Article

Head and neck mucosal melanoma: Experience with 42 patients, with emphasis on the role of postoperative radiotherapy

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Abstract

Treatment of head and neck mucosal melanoma remains a challenge. Surgery has traditionally been the main therapeutic approach. The role of postoperative radiotherapy has never been clearly established. The experience with a group of 42 patients (16 males, 26 females) with a primary head and neck mucosal melanoma is reported. Eleven of 19 patients (57.9%) receiving surgery alone developed a regional lymphatic metastasis. For patients receiving postoperative radiotherapy (19 patients), regional metastatic spread occurred in 4 patients (21%). Percentages of local failure were 57.9% (11/19) and 26.3% (5/19) for patients treated with surgery alone and for those treated with surgery and radiotherapy, respectively. Distant metastases occurred in 10 of 19 patients (52.6%) receiving surgery alone and in 9 of 19 patients (47.3%) receiving both therapies. The present evaluation confirms a poor prognosis for patients with head and neck mucosal melanoma, independent of the treatment modality.

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... The median age of the studied population was 65 years, with a range of 24e93 years. This wide range and high median age is consistent with the published literature (Jethanamest et al., 2011;Meleti et al., 2008), and reminds us that mucosal melanoma is a disease of the elderly but should not be ruled out in the young. Although some studies have shown a sex predominance (Patel et al., 2002;Meleti et al., 2008), large cohort studies have reported a similar incidence in both sexes (Nandapalan et al., 1998;DeMatos et al., 1998). ...
... This wide range and high median age is consistent with the published literature (Jethanamest et al., 2011;Meleti et al., 2008), and reminds us that mucosal melanoma is a disease of the elderly but should not be ruled out in the young. Although some studies have shown a sex predominance (Patel et al., 2002;Meleti et al., 2008), large cohort studies have reported a similar incidence in both sexes (Nandapalan et al., 1998;DeMatos et al., 1998). Our study population was no exception in this regard, so in agreement with most of the existing literature we could not find a gender-related difference in survival (Chan et al., 2012). ...
... Our own data showed a higher local and regional recurrence rate for OMM, but like most study groups we found that both subsites shared a similar overall and diseasespecific survival (Jethanamest et al., 2011;Lawaetz et al., 2016;Patel et al., 2002;McLean et al., 2008;Prasad et al., 2003). In contrast, Meleti et al. found that OMM had a significantly better 5year disease specific survival than SNMM, a finding that could only partly be explained by a higher percentage of deep tissue infiltration in the SNMM group (Meleti et al., 2008). Due to a very large sample size, Jethanamest at el. were able to conduct a subsite analysis and found that nasal cavity and oral cavity indeed share the same prognosis, but that the nasopharynx, oropharynx, and paranasal sinus do each have a significantly shorter survival value. ...
Article
Introduction: Head and neck mucosal melanoma (HNMM) is a rare tumor with a poor outcome. The objective of this study was to assess outcome and prognostic factors for a cohort of patients treated in a head and neck cancer center. In addition, a case series on sentinel lymph node biopsy (SLNB) was included to evaluate it as a method for staging the node-negative neck. Methods: A retrospective study design was chosen, and 50 patients who were treated from 1973 to 2015 in our institution for primary HNMM were included. The Kaplan-Meier method was used to estimate survival rates. Uni- and multivariate analyses were used to study the influence of possible risk factors on the patients' outcome. These risk factors included patient demographics, tumor characteristics, and treatment modalities. Results: All patients were treated surgically and 50% received adjuvant treatment. The median disease specific survival (DSS) was 38 months, with a 5-year survival rate of 44%. Positive surgical margin (p = 0.004) and distant failure (p = 0.005) were associated with a worse DSS. The median disease-free survival (DFS) was 27 months, with a 5-year disease-free rate of 12%. Only tumor depth >5 mm (p = 0.002) was associated with a worse DFS. Five clinically node-negative patients received SLNB and only the two SLN-positive individuals suffered from distant failure. Radiotherapy, chemotherapy, and AJCC/UICC stage had no influence on any outcome measure. Conclusions: Positive surgical margin and distant failure are the only independent prognostic factors for DSS. Tumor depth can predict distant failure. SLNB may be a valuable staging tool for the node-negative neck.
... The median age of the studied population was 65 years, with a range of 24e93 years. This wide range and high median age is consistent with the published literature (Jethanamest et al., 2011;Meleti et al., 2008), and reminds us that mucosal melanoma is a disease of the elderly but should not be ruled out in the young. Although some studies have shown a sex predominance (Patel et al., 2002;Meleti et al., 2008), large cohort studies have reported a similar incidence in both sexes (Nandapalan et al., 1998;DeMatos et al., 1998). ...
... This wide range and high median age is consistent with the published literature (Jethanamest et al., 2011;Meleti et al., 2008), and reminds us that mucosal melanoma is a disease of the elderly but should not be ruled out in the young. Although some studies have shown a sex predominance (Patel et al., 2002;Meleti et al., 2008), large cohort studies have reported a similar incidence in both sexes (Nandapalan et al., 1998;DeMatos et al., 1998). Our study population was no exception in this regard, so in agreement with most of the existing literature we could not find a gender-related difference in survival (Chan et al., 2012). ...
... Our own data showed a higher local and regional recurrence rate for OMM, but like most study groups we found that both subsites shared a similar overall and diseasespecific survival (Jethanamest et al., 2011;Lawaetz et al., 2016;Patel et al., 2002;McLean et al., 2008;Prasad et al., 2003). In contrast, Meleti et al. found that OMM had a significantly better 5year disease specific survival than SNMM, a finding that could only partly be explained by a higher percentage of deep tissue infiltration in the SNMM group (Meleti et al., 2008). Due to a very large sample size, Jethanamest at el. were able to conduct a subsite analysis and found that nasal cavity and oral cavity indeed share the same prognosis, but that the nasopharynx, oropharynx, and paranasal sinus do each have a significantly shorter survival value. ...
... Patients with OMM have a poor prognosis, regardless of treatment management, whether it is radical surgery alone or with adjuvant radiotherapy [40]. This could be explained by an increased tendency of OMM to metastasis, and a late diagnosis due to the location, the oral cavity being an area less visible than the skin. ...
... Surgical treatment is seldom performed alone as most studies show a lower OS rate [16,40−42] except one [4]. Adjuvant radiotherapy, chemotherapy or radio chemotherapy were performed with a 5year OS rate similar between those alternatives [40]. Melanoma is deemed as a radioresistant tumor, and mucosal melanoma, including OMM, are also considered as such [45]. ...
... Postoperative radiotherapy has been shown to improve local control without reducing the occurrence of distant metastasis. Indeed, 57.9% or patients treated with surgery alone presented with local failure versus 26.3% for those treated with surgery and postoperative radiotherapy [40]. Radiotherapy alone is limited to patients who cannot benefit from surgical treatment and survival is low [23,40], except in the Naganawa et al. study on inoperable patients were 3-year and 5-year OS rates were 68.4% and 57.4%, respectively [19]. ...
Article
Oral mucosal melanoma (OMM) is the subject of few studies, resulting in a lack of understanding. The aim of this study is to review the current literature on OMM. The term searched was “oral mucosal melanoma” between 01/01/2000 and 03/15/2021 in the PubMed Database (MEDLINE). Patients presenting with OMM and treated in our center between January 2009 and January 2020 were included in a case series. Demographics, location, risk factors, genetic mutations, treatment performed, and overall survival (OS) rates were evaluated. The PubMed database search yielded a total of 513 results, thirty-eight articles were finally included, which amounted to 2230 cases of OMM. 13 patients were included in the case series. A male-to-female ratio of 1.28:1.00 was found with a mean age at first diagnosis of 58.2 years old. Hard palate (1060 cases) and then gingiva (794 cases) were the two main locations. No risk factors could be identified. OMM were staged III or IV at diagnosis. Mutations were described as such: KIT in 14.6% of cases, BRAF in 7%, and NRAS in 5.6%. Treatment protocols varied but radical surgery was the cornerstone treatment associated with adjuvant therapies. Immunotherapy has not been evaluated for OMM. OS rates were 43.4% at 3 years, 33.1% at 5 year and 15.4% at 10 years. OMM show distinct features from cutaneous melanoma (CM): typical locations, no identified risk factors, different mutations profile, worse prognosis with advanced stage at diagnosis. Targeted therapies are still underused compared to CM.
... The main limitations were that only two studies 30,32 performed a prospective data collection (n = 103, 11%), and that less than half of patients (n = 448, 47.9%) were consecutively enrolled. In addition, only two case series 27,33 (n = 180, 19%) belonged to multi-center studies. ...
... Amit et al found that SNMM regional metastasis are more frequent in the ipsilateral levels I (56.6%) and II (35.8%), with a low rate of metastasis on the contralateral site. Another two papers 27,31 reported similar results, but the SNMM node metastases pattern could not clearly defined due to low sample. From this perspective, further studies are indeed suggested to clarify which levels should be included in a hypothetical END. ...
Article
Purpose: To systematically analyze the regional disease control after sinonasal mucosal melanoma (SNMM) primary treatment. Methods: The study was performed according to the PRISMA guidelines searching on Scopus, PubMed/MEDLINE, Cochrane Library, and Google Scholar databases. Results: A total of 15 studies with 936 patients (median age: 68.0 years, IQR 65-71) were included. Overall, the cumulative regional recurrence rate (RRR) was 18.4% (n = 917, 99% CI: 14.0%-23.4%), with a median follow-up of 30.0 months (n = 765, IQR 22.0-37.0). The RRR in clinical node negative patients was 17.0% (99% CI: 12.2%-22.5%), with a median follow-up of 22.0 months (n = 327, IQR 21.5-31.5). Conclusions: The RRR of SNMM after primary treatment is not to be neglected. Further prospective studies should be encouraged to clarify if elective treatment of the neck could be recommended at least in a subgroup of patients.
... While cutaneous forms represent the most common type of melanoma in humans, melanoma of the oral cavity is uncommon but aggressive with high metastatic rate, high local recurrence rate and poor clinical outcome. 28,29 Unfortunately, in both humans 30 and dogs, 31-33 the conventional cytotoxic chemotherapy plays an uncertain role in the treatment of malignant oral mucosal melanoma. MLN4924 is a novel first-class NAE inhibitor that has potent activity in malignant melanoma in people. ...
Article
MLN4924 (pevonedistat) is a potent and selective NEDD8‐activating enzyme (NAE) inhibitor. The NEDD8‐regulated neddylation system is responsible for the regulated degradation of intracellular proteins with important cellular functions in cancer cell growth, apoptosis, angiogenesis and metastasis. In human melanoma, inhibition of NAE results in induction of DNA re‐replication, S phase cell cycle arrest, DNA damage and apoptosis. The study aimed to assess the anti‐cancer effect of MLN4924 on canine malignant melanoma cell lines and patient samples and to elucidate the underlying mechanisms. Canine melanoma cell lines and primary patient samples were evaluated for cell viability after incubation with varying concentrations of MLN4924 or DMSO. Apoptosis, cell proliferation and senescence assays were performed to address underlying mechanisms of MLN4924‐ mediated anti‐tumor effects. Gene expression of 7 previously identified deregulated genes in human melanoma were compared in sensitive versus resistant samples. MLN4924 treatment significantly reduced the viability of canine melanoma cell lines and primary samples in a dose‐ and time‐dependent manners. MLN4924 promoted cell apoptosis and inhibited cell growth through induction of DNA re‐replication and cell senescence. While the majority of canine melanoma samples demonstrated sensitivity at nanomolar ranges, some samples were resistant to the treatment. Modulation of P21 levels correlated with canine melanoma cell sensitivity. These results provided justification for further exploration of MLN4924 as a treatment of canine melanoma. This article is protected by copyright. All rights reserved.
... Le mélanome muqueux constitue une forme rare mais en forte incidence chez l'homme ( Marcus et al, 2012). Localisé principalement dans le sinus nasal (plus de 73% des cas), il a un comportement agressif, avec des rechutes fréquentes et variables selon le traitement préconisé (26-58%) ( Gavriel et al, 2011) et des métastases ganglionnaires (21-58%) et à distance (53% des cas) ( Meleti et al, 2008). L'altération du gène Cdkn2a constitue chez l'homme comme chez le chien un facteur de prédisposition important ( Gillard et al, 2014 ;Haass et al, 2010). ...
Thesis
Full-text available
En recherche et développement pharmaceutiques un candidat thérapeutique doit passer plusieurs barrières précliniques afin de déterminer certains paramètres pharmacocinétiques et pharmacodynamiques avant toute administration à l’homme. Malgré les efforts investis en R&D ces dernières années, l’industrie du médicament a souffert d’un ralentissement dans le développement de nouvelles molécules innovantes. Car avant sa mise sur le marché, tout candidat doit justifier de la sécurité liée à son utilisation mais aussi de sa balance bénéfice/ risque. Les modèles standards utilisés en développement en oncologie ne sont pas assez prédictifs et bien souvent non-adaptés, avec une niche tumorale inexistante. C’est pourquoi il est aujourd’hui essentiel de travailler sur des systèmes plus sensibles et mimant plus fidèlement la pathologie humaine afin d’obtenir des médicaments plus efficaces et moins toxiques pour une meilleure prise en charge. L’utilisation du modèle spontané de cancers comme approche prédictive en oncologie comparée a été rapportée par plusieurs équipes à travers le monde. En effet, les fortes similitudes au niveau histologique, moléculaire et clinique rapportées entre les tumeurs humaines et canines, font de ce modèle un allié essentiel pour l’optimisation du développement pharmaceutique chez l’homme ayant un bénéfice réciproque à la fois à la médecine humaine et vétérinaire.Chez l’homme, les mélanomes constituent l’une des formes les plus agressives des cancers cutanés. Ils représentent 4 à 11% des néoplasies cutanées et seulement 2% des cancers de l’épiderme. Ce sont des tumeurs très immunogènes et de très mauvais pronostic au stade métastatique contribuant au développement d’une réponse immunitaire anti-tumorale bien souvent responsable d’échappements et de résistances au traitement. Et malgré l’amélioration de 50 à 80% de la survie globale à 5 ans ces vingt dernières années, son incidence ne cesse d’augmenter et environ 7000 cas sont rapportés chaque année en France avec plus de 75% de décès liés à ces tumeurs.Bien que rares, ces tumeurs représentent 7% des cancers diagnostiqués chez le chien et environ 160000 cas sont recensés chaque année au niveau mondial. Sa localisation est buccale dans plus de 50% des cas. C’est aussi l’un des cancers les plus agressifs chez le chien, avec une survie globale post-opératoire de 173 jours associé à des métastases ganglionnaires et pulmonaires le plus souvent.Le but de ce travail a été la validation préclinique et clinique du modèle tumoral spontané canin dans la compréhension des mécanismes de cancérogenèse, de dormance tumorale et de développement thérapeutique. Validation préclinique, dans un premier temps via le développement et la caractérisation de modèles cellulaires et murins de mélanomes canins. Puis, dans un second temps, la validation clinique par le biais d’essais thérapeutiques chez le patient chien.A partir de prélèvements issus de deux profils cliniques distincts, deux lignées cellulaires de mélanome canin ont été développées et caractérisées sur le plan pharmacologique, génomique et fonctionnel. Une liste d’altérations génétiques a été établie sur ces deux profils en accord avec la littérature et présentant des points communs avec la pathologie humaine. De plus, il est bien établi que l’hétérogénéité tumorale est responsable de résistances au traitements conduisant aux rechutes, c’est pourquoi nous nous sommes par la suite intéressés à l’étude des populations souches tumorales au sein de notre modèle et à l’identification de marqueur permettant le ciblage de ces cellules pouvant contribuer ainsi à l’avancement de l’enrichissement de l’arsenal thérapeutique oncologique.En conclusion, le patient chien est doté d’un système immunitaire intact et d’une niche tumorale complète, constituant ainsi un système in-vivo très intéressant pour l’homme, pouvant contribuer à avancer la recherche et améliorer grandement nos connaissances sur cette pathologie.
... Retrospective studies have compared the treatment outcomes of mucosal melanoma patients who underwent surgery alone with those of patients who underwent surgery plus RT [2,4,49,50,[60][61][62]. Most authors argue that postoperative RT has a role in improving locoregional control; however, no data have shown that postoperative RT conveys an overall survival benefit [4,31,43]. ...
Article
Full-text available
Sinonasal mucosal melanoma (SNMM) is a rare oncological entity that comprises most head and neck mucosal melanomas. SNMM has distinctive genetic background, different from cutaneous melanoma. Survival outcomes among SNMM patients are poor; while there is no clear consensus on the optimal management of SNMM, the primary treatment modality is generally considered to be wide surgical excision, and radiation therapy (RT) is often used in the postoperative adjuvant setting to improve locoregional control. Systemic therapies have demonstrated little or no survival benefit, and most SNMM patients die of distant metastatic disease. Owing to the rarity of the disease, the literature describing treatment approaches for SNMM is lacking and largely limited to isolated case reports and retrospective series. Here, we describe contemporary diagnostic and therapeutic approaches to SNMM based on the most recent molecular and outcome data.
... As stated, mucosal melanomas are found to be primary or secondary in nature. Primary mucosal melanomas are usually seen in older populations with an average age of 70 years and accounts for one percent of all melanomas [5][6][7]. Primary sites of mucosal melanomas can also occur along the gastrointestinal tract, however; they are more commonly in the oropharynx [ [3,8]. ...
Article
Full-text available
Considered to be rare, mucosal melanomas are rare type of melanoma that are found on mucosal surfaces and are primary or metastatic in origin. We report a case of a 66-year-old Hispanic female who presented with vague abdominal pain and upon further endoscopic work-up revealed 2 gastric lesions. Endoscopic biopsy results revealed gastric melanoma in the distal lesion. A PET/CT scan indicated it to be suspicious for the primary site of metastasis but was ultimately diagnosed as a benign nevus on biopsy. An extensive clinical exam showed no other probable sites of origin. The patient underwent a subtotal Billroth II gastrectomy and enterostomy tube placement for temporary feeding. Primary melanoma of the stomach is an exceptionally rare occurrence with limited cases that can be accounted for in literature; thus we report this case for review.
... Human mucosal melanoma is an aggressive histological subtype that is predominantly BRAF, RAS, and NF1 wild type (Triple Wild Type or TWT) with occasional mutations in KIT or NRAS. It carries a five-year survival rate between 12.3% and 35.3% [17][18][19][20][21][22][23][24][25][26]. Study of this subtype is limited by its low prevalence, accounting for only 1-2% of human melanomas in the United States with as few as 1,500 cases per year [27]. ...
Article
Full-text available
Canine malignant melanoma, a significant cause of mortality in domestic dogs, is a powerful comparative model for human melanoma, but little is known about its genetic etiology. We mapped the genomic landscape of canine melanoma through multi-platform analysis of 37 tumors (31 mucosal, 3 acral, 2 cutaneous, and 1 uveal) and 17 matching constitutional samples including long- and short-insert whole genome sequencing, RNA sequencing, array comparative genomic hybridization, single nucleotide polymorphism array, and targeted Sanger sequencing analyses. We identified novel predominantly truncating mutations in the putative tumor suppressor gene PTPRJ in 19% of cases. No BRAF mutations were detected, but activating RAS mutations (24% of cases) occurred in conserved hotspots in all cutaneous and acral and 13% of mucosal subtypes. MDM2 amplifications (24%) and TP53 mutations (19%) were mutually exclusive. Additional low-frequency recurrent alterations were observed amidst low point mutation rates, an absence of ultraviolet light mutational signatures, and an abundance of copy number and structural alterations. Mutations that modulate cell proliferation and cell cycle control were common and highlight therapeutic axes such as MEK and MDM2 inhibition. This mutational landscape resembles that seen in BRAF wild-type and sun-shielded human melanoma subtypes. Overall, these data inform biological comparisons between canine and human melanoma while suggesting actionable targets in both species.
... Adjuvant postoperative radiotherapy in stage III/ IVa disease appears to improve locoregional recurrence (level of evidence, 2C) but without improvement in the rate of distant metastasis. 95 Chemotherapy is palliative and has not been shown to improve survival. The use of immunotherapy in the management of metastatic OMM has not been as well investigated as in cutaneous melanoma; however, case series using PD-1 inhibitor alone or in combination with ipilimumab has demonstrated benefits. ...
Article
The second article in this continuing medical education series discusses the clinical and histopathologic features of common premalignant and malignant lesions of the oral cavity. It is imperative for dermatologists to be able to appropriately recognize suspicious lesions, determine the need to obtain a biopsy specimen, counsel, and refer patients presenting with premalignant or malignant conditions. Given the higher rates of mortality and morbidity of oral mucosal malignancies because of late diagnosis, appropriate treatment with multidisciplinary care in a timely manner is essential to patients with these neoplasms.
... Adjuvant postoperative radiotherapy in stage III/ IVa disease appears to improve locoregional recurrence (level of evidence, 2C) but without improvement in the rate of distant metastasis. 95 Chemotherapy is palliative and has not been shown to improve survival. The use of immunotherapy in the management of metastatic OMM has not been as well investigated as in cutaneous melanoma; however, case series using PD-1 inhibitor alone or in combination with ipilimumab has demonstrated benefits. ...
Article
A diverse spectrum of benign oral mucosal lesions exists, presenting as either isolated oral findings or in association with dermatologic conditions. Oral lesions can closely resemble one another; therefore, it is important for clinicians to be able to recognize their distinctive features, to be able to recognize benign versus malignant disease, and to recognize when obtaining a biopsy specimen is warranted. The first article in this continuing medical education series reviews oral anatomy, the clinical attributes of several benign lesions of the oral cavity, and appropriate management and therapeutic modalities.
... In humans, melanoma is one of the most aggressive types of cancer. Whereas cutaneous forms represent the most common cases, melanoma of the oral cavity is rare but very aggressive, highly metastatic [1] and associated with frequent relapse and poor outcomes [2]. These forms mainly arise in the sino-nasal cavity (more than 73% of cases) and are highly immunogenic tumors contributing to an immune anti-tumor reaction that can lead to tumor escape and resistance to most standard treatment protocols [3]. ...
Article
Full-text available
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. Electronic supplementary material The online version of this article (10.1186/s12885-018-5114-y) contains supplementary material, which is available to authorized users.
... In the present study, the 3-year OS rate was 44.4%, which is consistent with previous reports. [23][24][25] Although primary surgery with postoperative radiotherapy with or without AC yielded an excellent local control, we must note that the survival of HNNM was not sufficient enough. Considering that more than 50% of patients suffered distant metastasis within 3 years, the lack of long-term survival benefit from local therapy is likely because of distant metastasis being the major limiting factor. ...
Article
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Background: There still remains no well-established treatment strategy for head and neck mucosal melanoma (HNMM). We aim to evaluate the effectiveness and safety of primary surgery with postoperative radiotherapy for this disease. Patients and methods: A single-arm, Phase II clinical trial was conducted at Sun Yat-Sen University Cancer Center. Patients with nonmetastatic, histologically proven HNMM were prospectively enrolled. Patients received primary surgery followed by intensity-modulated radiotherapy with an equivalent dose at 2 Gy per fraction of 65–70 Gy to CTV1 (high-risk regions including tumor bed) and 50–55 Gy to CTV2 (low-risk regions). Additional use of adjuvant chemotherapy (AC) depended on consultation from a multidisciplinary team. This trial is registered with ClinicalTrials.gov, number NCT03138642. Results: A total of 33 patients were enrolled and analyzed between July 2010 and November 2016. There were 18 (54.5%) patients with T3 disease and 15 (45.5%) patients with T4a disease. The median age at diagnosis was 58 years (range 27–83 years), and 61% of the cohort were males. The overall median follow-up duration was 25.3 months (range 5.3–67.1 months). The 3-year overall survival (OS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were 44.4, 91.7, 78.1, and 41.7%, respectively. Patients with T4a disease showed significantly inferior OS (P=0.049) and DMFS (P=0.040) than those with T3 disease. Prophylactic neck radiation (PNR) was nearly associated with superior RRFS (P=0.078). However, there was no significant difference in OS, LRFS, RRFS, and DMFS for patients treated with or without AC (P>0.05 for all). Toxicities were generally mild to moderate. Conclusion: Primary surgery with postoperative radiotherapy yielded excellent local control and acceptable toxicity profile for HNMM. Nevertheless, high rates of distant metastases resulted in limited survival.
... 13 Despite of aggressive surgery, recurrence develops in 29-79% of patients. 14,15 Radiotherapy can be used for locoregional control. Despite of that, no significant effect has been specified on survival. ...
... Treatment of lacrimal sac mel- anomas is wide local surgical excision associated to adjuvant radiotherapy to prevent local recurrence. 13 However, regional and distant metastases can occur due to the vascular connec- tions of mucosal tissues. 14,15 ...
... Obtaining negative pathological margins can be a challenge due to constraints depending on anatomic site and the lentiginous, multifocal pattern of growth. Even with negative margins, local recurrence is common, as are distant metastatic recurrences (21,22). Moreover, there can be considerable morbidity associated with extensive surgery due to the anatomic sites involved. ...
Article
Full-text available
Acral and mucosal melanomas (MM) are rare subtypes of melanoma that are biologically and clinically distinct from cutaneous melanoma. Despite the progress in the treatment of cutaneous melanomas with the development of targeted and immune therapies, the therapeutic options for these less common subtypes remain limited. Difficulties in early diagnosis, the aggressive nature of the disease, and the frequently occult sites of origin have also contributed to the poor prognosis associated with acral and MM, with substantially worse long-term prognosis. The rarity of these subtypes has posed significant barriers to better understanding their biological features and investigating novel therapies. Consequently, establishing standardized treatment guidelines has been a challenge. In this review, we provide a brief overview of the current knowledge regarding acral and MM, focusing on their epidemiology, genetic backgrounds, and unique clinical characteristics. Further discussion centers around the management of primary and advanced disease and the role of emerging targeted and immune therapies for these subtypes, specifically focusing on issues relevant to medical oncologists.
... therapy are controversial. [6][7][8] Most patients will experience persistent disease or recurrence, for which treatment options are limited. Distant metastasis is the most common cause of treatment failure, having been reported in 35% of patients. ...
Article
Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic (p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57–0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25–1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.
... Several similar biological and clinical features have been reported between canine melanoma and the corresponding human cancer [8]. In humans, mucosal melanoma of the oral cavity is rare but is highly aggressive and metastatic [9], with frequent relapse and poor outcomes [10]. Recently, we isolated and characterized two canine oral melanoma cell lines (OCR_OCMM1 and OCR_OCMM2) from spontaneous mucosal melanoma tumors from canine patients with distinct clinical profiles and metastasis patterns [11]. ...
Article
Full-text available
Mucosal melanoma represents one of the most highly metastatic and aggressive subtypes of melanoma. The biology of mucosal melanoma is poorly documented, and the lack of experimental models makes it difficult to design and test new therapies. Dogs are frequently affected by melanomas of the oral cavity, making spontaneous canine melanoma a potentially predictable model for their human counterpart. We recently established and characterized two new canine mucosal melanoma cell lines named OCR_OCMM1 and OCR_OCMM2. Here, we identified quiescent cancer stem cell (CSC) subpopulations in both canine cell lines that displayed similarities to human quiescent CSCs: canine melanoma CSCs had the ability to self-renew, produced non-stem cell (SC) progeny and formed melanospheres that recapitulated the phenotypic profile of the parental tumor. These CSCs also formed melanoma in immunodeficient mice, and the inhibition of PI3K/AKT signaling expanded the CSC pool. A subset of non-CSCs transitioned to become CSCs. OCR_OCMM1 and OCR_OCMM2 displayed different CSC compartment behaviors in regard to their initial size and expansion abilities. Collectively, this study showed that the OCR_OCMM1 and OCR_OCMM2 canine melanoma cell lines are powerful cellular tools to study melanoma SCs, not only for mucosal but also for the more common human cutaneous melanoma.
... The systemic treatment is evolving, many trials investigating the adjuvant treatment with interferonalpha (IFN-α) showed an improvement of the survival rate [22]. The use of immunochemotherapy and BRAF inhibitors are still under trials [23]. ...
Article
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The melanoma, having its origin in the melanocyte cells, is one of the most aggressive forms of skin cancer in the world with one of the highest rates of brain metastasis. The incidence of cutaneous melanoma in the Mediterranean countries varies from three to five cases∕100 000 people∕year. Its prognosis is based on an early diagnosis. Sinonasal mucosal melanoma (SNMM) is an extremely rare tumor, accounting for 0.3-2% of all melanomas. The non-specific symptomatology is often delaying the presentation of the patient at the hospital and therefore the diagnosis. The SNMM is a highly aggressive tumor, and the presence of metastasis at the diagnosis usually implies a poor prognosis. The management of the melanomas requires a precise pre-therapeutic assessment and a multidisciplinary approach for the diagnosis, with surgical treatment or radiotherapy required in order to ensure a better a quality of life. In this paper, we retrospectively analyzed two cases of mucosal melanoma and one case of cutaneous melanoma of the nose.
... The multidisciplinary approach for the optimal management of treatment choices, side effects, and follow-up is recommended for MM, especially the T4b disease of the head and neck [54]. A multidisciplinary team (MDT) comprised of surgeons, medical oncologists, radiotherapists, radiologists, and pathologists is of particular importance for clinical decision-making in tricky cases when a tumor is technically resectable at the risk of a highly morbid surgery, exemplified by a massive sinonasal melanoma that requires facial reconstruction. ...
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Purpose of Review This review mainly focuses on the unique features and the development of available therapeutic options for mucosal melanoma in different treatment settings, i.e., neoadjuvant, adjuvant, and palliative. Recent Findings Mucosal melanoma is distinct from cutaneous melanoma in epidemiology, clinical features, and molecular landscape, characterized by more aggressive biological behavior, lower mutational burden, more chromosomal structure variants, unique driver mutation profile, and distinct tumor microenvironment. Systemic therapy is generally less effective to mucosal melanoma than its cutaneous counterpart. Therapeutic landscape for mucosal melanoma has evolved substantially in recent years: with new targeted therapy options as well as combination therapies built on the backbone of anti-PD-1/PD-L1 antibodies available (esp. anti-angiogenic agent and PD-1/PD-L1 combination), which, based on early phase trial data, seem to be promising. Summary Mucosal melanoma is unique and distinct from cutaneous subtype. Unraveling the unique features of mucosal melanoma is a key to improve clinical outcomes.
... when compared to 1:1.2 ratio seen in cutaneous melanoma [1]. Also, head and neck MM has been observed in younger population [12,13]. G.I. mucosal melanomas are usually diagnosed late, have a more aggressive course due to the rapid lympho-vascular spread, and hence are associated with poorer outcomes [14][15][16]. ...
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Aim Gastrointestinal malignant melanoma is a rare mucosal melanoma (MM). Other MM include the respiratory and the genitourinary tract. All mucosal melanomas have a poor prognosis when compared to cutaneous melanomas. Ano-rectal melanomas are by far the most common and most studied gastrointestinal MM. Large-scale clinical data is lacking due to the rarity of the disease. We aim to analyze epidemiology and survival of the Gastrointestinal (G.I.) MM over 45 years using a national database. Methods The Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients with biopsy-proven G.I. Melanomas. We selected tumor site, intervention, and survival information for oncology codes as per the international classification of diseases. Survival analysis was performed using the SPSS v 27 ® IBM software. Results Of the 1105 biopsy-proven confirmed cases of primary G.I. melanoma's, 191 (17.3%) received chemotherapy (C.T.), 202 (18.3%) received radiotherapy (R.T.), 63 (5.7%) received both C.T and R.T., while 684 (61.9%) of the population received surgery alone or combined with C.T. and/or R.T. Statistically significant improvement in survival was noted in all treatment strategies that utilized surgery and also when site-specific MM cohorts underwent a surgical approach with or without C.T and/or R.T. Conclusion This is the most extensive study reporting epidemiological and survival data of treatment strategy outcomes of primary G.I. mucosal melanoma elucidating best overall survival with a management strategy involving surgical intervention.
... Meleti et al. reported local recurrence occurred in 57.9% and 26.3% of patients with "surgery alone" and "surgery and adjuvant radiotherapy," respectively. The rates of distant metastases were just over a half (52.6%) of patients with "surgery alone" and close to one-half (47.3%) in patients with "surgery and adjuvant radiotherapy" [14]. In a systematic review, the local, regional and distant recurrences rates were 19-61%, 7-36%, and 18-76%, respectively [8]. ...
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Introduction Mucosal melanoma of paranasal sinuses is a rare disease with a challenging treatment and a poor prognosis. In this paper, we reported the successful multimodality treatment of malignant mucosal melanoma of frontal sinus. Case presentation A 65-year-old female presented with a frequent nosebleed for one month before admission. Computed tomography and magnetic resonance imaging showed a mass in the right frontal and ethmoidal sinuses with adjacent bone erosion and right orbit invasion. Biopsy revealed malignant melanoma. No metastasis was found. The definitive diagnosis was malignant mucosal melanoma of paranasal sinuses AJCC stage IVb (T4bN0M0). We used right frontobasal craniotomy to resect tumor for local control of the disease. Immunohistochemical staining was Melan A(+), S100(+), and HMB45(+). A week postoperative, she received adjuvant radiotherapy and immunotherapy (pembrolizumab). For three months postoperative, the patient had no recurrence and metastasis, no headache and no new neurological deficits. She returned to her daily activities. Clinical discussion Mucosal melanoma of paranasal sinuses is usually aggressive and diagnosed at an advanced stage. Management options are surgery, radiation therapy, chemotherapy, and immunotherapy. These options were performed on a case-by-case basis and depend on the extent and location of the tumor. Despite that, the prognosis remains very poor, with a high rate of local recurrences and distant metastases. Therefore, post-treatment lifetime and frequent follow-ups are highly recommended. Conclusion The critical issues in management of mucosal melanoma are early diagnosis, multimodality treatment, and frequent follow-ups.
... За дефиниране на оптималното лечeбно поведение от значение е ТNМ класификацията (различна от кожните меланоми), определяща биологичното развитие на мукозните меланоми [2]. Лечебен метод на избор за оралните мукозни меланоми е радикалната хирургия (с чисти резекционни ръбове) [1, 2, 10,17,19,[22][23][24]. Хирургичната резекция е метод на първи избор и за синоназалните меланоми [14,15]. ...
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Summary Background: Primary sinonasal malignant melanoma represents a rare entity with poor prognosis. In order to increase the diseasefree survival complex treatment approach is recommended (incl. surgery, postoperative radiotherapy (RT) and combined chemotherapy (CCT). Methods: A clinical case of a 64-year old male patient with locally advanced sinonasal malignant amelanotic melanoma with a 2-year follow-up is presented. The optimal treatment strategy is discussed, based on the literature review. Results: In a case of locally advanced sinonasal malignant amelanotic melanoma local tumoral control was achieved by using combined treatment modalities (surgery with mediofacial resection, postoperative RT, several courses of CCT and surgery again). After two years regional disease recurred with involvement of the contralateral neck lymph nodes. There was no evidence of distant spread. Conclusions: The late lymphatic spread of the mucosal melanoma points out the necessity of thorough staging of the neck lymph nodes already at first presentation. In locally advanced mucosal melanoma postoperative RT should be carried out. There is still no uniform opinion on the optimal radiation schedule, the fractionation, the overall dosis and the target volume. Keywords: sinonasal mucosal melanoma, nasal cavity, surgery, radiotherapy
... Also, patients treated with definitive radiotherapy had poorer OSR outcomes with respect to surgery or combined therapy (surgery plus radiotherapy) [31]. Despite the fact that it did not affect OSR, there are some data that show a beneficial effect of adjuvant radiotherapy on locoregional control [25,27,30,[37][38][39]. In contrast, other studies showed no impact of RT in locoregional control of disease [17,23,40]. ...
Article
Objective: Primary mucosal malignant melanoma of the head and neck (HN-PMMM) is an aggressive and uncommon neoplasm. Herein, we present a series of 33 patients and the results of treatment, and aimed to determine prognostic factors in HN-PMMM. Methods: Patients who were diagnosed as having HN-PMMM in our reference hospital, between 2005 and 2014 were evaluated. Thirty-three of these patients who had follow-up data were included. Surgical margin status was extracted from the original pathology reports. Archived materials were retrieved for the histopathologic findings: ulceration, necrosis, lymphovascular invasion, perineural invasion, pigmentation, and presence of an in situ component. Mitotic activity was evaluated using phosphohistone H3 (PHH3) immunohistochemical staining. Results: We found an association of PHH3 mitotic activity with overall survival in a univariate analysis and to our knowledge, this is the first report among the available case series of HN-PMMM to evaluate mitotic activity using immunohistochemical staining. We also investigated the relationship between multicentricity and locoregional recurrence, which the authors believe is also a first. Conclusion: PHH3 mitotic activity can be used a prognostic factor for head and neck mucosal malignant melanoma.
... Adjuvant radiation in head and neck mucosal melanoma can improve locoregional control 7,17,[22][23][24][25] and is recommended in the NCCN guidelines for T4a and strongly considered for T3 lesions. However, it has not been shown to have any survival benefit. ...
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Noncutaneous melanomas are rare subtypes of melanoma with high rates of metastatic disease and poor overall survival. One-third to one-half of cases are amelanotic, which may contribute to a delay in diagnosis. Immunohistochemistry staining with typical melanoma markers helps confirm the diagnosis. There is no standard staging system across mucosal melanomas. Elective nodal dissection is not recommended and there is a paucity of data to support use of sentinel lymph node biopsy. Mutational analysis should be routinely performed. Systemic therapy options include targeted inhibitors, immunotherapy, and cytotoxic chemotherapy, although further studies are needed to confirm their efficacy.
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Malignant melanomas (MMs) were the fifth most common cancer in men and the sixth most common cancer in women in 2018, respectively. These are characterized by high metastatic rates and poor prognoses. We systematically reviewed safety and efficacy of carbon‐ion radiotherapy (CIRT) for treating MMs. Eleven studies were eligible for review, and the data showed that MM patients showed better local control with low recurrence and mild toxicities after CIRT. Survival rates were slightly higher in patients with cutaneous or uveal MMs than in those with mucosal MMs. CIRT in combination with chemotherapy produced higher progression‐free survival rates than CIRT only. In younger patients, higher rates of distant metastases of gynecological MMs were observed. The data indicated that CIRT is effective and safe for treating MMs; however, a combination with systemic therapy is recommended to ensure the best possible prognosis for MMs.
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Primary mucous melanoma (MM) of the nasal cavity and paranasal sinuses remains a rare malignancy. The peak of incidence is between 50 and 60 years old, being epistaxis and unilateral nasal obstruction the most frequent symptoms. Surgical resection is the primary treatment with radiotherapy and adjuvant chemotherapy if necessary, the prognosis depends on the spreading. We present the case of an 81-year-old female patient attending for hemoptysis and halitosis of a year of evolution. The nasofibrolaryngoscopy showed a brownish, excrescent, irregular and friable lesion, outgrowth of the right tube rim. Histopathology result was nasopharyngeal MM. Immunohistochemical profile: S100 +, MelanA +, HMB45 +, SOX10 +, AE1AE3 negative. PET-CT showed a hypercaptation at the level of the right tube rim, without evidence of adenopathies or distant metastases. Complete tumor resection was performed by endoscopic surgery. Melanoma Oncology Committee decided no need of adjuvant therapy due to the complete resection of the lesion and considering the age and cognitive deterioration of the patient.
Article
Objectives To evaluate hospital-based data of head and neck mucosal melanoma patients in order to identify predictors of survival. Materials and methods The National Cancer Data Base was used to identify 1368 patients with head and neck mucosal melanoma diagnosed between the years of 2004 and 2012. The Kaplan-Meier method was utilized to estimate overall survival, and multivariate Cox regression analyses were performed to assess the impact of covariates on survival after adjusting for confounding variables. Results Median follow-up was 55.2 months. Median survival of all patients was 29.3 months, and the 5-year survival was 27.4%. After adjusting for other prognostic factors in multivariate analysis, paranasal sinus location [hazard ratio (HR) = 1.54, 95% Confidence Interval (CI) = 1.30–1.82, P < 0.001)] and the use of radiotherapy alone for definitive local treatment (HR = 2.27, 95% CI = 1.72–2.98, P < 0.001) were associated with worse survival. Similar results were seen in the subgroup of patients with complete clinical staging information. In terms of patterns of care, the use of combined surgery and radiotherapy as the primary local treatment modality has significant increased from 2004 and 2012 (P = 0.03). Conclusion Outcomes in mucosal melanoma of the head and neck remain suboptimal, despite increased use of multimodality local therapy, likely due to the high risk of distant metastases. Mucosal melanomas arising from the paranasal sinuses have particularly poor prognosis. Novel therapeutic paradigms for head and neck mucosal melanoma, incorporating systemic therapies to decrease the risk of distant relapse, should be pursued in clinical trials.
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The oral cavity of the dog can be the site of several types of pathology including both benign and malignant lesions. The aim of this study was to analyze the frequency and clinical-pathological characteristics of oral lesions present in a cohort of Portuguese dogs. A retrospective observational cross-sectional study on 704 canine oral lesions submitted for histopathological diagnosis to a Veterinary Pathology Center in the north of Portugal from 2010 to 2017 was performed. Gender, age, location of the lesion and the histopathological diagnosis was analysed. From the 704 cases included, 307 (43.6%) were females and 397 (56.4%) males. The mean age was 9.53 ± 3.6 years-old (range 3 to 240 months). The site most frequently affected was the gingiva (n = 283; 40.2%). 342 (48.6%) cases were malignant neoplasms, most represented by oral melanoma (n = 129; 37.7%). 256 (36.4%) cases were benign neoplasms, most represented by fibromatous epulis of periodontal ligament origin/peripheral odontogenic fibroma (FEPLO/POF) (n = 208;81.3%). 106 (15%) were non-neoplastic lesions, most represented by gingival hyperplasia (n = 25, 23.6%). This study provides useful information about frequency and distribution of oral lesions in dogs over a period of eight years allowing valuable comparison with other countries and other species. The most common benign tumours were FEPLO/POF while oral melanoma was the most common malignant tumour.
Chapter
Radiotherapy works by inducing DNA damage in cancer cells, and there are several different methods of radiotherapy delivery including external beam radiotherapy, stereotactic radiosurgery, stereotactic body radiotherapy, radiospheres, brachytherapy, and particle therapy. Historically, melanoma has been deemed a radioresistant tumor, due to early in vitro studies demonstrating a broad shoulder in cell survival curves as well as a high repair rate, inferring a better tumor response with higher radiation doses. For this reason, hypofractionated regimens have become commonplace in the treatment of melanoma given the tolerability, convenience, and low risk of late effects. Nonetheless, in the treatment of primary melanoma, maximal safe surgical resection offers the greatest likelihood of local control. Radiotherapy as a primary treatment is often offered in well-defined situations, such as medical inoperability due to patient comorbidities or tumor location. Clinically, radiation oncologists most frequently see patients with melanoma for consultation in regard to palliation of metastatic disease (for example, stereotactic radiosurgery for brain metastasis or stereotactic body radiotherapy for lung metastasis). The multiple advancements (including technological developments as well as evolution of systemic therapy and immunotherapy) in the treatment of patients with melanoma highlight the importance of multidisciplinary management in this disease.
Chapter
This chapter discusses the range of oral cavity precursor lesions, the many histologic variants of oral squamous carcinoma, the Risk Model, resection margin assessment, and summarizes the new staging criteria (8th AJCC). Kaposi’s sarcoma is also discussed here, as the oral cavity is the most common extra-cutaneous site for this tumor.
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Purpose of review: This review describes the long scientific background followed to design guidelines and everyday clinical practice applied to melanoma patients. Surgery is the first option to cure melanoma patients (PTS) at initial diagnosis, since primary cutaneous lesions are usually easily resectable. An excisional biopsy of the lesion, with minimal clear margins, can be obtained in the vast majority of cases. Punch biopsies may be proposed only in case of large lesions located on specific cosmetic or functional areas like the face, extremities, or genitals where a mutilating complete resection would not be performed without prior histological diagnosis. Recent findings: After the histologic confirmation of melanoma, definite surgical excision of the scar and surrounding tissue is planned, to obtain microsatellite free margins. The width of these margins has been identified following the results of several clinical trials and it is either 1 or 2 cm, depending on the Breslow thickness of the primary tumor. Following the latest staging system proposed by the American Joint Cancer commission (AJCC), a sentinel node biopsy (SNB) is usually performed in case of a primary lesion > 0.8 mm thickness or for high-risk thinner lesions, if no evidence of nodal involvement has been identified clinically or radiographically. Surgical management of primary melanoma is well established. There is debate on the optimal surgical margins for 1-2 mm melanomas. There are specific considerations for special primaries (bulky, extremity, mucosal). Sentinel node (SN) evaluation does not improve survival, but is routinely used as staging.
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Introducción: Los melanomas de mucosa nasosinusales, representa una de las patologías de menor proporción en las tumoraciones de nariz y senos paranasales y como consecuencia diagnósticos tardíos. Reporte de caso: paciente masculino de la sexta década de la vida, que inicio con cuadro de obstrucción nasal y epistaxis leve, fue enviado para su valoración nuestro hospital de tercer nivel, donde se sometió a biopsia, presentando el resultado histopatológico de melanoma de mucosa nasal. Conclusión: las lesiones se presentaron principalmente como epistaxis y obstrucción nasal, involucraron a la cavidad nasal y senos paranasales y el lado izquierdo fue el más común involucrado. Los estadios de la enfermedad avanzada y metástasis a distancia se presentaron con gran frecuencia y en general con una pobre supervivencia a 5 años.
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Objectives: To analyze head and neck mucosal melanoma (MM) treatment patterns, and their association with survival, relative to National Comprehensive Cancer Network (NCCN) guidelines. Material & methods: Adult head and neck MM patients with clinically-staged T3/4aN0 disease were identified in a retrospective analysis of the National Cancer Database (2010-2014) and stratified into sinonasal cavity (SN) and oral cavity, oropharynx, larynx, or hypopharynx (non-SN) cohorts. Results: We identified 353 SN and 79 non-SN MM cases. The majority of patients were treated with surgery (SN: 92.4%; non-SN 84.8%), within NCCN guidelines. Treatment within the non-SN MM NCCN recommendation of elective neck dissection (END) was approximately 26.6%. END is not recommended for SN MM and was not performed in 91.5% of cases. Radiotherapy (RT) is recommended in both SN and non-SN MM and was utilized in 63.5% of SN patients and 46.8% of non-SN patients. END was not independently associated with OS compared to surgery alone (SN HR: 1.350 [95% CI: 0.733-2.485]; non-SN HR: 3.460 [95% CI: 0.912-13.125]). RT was independently associated with improved OS in SN MM cases (HR: 0.679 [95% CI: 0.479-0.963]), but not in non-SN MM cases (HR: 0.824 [95% CI: 0.331-2.051]). Conclusion: The majority of patients with head and neck MM are not treated within NCCN guidelines. The use of recommended END in non-SN patients is low. Similarly, adjuvant RT utilization is low. Our analysis shows that while greater use of RT may increase survival rates in this disease, the utility of END is unclear.
Article
Objectives/Hypothesis The ideal strategy in the treatment of mucosal melanoma of the head and neck (MMHN) remains unclear. Our objective was to evaluate the importance of surgical margins, radiotherapy, and systemic therapy in MMHN. Study Design Retrospective Single Institutional Review. Methods Retrospective review of patients with MMHN treated at a tertiary care oncology center between 1999 and 2016. Results Seventy‐six patients were included, 60 of whom were treated with curative intent. Negative or close margins compared with positive margins were associated with higher 3‐year overall survival (OS) (62% vs. 29% vs. 13% P = .012), disease‐free survival (33% vs. 29% vs. 4% P = .003), and distant control (48% vs. 29% vs. 22% P = .039). Cases with pre‐/postoperative radiotherapy had a marginally higher locoregional control versus without (69% vs. 59%, P = .117). Immunotherapy for recurrent and/or metastatic disease was associated with an increase in 3‐year OS (15% vs. 3% P = .01). Conclusion Achieving negative surgical margins is relevant in disease control. Despite small sample size, our data suggest that radiotherapy may enhance surgical outcomes. Immunotherapy has therapeutic benefit. Level of Evidence 3 Laryngoscope, 2021
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Context Unresectable colorectal hepatic metastases can be treated with radioembolization. Aims The aim of this study is to analyze the response and survival benefits of transarterial radioembolization (TARE) with Iodine-131 (¹³¹I) Lipiodol for hepatic metastases from gastrointestinal malignancies. Settings and Design Retrospective study of 20 patients with pathologically proven hepatic metastases from primary gastrointestinal malignancies referred for palliative therapy with TARE. Subjects and Methods At baseline, standard laboratory and imaging data were recorded. All patients fulfilling the inclusion/exclusion criteria underwent TARE with ¹³¹I Lipiodol. Post procedure, the patients were reviewed after 1 month with follow-up positron emission tomography–computed tomography and tumor marker levels to evaluate treatment response with continued follow-up till December 2016 and overall survival calculated. Statistical Analysis Used Data were analyzed using a statistical analysis package (Social sciences, version 15.0 for Windows; SSPS Inc.). Survival data were plotted using Kaplan–Meier survival curves. Results At the end of follow-up period, 15 of 20 patients were alive. The mean and median survival was 38.88 ± 5.0 months (95% confidence interval [CI], 29.03–48.74 months, P = 0.17) and 49.3 ± 12.4 months (95% CI, 25.0–73.7 months, P = 0.17), respectively. 66 months survival was 75%. Response evaluation in 10 patients showed partial response in 3 (30%), stable disease in 2 (20%) and progressive disease in 5 (50%) patients. All patients with partial response showed a reduction in serum tumor marker levels. Conclusions TARE with ¹³¹I-Lipiodol is highly effective with a significant survival benefit in refractory cases of hepatic metastases from gastrointestinal malignancies.
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Objective Sinonasal malignant melanoma is a relatively rare malignancy with poor prognosis, and effective treatments remain elusive. This analysis aimed to explore whether post-operative radiotherapy conferred any survival advantages in patients with this disease when compared with surgery alone. Methods Published studies were identified by searching four electronic databases. The endpoints evaluated were: rates of overall survival, disease-free survival and local control. Results Twenty-eight studies including 1392 patients were identified. The results indicated that post-operative radiotherapy led to a significantly better three-year overall survival rate ( p = 0.02), and suggested a borderline significant benefit for five-year overall survival ( p = 0.05), when compared with surgery alone. However, no statistical advantage was found for disease-free survival, local control or one-year overall survival. Conclusion This meta-analysis indicated that adjuvant radiotherapy prolonged survival, but showed no benefit for disease-free survival or local control.
Article
Introduction: Mucosal melanoma (MM) is a rare condition with a poor prognosis. Surgery is the corner stone of treatment, however, radiotherapy has been commonly employed as a treatment strategy and recent studies suggesting that survival outcomes may be improving are emerging. Methods: A systematic review and meta-analysis comparing risk ratios of radiotherapy and surgery and radiotherapy (SRT) with surgery for 5-year overall survival, local recurrence and distant metastasis in head and neck mucosal melanoma (HNMM). Results: SRT has a lower risk of death compared to surgery [RR 0.93 [95% CI = 0.87, 0.98] (P = .01)] and a reduced risk of local recurrence [RR 0.63 [95% CI = 0.48, 0.82] (P = .005)]. SRT has no effect on distant metastasis. Radiotherapy has worse survival when compared to surgery [RR 1.2 [95% CI = 1.03, 1.33] (P = .0006)]. Conclusions: SRT confers a moderate survival advantage in HNMM compared to surgery. This is most likely secondary to reduced local recurrence
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The management for mucosal melanoma of the head and neck is controversial in view of the poor prognosis. Thirty-five patients seen from 1955 to 1991 were analyzed retrospectively. Almost all (34/35) presented with localized disease. Primary treatments included radical surgery (15), local resection (11), radiation therapy (6), or systemic treatment (2). While the rate of local recurrence was high (27/34), only 5 patients developed distant disease before local relapse. Furthermore, only 5/21 achieved successful local salvage. Patients with their disease controlled locally had significantly longer survival than those with persistent local disease (P = .0001). The 5- year disease-specific survival was 45%. The authors conclude that mucosal melanoma of the head and neck is not necessarily incurable. When local control is achieved, survival rate is significantly improved. Aggressive local treatments should be initiated at presentation of this disease.
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Malignant melanoma rarely develops in the mucous membranes. Statistical data indicate that rhinosinusal mucosal melanoma was reported in less than 1% of all melanic tumors and in 2-8% of all cancers developed in the nasal fossae and sinuses. Due to reduce and non-specific symptoms and a high degree of invasion away, patients come for a medical expertise in advanced stages of the disease, which is leading to a poor prognosis. The average five-year survival is 20-30%. We present the case of a 65-year-old female patient coming from a rural environment, hospitalized for unilateral nasal obstruction and nasal mucosal changes of a blackish appearance on all of the walls. The endoscopic examination revealed a matter and of a blackish appearance nasal mucosa along the whole length of the left nasal cavity (septum, turbinates, floor, ceiling). Presumptive diagnosis of melanoma led to the excision of inferior and middle turbinate mucosa, floor and ceiling mucosa and the excision of the nasal septum, keeping the columella and the posterior portion. Histopathological and mostly immunohistochemical exams confirmed the diagnosis of malignant melanoma. To determine the phenotype of tumor cells, it was evaluated their immunostaining for HMB-45, Melan-A, S-100, vimentin, cyclin D1 and CD44 markers. The patient followed oncologic treatment and radiochemotherapy, presenting a favorable evolution with the absence of loco-regional recurrence or distant metastasis 24 months postoperatively.
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Formaldehyde is a well known nasal carcinogen in rodents, but so far there has been no convincing evidence that workers occupationally exposed to formaldehyde have an increased risk of nasal cancer. In this study three cases of malignant melanoma of the nasal mucosa in persons occupationally exposed to formaldehyde for a long time are presented. The occurrence of such a rare tumour in patients with significant exposure to a known carcinogen warrants further investigation.
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Primary sinonasal tract mucosal malignant melanomas are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management. A total of 115 cases of sinonasal tract mucosal malignant melanoma included 59 females and 56 males, 13-93 years of age (mean 64.3 years). Patients presented most frequently with epistaxis (n = 52), mass (n = 42), and/or nasal obstruction (n = 34) present for a mean of 8.2 months. The majority of tumors involved the nasal cavity (n = 34), septum alone, or a combination of the nasal cavity and sinuses (n = 39) with a mean size of 2.4 cm. Histologically, the tumors were composed of a variety of cell types (epithelioid, spindled, undifferentiated), frequently arranged in a peritheliomatous distribution (n = 39). Immunohistochemical studies confirmed the diagnosis of sinonasal tract mucosal malignant melanomas with positive reactions for S-100 protein, tyrosinase, HMB-45, melan A, and microphthalmia transcription factor. Sinonasal tract mucosal malignant melanomas need to be considered in the differential diagnosis of most sinonasal malignancies, particularly carcinoma, lymphoma, sarcoma, and olfactory neuroblastoma. Surgery accompanied by radiation and/or chemotherapy was generally used. The majority of patients developed a recurrence (n = 79), with 75 patients dying with disseminated disease (mean 2.3 years), whereas 40 patients are either alive or had died of unrelated causes (mean 13.9 years). A TNM-type classification separated by anatomic site of involvement and metastatic disease is proposed to predict biologic behavior.
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The mucous malignant melanoma of the nasal cavity and paranasal sinuses represent not frequent neoplasms of cervicofacial district. They are considered a pathology with prognosis generally harder, compared to the cutaneous melanomas, because the survival is approximately 5-40% of cases. This medical report is probably connected either to a later diagnosis or to a greater biological aggressiveness of such neoplasms. The surgical treatment set up as the only one possible object, even if, it is necessary to emphasise that often the radicality of these kinds of operation is very difficult to achieve. What we have above mentioned is due whether to the extension of the neoplasia at diagnosis, or to the anatomical places of onset: these are elements that establish an high proportion of local recurrences. The Authors report two clinical cases, introduced to the observation for the onset of anterior relapsing epistaxis and diagnosed like mucous malignant melanomas. The two cases have different starting-point: one starts from the right maxillary sinus, the other one from left ethmoid sinus. The Authors dwell consequently: they review also what is quoted in literature in accordance with a right interpretation of symptoms, generally insufficient, that joins this pathology and on the exact formulation of the diagnostic iter of these neoplasias; only such elements allow an early diagnosis as soon as is possible, in order to avoid the local recurrences.
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BACKGROUND Fortunately, primary malignant mucosal melanoma of the head and neck is a rare entity. A paucity of data elucidating the predictive factors as well as the unpredictable and aggressive biologic behavior of mucosal melanoma compound the vexing clinical situation. This review summarizes what the literature reveals about the epidemiology, patient survival, patterns of local recurrence, and local and distant metastasis of the disease. Over 1000 patients with this disease have been reported. Survivals at 5 and 10 years is 17% and 5%, respectively. Approximately 19% of patients present with lymph node metastasis and another 16% develop lymph node metastases after treatment, whereas 10% present with distant metastasis. Local metastasis does not affect survival; this is in sharp contrast with skin melanoma. Over 50% of patients experience local treatment failure, and salvage treatment is effective in only 25% of these cases. Local failure is the harbinger of distant metastases. Patients with nasal mucosal melanoma have a 31% 5-year survival rate, whereas sinus melanoma patients fare poorly, with a 0% rate of 5-year survival.METHODS The authors conducted a retrospective review of 14 patients with characteristics similar to those in the literature in terms of outcome.RESULTSThe 5-year survival rate for these patients was 14%. Whole-body positron emission tomography was performed on 3 patients to detect metastatic disease. The patterns of local recurrence, distant metastasis, and survival for these patients were compared with the same data for patients described in the literature.CONCLUSIONS Surgery appears to have the greatest efficacy in the management of mucosal melanoma, although radiation therapy may play an increasingly important role in the future. Cancer 1997; 80:1373-86. © 1997 American Cancer Society.
Article
The management for mucosal melanoma of the head and neck is controversial in view of the poor prognosis. Thirty-five patients seen from 1955 to 1991 were analyzed retrospectively. Almost all (34/35) presented with localized disease. Primary treatments included radical surgery (15), local resection (11), radiation therapy (6), or systemic treatment (2). While the rate of local recurrence was high (27/34), only 5 patients developed distant disease before local relapse. Furthermore, only 5/21 achieved successful local salvage. Patients with their disease controlled locally had significantly longer survival than those with persistent local disease (P = .0001). The 5-year disease-specific survival was 45%.The authors conclude that mucosal melanoma of the head and neck is not necessarily incurable. When local control is achieved, survival rate is significantly improved. Aggressive local treatments should be initiated at presentation of this disease.
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This paper is a review of 120 cases of primary malignant melanoma of the oral cavity occurring in the Japanese. We have collected 18 cases from our own department and the remainder from the literature. Since malignant melanoma arising from the oral mucosa and ectopic pigmentation are relatively common in Japan, an assumption has grown as to a possible relationship to histogenesis. The analysis of the material and the discussion are focused on these points. Malignant melanoma of the oral cavity is not rare in the Japanese. Some of the cases do not seem to have any relation to oral melanosis, but almost two-thirds of the cases were found associated with it (36.2% of melanoma was associated with pre-existing melanosis, and 29.8% with concurrent or later-developing melanosis). The biological behavior and histologic patterns of these melanoses were similar to those of lentigo maligna of the skin. The pre-existing melanoses seemed to be the most common precancerous lesion of the oral mucosa as far as malignant melanoma was concerned.
Article
To determine whether surgery combined with radiotherapy confers any survival benefit on radical local excision alone in the management of mucosal malignant melanoma of the nose and sinuses. Retrospective review. From a cohort of 72 patients treated between 1963 and 1996 within a single unit, complete data were available for 58 individuals who were examined to determine whether there was any significant statistical difference in local control and/or survival between those receiving surgery and those receiving combined surgery and radiotherapy. There were 30 men and 28 women. Their ages ranged from 39 to 90 years (mean, 64 y). Twenty-nine patients underwent surgery alone; 23 patients underwent surgery and radiotherapy; 6 patients received surgery and chemotherapy; and 3 patients received surgery, chemotherapy, and radiotherapy. Primary surgery included lateral rhinotomy (42 cases), maxillectomy (8 cases [orbital clearance in 3 cases]), craniofacial resection (3 cases), total rhinectomy (3 cases), and endoscopic clearance (2 cases). Survival ranged from 1 to 228 months with rapid patient loss due to local (and/or systemic) disease during the first 36 months, irrespective of the treatment modality. Overall 5-year actuarial survival was 28%, and overall 10-year actuarial survival 20%, with a median survival of 21 months. There was no statistical difference in local control or survival between patients receiving surgery alone and those receiving surgery and radiotherapy, irrespective of whether this treatment was given in the early part of the series (i.e., before 1983) or thereafter. The addition of chemotherapy had no impact on survival, nor did the site of the tumor, the surgical procedure, the presence of lymph node metastases or the age of the patient. In this large cohort of sinonasal melanoma, overall survival was poor and did not appear to be improved by the addition of radiotherapy.
Article
BACKGROUND This study reviews the case-mix characteristics, management, and outcomes of melanoma cases occuring in the U. S. within the last decade.METHODS Analyses of the National Cancer Data Base (NCDB) were performed on cases diagnosed between 1985 through 1994. A total of 84,836 cases comprised of cutaneous and noncutaneous melanomas were evaluated.RESULTSThe percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, respectively. For cutaneous melanomas, the proportion of patients presenting with American Joint Committee on Cancer Stages 0, I, II, III, and IV were 14.9%, 47.7%, 23.1%, 8.9%, and 5.3%, respectively. Factors associated with decreased survival included more advanced stage at diagnosis, nodular or acral lentiginous histology, increased age, male gender, nonwhite race, and lower income. Multivariate analysis identified stage, histology, gender, age, and income as independent prognostic factors. For ocular melanomas, 85.0% were uveal, 4.8% were conjunctival, and 10.2% occurred at other sites. During the study period, there was a large increase in the proportion of ocular melanoma patients treated with radiation therapy alone. For mucosal melanomas, the distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites was 55.4%, 18.0%, 23.8%, and 2.8%, respectively. Patients with lymph node involvement had a poor prognosis. For unknown primary melanomas, the distribution of metastases as localized to a region or multiple sites at presentation was 43.0% and 57.0%, respectively. Surgical treatment of patients with unknown primary site of the melanoma resulted in better survival compared with no treatment.CONCLUSIONS Treatment of early stage cutaneous melanoma resulted in excellent patient outcomes. In addition to conventional prognostic factors, socioeconomic factors were found to be associated with survival. Cancer 1998;83:1664-1678. © 1998 American Cancer Society.
Article
Pigmented nevi of the oral mucosa are rare benign melanocytic tumours. Epidemiological data are scanty, and the etiology and pathogenesis of these lesions are poorly understood. Reports are mainly based on isolated cases or a relatively small series of cases. Some reviews have drawn attention to the frequent localization of these lesions on the hard palate, the site of preference for oral malignant melanoma (OMM). However, as yet, there is no direct proof that oral melanocytic nevi (OMNs) constitute precursor lesions of OMM. 119 cases of OMNs, registered at the nationwide Registry of Pathology (PALGA) in The Netherlands during the period 1980-2005, have been evaluated. Subepithelial OMNs were the most commonly recorded lesions (96 cases), followed by blue (10 cases), compound (7 cases) and junctional OMNs (5 cases). Only one case of a combined nevus was recorded. None of the patients developed OMM during a mean follow-up period of 8.6years. We present an analysis of this series of cases, together with a review of the literature. The findings of the present evaluation do not give support for the hypothesis of OMN being a marker for an increased risk of future development of OMM.
Article
Diagnosis, therapy, and prognosis of 40 patients with malignant melanoma of the mucous membranes, treated at one hospital from 1971 to 2006, were evaluated in a retrospective study. The survival rate was compared with that established by the German-Austrian-Swiss Study Group on Tumors of the Head and Neck (DÖSAK) for 121 cases. The cumulated 5-year survival rate amounting to 33% (DÖSAK study 35%) emphasizes the unfavorable prognosis of this tumor. Age, sex, or tumor location had no significant impact on a patient's survival. A modified surgical concept has been developed for the treatment of the primary tumor and its lymphatic drainage area to maintain a patient's quality of life. The entire tumor should be resected under histologic control ensuring a 5-mm safety margin of healthy tissue. Bone should only be resected if invaded by the tumor. Large resections of the upper or lower jaw should be avoided. A neck dissection does not improve the prognosis and should be performed only in the case of histologically confirmed invasion of lymph nodes.
Article
Mucosal melanoma of the head and neck is a rare condition. This study presents a review of 26 patients with such tumors, followed up at a minimum of 5 years. The 5-year survival rate in this group was 38%. Recurrences with a fatal outcome, however, have been encountered up to 12 years after initial diagnosis. Primary radical surgery offers the best chance for local control. Nasal-cavity lesions seem to be associated with a better prognosis than oral-cavity tumors. Analysis of pathologic features by microstage measurement showed that the majority of tumors were of considerable thickness. This factor may partially explain the poor prognosis associated with mucosal melanomas in comparison to their cutaneous counterparts. Local recurrences and distant metastases were the principal causes of treatment failure. A persistent treatment policy, however, may still substantially prolong survival in such cases. Regional lymph-node metastasis did not pose a significant problem in the management of these tumors. Recognition of the nature and significance of the appearance of oral melanosis is stressed.
Article
Only 3 per cent of all melanomas arise in the mucosa of the head and neck region. Melanomas of mucosal origin in this series differed from their cutaneous counterpart in that size of the primary lesion did not influence prognosis. Regional lymph node metastases were infrequent and did not seem to influence prognosis. Nearly all the primary lesions on microscopic review showed the presence of intralesional lymphatic and blood vessel invasion. Local recurrence at the primary site was the most common cause of treatment failure, in spite of seemingly adequate surgical resection. Surgical treatment offers long-term cure to only a limited number of patients.
Article
Twenty-six patients with mucosal malignant melanoma of the upper respiratory tract and of the oral cavity were seen at the oncologic departments of eastern Denmark from 1955 to 1989. There were 17 males and nine females with an average age of 65 years. Primary symptoms lasted from one to 24 months and depended on localization of tumor. Five patients had lymph node metastases at the time of diagnosis; one also had distant metastases. Ten patients had surgery as primary treatment, 10 had combined surgery and radiotherapy and six had radiotherapy. Complete remission after primary treatment was seen in 22 cases (85%) and lasted from three to 94 months. Seventeen patients had recurrence, six of these had recurrence twice or three times. The five-year crude survival was 35% and only one patient (4%) lived more than 10 years. Recurrence-free survival among the 22 patients with initially complete response was 14%.
Article
Forty-two patients with mucosal melanoma of the head and neck were treated at the M. D. Anderson Cancer Center from 1944-1989. Their records were evaluated regarding: location of the primary, stage of the disease at presentation, type of treatment, location of recurrences, and overall survival. These patients received the majority of their therapy at M. D. Anderson Cancer Center. The treatment consisted of surgery, radiotherapy, chemotherapy, immunotherapy, or a combination of these. The 5-year survival rate was 40%. Twenty-four of 27 patients who died with metastatic melanoma had local or regional disease concomitantly. Forty percent of patients were free of disease at 5 years; however, only 26% had long-term survival. Although the majority of patients eventually succumbed to their disease, local and regional control was obtained initially in 92% of the group. These data indicate that prolonged survival is possible with mucosal melanoma of the head and neck; however, recurrence or metastasis remain possible many years after the initial diagnosis.
Article
• Melanoma involving the nasal and paranasal sinus mucosa is a rare disease that is difficult to treat and generally has a poor prognosis. Data on 17 patients treated at the UCLA Medical Center during the period 1970 to 1985 were reviewed in a retrospective manner. The five-year disease-free survival was 25% (3/12). Surgery, with or without radiation therapy, is the mode of treatment to control disease in most patients. Treatment failures, which include both local recurrence and distant metastases, may occur many years after initial therapy. We found a correlation between the thickness of tumor and the clinical outcome. (Arch Otolaryngol Head Neck Surg 1987;113:1086-1089)
Article
In this report 21 cases of primary malignant melanoma arising from the mucosa of the upper aerodigestive tract are reviewed. The patients ranged in age from 30 to 86; mean age was 67 years. There were 10 men and 11 women. All but one patient were white. Sites of involvement were: nose and paranasal sinuses, oral cavity and labial mucosa, parotid duct, and larynx. Surgery was the primary method of treatment. The 2-year survival rate was 44% (7/16) and the 5-year survival rate was 13% (2/15). Regional metastases were seen in 19% (4/21) while distant metastases was seen in 55% (11/21). The local recurrence rate was 69% (11/16). Distant metastases were usually associated with uncontrolled disease at the primary site. This fact as well as the low incidence of regional metastases lead us to conclude that better local control rather than regional lymphatic control is necessary if decreased distant metastases and increased survival are to be achieved.
Article
Malignant melanoma of the oral cavity is rare, accounting for about 1% to 8% of all melanomas. There have been no prospective studies of melanoma in this location, and all previous papers have reported small numbers of cases or have retrospectively reviewed case reports from the literature. The authors report six new cases and review 171 cases published since the last major review in 1975. The classification of oral melanomas with radial growth phases is discussed.
Article
Malignant melanoma at present seems to be incurable when it arises in the nasal or sinus cavities. However, we are able to provide a longer and more comfortable life expectancy by constant surveillance and treatment. Surgery seems to be the treatment of choice. Although ineffective for cure, radiation may play a role in the treatment of inoperable recurrences and help to prolong life. The risk of death by melanoma is constant throughout the course of the disease. Recognition of recurrence or metastasis and effective treatment of it do lengthen survival.
Article
A review of 120 cases of primary malignant melanoma of the oral cavity occurring in the Japanese is presented. 18 cases from personal experience and the remainder from the literature were collected. Since malignant melanoma arising from the oral mucosa and ectopic pigmentation are relatively common in Japan, an assumption has grown as to a possible relation to histogenesis. The analysis of the material and the discussion are focused on these points. Malignant melanoma of the oral cavity is not rare in the Japanese. Some of the cases do not seem to have any relation to oral melanosis, but almost 67% of the cases were found associated with it (36.2% of melanoma was associated with pre existing melanosis, and 29.8% with concurrent or later developing melanosis). The biological behavior and histologic patterns of these melanoses were similar to those of lentigo maligna of the skin. The pre existing melanoses seemed to be the most common precancerous lesion of the oral mucosa as far as malignant melanoma was concerned.
Article
A study of pigmentation of the nasal cavity in Ugandan Africans together with four cases of primary malignant melanoma of the nose are presented. The findings suggest that 13.5% of Africans have discrete ectopic areas of visible pigment. Microscopically, this pigment exists in dendritic melanocytes in both stratified squamous and columnar epithelium. The authors postulate that these areas of potentially unstable pigment cells are the basis for the production of primary malignant melanoma in the nasal cavity and may explain the higher incidence in pigmented races, particularly indigenous Africans.
Article
Mucosal melanomas of the nasal cavity and paranasal sinuses are rare and do poorly. Seventeen patients treated from 1981 to 1993 at a single referral center were retrospectively reviewed. Thirteen patients underwent surgical resection, with seven receiving postoperative radiotherapy. Eight had microscopically negative margins. The actuarial 2-year and 5-year survivals for this group of 13 were 67% (8 of 12) and 20% (2 of 10). The local recurrence rate was 85% (11 of 13) and distant metastases occurred in 31% (4 of 13) patients. In the absence of metastatic disease, resection of recurrent tumor correlated with disease-free intervals ranging from 3 months to 40 months. Those who received postoperative radiotherapy appeared to have done better with increased disease-free intervals and prolonged survival. Negative surgical margins were not predictive of a more favorable outcome. Surgical resection followed by postoperative radiotherapy is appropriate and resection of recurrent tumor should be considered.
Article
A review of oral malignant melanoma and data of eight patients are presented. The dismal prognosis of the condition is probably mainly due to its long, 'silent' course. In one-third of cases melanosis precedes the tumour--it is this condition that should alert clinicians. Therefore, pigmented oral lesions should be viewed with suspicion and biopsy is mandatory when the clinical diagnosis is uncertain. Early detection is essential to successful treatment. In spite of aggressive treatment modalities, survival in patients with advanced stage disease remains poor.
Article
A series of 48 cases of malignant mucosal melanomas treated at the Milan Cancer Institute from 1975 to 1990 is retrospectively reviewed. There were 34 males and 14 females, and their ages ranged from 21 to 79 years (mean, 58). The site of origin of the tumor was the nasal cavity in 26 cases, the oral cavity in 15, larynx in two, lip mucosa in two, pharynx in two and upper esophagus in one. At presentation, the neoplasm was limited to the primary site in 60.4% of the patients. Most patients (34) were treated with surgery alone. Nine were treated with surgery combined with chemo- and/or radiotherapy and five with radiotherapy combined with chemotherapy and/or immunotherapy. Only when surgery was part of the treatment (42 of 48 cases) the patients were rendered disease free, but no further relapse of disease was documented in only five of these patients. The observed 2- and 5-year survival rate of the entire group was 45% and 21%, respectively. The 4-year disease-free survival rate was 7%. The median interval between therapy and the first relapse was 8.5 months (range, 1-66). In 44% of the patients the first recurrence of the tumor was at the primary site.
Article
An analysis has been made of the effect of radiation therapy in 28 patients with a malignant melanoma (Stage I: 18 cases; Stage II: 10 cases) in the mucosa of the upper jaw. Treatment had been provided by one of the following methods: intraoral mold (10 cases), interstitial brachytherapy (two cases), intraoral electron therapy (nine cases), or external irradiation (seven cases). The results have shown that the survival rate for all 28 patients was 25%, and that the survival rate for stage I patients treated by intraoral electron or brachytherapy was 47%. The primary tumor control rate in percentages was 79% (22/28) in all 28 radiotherapy patients; 92% (11/12) for tumors treated by a mold or an interstitial implant; 67% (6/9) for tumors treated by an intraoral cone; and 71% (5/7) for tumors treated by external irradiation with or without surgery. A neck metastasis that was found in 19 patients was treated by surgery, radiotherapy, and/or immunochemotherapy, and the result was successful in nine patients. The major factor in the failure of treatment was a distant, metastatic dissemination. This analysis revealed that radiotherapy has achieved similar or better results than surgery and may be advocated for the management of a localized malignant melanoma in the mucosa of the upper jaw.
Article
Fortunately, primary malignant mucosal melanoma of the head and neck is a rare entity. A paucity of data elucidating the predictive factors as well as the unpredictable and aggressive biologic behavior of mucosal melanoma compound the vexing clinical situation. This review summarizes what the literature reveals about the epidemiology, patient survival, patterns of local recurrence, and local and distant metastasis of the disease. Over 1000 patients with this disease have been reported. Survivals at 5 and 10 years is 17% and 5%, respectively. Approximately 19% of patients present with lymph node metastasis and another 16% develop lymph node metastases after treatment, whereas 10% present with distant metastasis. Local metastasis does not affect survival; this is in sharp contrast with skin melanoma. Over 50% of patients experience local treatment failure, and salvage treatment is effective in only 25% of these cases. Local failure is the harbinger of distant metastases. Patients with nasal mucosal melanoma have a 31% 5-year survival rate, whereas sinus melanoma patients fare poorly, with a 0% rate of 5-year survival. The authors conducted a retrospective review of 14 patients with characteristics similar to those in the literature in terms of outcome. The 5-year survival rate for these patients was 14%. Whole-body positron emission tomography was performed on 3 patients to detect metastatic disease. The patterns of local recurrence, distant metastasis, and survival for these patients were compared with the same data for patients described in the literature. Surgery appears to have the greatest efficacy in the management of mucosal melanoma, although radiation therapy may play an increasingly important role in the future.
Article
Two hundred and fifty-nine patients with mucosal melanoma of the head and neck were reviewed. The data of these patients were obtained from the records of the Department of Head and Neck Oncology at the University of Liverpool and from the Merseyside and Cheshire Cancer Registry. Survival curves were constructed using the life table method and differences were investigated by the Log Rank Test. Prognostic factors were further analysed by Cox’s proportional hazards model. Melanomas of the nasal cavities and sinuses accounted for 69%; 22% occurred in the oral cavity and 9% in the pharynx, larynx and upper oesophagus. In 49% treatment was by wide local resection and in 8% by irradiation. Thirty-six per cent had combined modalities of treatment. Primary site recurrence occurred in 52% and 36% developed nodal recurrence. The tumour specific survival at 5 years was 45% at 10 years 28%, at 20 years 17% and closely resembled the observed survival. Young male patients tended to have a favourable prognosis as did those treated surgically. Radiotherapy on its own was ineffective. Amelanotic melanoma had a particularly poor survival. Whereas site had no effect on survival. The study confirms the poor prognosis of mucosal melanoma of the head and neck. Young patients should be offered radical surgical treatment combined with radical radiotherapy if feasible as this offers the best chance of cure.
Article
This study reviews the case-mix characteristics, management, and outcomes of melanoma cases occuring in the U.S. within the last decade. Analyses of the National Cancer Data Base (NCDB) were performed on cases diagnosed between 1985 through 1994. A total of 84,836 cases comprised of cutaneous and noncutaneous melanomas were evaluated. The percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, respectively. For cutaneous melanomas, the proportion of patients presenting with American Joint Committee on Cancer Stages 0, I, II, III, and IV were 14.9%, 47.7%, 23.1%, 8.9%, and 5.3%, respectively. Factors associated with decreased survival included more advanced stage at diagnosis, nodular or acral lentiginous histology, increased age, male gender, nonwhite race, and lower income. Multivariate analysis identified stage, histology, gender, age, and income as independent prognostic factors. For ocular melanomas, 85.0% were uveal, 4.8% were conjunctival, and 10.2% occurred at other sites. During the study period, there was a large increase in the proportion of ocular melanoma patients treated with radiation therapy alone. For mucosal melanomas, the distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites was 55.4%, 18.0%, 23.8%, and 2.8%, respectively. Patients with lymph node involvement had a poor prognosis. For unknown primary melanomas, the distribution of metastases as localized to a region or multiple sites at presentation was 43.0% and 57.0%, respectively. Surgical treatment of patients with unknown primary site of the melanoma resulted in better survival compared with no treatment. Treatment of early stage cutaneous melanoma resulted in excellent patient outcomes. In addition to conventional prognostic factors, socioeconomic factors were found to be associated with survival.
Article
Oral mucosal malignant melanoma is a rare disease. We reviewed 30 years of data from a tumor registry and identified 65 patients who had head and neck melanomas. Two thirds (43) of the 65 patients were identified as male, with the mean age in the sixth decade. Of the 65 patients, only 6 had melanoma that arose from the oropharyngeal mucosa. Of the lesions involving the oral mucosa, each lesion manifested itself as a mass or was associated with symptoms of discomfort; only one third (2) of the lesions were pigmented. The clinician must carefully examine the head, neck, and oral cavity, and any pigmented lesion that is not recognized as a specific entity, such as amalgam tattoo, should be biopsied. The more common presentation of amelanotic malignant melanoma requires a high index of suspicion for masses identified in the mouth and requires biopsy for definitive diagnosis. The prognosis for oral mucosal malignant melanoma is poor.
Article
The vast majority of healthy individuals have some form of melanocytic lesions with most having several cutaneous melanocytic nevocellular nevi. The incidence of cutaneous melanoma, despite improved prevention and early diagnosis of precursor melanocytic lesions, is on the increase with a projection that one in 75 persons born in the year 2000 will develop cutaneous melanoma in his/her lifetime. With cutaneous melanoma, the number, location and type of nevi, sun exposure and inability to tan, and presence or absence of dysplastic nevi affect transformation to a malignant process. Certain familial factors, syndromes, cytogenetic abnormalities, and mutations in tumor suppressor genes also influence tumor formation.
Article
Cutaneous malignant melanoma (CMM) is an aggressive malignant neoplasm of the melanocytes. CMM is less common than basal cell and squamous cell carcinoma (SCC), but far more fatal. Therefore, early detection is paramount and is associated with a high chance of cure. In contrast, late-stage disease has a dismal chance for cure. Because as many as one third of CMMs arise from the skin of the head and neck region, it is critical that head and neck surgeons have a thorough understanding of the natural history, diagnosis, staging, and treatment of CMM. It is also important that clinicians are aware of the less common types of melanoma arising in the head and neck, including mucosal melanoma and desmoplastic melanoma.
Article
The current study was conducted to identify histologic predictors of survival in patients with localized, lymph node-negative (Stage I, N0M0) primary mucosal melanomas of the head and neck (HNMM). The histology of 39 sinonasal, 20 oral, 1 pharyngeal, and 1 laryngeal Stage I HNMM was reviewed by 2 pathologists without knowledge of patient outcome. The invasion was evaluated as Level I: melanoma in situ (without invasion or with microinvasion only); Level II: invasion into the lamina propria only; and Level III: invasion into deep tissue (e.g., skeletal muscle, bone, or cartilage). The tumor architecture was defined as pseudopapillary when tumor cells clustered around blood vessels resembling papillae and sarcomatoid when they resembled high-grade pleomorphic sarcoma. Survival analysis was performed with Kaplan–Meier survival curves using disease-specific survival (DSS) as the endpoint. The 5-year DSS rate was 43% (median, 41.5 months). The median survival was found to decrease significantly with increasing level of invasion: Level I (n = 4): 138 months; Level II (n = 29): 69 months; and Level III (n = 28): 17 months (P = 0.003). The presence of pseudopapillary and sarcomatoid architecture (n = 20) and undifferentiated cells (n = 16) were found to be associated with a significantly poor DSS (P < 0.05). However, on multivariate analysis, only the level of invasion remained an independent predictor of survival (P = 0.03). Tumor thickness, vascular invasion, and necrosis were found to have no significant influence on survival. Microstaging according to invasion into three tissue compartments was found to be a significant and independent predictor of poor survival in patients with localized, lymph node-negative, Stage I HNMM. The presence of sarcomatoid and pseudopapillary architecture and undifferentiated cells also appear to be associated with significantly poor DSS. Cancer 2004.
Article
Malignant melanoma arising in the head and neck mucosa is a rare entity with incidence ranging from 2% to 10%. Because of the lack of data, the biological behaviour of these lesions still remains unpredictable and outcome dismal. We carried out a literature review for cases of mucosal melanoma of the head and neck reported from India and performed a pooled analysis on the available data. A total of 60 cases of head and neck melanomas were reported, of which 46 were in men. Palate and alveolus were the commonest sites. A total of 29 (48.3%) patients had regional node metastasis at presentation while five (12%) had distant metastasis. Three-year overall survival of 27.7% was observed. However, the disease-free survival rates at 3, 5 and 6 years were 39.4%, 39.4% and 13.1%, respectively. Metastasis at presentation and use of adjuvant radiotherapy were found to be the only significant predictors of survival. Malignant mucosal melanoma has aggressive biological behaviour and poor outcome. Radical surgery and adjuvant radiotherapy may provide a better local control and may help in improving survival.
Article
While mucosal-based melanomas of the head and neck region are uncommon lesions, when they do arise they usually follow an inexorably aggressive course. Experience with these tumors is, necessarily, limited; as such, well-worked out treatment protocols for the treatment of such lesions are in short supply. It appears as though mucosal melanomas (MuMs) develop more frequently in the nasal cavity and paranasal sinus region, and less often in the oral cavity. It seems that the incidence of nodal metastasis is significantly lower for sinonasal MuMs than it is for MuMs of the oral cavity; this observation may influence decisions about performing neck dissection as a function of location of the primary MuM. At present, surgical excision remains the mainstay of treatment; however, anatomical complexities within the region can hamper attempts at complete excision. Radiotherapy has not traditionally been relied on for routine treatment of MuM, although some recent reports have challenged this view. Chemotherapy is, at present, employed principally in the treatment of disseminated disease and for palliation. As a diagnostic matter, MuM belongs to the class of tumors that, on light microscopy, may with some regularity be confused with other malignancies (including sarcomas, plasmacytomas, and carcinomas); as a consequence, this is a diagnosis which is often best confirmed by way of ancillary testing via immunohistochemical studies. A better grasp of the best means of treating MuM will likely come only when large referral centers are able to pool their experiences with these uncommon yet virulent malignancies.
Article
Mucosal melanoma of the head and neck is uncommon, and has a poor prognosis due to locoregional and distant failure. The optimal treatment paradigm for patients with this disease has yet to be determined. To compare the outcomes of patients treated with various commonly used protocols for mucosal melanoma of the head and neck. Retrospective study. Academic tertiary referral center. The medical records of 48 consecutive patients treated at a single institution from January 1, 1985, to December 31, 1998, were reviewed. Patients were treated with surgery alone, surgery and adjuvant radiotherapy, or surgery and biochemotherapy, with or without adjuvant radiotherapy. The outcomes of disease recurrence and survival were correlated with the treatment received. Twenty patients received surgical treatment alone; in 9 patients (45%), this treatment failed locoregionally, and 10 (50%) of the patients developed distant metastases. The 5-year survival rate was 45% (9 of 20 patients). Twenty-four patients received postoperative adjuvant radiotherapy; in 4 patients (17%), this treatment failed locally, and 11 (46%) of the patients developed distant metastases. The 5-year survival rate was 29% (7 of 24 patients). The addition of radiotherapy tended to decrease the rate of local failure (P =.13), but did not significantly improve survival (P =.73), because of the high rate of distant metastatic disease.
Article
Major advances in the understanding of the causes and risk factors for melanoma and for the prevention and management of this tumor have taken place since the beginning of the past century, when the diagnosis of melanoma was synonymous with death. As many as 80% of early melanomas can be cured, and a high rate of locoregional control for even far-advanced melanoma is plausible. The major challenge for the years to come lies in curtailing the steady rise in the incidence of melanoma by increasing patient education and adopting measures to prevent the increasing mortality rates associated with this disease. Cure rates can be improved by early diagnosis by physicians and instant referral to experienced oncologists. Finally, new advances in diagnostic and treatment strategies carry the hope for further improvements in locoregional control and survival rates.