UNIVERSIDADE ESTADUAL DE CAMPINAS FACULDADE DE ODONTOLOGIA DE PIRACICABA
WALDNER RICARDO SOUZA DE CARVALHO
UM ESTUDO MULTICÊNTRICO DOS SARCOMAS BUCAIS
NO BRASIL
MULTICENTER STUDY OF ORAL SARCOMAS IN BRAZIL
Piracicaba 2019
WALDNER RICARDO SOUZA DE CARVALHO
UM ESTUDO MULTICÊNTRICO DOS SARCOMAS BUCAIS
NO BRASIL
MULTICENTER STUDY OF ORAL SARCOMAS IN BRAZIL
Tese apresentada à Faculdade de Odontologia de Piracicaba da Universidade Estadual de Campinas como parte dos requisitos exigidos para a obtenção do título de Doutor em Estomatopatologia, na Área de Patologia.
Thesis presented to the Piracicaba Dental School of the University of Campinas in partial fulfillment of Doctor in Oral Medicine and Oral Pathology, in Pathology area.
ORIENTADOR: PROF. DR. HELDER ANTONIO REBÊLO PONTES Coorientador: PROF. DR. FELIPE PAIVA FONSECA
ESTE EXEMPLAR
CORRESPONDE A VERSÃO FINAL DA TESE DEFENDIDA PELO
ALUNO WALDNER RICARDO
SOUZA DE CARVALHO E
ORIENTADA PELO PROF. DR.
HELDER ANTONIO REBÊLO
PONTES.
Piracicaba 2019
Ficha catalográfica
Universidade Estadual de Campinas
Biblioteca da Faculdade de Odontologia de Piracicaba Marilene Girello - CRB 8/6159
Informações para Biblioteca Digital
Título em outro idioma: Munticenter study of sarcomas in Brazil Palavras-chave em inglês:
Mesenchymal stem cells Mouth neoplasms
Área de concentração: Patologia Titulação: Doutor em Estomatopatologia Banca examinadora:
Helder Antonio Rebêlo Pontes [Orientador] Eduardo Hochuli Vieira
Ricardo Alves de Mesquita Nicolau Conte Neto
Alan Roger dos Santos Silva Data de defesa: 26-09-2019
Programa de Pós-Graduação: Estomatopatologia
Identificação e informações acadêmicas do(a) aluno(a)
- ORCID do autor: https://orcid.org/0000-0002-2528-2310 - Currículo Lattes do autor: http://lattes.cnpq.br/8960521334274213
Carvalho, Waldner Ricardo Souza de, 1982-
C253e CarUm estudo multicêntrico dos sarcomas bucais no Brasil / Waldner Ricardo Souza de Carvalho. – Piracicaba, SP : [s.n.], 2019.
CarOrientador: Helder Antonio Rebêlo Pontes. CarCoorientador: Felipe Paiva Fonseca.
CarTese (doutorado) – Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba.
Car1. Células mesenquimais estromais. 2. Neoplasias bucais. I. Pontes, Helder Antonio Rebêlo. II. Fonseca, Felipe Paiva, 1986-. III. Universidade Estadual de Campinas. Faculdade de Odontologia de Piracicaba. IV. Título.
A Comissão Julgadora dos trabalhos de Defesa de Tese de Doutorado, em sessão pública realizada em 26 de Setembro de 2019, considerou o candidato WALDNER RICARDO SOUZA DE CARVALHO aprovado.
PROF. DR. HELDER ANTONIO REBÊLO PONTES
PROF. DR. EDUARDO HOCHULI VIEIRA
PROF. DR. RICARDO ALVES DE MESQUITA
PROF. DR. NICOLAU CONTE NETO
PROF. DR. ALAN ROGER DOS SANTOS SILVA
A Ata da defesa, assinada pelos membros da Comissão Examinadora, consta no SIGA/Sistema de Fluxo de Dissertação/Tese e na Secretaria do Programa da Unidade
UNIVERSIDADE ESTADUAL DE CAMPINAS
Faculdade de Odontologia de Piracicaba
DEDICATÓRIA
Dedico este trabalho na sua integralidade ao Prof. Dr. Helder Antonio Rebêlo Pontes, que dedica sua vida pessoal e profissional, incondicionalmente, aos mais necessitados e menos favorecidos.
AGRADECIMENTOS
Sempre achei esta a pior parte da tese para escrever, talvez porque a vida não se coloca em análise de regressão e não é pelo valor p que descobrimos a significância das pessoas na nossa trajetória.
Primeiramente agradeço ao grande Pai Celestial que me colocou sempre no caminho do bem e colocou em meu caminho pessoas que foram absolutamente importantes para a execução desta obra.
Agradeço ao Prof. Helder Antonio Rebêlo Pontes, uma das pessoas mais importantes em minha vida, e não seria diferente, para a elaboração e conclusão deste trabalho. Meu muito obrigado pela idealização de um projeto que visa ajudar milhares de pessoas, obrigado por me escolher e me confiar à execução desta obra. Noites de sono e fins de semana sentado cuidando desta tese. O senhor realmente é um exemplo de todas as qualidades que um Homem possa ter. Meus mais profundos e sinceros agradecimentos.
Agradeço imensamente ao meu co-orientador Prof. Dr. Felipe Paiva, que desde o início desta obra sempre esteve disposto a ajudar. Obrigado por me atender todas as vezes que bati em sua porta, como eu sempre disse, se um dia eu não conseguir lhe retribuir, Deus o fará. Obrigado por me guias nos primeiros passos da pós-graduação. Muito obrigado por tudo.
A minha abençoada família, meus pais, meu presente de Deus que é minha esposa Leila, meu filho Ricardo Carvalho e meus irmãos Nicolau Conte e Anderson Kikuchi.
Ao acadêmico Lucas Lacerda, aluno exemplar e incansável, pois mesmo atravessando momentos difíceis com a saúde, não mediu esforços em todas as fases deste estudo.
Estas pessoas fizeram e fazem parte da minha trajetória pessoal e profissional e jamais poderiam deixar de serem citados pois me ajudaram direta ou indiretamente, entre eles Prof. Eduardo Hochuli, Prof Mário Gabrielli, Profa. Marisa Gabrielli, Prof. José Scarso Filho, Prof. Valdrido Pereira Filho, Prof. Marcelo Monazzi, Prof. Leandro Kluppel, Profa Flávia Pontes, bem como os professores da FOP-UNICAMP Oslei Paes de Almeida, Alan Roger, Márcio Ajudarte, Pablo Vargas.
Meus infindáveis agradecimentos, pois se vocês não tivessem entendido o projeto do Professor Helder Antonio Rebêlo Pontes, nada disto teria acontecido.
Enfim, a todos os colegas de doutorado, especialmente Maurício e Ligia Akiko. Meus sinceros agradecimentos e obrigado pelo companheirismo incondicional.
RESUMO
Os sarcomas representam um grupo raro e heterogêneo de tumores sólidos derivados de células progenitoras mesenquimais. Estas entidades podem apresentar mais de 50 subtipos histológicos distintos, podem ocorrer em qualquer idade e não estão limitadas a uma área específica do corpo humano. A raridade da doença, combinada com um número diversificado de subtipos histológicos, pode dificultar o diagnóstico dessas lesões. O objetivo deste estudo foi investigar a prevalência de sarcomas orais nas regiões geográficas do Brasil. Foi realizado um estudo transversal nos prontuários de 12 centros independentes de diagnóstico bucal e maxilofacial de todas as regiões do Brasil (Norte, Sul, Nordeste, Sudeste e Centro-Oeste) de janeiro de 2007 a dezembro de 2016. Foram analisadas 176.537 amostras. As amostras foram revisadas por um patologista experiente e especialista na área. Sarcomas orais foram recuperados, e cada um dos centros analisados recuperou dados referentes ao sexo, idade, tempo de evolução (meses), aspectos clínicos, localização do tumor primário, tamanho do tumor ao diagnóstico (cm), aspectos radiográficos e diagnóstico histopatológico final. Os dados coletados foram tabulados no Microsoft Excel® para análise epidemiológica. A análise descritiva e quantitativa dos dados foi realizada no software Statistical Package for the Social Sciences (SPSS), versão 22.0 (SPSS Inc., Chicago, IL, EUA). De 176.537 amostras, um total de 200 pacientes (0,11%) afetados por sarcomas orais foram identificados nos centros estudados. Um total de 48 casos foram excluídos das amostras porque não preencheram os critérios para diagnóstico ou foram diagnosticados como sarcoma indiferenciado. A região Sudeste apresentou a maior quantidade de casos (121 casos; 60,5%), seguida pelo norte (40 casos; 20%), o nordeste (19 casos; 9,5%), centro-oeste (14 casos; 7%) e sul (6 casos; 3%). Os subtipos histológicos mais comuns foram o osteossarcoma (74 casos; 37%), seguido pelo sarcoma de Kaposi (52 casos; 26%), condrossarcoma (17 casos; 8,5%) e leiomiossarcoma (12 casos; 6%). As lesões foram mais prevalentes no sexo masculino do que no sexo feminino (relação homem: mulher de 1,27: 1), e a média de idade foi de 32,2 anos (variação de 3-87 anos). Clinicamente, os pacientes apresentaram inchaço (108 casos), dor (36 casos), sangramento (27 casos) e parestesia (7 casos) em um tempo médio de evolução de 5,14 meses (variação <1-156 meses). As lesões
apresentaram a mandíbula (90 casos), palato (30 casos), maxila (24 casos) e gengiva (14 casos) como os locais primários mais comumente observados e o tamanho médio do tumor foi de 3,4 cm em seu maior diâmetro (faixa de 0,3 -15 cm). Radiograficamente, as lesões apresentam-se principalmente como aspecto radiolúcido, mostrando destruição óssea cortical e limites mal definidos. Conclui-se, portanto, que os sarcomas orais são lesões raras com mais de 50 subtipos descritos. Osteossarcomas, sarcomas de Kaposi e condrossarcomas foram os principais sarcomas da cavidade bucal no Brasil.
Palavras-chave: Epidemiologia; tumores mesenquimais; sarcomas; boca; regiões maxilofaciais.
ABSTRACT
Sarcomas represent a rare and heterogeneous group of solid tumours derived from mesenchymal progenitor cells. These entities can present more than 50 distinct histologic subtypes, may occur at any age and are not limited to a specific area of the human body. The rarity of the disease, combined with a diverse number of subtypes, can make these lesions very difficult to study. The aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil. A cross-sectional study was performed in the files from 12 independent oral and maxillofacial diagnostic centres of all regions of Brazil (North, South, Northeast, Southeast and Midwest) were reviewed from January of 2007 to December 2016. A total of 176,537 samples were analysed. The samples were evaluated by an experienced pathologist and expert in the area. Oral sarcomas were retrieved, and each of the analysed centres retrieved data regarding the gender, age, evolution time (months), clinical aspects, primary tumour site, tumour size at diagnosis (cm), radiographic aspects and final histopathological diagnosis. The collected data were tabulated in Microsoft Excel® for epidemiologic analysis. Descriptive and quantitative data analysis was performed using the Statistical Package for Social Sciences (SPSS) software, version 22.0 (SPSS Inc., Chicago, IL, USA). From 176,537 samples, a total of 200 patients (0.11%) affected by oral sarcomas were identified at the centres studied. A total of 48 cases were excluded from the samples because did not meet the criteria for diagnosis or were diagnosed as undifferentiated sarcoma. Southeast region showed the highest amount of cases (121 cases; 60.5%), followed by the north (40 cases; 20%), the northeast (19 cases; 9.5%), the midwest (14 cases; 7%) and the south (6 cases; 3%). The most common histological subtypes were osteosarcoma (74 cases; 37%), followed by Kaposi’s sarcoma (52 cases; 26%), chondrosarcoma (17 cases; 8.5%) and leiomyosarcoma (12 cases; 6%). Lesions were more prevalent in males than females (male:female ratio of 1.27:1), and the mean age was 32.2 years old (range of 3-87 years old). Clinically, patients presented with swelling (108 cases), pain (36 cases), bleeding (27 cases) and paraesthesia (7 cases) at a mean evolution time of 5.14 months (range < 1-156 months). The lesions presented the mandible (90 cases), palate (30 cases), maxilla (24 cases) and gingiva (14 cases) as the most commonly observed primary sites and the mean tumour size
was 3.4 cm at its largest diameter (range of 0.3-15 cm). Radiographically, the lesions mainly presented as a radiolucent aspect showing cortical bone destruction and ill-defined limits. In conclusion, oral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas, Kaposi´s sarcomas and chondrosarcomas were the main sarcomas of the oral cavity in Brazil.
SUMÁRIO
1 INTRODUÇÃO ... 13
2 ARTIGO: Multicenter study of oral sarcomas in brazil ... 16
3 CONCLUSÃO ... 40
REFERÊNCIAS ... 41
ANEXOS... 44
Anexo 1- Verificação de originalidade e prevenção de plágio...44
Anexo 2 - Certificado do Comitê De Ética em Pesquisa ... 45
13 1 INTRODUÇÃO
Os sarcomas são lesões malignas originadas de tecido mesenquimal (não epitelial) e são amplamente classificadas em sarcomas de tecido mole e osso. Os sarcomas de tecido mole podem surgir dos músculos, vasos sanguíneos, nervos, gordura e tecidos fibroconectivos. Os sarcomas ósseos são principalmente osteossarcoma, condrossarcoma e sarcoma de Ewing (Makary et al., 2017; Lee et al., 2015).
Esse grupo de lesões é raro quando comparado com o carcinoma, correspondendo de 1% a 2% de todas as neoplasias de cabeça e pescoço, dos quais aproximadamente 80% originam-se de tecidos moles e 20% dos ossos (O’Neill et al., 2013).Na boca, essas entidades são ainda mais raras, correspondendo a menos de 1% de todas as lesões que afetam este sítio anatômico (Alishahi et al., 2015; Siegel et al., 2018). Elas apresentam mais de 50 subtipos histológicos. A raridade da doença associada à grande quantidade de subtipos histológicos dificultam o diagnóstico final das lesões (Siegel et al., 2018; González-González et al., 2012).
A patogênese desse grupo de lesões está associada a vários fatores associados/predisponentes, os quais podem ser predisposição genética, mutações genéticas adquiridas, a exposição à radiação/quimioterapia, carcinogênicos químicos, irritação crônica, linfoedema, infecções virais (associação com o vírus da imunodeficiência humana no sarcoma de Kaposi e com o vírus do Epstein-Barr em tumores de músculo liso de pacientes imunocomprometidos) (Zahm&Fraumeni, 1997; Siegel et al., 2018).
Em torno de 70% a 80% dos sarcomas que acometem a região de cabeça e pescoço ocorrem em adultos, sendo os mais comuns o angiossarcoma, sarcoma pleomórfico indiferenciado, sarcoma de Kaposi e fibrossarcoma. Pacientes pediátricos são afetados entre 20% e 30% dos casos, apresentando o osteossarcoma, rabdomiossarcoma e sarcoma de Ewing como as lesões que mais acometem essa faixa etária (Potter & Sturgis, 2003).
As lesões tendem a apresentar, dependendo da sua origem histológica, comportamentos biológicos agressivos. Na boca, essas lesões mostram-se, geralmente, como tumefações, causando sangramento, dor ou parestesia (Chidzonga&Mahomva, 2007; de Bree et al., 2010; El-Naggar et al.,
14 2017). Entretanto, podem apresentar outras manifestações, em decorrência do envolvimento com estruturas adjacentes da região de cabeça e pescoço, tal como diplopia, proptose, dor facial e cefaléia quando se infiltram para base do crânio; obstrução nasal, epistaxe e dor quando há envolvimento sinonasal; e disfonia ou dispneia quando afetam a laringe (Pandey et al., 2003; Pontes et al., 2012; Pontes et al., 2018).
Os aspectos de imagem que essas lesões apresentam são de suma importância para traçar o manejo do paciente e avaliar o estágio da doença. Entretanto, o diagnóstico nem sempre é presuntivo por meio das características imaginológicas das lesões, uma vez que elas não apresentam características específicas e podem ser apresentadas em uma vasta gama de tumores benignos e malignos (Smith et al., 2012; Yeang et al., 2013). Este grupo de neoplasias apresentam-se como lesões radiolúcidas, mostrando limites mal definidos e destruição da cortical óssea quando avaliados os tecidos duros por meio da radiografia panorâmica e da tomografia computadorizada. Além disso, podem-se ser apresentadas com margens mal definidas e intensidade de sinal não homogênea na ressonância magnética, com espessamento tecidual em largura e profundidade, características consistentes com as lesões malignas (Chung et al., 2012; Berquist et al., 1990).
O estadiamento dessas lesões é classificado de acordo com as diretrizes do “American Joint Committee on Cancer”. As biópsias incisionais são de suma importância para o diagnóstico final da lesão e a classificação do estadiamento. Esses tipos tumorais podem ser classificados histologicamente em três graus histológicos: baixo grau, grau intermediário e alto grau. Essa definição é baseada na classificação da “Federation Nationale des Centers de Lutte Contrele Cancer” em consideração fatores como o grau de diferenciação, mitose e necrose tumoral para chegar ao grau histológico (El-Naggar et al. 2017).
Embora os avanços referentes a terapia dessas lesões, ainda existem muitas discussões acerca da melhor forma terapêutica, de forma a favorecer o prognóstico do paciente (Martínez Martínez et al., 2014; Nagata et al., 2014). A ressecção cirúrgica tem sido empregada como a principal forma de tratamento das lesões. Entretanto, nas últimas décadas, em decorrência do avanço dos quimioterápicos e da radioterapia como forma neoadjuvante, novos
15 conceitos têm sido empregados no tratamento dessas entidades. Estudos têm mostrado que o grau de disseminação dessas lesões, em decorrência da sua origem mesenquimal, em contraste à maioria dos cânceres de origem epitelial, predispõe um padrão diferente de disseminação e infiltração no osso esponjoso e nas estruturas da região de cabeça e pescoço (Zagars et al., 2003; Peng et al., 2014; Wanebo et al., 1992).
Estudos clínicos e patológicos podem ajudar a entender o comportamento biológico dos sarcomas orais e estudos epidemiológicos podem contribuir para determinar o número de pessoas afetadas em todo o mundo. Assim, estudos epidemiológicos baseados em resultados histopatológicos e imunoistoquímicos podem fornecer dados mais precisos sobre essas lesões (Siegel et al., 2018; Woods et al., 2018).Considerando as informações disponíveis na literatura acerca dos aspectos clinico-patológicos dos sarcomas de boca, este estudo tem como objetivos avaliar as características epidemiológicas, clinico-patológicas e de imagem dos sarcoma de boca no Brasil, por meio de um estudo multicêntrico de doze centros de referência em patologia oral e maxilofacial.
16 2 ARTIGO
A MULTICENTER STUDY OF ORAL SARCOMAS IN BRAZIL
Waldner Ricardo Souza de Carvalho1,2, Lucas Lacerda de Souza1, Flávia Sirotheau Corrêa Pontes1,Daniel Cavallero Colares Uchôa1, Davi Lavareda Corrêa1, Cinthia Verónica Bardalez López de Cáceres2, Márcio Ajudarte Lopes2, Alan Roger Santos-Silva2,Pablo Agustin Vargas2, Bruno Augusto Benevenuto de Andrade3, Mário Romañach3, Ricardo Santiago Gomez4, Sara Ferreira dos Santos Costa4, Aline Carvalho Batista5, Elismauro Francisco Mendonça5, Décio dos Santos Pinto Júnior6, Rogério Gondak7, Danyel Elias da Cruz Perez8, Cassiano Nonaka9, Jean Nunes dos Santos10, Tatiana Nayara Libório-Kimura11, Jeconias Câmara11, Fábio Ramôa Pires12, Lélia Batista de Souza13,Manoela Domingues Martins14, Oslei Paes de Almeida2, Felipe Paiva Fonseca4 and Hélder Antônio Rebelo Pontes1,2.
1Service of Oral Pathology, João de Barros Barreto University Hospital, Federal University of Pará, Belém/Brazil.
2Oral Diagnosis Department (Pathology and Semiology), Piracicaba Dental School, University of Campinas, Piracicaba/Brazil.
3Oral Pathology, Dental School, Federal Universityof Rio de Janeiro, Rio de Janeiro/Brazil.
4Department of Oral Surgery and Pathology, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte/Brazil.
5Dental School, Federal University of Goiás, Goiania/Brazil.
6Oral Pathology Department, Dental School, University of São Paulo, São Paulo/Brazil.
7Department of Pathology, Federal University of Santa Catarina, Florianópolis/Brazil.
8Oral Pathology Department, Dental School, Federal University of Pernambuco, Recife/Brazil.
9Post-graduate Program of Dentistry, State University of Paraíba, Campina Grande/Brazil.
10Laboratory of Oral Surgical Pathology, School of Dentistry, Federal University of Bahia, Salvador/Brazil.
17 11Department of Pathology and Legal Medicine, Federal University of Amazonas, Manaus/Brazil.
12Oral Pathology, Dental School, StateUniversityof Rio de Janeiro, Rio de Janeiro/Brazil.
13Postgraduate Program in Oral Pathology, Federal University of Rio Grande do Norte, Natal/Brazil.
14Department of Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Running tittle: Oral sarcomas in Brazil.
Keywords: Epidemiology; mesenchymal tumours; sarcomas; mouth; maxillofacial regions.
ABSTRACT
Objectives: The aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil. Materials and methods: A cross-sectional study was conducted on biopsies obtained from January 2007 to December 2016 at twelve Brazilian oral and maxillofacial pathology centres. Gender, age, evolution time, clinical aspects, tumour location, tumour size at diagnosis, radiographic aspects and histopathological diagnosis were evaluated. Data were analysed using descriptive statistical methods. Results: From 176,537, a total of 200 (0.11%) oral sarcomas were reported, and the most prevalent were osteosarcomas (74 cases; 37%) and Kaposi’s sarcomas (52 cases; 26%). Males were more affected than females at a mean age of 32.2 years old (range of 3-87 years). The most common symptoms were swelling¸ localised pain and bleeding at a mean evolution time of 5.14 months (range < 1-156 months). The lesions were mostly observed in the mandible (90 cases; 45%), with a mean tumour size of 3.4 cm (range of 0.3-15 cm). Radiographically, the lesions presented a radiolucent aspect showing cortical bone destruction and ill-defined limits. Conclusions:Oral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas and Kaposi´s sarcomas were the main sarcomas of the oral cavity in Brazil.
18 INTRODUCTION
Sarcomas represent a rare and heterogeneous group of solid tumours derived from mesenchymal progenitor cells (Alishahiet al., 2015;Guevara-Canaleset al., 2012; de Bree et al., 2010).They account for less than 1% of all cancers (Yamaguchiet al., 2004).These entities can present more than 50 distinct histologic subtypes, may occur at any age and are not limited to a specific area of the human body (Siegelet al., 2018; González-Gonzálezet al., 2012). The rarity of the disease, combined with a diverse number of subtypes, can make these lesions very difficult to study (González-Gonzálezet al., 2012;Gorsky&Epstein, 2000).
Sarcomas represent nearly 1% of all neoplasms in the head and neck region, and are even rare in the oral cavity, representing less than 1% of all lesions in this anatomical site (Alishahiet al., 2015;Siegelet al., 2018). Patients affected by this group of tumours are associated with management challenges and a high risk of morbidity/mortality (Gorsky&Epstein, 2000).The poor prognosis is directly related to the difficulty of obtaining sufficient surgical margins since most parts of the lesions are close to vital organs, and can also cause significant sequelae to the patients (Alishahiet al., 2015;Lee et al., 2015;Chenet al., 2016).
Clinical and pathological studies can help to understand the biological behaviour of oral sarcomas and epidemiological studies can contribute to determining the number of people affected worldwide (Guevara-Canaleset al., 2012;Siegelet al., 2018;Woodset al., 2018).Thus, epidemiological studies based on histopathological and immunohistochemical results may provide more accurate data. Based on it, the aim of the present study was to determine the frequency of oral sarcomas in 12 representative Brazilian oral and maxillofacial pathology centres.
MATERIALS AND METHODS Study design and ethical approval
A cross-sectional study was performed in the files from 12 independent oral and maxillofacial diagnostic centres of all regions of Brazil (North, South, Northeast, Southeast and Midwest) were reviewed from January of 2007 to December 2016. A total of 176,537 samples were analysed. The
19 diagnostic centres were: Service of Oral Pathology, João de Barros Barreto University Hospital, Federal University of Pará; Department of Oral Diagnosis (Pathology and Semiology), Piracicaba Dental School, University of Campinas; Oral Pathology, Dental School, Federal University of Rio de Janeiro; Department of Oral Surgery and Pathology, School of Dentistry, Federal University of Minas Gerais; Dental School, Federal University of Goiás; Oral Pathology Department, Dental School, University of São Paulo; Department of Pathology, Federal University of Santa Catarina; Oral Pathology Department, Dental School, Federal University of Pernambuco; Post-graduate Program of Dentistry, State University of Paraíba; Laboratory of Oral Surgical Pathology, School of Dentistry, Federal University of Bahia; Department of Pathology and Legal Medicine, Federal University of Amazonas; Postgraduate Program in Oral Pathology, Federal University of Rio Grande do Norte.The samples were evaluated by an experienced pathologist and expert in the area.The ethical committee of the João de Barros Barreto University Hospital approved this work under approval number 2.518.285. The patient’s identity remained anonymous according to the Declaration of Helsinki.
Samples
Oral sarcomas were retrieved, and each of the analysed centres retrieved data regarding the gender, age, evolution time (months), clinical aspects, primary tumour site, tumour size at diagnosis (cm), radiographic aspects and final histopathological diagnosis. All lesions were classified according to the World Health Organisation Classification of Head and Neck Tumours Update published in 2017 (El-Naggaret al., 2017).The exclusion criteria were patients that the final diagnosis of the lesion did not follow the criteria established by the World Health Organisation Classification and a final diagnosis was not possible to confirm.
Data analysis
The collected data were tabulated in Microsoft Excel® for epidemiologic analysis. Descriptive and quantitative data analysis was performed using the Statistical Package for Social Sciences (SPSS) software,
20
RESULTS
From 176,537 samples, a total of 200 patients (0.11%) affected by oral sarcomas were identified at the centres studied. A total of 48 cases were excluded from the samples because did not meet the criteria for diagnosis or were diagnosed as undifferentiated sarcoma. Figure1 shows the distribution of the lesions in the country, evidencing that the southeast region showed the highest amount of cases (121 cases; 60.5%), followed by the north (40 cases; 20%), the northeast (19 cases; 9.5%), the midwest (14 cases; 7%) and the south (6 cases; 3%).
21
The most common histological subtypes were osteosarcoma (74 cases; 37%), followed by Kaposi’s sarcoma (52 cases; 26%), chondrosarcoma (17 cases; 8.5%) and leiomyosarcoma (12 cases; 6%). Lesions were more prevalent in males than females (male:female ratio of 1.27:1), and the mean age was 32.2 years old (range of 3-87 years old). Clinically, patients presented with swelling (108 cases), pain (36 cases), bleeding (27 cases) and paraesthesia (7 cases) at a mean evolution time of 5.14 months (range < 1-156 months). The lesions presented the mandible (90 cases), palate (30 cases), maxilla (24 cases) and gingiva (14
22
cases) as the most commonly observed primary sites and the mean tumour size was 3.4 cm at its largest diameter (range of 0.3-15 cm). Radiographically, the lesions mainly presented as a radiolucent aspect showing cortical bone destruction and ill -defined limits. Bone and cartel age sarcomas (BCS) were the most frequent sarcomas of the oral cavity with 91 cases (45.5%) (Table 1). Osteosarcomas were the most common (74 cases; 37%), followed by chondrosarcomas (17 cases; 8.5%). BCS were more prevalent in females than in males (male:female ratio of 1:1.43) at a mean age of 31.1 years old (range of 5-87). The most observed clinical aspects were swelling (41 cases; 45%), pain (22 cases; 24.2%), bleeding (8 cases; 8.8%) and paraesthesia (4 cases; 4.4%), and the mean evolution time was 13.15 months (range of 1-156 months). BCS predominantly arose in the mandible (64 cases) and maxilla (15 cases) and demonstrated a tumour size of 3.45 cm on its highest diameter (range of 1.5-8 cm). Radiographically, the lesions showed radiolucent (20 cases) or radiopaque (3 cases) images, with cortical bone destruction (6 cases), sunray aspect (4 cases) and ill-defined limits (4 cases),while 54 cases did not report any radiographic abnormality.
23
Table 1: Clinicopathological characteristics of bone and cartilagesarcomas. Bone and cartilage tumours
Patients (No) Sex (M:F) Mean age (range) Evolution time
(months) Clinical aspects Main locations
Tumor size (cm) Radiographic aspects Osteosarcoma 74 1:1.51 31.8 (5-87) 7.3 (1-120) Swelling (35); Pain (17); Bleeding (8); Paresthesia (3); ND (11) Mandible (55); Maxilla (10); Palate (2); ND (7) 4.1 (1.5-8) Radiolucent image (17); Sun-ray aspect (4); Ill-defined limits (4); Cortical
bone destruction (4); ND (45) Chondrosarcoma 17 1:1.12 30.4 (14-61) 19 (1-156) Swelling (6); Pain (5); Paresthesia (1); ND (5) Mandible (9); Maxilla (5); ND (3) 2.8 (1.5-5) Radiolucent image (3); Radiopaque image (3); Cortical bone destruction
(2); ND (9) Total 91 1:1.43 31.1 (5-87) 13.15 (1-156) Swelling (41); Pain (22); Bleeding (8); Paresthesia (4); ND (16) Mandible (64); Maxilla (15); Palate (2); ND (10) 3.45 (1.5-8) Radiolucent image (20); Radiopaque image (3);
Sun-ray aspect (4); Ill-defined limits (4); Cortical
bone destruction (6) and ND (54)
24
Odontogenic sarcomas (OS) represented four cases (2.0%), and all the cases were ameloblasticfibrosarcomas (Table 2). Concerning the gender, OS did not demonstrate any gender predominance (male:female ratio of 1:1) and the mean age was 14.7 years old (range of 3-23 years). Regarding the patient’s clinical signs and symptoms, patients showed swelling (2 cases 50%), bleeding (1 case; 25%) and paraesthesia (1 case; 25%) at a mean evolution time of 6 months (range of 2-12 months). OS were all located in the mandible (4 cases), with a mean tumour size of 4 cm at its largest diameter (range of 3-8 cm). Radiographically, the lesions showed a radiolucent aspect in three cases (75%), and a multilocular aspectwas found in one case (25%).
Table 2: Clinicopathological characteristics of odontogenic sarcomas. Odontogenic Sarcomas Patients (No) Sex (M:F) Mean age (range) Evolution time (months)
Clinical aspects Main locations Tumor size (cm) Radiographic aspects Ameloblastic fibrosarcoma 4 1:1 14.7 (3-23) 6 (2-12) Swelling (2); Bleeding (1); Paresthesia (1) Mandible (4) 4 (3-8) Radiolucent image (3); Multilocular lesion (1) Total 4 1:1 14.7 (3-23) 6 (2-12) Swelling (2); Bleeding (1); Paresthesia (1) Mandible (4) 4 (3-8) Radiolucent image (3); Multilocular lesion (1) Abbreviations: No (Number); M (Male); F (Female) cm (centimeters); ND (not described).
Soft tissue sarcomas (STS) were found in 43 cases (21.5%) (Table 3). The most common lesions were leiomyosarcomas (12 cases; 6%), rhabdomyosarcomas (7 cases, 3.5%) and fibrosarcoma (6 cases, 3%). The lesions presented a slight male predilection (male:female ratio of 1.2:1) at a mean age of 33.8 years old (range of 3-69 years). Clinically, patients mainly
25
demonstrated swelling (27 cases), pain (7 cases) and bleeding (3 cases) at a mean evolution time of 7.6 months (range of 1-60 months). The lesions were mostly located in the maxilla (7 cases; 16.3%), mandible (8 cases; 18.6%) and cheek (7 cases; 16.3%), and demonstrated a mean tumour size of 4.21 cm on its highest diameter (range of 0.4-15 cm). When radiographically evaluated, the lesions more commonly showed radiolucent images (10 cases) with ill-defined limits (5 cases) and cortical bone destruction (6 cases), whereas 19 cases did not report any image aspect.
Table 3: Clinicopathological characteristics of soft tissue sarcomas. Soft tissue tumours Patients (No) Sex (M:F) Mean age (range) Evolution time (months)
Clinical aspects Main locations Tumor size (cm) Radiographic aspects Pleomorphic sarcoma 3 2:1 56 (56) 4.3 (1-9) Swelling (2); Pain (1); Bleeding (1) Oropharynx (1); Floor of the mouth (1); Alveolar ridge (1) 5.2 (4.5-6)
Radiolucent image (1); Ill-defined limits (1); Cortical
bone destruction (1); ND (1) Synovial sarcoma 5 1.5:1 19.2 (10-35) 5.3 (1-12) Swelling (5); Pain (2); Bleeding (2) Maxilla (4); Floor of the mouth (1)
5 (1-4) Radiolucent image (2); Ill-defined limits (1); Cortical
bone destruction (1); ND (1)
Fibrosarcoma 6 1:1.5 35 (3-52) 2 (1-2) Swelling (5); Pain (1) Mandible (5); Gingiva (1)
4 (3-5) Radiolucent image (4); Ill-defined limits (1); Cortical
26
bone destruction (1)
Alveolar soft-part sarcoma
1 1:0 24 (-) 2 (-) Swelling (1) Gingiva (1) 3 (-) Mixed image (1); Cortical bone destruction (1) Rhabdomyosarcoma 7 2.5:1 20.3
(4-57)
4.8 (1-12) Swelling (6); Pain (1) Mandible (1); Cheek (2); Gingiva (1); Lip (1); Maxilla (1);
ND (1)
4.3 (4-5) Radiolucent image (2); Cortical bone destruction
(2); ND (3) Leiomyosarcoma 12 1.4:1 44.7 (15-69) 10.3 (1-60) Swelling (3); Pain (2); ND (7) Mandible (1); Cheek (1); Gingiva (2); Tongue (2); Maxilla (2); Alveolar ridge (3); ND (1) 6.5 (1-15) Hypodense image (1); ND (11) Liposarcoma 4 1:1 32.3 (18-59) 18.3 (7-36) Swelling (4) Cheek (3); ND (1) 2.6 (0.4-4) Ill-defined limits (2); ND (2)
Spindle cell sarcoma 2 0:2 12 (-) ND (2) ND (2) Mandible (1);
Palate (1)
27 Dermatofibrosarcoma 1 0:1 44 (-) 5 (-) ND (1) Cheek (1) 2.5 (-) ND (1) Mixoid sarcoma 2 1:1 50.5 (37-64) 24 (12-36) Swelling (1); ND (1) Gingiva (1); ND (1) 5 (-) Radiolucent image (1); Mixed image (1) Total 43 1.2:1 33.8 (3-69) 7.6 (1-60) Swelling (27); Pain (7); Bleeding (3); ND (11) Oropharynx (1); Floor of the mouth (2); Alveolar ridge (4); Maxilla (7); Mandible (8); Gingiva (6); Cheek (7); Lip (1); Tongue (2); Palate (1); ND (4) 4.21 (0.4-15) Radiolucent image (10); Mixed image (2); Ill-defined limits (5); Cortical
bone destruction (6); Hypodense image (1); ND
(19)
Abbreviations:No (Number); M (Male); F (Female) cm (centimeters); ND (not described).
Neuroectodermal sarcomas (NRS) corresponded to 3% of all cases (6 cases) (Table 4). Most patients were affected by Ewing’s sarcoma (5 cases, 2.5%), and there was a case of a neurosarcoma (1 case, 0.5%). NRS did not demonstrate a gender predominance and demonstrated a mean age of 27.3 years old (range of 14-67 years). Clinically, patients presented swelling (3 cases), pain (3 cases) and bleeding (2 cases), with a mean evolution time of 5.25 months (range of 1-12 months). The lesions were predominantly located in the mandible (5 cases; 83.3%) and showed a mean tumour size of 6 cm on its largest diameter (range of
28
2-10 cm). Under radiographic aspects, the images presented as radiolucent (2 cases) or radiopaque (1 case) with ill-defined limits (1 case), while two cases did not report any radiographic aspect.
Table 4: Clinicopathological characteristics of neuroectodermal sarcomas. Neuroectodermal tumours Patients (No) Sex (M:F) Mean age (range) Evolution time (months)
Clinical aspects Main locations Tumor size (cm) Radiographic aspects Ewing's sarcoma 5 1:1.5 19.4 (14-34) 5.6 (1-12) Swelling (2); Pain (2); Bleeding (2); ND (1)
Mandible (5) 8 (6-10) Radiolucent image (2); Radiopaque image (1);
Ill-defined limits (1); ND (1)
Neurosarcoma 1 - 67 (-) 4 (-) Swelling (1); Pain (1) Lip (1) 2 (-) ND (1)
Total 6 1:1 27.3 (14-67) 5.25 (1-12) Swelling (3); Pain (3); Bleeding (2); ND (1) Mandible (5); Lip (1) 6 (2-10) Radiolucent image (2); Radiopaque image (1);
Ill-defined limits (1); ND (2) Abbreviations: No (Number); M (Male); F (Female) cm (centimeters); ND (not described).
Vascular sarcomas (VS) were found in 54 cases (27%) (Table 5). Kaposi’s sarcomas were the most common lesion (52 cases; 26%), followed by angiosarcomas (2 cases; 1%). VS were mainly observed in male patients, with a male:female ratio of 7.3:1 at a mean age of 39.5 years old (range 18-83 years). Concerning the patient’s clinical signs and symptoms, the patients
29
showed swelling (34 cases), pain (3 cases), bleeding (12 cases) and paraesthesia (1 case) at a mean evolution time of 10 months (range of 1-60 months). These lesions were mainly located in the palate (27 cases; 50%), gingiva (8 cases; 15.7%) and mandible (5 cases 2.5%) with a mean tumour size of 2.9 cm on its largest diameter (range of 0.3-7 cm). Radiographically, the lesions showed a radiolucent (2 cases) or radiopaque (1 case) aspect with ill-defined (1 case) and cortical bone destruction (1 case), while no radiographic aspect was reported in 49 cases (90.7%).
Table 5: Clinicopathological characteristics of vascular sarcomas. Vascular tumours Patients (No) Sex (M:F) Mean age (range) Evolution time (months)
Clinical aspects Main locations Tumor size (cm)
Radiographic aspects
Angiosarcoma 2 1:1 72 (-) 7.5 (1-12) Swelling (2); Pain (1); Bleeding (1) Maxilla (2) 2 (1-3) ND (2) Kaposi's sarcoma 52 8.6:1 35.5 (18-83) 9.8 (1-60) Swelling (32); Pain (2); Bleeding (11); Paresthesia (1); ND (6) Labial commissure (1); Gingiva (8); Tongue (3); Mandible (5); Maxilla (1); Cheek (1); Oropharynx (2); Palate (27); Alveolar ridge (1); 2.7 (0.3-7) Radiolucent image (2); Radiopaque image (1);
Ill-defined (1); Cortical bone destruction (1); ND (47)
30 Uvula (1); ND (2) Total 54 7.3:1 39.5 (18-83) 10 (1-60) Swelling (34); Pain (3); Bleeding (12); Paresthesia (1); ND (6) Labial commissure (1); Gingiva (8); Tongue (3); Mandible (7); Maxilla (2); Cheek (1); Oropharynx (2); Palate (27); Alveolar ridge (1); Uvula (1); ND (2) 2.9 (0.3-7) Radiolucent image (2); Radiopaque image (1);
Ill-defined (1); Cortical bone destruction (1); ND (49)
Abbreviations: No (Number); M (Male); F (Female) cm (centimeters); ND (not described).
Metastatic Sarcomas (MS) were found in only two cases corresponding to 1.0% of all the samples (Table 6), including one case of an osteosarcoma and one case of a primitive neuroectodermal tumour (PNET). Regarding the clinical signs and symptoms, swelling, pain, bleeding and paraesthesia were observed in the patient affected by the osteosarcoma, whereas the
31
PNET-affected patient did not demonstrate any significant sign or symptom. Osteosarcomas showed a mean evolution time of 2 months and a tumour size of 1 cm at its largest diameter, while this information was not found for PNET; both lesions affecte d the mandible. Radiographically, osteosarcoma metastasis showed a periodontal ligament thickening, while in PNET metastasis no alteration was described.
Table 6: Clinicopathological characteristics of metastatic sarcomas. Metastatic tumours Patients (No) Sex (M:F) Mean age (range) Evolution time (months)
Clinical aspects Main locations Tumor size (cm) Radiographic aspects Osteosarcoma metastasis 1 - 22 (-) 2 (-) Swelling (1); Pain (1); Bleeding (1); Paresthesia (1)
Mandible (1) 1 (-) Periodontal ligament thickening (1)
32 Total 2 1:1 21 (20-22) 2 (-) Swelling (1); Pain (1); Bleeding (1); Paresthesia (1); ND (1)
Mandible (2) 1 (-) Periodontal ligament thickening (1); ND (1)
Abbreviations: No (Number); M (Male); F (Female) cm (centimeters); ND (not described); PNET (primitive neuroectodermal tumor).
DISCUSSION
Sarcomas of the jaws account for about 1% of all malignant tumours that occur in the oral cavity (Alishahi et al., 2015;Siegelet al., 2018). Their rarity has led pathologists, clinicians and researches to explore the biological behaviour of these lesions aiming to understand their pathogenesis and prognosis associated factors (González-Gonzálezet al., 2012;Gorskyet al.,
33
in establishing the distribution of the lesions worldwide (Gorskyet al., 2000). Thus, the aim of this study was to evaluate the epidemiological characteristics of 200 oral sarcomas from independent oral and maxillofacial diagnostic centres from geographic regions of Brazil and could represent the service in the country.
BCS represented the most common group in the current study (91 cases; 45.5%). Similarly, Alishahi et al., in an epidemiological study in Iran, showed that BCS were the most common group (Alishahiet al., 2015). Osteosarcomas represented the highest amount of cases (74 cases; 37%) followed by chondrosarcomas (17 cases; 8.5%), consistent with other previous studies (Alishahiet al., 2015;Gorskyet al., 2000;Chidzonga&Mahomva, 2007).The lesions were more prevalent in females at a mean age of 31.1 years old. Lee et al., in a retrospective cohort study with 541 patients, demonstrated that females were slightly more affected at a mean age of 41.3 years old (Leeet al., 2015). Clinically, the lesions showed swelling in 45% and pain in 24.2% at a mean evolution time of 13.15 months. Previous study has demonstrated that swelling is the first sign of the lesions (Gorsky&Epstein, 2000). This group of tumours generally affects the mandible (64 cases) and maxilla (15 cases) with a mean tumour size of 3.45 cm (Gorsky&Epstein, 2000; Ponteset al., 2012). Under radiographic evaluation, the lesions usually manifest as a radiolucent lesion with bone destruction, a sunray aspect and ill-defined limits(Chidzonga&Mahomva, 2007; Pontes et al., 2012; Prado et al., 2009).
OS were observed in 2% of all cases (4 cases), and all were ameloblasticfibrosarcomas. Martínez et al. in an epidemiological study of odontogenic malignant lesions in Latin America observed that ameloblasticfibrosarcomas represented 24% of all samples(MartínezMartínezet al., 2014).In the current study, the patients did not present a gender predominance at a mean age of 14.7 years old. Chrcanovic et al. showed that male patients are slightly more affected than females at a mean age of 27.7 years old (Chrcanovicet al., 2018). Clinically, the lesions demonstrated swellings in 50%, bleeding in 25% and paraesthesia in 25% at a mean evolution time of 6 months, as previously reported in the literature (Chrcanovicet al., 2018;Laiet al., 2012;Al Shetawiet al., 2015). The mandible was affected in all cases with a mean tumour size of 4 cm (Chrcanovicet al., 2018).The radiographic features ranged from a multilocular radiolucent aspect to mixed images (Chrcanovicet al., 2018; Al Shetawiet al., 2015).
34
STS was found in 21.5% of all samples (43 cases). Chidzonga and Mahomva, in an epidemiological study in Zimbabwe, showed that this group of lesions represented 50% of the analysed samples (Chidzonga&Mahomva, 2007). Leiomyosarcomas were the most prevalent lesion (12 cases; 6%), followed by rhabdomyosarcomas (7 cases, 3.5%) and fibrosarcomas (6 cases, 3%). Pandey et al. showed that rhabdomyosarcomas were the most prevalent in their analysis (Pandeyet al., 2003). STS demonstrated a slight male predilection at a mean age of 33.8 years old. A previous study developed by González-González et al. showed that these lesions were more prevalent in male patients (male/female ratio of 1.5:1) and the average age was 43.1 years old (González-Gonzálezet al., 2012). Clinically, the lesions showed swelling in 62.8% and pain in 16.3% at a mean evolution time of 7.6 months. Pontes et al. showed that the clinical aspects might vary significantly, ranging from asymptomatic lesions to painful swellings (Ponteset al., 2018). The lesions were more commonly observed in the maxilla, mandible and cheek with a tumour size of 4.21 cm, consistent with other previous studies (de Breeet al., 2010;Pandeyet al., 2003). Radiographically, the lesions were observed as radiolucent lesions, with ill-defined limits and cortical bone destruction (de Breeet al., 2010;Ponteset al., 2018).
NRS were seen in 3% of all samples (6 cases). Sumida et al., in a Japanese epidemiological study, showed that NRS represented just 5.25% of all the analysed sarcomas (Sumidaet al., 2015). Ewing sarcoma was the most prevalent histological type (5 cases, 2.5%), followed by neurosarcoma (1 case, 0.5%). This group of lesions did not demonstrate any gender prevalence and showed a mean age of 27.3 years old. Previous studies demonstrated that the tumours were more common in males in the first decade of life (Owoshoet al., 2016;Iatrouet al., 2018). Concerning the clinical aspects, swelling was evidenced in 50%, pain in 50% and bleeding in 33.3% at a mean evolution time of 5.25 months. Margaix-Muñoz et al. reported that the main clinical aspects were swelling (70.4%) and pain (28.2%) (Margaix-Muñozet al., 2017). The current cases affected the mandible more, and the mean tumour size was 6 cm, consistent with other previous results (Owoshoet al., 2016; Iatrouet al., 2018). Radiographically, the tumours exhibited radiolucent or radiopaque images with ill-defined limits (Owoshoet al., 2016;Margaix-Muñozet al., 2017).
35
VS were found in 54 cases (27%). Wu et al. in a Chinese study observed that these lesions affected just 6.5% when compared with the whole human body (Wuet al., 2014). Our findings showed that Kaposi’s sarcomas were the most common lesion (52 cases; 26%), followed by angiosarcomas (2 cases; 1%). The lesions were more frequent in male patients at a mean age of 39.5 years old. Previous studies demonstrated that males in the fourth decade of life are more affected, such as in our results (Chidzonga, 2003; Ramírez-Amador et al., 2009). In addition, the clinical aspects showed that patients commonly demonstrated swelling and bleeding, while pain and paraesthesia were uncommon, at a mean evolution time of 10 months. Regarding the previous literature, the studies demonstrated similar findings and emphasised the progression of Kaposi’s sarcoma due to systemic problems (Wuet al., 2014;Chidzonga, 2003;Nagataet al., 2014). The lesions mainly affected the palate, gingiva and mandible, with a mean tumour size of 2.9 cm (Chidzonga, 2003; Ramírez-Amadoret al., 2009). Radiographic aspects showed radiolucent or radiopaque lesions with ill-defined limits and bone destruction, consistent with previous studies (Ramírez-Amadoret al., 2009;Nagataet al., 2014).
MS represented 1% of all samples of the current study. Maschino et al. observed in a French epidemiological study that this group of lesions represented just 0.48% of all treated malignancies of their institute over a period of 27 years (Maschinoet al., 2013). Our results evidenced one case of a metastatic osteosarcoma and one of a metastatic PNET. Clinically, osteosarcomas presents as a swelling with ulceration areas, demonstrating pain and bleeding, showing an evolution time of two months and a mean tumour size of 1 cm (Marianoet al., 2013). Our study did not describe any clinical aspect for PNET, although Pereira et al. reported a case of a metastatic PNET that presented as a painful ulcerated swelling with one month of evolution (Pereiraet al., 2005). At the radiographic examination, the osteosarcoma case showed periodontal ligament thickening, which has been previously demonstrated in the literature(Marianoet al., 2013).
Unfortunately, a limitation of the current study is that staging, grading, treatment and follow-up were not available because the investigation involved only retrospective data.Thus, it was not possible to perform the sample calculation in an
epidemiological study.After diagnosis, patients were referred to treatment in hospitals
36
Because of the rarity of these lesions, multicentre prospective studies are crucial to integrate clinical, radiographic and histopathologic information of these group of tumours. In addition, it is relevant to emphasise that the notification of malignant neoplasms is important because it can lead to early-diagnosis measures leading to a better prognosis and a more effective treatment for the population.
CONCLUSION
Oral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas, Kaposi´s sarcomas and chondrosarcomas were the main sarcomas of the oral cavity in Brazil.
ACKNOWLEDGMENTS No acknowledgments.
CONFLICT OF INTEREST STATEMENT None.
REFERENCES
Al Shetawi AH, Alpert EH, Buchbinder D, Urken ML. Ameloblasticfibrosarcoma of the mandible: A case report and a review of the literature. J Oral MaxillofacSurg 2015;73(8):1661.e1-7.
Alishahi B, Kargahi N, Homayouni S. Epidemiological Evaluation of Head and Neck Sarcomas in Iran (the Study of 105 Cases Over 13 Years). Iran J Cancer Prev 2015;8(4):e3432.
Chen YM, Shen QC, Gokavarapu S, Ong HS, Cao W, Ji T. Osteosarcoma of the Mandible: A Site-Specific Study on Survival and Prognostic Factors. J CraniofacSurg 2016;27(8):1929-1933.
Chidzonga MM, Mahomva L. Sarcomas of the oral and maxillofacial region: a review of 88 cases in Zimbabwe. Br J Oral MaxillofacSurg 2007;45(4):317-8.
Chidzonga MM. HIV/AIDS orofacial lesions in 156 Zimbabwean patients at referral oral and maxillofacial surgical clinics. Oral Dis 2003;9(6):317-22.
37
Chrcanovic BR, Brennan PA, Rahimi S, Gomez RS. Ameloblastic fibroma and ameloblasticfibrosarcoma: A systematic review. J Oral Pathol Med 2018;47(4):315-325.
de Bree R, van der Waal I, de Bree E, Leemans CR. Management of adult soft tissue sarcomas of the head and neck. Oral Oncol 2010;46(11):786-90.
El-Naggar AK, Chan JK, Grandis JR, Takata T, Slootweg PJ. World Health Organization classification of head and neck tumours. Lyon, France: IARC Press; 2017.
González-González R, Bologna-Molina R, Molina-Frechero N, Domínguez-Malagon HR. Prognostic factors and treatment strategies for adult head and neck soft tissue sarcoma. Int J Oral MaxillofacSurg 2012;41(5):569-75.
Gorsky M, Epstein JB. Craniofacial osseous and chondromatous sarcomas in British Columbia: A review of 34 cases. Oral Oncol 2000;36(1):27-31.Guevara-Canales JO, Sacsaquispe-Contreras SJ, Morales-Vadillo R, Sánchez-Lihón J. Epidemiology of the sarcomas of the jaws in a Peruvian population. Med Oral Patol Oral Cir Bucal 2012;17(2):e201-5.
Iatrou I, Theologie-Lygidakis N, Schoinohoriti O, Tzermpos F, Mylonas AI. Ewing's sarcoma of the maxillofacial region in Greek children: Report of 6 cases and literature review. J CraniomaxillofacSurg 2018;46(2):213-221.
Lai J, Blanas N, Higgins K, Klieb H. Ameloblasticfibrosarcoma: report of a case, study of immunophenotype, and comprehensive review of the literature. J Oral MaxillofacSurg 2012;70(8):2007-12.
Lee RJ, Arshi A, Schwartz HC, Christensen RE. Characteristics and prognostic factors of osteosarcoma of the jaws: A retrospective cohort study. JAMA Otolaryngol Head Neck Surg 2015;141(5):470-7.
Margaix-Muñoz M, Bagán J, Poveda-Roda R. Ewing sarcoma of the oral cavity. A review. J ClinExpDent 2017;9(2):e294-e301.
Mariano FV, Corrêa MB, da Costa MV, de Almeida OP, Lopes MA. Labial mucosa metastasis of fibule giant cell-rich osteosarcoma: An unusual presentation. QuintessenceInt 2013;44(10):783-91.
Martínez Martínez M, Mosqueda-Taylor A, Carlos R, Delgado-Azañero W, de Almeida OP. Malignant odontogenic tumors: a multicentric Latin American study of 25 cases. Oral Dis 2014;20(4):380-5.
38
Maschino F, Guillet J, Curien R, Dolivet G, Bravetti P. Oral metastasis: A report of 23 cases. Int J Oral MaxillofacSurg 2013;42(2):164-8.
Nagata M, Yoshitake Y, Nakayama H, Yoshida R, Kawahara K, Nakagawa Y, et al. Angiosarcoma of the oral cavity: A clinicopathological study and a review of the literature. Int J Oral MaxillofacSurg 2014;43(8):917-23.
Owosho AA, Ko E, Rosenberg HI, Yom SK, Antonescu CR, Huryn JM, et al. Primary Ewing family of tumors of the jaw has a better prognosis compared to tumors of extragnathic sites. J Oral MaxillofacSurg 2016;74(5):973-81.
Pandey M, Chandramohan K, Thomas G, Mathew A, Sebastian P, Somanathan T, et al. Soft tissue sarcoma of the head and neck region in adults. Int J Oral MaxillofacSurg 2003;32(1):43-8.
Pereira CM, de Abreu Alves F, Corrêa ME, Lima CS, de Almeida OP. Mouth metastasis of peripheral primitive neuroectodermaltumor. Oral Dis 2005;11(1):44-5.
Prado FO, Nishimoto IN, Perez DE, Kowalski LP, Lopes MA. Head and neck chondrosarcoma: analysis of 16 cases. Br J Oral MaxillofacSurg 2009;47(7):555-7.
Pontes HA, Pontes FS, de Abreu MC, de Carvalho PL, de Brito Kato AM, Fonseca FP, et al. Clinicopathological analysis of head and neck chondrosarcoma: three case reports and literature review. Int J Oral MaxillofacSurg 2012;41(2):203-10. Pontes FS, de Oliveira JI, de Souza LL, de Almeida OP, Fregnani ER, Vilela RS, et al. Clinicopathological analysis of head and neck rhabdomyosarcoma: A series of 10 cases and literature review. Med Oral Patol Oral Cir Bucal 2018;23(2):e188-e197.
Ramírez-Amador V, Martínez-Mata G, González-Ramírez I, Anaya-Saavedra G, de Almeida OP. Clinical, histological and immunohistochemical findings in oral Kaposi's sarcoma in a series of Mexican AIDS patients. Comparative study. J Oral Pathol Med 2009;38(4):328-33.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68(1):7-30.
Sumida T, Otawa N, Kamata YU, Yamada T, Uchida K, Nakano H, et al. A clinical investigation of oral sarcomas at multi-institutions over the past 30 years. Anticancer Res. 2015 Aug;35(8):4551-5.
39
Woods RH, Potter JA, Reid JL, Louise J, Bessen T, Farshid G, et al. Patterns of head and neck sarcoma in Australia. ANZ J Surg 2018;88(9):901-906.
Wu XJ, Pu XM, Kang XJ, Halifu Y, An CX, Zhang DZ, et al. One hundred and five Kaposi sarcoma patients: a clinical study in Xinjiang, Northwest of China. J EurAcadDermatolVenereol 2014;28(11):1545-52.
Yamaguchi S, Nagasawa H, Suzuki T, Fujii E, Iwaki H, Takagi M, et al. Sarcomas of the oral and maxillofacial region: A review of 32 cases in 25 years. Clin Oral Investig 2004;8(2):52-5
40
3 CONCLUSÃO
Os sarcomas orais são raras lesões que acometem a cavidade oral, onde o osteossarcoma, o sarcoma de Kaposi e o condrossarcoma foram os principais sarcomas que acometem este sítio anatômico no Brasil.
41
REFERÊNCIAS
Alishahi B, Kargahi N, Homayouni S. Epidemiological Evaluation of Head and Neck Sarcomas in Iran (the Study of 105 Cases Over 13 Years). Iran J Cancer Prev 2015;8(4):e3432.
Chidzonga MM, Mahomva L. Sarcomas of the oral and maxillofacial region: a review of 88 cases in Zimbabwe. Br J Oral MaxillofacSurg 2007;45(4):317-8.
Chung WJ, Chung HW, Shin MJ, Lee SH, Lee MH, Lee JS, Kim MJ, Lee WK. MRI to differentiate benign from malignant soft-tissue tumors of the extremities: a simplified systematic imaging approach using depth, size and heterogeneity of signal intensity. Br J Radiol 2012; 85:e831–e836
deBree R, van der Waal I, de Bree E, Leemans CR. Management of adult soft tissue sarcomas of the head and neck. Oral Oncol 2010;46(11):786-90.
El-Naggar AK, Chan JK, Grandis JR, Takata T, Slootweg PJ. World Health Organization classification of head and neck tumours. Lyon, France: IARC Press; 2017.
González-González R, Bologna-Molina R, Molina-Frechero N, Domínguez-Malagon HR. Prognostic factors and treatment strategies for adult head and neck soft tissue sarcoma. Int J Oral MaxillofacSurg 2012;41(5):569-75.
Ilstrup DM. Value of MR imaging in differentiating benign from malignant soft-tissue masses: study of 95 lesions. AJR 1990; 155:1251–1255.
Lee RJ, Arshi A, Schwartz HC, Christensen RE.Characteristics and prognostic factors of osteosarcoma of the jaws: a retrospective cohort study.JAMA Otolaryngol Head Neck Surg. 2015 May 1;141(5):470-7.
Makary RF, Gopinath A, Markiewicz MR, Fernandes R.Margin Analysis: Sarcoma of the Head and Neck.Oral MaxillofacSurgClin North Am. 2017 Aug;29(3):355-366.
Martínez Martínez M, Mosqueda-Taylor A, Carlos R, Delgado-Azañero W, de Almeida OP. Malignant odontogenic tumors: a multicentric Latin American study of 25 cases. Oral Dis 2014;20(4):380-5.
42
Nagata M, Yoshitake Y, Nakayama H, Yoshida R, Kawahara K, Nakagawa Y, et al. Angiosarcoma of the oral cavity: A clinicopathological study and a review of the literature. Int J Oral MaxillofacSurg 2014;43(8):917-23.
O’Neill JP, Bilsky MH, Kraus D. Head and neck sarcomas: epidemiology, pathology, and management. NeurosurgClin N Am 2013;24(1):67–78.
Pandey M, Chandramohan K, Thomas G, Mathew A, Sebastian P, Somanathan T, Abraham EK, Rajan B, Krishnan Nair M.. Soft tissue sarcoma of the head and neck region in adults. Int J Oral MaxillofacSurg 2003;32(1):43-8.
Peng KA, Grogan T, Wang MB. Head and neck sarcomas: analysis of the SEER database. OtolaryngolHead Neck Surg 2014;151(4):627–33.
Potter BO, Sturgis EM. Sarcomas of the head and neck. SurgOncolClin N Am 2003;12(2):379–417.
Pontes HA, Pontes FS, de Abreu MC, de Carvalho PL, de Brito Kato AM, Fonseca FP, de Freitas Silva BS, Neto NC. Clinicopathological analysis of head and neck chondrosarcoma: three case reports and literature review. Int J Oral MaxillofacSurg 2012;41(2):203-10.
Pontes FS, de Oliveira JI, de Souza LL, de Almeida OP, Fregnani ER, Vilela RS, Silva WM, Fonseca FP, Pontes HA. Clinicopathological analysis of head and neck rhabdomyosarcoma: A series of 10 cases and literature review. Med Oral Patol Oral Cir Bucal 2018;23(2):e188-e197.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68(1):7-30.
Smith VA, Overton LJ, Lentsch EJ. Head and neck soft tissue sarcomas: unique lack of significance of synchronous node metastases. J SurgOncol 2012;106(7):837–43.
Wanebo HJ, Koness RJ, MacFarlane JK, Eilber FR, Byers RM, Elias EG, Spiro RH. Head and neck sarcoma: report of the Head and Neck Sarcoma Registry. Society of Head and Neck Surgeons Committee on Research. Head Neck 1992;14(1):1–7.
Woods RH, Potter JA, Reid JL, Louise J, Bessen T, Farshid G, Neuhaus SJ. Patterns of head and neck sarcoma in Australia. ANZ J Surg 2018;88(9):901-906.
43
Yeang MS, Tay K, Ong WS, Thiagarajan A, Tan DS, Ha TC, Teo PT, Soo KC, Tan HK, Iyer NG. Outcomes and prognostic factors of post-irradiation and de novo sarcomas of the head and neck: a histologically matched case-control study. Ann SurgOncol 2013; 20(9):3066–75.
Zahm SH, Fraumeni JF Jr. The epidemiology of soft tissue sarcoma. SeminOncol 1997;24(5):504–14.
Zagars GK, Ballo MT, Pisters PW, Pollock RE, Patel SR, Benjamin RS, Evans HL. Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients. Cancer 2003;97(10):2530–43.
44 ANEXOS
Anexo 1 - Verificação de originalidade e prevenção de plágio
UM ESTUDO MULTICÊNTRICO DOS SARCOMAS BUCAIS NO BRASIL
45 Anexo 2 - Certificado do Comitê De Ética em Pesquisa
47
