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Oral soft-tissue sarcomas diagnosed in an oral pathology service: a 16year experience

| Objective: This study analyzed the prevalence and clinic-pathological features of soft-tissue sarcomas diagnosed in a single-center of oral pathology from a School of Dentistry in Brazil. Materials and methods: All consecutive cases of intra-oral soft-tissue sarcomas diagnosed between January of 2002 and December of 2018 were retrieved from the files; patient data (sex, age and race) and characteristics of the lesions (site, size, clinical aspect and duration of injury) were collected. Results: Among a total of 62,255 biopsies diagnosed in the studied period, soft-tissue oral sarcomas comprised 76 cases (0.12%). Kaposi sarcoma, rhabdomyosarcoma, leiomyosarcoma encompassed 64.5% of the cases, and 53% of these were diagnosed as Kaposi Sarcoma. Male patients were more affected (59.2%) and white patients comprised 50%. In general, 39.4% of the patients were between 21-40yo. Conclusion: Soft-tissue sarcomas are rare in oral soft-tissue and in our pathology service, they comprised only 0.12% of all diseases diagnosed in the studied period. Kaposi sarcoma was the most frequent, followed by leiomyosarcoma and rhabdomyosarcoma. Thus, it is important for stomatologists and pathologists to be aware of their characteristics when examining oral mucosa, mainly their peculiarities regarding patient’s age, clinical appearance, and site of occurrence. DESCRIPTORS | Sarcoma; Epidemiology; Diagnosis; Histopathology; Soft-Tissue. RESUMO | Sarcomas de tecido mole oral diagnosticado em um serviço de patologia orai: uma experiência de 16 anos • Objetivo: Este estudo analisou a prevalência e as características clinico-patológicas de sarcomas de tecidos moles diagnosticados em um único centro de patologia oral de uma escola odontológica no Brasil. Materiais e métodos: Todos os casos consecutivos de sarcomas de tecido mole intraoral, diagnosticados entre janeiro de 2002 e dezembro de 2018, foram obtidos de arquivos; os dados dos pacientes (sexo, idade e raça) e as características da lesão (local, tamanho, aspecto clínico e duração da lesão) foram coletados. Resultado: De 62.255 biopsias diagnosticadas no período estudado, sarcoma oral de tecidos moles abrangia somente 76 dos casos (0,12%). Desses, sarcoma de Kaposi, rabdomiossarcoma e leiomiossarcoma correspondiam a 64,5%; dos quais, 53% foram diagnosticados como sarcoma de Kaposi. Pacientes masculinos foram os mais afetados (59,2%) e 50% dos pacientes eram brancos. Em geral, 39,4% dos pacientes tinham entre 21-40 anos de idade. Conclusão: Sarcomas de tecido mole são raros em tecido mole oral e, em nosso serviço de patolologia, totalizavam apenas 0,12% de todas as doenças diagnosticadas no período do estudo. Sarcoma de Kaposi foi o mais frequente, seguido por leiomiossarcoma e rabdomiossarcoma. Por isso é importante para estomatologistas e patologistas estarem atentos às características durante o exame da mucosa oral, principalmente às suas peculiaridades referentes à idade do paciente, a aparência clínica da lesão e o local da ocorrência. DESCRITORES | Sarcoma; Epidemiologia; Diagnóstico; Histopatologia; Tecidos Moles. CORRESPONDING AUTHOR | Paulo Sérgio Souza Pina Department  of  Stomatology,  University  of  São Paulo  • Av. Prof. Lineu Prestes, 2227 São  Paulo,  SP,  Brasil  • 05508000 E-mail: ps.souzapina@usp.br • Received April 16, 2021  • Accepted August 10, 2021 • DOI http://dx.doi.org/10.11606/issn.2357-8041.clrd.2019.184424 Oral soft-tissue sarcomas diagnosed in an oral pathology service: a 16year experience 2 ● Clin Lab Res Den 2021: 1-9 INTRODUCTION Sarcomas are uncommon, malignant, and usually aggressive neoplasms that only rarely involve the oral soft-tissues. They are solid tumors of mesenchymal cells and exhibit a variety of clinical and pathologic characteristics with different prognostic implications.1 They correspond to less than 1% of all oral cancers2 and comprise only around 10% of all sarcomas of the body in adults;3,4 in children, however, 21% of all malignancies are sarcomas,5 of which 7%-10% affect the soft tissues.4,6 Around 87% of head and neck soft-tissue sarcomas are extragnathic, being the maxilla responsible for 8% of the cases, and the mandible, 5%.4 Nevertheless, rhabdomyosarcomas are more frequent in the head and neck region than in any other part of the body.1 Sarcomas occur mostly in males, and the mean age of occurrence is between 50-55 years. Most oral soft-tissue sarcomas are complex, and there is a large spectrum of histopathological subtypes, what can modify the prognosis.3 In general, soft-tissue sarcomas are largely variable due to their rarity, diversity, and heterogeneity.2,7 Moreover, acquired genetic mutations and genetic predisposition, along with chemical carcinogens and viral infections, or even previous exposure to radiation or chemotherapy, play an important role in the pathogenesis of these tumours.4,8 Although imaging exams such as ultrasound and magnetic resonance are used for diagnosing soft-tissue sarcomas, biopsy is essential for tumor differentiation and grading. However, excisional biopsies must be avoided to prevent contamination of the site, and, consequently, to reduce the risk of jeopardizing the treatment and outcomes.4 The increased use of immunohistochemistry and molecular markers have improved the ability to definitively subclassify sarcomas.1 A meticulous histopathologic analysis with the use of immunohistochemistry and, sometimes, the use of molecular techniques are essential.9 The treatment of soft tissue sarcomas of the head and neck is complex, and the outcomes depend on grade, histopathological type, and extent of the tumour.2,4 Surgical resection with negative margins is the primary treatment of choice, and postoperative radiation can improve the prognosis,9,10 being mainly reserved for patients with high-grade or advanced disease.4 Although the role of chemotherapy in these lesions is not well known yet,9 this treatment is considered in cases that have a high risk of lung metastases, and when local relapse cannot be surgically salvaged.4,11 However, because of the challenges in achieving local control, the threshold for using neo-adjuvant chemotherapy in head and neck soft-tissue sarcomas may be lower than in soft tissue sarcomas of the extremities.2 Epidemiological studies based on clinical, histopathological and immunohistochemical results can contribute to determine accurate data.12 Due to the rarity of these neoplasms in the oral mucosa, this paper reports a retrospective study which analyzes the prevalence of intra oral soft-tissue sarcomas (IOSTS) in an Oral and Maxillofacial Pathology Service from a School of Dentistry in Brazil. MATERIALS AND METHODS A cross-sectional study was performed in the files from the Oral and Maxillofacial Pathology Department of the School of Dentistry at the University of São Paulo, São Paulo – Brazil. Cases diagnosed as intraoral soft-tissue sarcomas (IOSTS), comprising the period from January 2002 to December 2018, were reviewed. The study was performed after the approval of the local ethics committee (number 1.824.891) Clinical aspects of the patients and of their tumors were obtained from the records of the histopathological diagnosis requirement. Patient data (sex, age, and race) and tumor data (site, clinical aspect, size, time of evolution) were collected from each case. All morphological and immunohistochemical slides were reviewed for diagnosis confirmation. The sarcomas which originated in hardtissues or cartilage were excluded. Pina PSS • Bergamini ML • Coracin FL • Sousa SCOM Clin Lab Res Den 2021: 1-9 ●  3 Analysis of global prevalence (sarcomas/total biopsies), type of sarcoma, as well as prevalence by sex, age group, and location in the mucosa were performed. RESULTS One-hundred and ninety-five cases (0.31%) diagnosed as sarcomas were retrieved from a total of 62,255 biopsies diagnosed in the time ranged. Out of this total, 76 cases were diagnosed as intra oral soft-tissue sarcomas (IOSTS), with a 0.12% prevalence from 2002 to 2018. To identify whether the prevalence of the tumors changed over time we considered the periods: 2002-2003 (prevalence 0.18%), 2004-2008 (0.14%), 2009-2013 (0.14%), 2014-2018 (0.05%). All hematoxylin-eosin stained slides were reviewed by two pathologists, as well as immunohistochemical results (when available), for diagnosis accuracy. Figure 1 illustrates the most typical histological aspects of the 4 (four) most frequent intra oral soft tissue sarcomas. FIGURE 1 | The most typical histopathological aspect of the four most frequent oral soft tissue sarcomas – hematoxylin-eosin stain in magnification of ×100 and positive immunohistochemical (inset): (A) a leiomyosarcoma showing spindle cell fascicles with abundant eosinophilic cytoplasm, no precise limits and cigar-shaped nuclei, and a mitosis (arrow). Positive for smooth muscle actin (SMA) (inset); (B) a liposarcoma depicting variable-sized lipoblasts with atypical and vacuolated cells; Inset showing positivity for S-100; (C) an alveolar rhabdomyosarcoma showing intersecting fascicles of mitotically active, large round cells with scanty cytoplasm and large nuclei. Nuclei positive for myogenin (inset); and (D) a Kaposi sarcoma which shows neoplastic proliferation of bulky spindle cells with imprecise limits and poorly formed vascular slits. Nuclei positive for HHV-8 (as seen in the inset). IOSTS represented 2.64% of all malignant lesions diagnosed at any anatomical location in the service (2.872). Table 1 shows the demographic data of the patients. There was a predominance of males (45 cases, 59.2%). Although in 22 cases the skin color was not informed, most of the patients were white (38 cases or 50%), in the 3rd or 4th decades of life (14 and 16 patients, respectively). The mean age was 33.9yo (range: 0-71yo). TABLE 1 | Demographic characteristics of the patients. DEMOGRAPHIC DATA FREQUENCY (%)* Gender Male 45 (59.2%) Female 31 (40.8%) Race White 38 (50%) Black 11 (14.5%) Mixed 5 (6.6%) Not informed 22 (28.9%) Age group (years) 1-10 10 (13.2%) 11-20 09 (11.8%) 21-30 14 (18.4%) 31-40 16 (21%) 41-50 10 (13.2%) 51-60 06 (7.9%) 61-70 07 (9.2%) >70 01 (1.3%) Not informed 03 (3.9%) * Represents the total of all 80 cases. The distribution of IOSTS showed that Kaposi sarcoma was the most frequent tumor, corresponding to 34.2% of all cases (26 cases), followed by leiomyosarcomas (13 cases – 17.1%) and rhabdomyosarcomas (10 cases – 13.2%), making up 64.5% of all the cases diagnosed in the period. In addition, Kaposi sarcoma demonstrated to be more frequent in males (22/26 cases) and mostly in HIV+ patients (18/26 confirmed cases) (Table 2). Of the HIV+ patients, 4 (four) were not aware of it when the Kaposi sarcoma was diagnosed. The other patients were in antiretroviral treatment and for one patient the lesion was a recurrence. Oral soft-tissue sarcomas diagnosed in an oral pathology service: a 16year experience 4 ● Clin Lab Res Den 2021: 1-9 TABLE 2 | Histological type of oral soft-tissue sarcomas and gender distribution. TUMOUR TYPE SEX Male Female Total (Frequency – %)* Kaposi sarcoma 22 4 26 (34.2%) Leiomyosarcoma 7 6 13 (17.1%) Rhabdomyosarcoma 5 5 10 (13.2%) Malignant schwannoma 3 2 5 (6.6%) Liposarcoma 1 3 4 (5.3%) Myxoid sarcoma 2 2 4 (5.3%) Synovial sarcoma 1 1 2 (2.6%) High-grade sarcoma 1 1 2 (2.6%) Spindle cell sarcoma 0 2 2 (2.6%) Alveolar sarcoma 0 2 2 (2.6%) Carcinosarcoma 1 0 1 (1.3%) Hystocitic sarcoma 0 1 1 (1.3%) Dendritic cells sarcoma 0 1 1 (1.3%) Undifferentiated sarcoma 1 0 1 (1.3%) Pleomorphic sarcoma 1 0 1 (1.3%) Myofibroblastic sarcoma 0 1 1 (1.3%) TOTAL 45 31 76 (100%) * Represents the total of all 80 cases. TABLE 3 | Distribution of oral soft-tissue sarcomas and their main site of location. TUMOUR TYPE LOCATION NI Palate Gingiva Buccal mucosa Tongue Alveolar ridge Others Kaposi sarcoma 14 3 0 2 1 5 2 Leiomyosarcoma 5 1 2 2 1 2 0 Rhabdomyosarcoma 1 1 3 0 1 3 1 Liposarcoma 0 0 1 2 0 0 1 Malignant schwannoma 2 2 1 0 0 0 0 While rhabdomyosarcoma was the most common histopathological type seen in pediatric patients (5 cases – 50%), Kaposi sarcoma was frequently diagnosed in adults in the third (10 cases – 38.46%) and fourth (9 cases – 34.61%) decades of life. The palate was the most common primary affected site (24 cases, 31.6%), followed by gingiva (11 cases – 14.5%), buccal mucosa (9 cases – 11.8%), tongue (8 cases – 10.5%), upper and lower alveolar ridge (6 cases – 7.9%). Other locations of involvement were lips, floor of mouth, upper buccal vestibule, retromolar region, soft palate, and peri-implant mucosa. In six cases there was no site of involvement registered (Table 3). Figure 2 illustrates both clinical and histological appearance of a rare synovial sarcoma located in retromolar area. Table 4 shows that clinical presentation varied between a nodule or a solid mass (28 cases, 36.8%), followed by ulcer (4 cases – 5.3%) and maculae (3 cases – 3.9%) and, in 19 cases (25%), the patients stated that the lesions were asymptomatic.


INTRODUCTION
Sarcomas are uncommon, malignant, and usually aggressive neoplasms that only rarely involve the oral soft-tissues. They are solid tumors of mesenchymal cells and exhibit a variety of clinical and pathologic characteristics with different prognostic implications. 1 They correspond to less than 1% of all oral cancers 2 and comprise only around 10% of all sarcomas of the body in adults; 3,4 in children, however, 21% of all malignancies are sarcomas, 5 of which 7%-10% affect the soft tissues. 4,6 Around 87% of head and neck soft-tissue sarcomas are extragnathic, being the maxilla responsible for 8% of the cases, and the mandible, 5%. 4 Nevertheless, rhabdomyosarcomas are more frequent in the head and neck region than in any other part of the body. 1 Sarcomas occur mostly in males, and the mean age of occurrence is between 50-55 years. Most oral soft-tissue sarcomas are complex, and there is a large spectrum of histopathological subtypes, what can modify the prognosis. 3 In general, soft-tissue sarcomas are largely variable due to their rarity, diversity, and heterogeneity. 2,7 Moreover, acquired genetic mutations and genetic predisposition, along with chemical carcinogens and viral infections, or even previous exposure to radiation or chemotherapy, play an important role in the pathogenesis of these tumours. 4,8 Although imaging exams such as ultrasound and magnetic resonance are used for diagnosing soft-tissue sarcomas, biopsy is essential for tumor differentiation and grading. However, excisional biopsies must be avoided to prevent contamination of the site, and, consequently, to reduce the risk of jeopardizing the treatment and outcomes. 4 The increased use of immunohistochemistry and molecular markers have improved the ability to definitively subclassify sarcomas. 1 A meticulous histopathologic analysis with the use of immunohistochemistry and, sometimes, the use of molecular techniques are essential. 9 The treatment of soft tissue sarcomas of the head and neck is complex, and the outcomes depend on grade, histopathological type, and extent of the tumour. 2,4 Surgical resection with negative margins is the primary treatment of choice, and postoperative radiation can improve the prognosis, 9,10 being mainly reserved for patients with high-grade or advanced disease. 4 Although the role of chemotherapy in these lesions is not well known yet, 9 this treatment is considered in cases that have a high risk of lung metastases, and when local relapse cannot be surgically salvaged. 4,11 However, because of the challenges in achieving local control, the threshold for using neo-adjuvant chemotherapy in head and neck soft-tissue sarcomas may be lower than in soft tissue sarcomas of the extremities. 2 Epidemiological studies based on clinical, histopathological and immunohistochemical results can contribute to determine accurate data. 12 Due to the rarity of these neoplasms in the oral mucosa, this paper reports a retrospective study which analyzes the  Analysis of global prevalence (sarcomas/total biopsies), type of sarcoma, as well as prevalence by sex, age group, and location in the mucosa were performed.

RESULTS
One-hundred and ninety-five cases (0.31%)  Figure   1 illustrates the most typical histological aspects of the 4 (four) most frequent intra oral soft tissue sarcomas.

IOSTS represented 2.64% of all malignant lesions
diagnosed at any anatomical location in the service (2.872). Table 1 shows the demographic data of the patients. There was a predominance of males (45 cases, 59.2%). Although in 22 cases the skin color was not informed, most of the patients were white (38 cases or 50%), in the 3 rd or 4 th decades of life (14 and 16 patients, respectively). The mean age was 33.9yo (range: 0-71yo).    (Table 3). Figure 2 illustrates both clinical and histological appearance of a rare synovial sarcoma located in retromolar area.

DECLARATIONS
Conflicts of interest: The authors declare that they have no conflicts of interest to disclose.
Funding: Not applicable.