim of this study was to establish and characterize xenograft-derived canine melanoma cell lines with different morphologies, genetic features and pharmacological sensitivities that constitute good predictive models for comparative oncology. These cell lines are relevant tools to advance the use of canine mucosal melanomas as natural models for the benefit of both veterinary and human medicine.
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Affiliation(s)
- Zacharie Segaoula
- University of Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Jean-Pierre AUBERT Research Centre of Neuroscience and Cancer, F-59000 Lille, France
- OCR (Oncovet Clinical Research), SIRIC ONCOLille, Parc Eurasante, Rue du Dr Alexandre Yersin, F-59120 Loos, France
| | - Aline Primot
- CNRS-University of Rennes 1, UMR 6290, Institute of Genetique and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
| | | | - Benoit Hedan
- CNRS-University of Rennes 1, UMR 6290, Institute of Genetique and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
| | - Emmanuel Bouchaert
- OCR (Oncovet Clinical Research), SIRIC ONCOLille, Parc Eurasante, Rue du Dr Alexandre Yersin, F-59120 Loos, France
| | - Kevin Minier
- Oncovet Cancer Centre, Avenue Paul Langevin, 59650 Villeneuve d’Ascq, France
| | - Laurent Marescaux
- Oncovet Cancer Centre, Avenue Paul Langevin, 59650 Villeneuve d’Ascq, France
| | - François Serres
- OCR (Oncovet Clinical Research), SIRIC ONCOLille, Parc Eurasante, Rue du Dr Alexandre Yersin, F-59120 Loos, France
- Oncovet Cancer Centre, Avenue Paul Langevin, 59650 Villeneuve d’Ascq, France
| | - Sylvie Galiègue-Zouitina
- University of Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Jean-Pierre AUBERT Research Centre of Neuroscience and Cancer, F-59000 Lille, France
| | - Catherine André
- CNRS-University of Rennes 1, UMR 6290, Institute of Genetique and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
| | - Bruno Quesnel
- University of Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Jean-Pierre AUBERT Research Centre of Neuroscience and Cancer, F-59000 Lille, France
- CNRS-University of Rennes 1, UMR 6290, Institute of Genetique and Development of Rennes, Faculty of Medicine, SFR Biosit, Rennes, France
| | - Xavier Thuru
- University of Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Jean-Pierre AUBERT Research Centre of Neuroscience and Cancer, F-59000 Lille, France
| | - Dominique Tierny
- OCR (Oncovet Clinical Research), SIRIC ONCOLille, Parc Eurasante, Rue du Dr Alexandre Yersin, F-59120 Loos, France
- Oncovet Cancer Centre, Avenue Paul Langevin, 59650 Villeneuve d’Ascq, France
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The existence of early stage oral mucosal melanoma: A 10-year retrospective analysis of 170 patients in a single institute. Oral Oncol 2018; 87:70-76. [PMID: 30527246 DOI: 10.1016/j.oraloncology.2018.10.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 10/15/2018] [Accepted: 10/17/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND Oral mucosal melanoma (OMM) is an aggressive tumor with an extremely low incidence, and the current TNM Staging System has classified all OMMs as high stage. However, controversy remains regarding the existence of early stage OMMs. PATIENTS AND METHODS The clinical and pathological features, treatments and outcomes of 170 OMM patients treated in a single institution from January 2007 to July 2017 were retrospectively analyzed. Multivariate analysis was performed to identify significant prognostic factors for overall survival (OS). RESULTS Multivariate analysis identified positive cervical lymph nodes (p < 0.0001), nodular OMMs (p < 0.0001), ulceration (p = 0.002), and level III or level IV invasion (p < 0.0001) as independent poor prognostic factors for OS. Nodular OMM patients with a tumor size ≤1 cm had a better outcome than those with a tumor size >1 cm (p < 0.0001). Twenty-two patients with superficial invasion had a favorable survival without the need of adjuvant therapy (postoperative chemotherapy or radiotherapy), and the current TNM Staging System was not suitable for those patients. Patients with deep invasion were more likely to suffer from recurrence and distant metastasis. CONCLUSIONS Tumor size ≤1 cm and OMM in situ, although extremely rare, do exist. It is advisable for AJCC to consider tumor size ≤1 cm and OMM in situ as the early stage of OMM when updating the new Oral Melanoma Staging System.
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Duan N, Zhang YH, Wang WM, Wang X. Mystery behind labial and oral melanotic macules: Clinical, dermoscopic and pathological aspects of Laugier-Hunziker syndrome. World J Clin Cases 2018; 6:322-334. [PMID: 30283795 PMCID: PMC6163135 DOI: 10.12998/wjcc.v6.i10.322] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Revised: 06/28/2018] [Accepted: 07/23/2018] [Indexed: 02/05/2023] Open
Abstract
Labial and oral melanotic macules are commonly encountered in a broad range of conditions ranging from physiologic pigmentation to a sign of an underlying life-threatening disease. Although Laugier-Hunziker syndrome (LHS) shares some features of labial and oral pigmentation with a variety of conditions, it is a benign and acquired condition, frequently associated with longitudinal melanonychia. Herein, the demographic, clinical, dermoscopic, and pathological aspects of LHS were reviewed comprehensively. The important differential diagnoses of mucocutaneous and nail pigmentation are provided. An accurate diagnosis is crucial to design a reasonable medical strategy, including management options, malignant transformation surveillance, and psychological support. It is important that clinicians conduct long-term follow-up and surveillance due to the potential risks of malignant transformation and local severe complications in some conditions.
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Affiliation(s)
- Ning Duan
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Yang-Heng Zhang
- Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Wen-Mei Wang
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu Province, China
| | - Xiang Wang
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu Province, China
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