Abstract In the modern world, cancer is a growing cause of mortality, but archeological studies have shown that it is not exclusive to modern populations. The aim of this study is to examine the epidemiologic, social, and clinicopathologic features of head and neck cancers in ancient populations. To do this, we extracted all records that described malignant lesions in the head and neck region available in the Cancer Research in Ancient Bodies Database (CRAB). The estimated age, sex, physical condition of the remains (skeletonized, mummified), anatomic location of tumors, geographic location, chronology, tumor type, and methods of tumor diagnosis were collected. One hundred and sixty-seven cases were found, mostly originating from Europe (51.5%). Most records were of adults between 35 and 49 years of age (37.7%). The most involved site was the skullcap (60.4%), and the most common malignancies were metastases to the bone (65.3%) and multiple myeloma (17.4%). No primary soft tissue malignancies were registered. The results of our study indicate that head and neck cancers were present in ancient civilizations, at least since 500,000 BCE. The available data can help to improve the current understanding of the global distribution of head and neck cancer and its multidimensional impacts on populations in the contemporary world.

Abstract Objective: To evaluate the preoperative muscle mass of patients with head and neck cancer (HNC) with computed tomography (CT), comparing the results obtained through analysis of cross-sectional areas at the level of the third lumbar vertebra (L3) with those obtained through analysis of cross-sectional areas at the levels of the third cervical and fourth thoracic vertebrae (C3 and T4, respectively). Materials and Methods: A total of 63 patients with HNC were evaluated preoperatively. Using CT, we assessed muscle mass at L3, as well as at C3 and T4. Results: Most (73.0%) of the patients had low muscle mass at L3, whereas 50.8% had a normal body mass index. The cross-sectional area at L3 correlated strongly with those at C3 and T4 (r = 0.831 and r = 0.763, respectively; p < 0.001 for both). In addition, the muscle mass index at L3 correlated strongly with those at C3 and T4 (r = 0.781 and r = 0.715, respectively; p < 0.001 for both). Conclusion: Low muscle mass appears to be highly prevalent in patients with HNC. Measurements at C3 and T4 could represent alternative means of assessing muscle mass in such patients.

Resumo Objetivo: Avaliar e comparar a massa muscular de pacientes com câncer de cabeça e pescoço (CCP) durante o período pré-operatório com tomografia computadorizada (TC), por meio da análise das áreas transversais no nível da terceira vértebra lombar (L3) em comparação com níveis cervical (C3) e torácico (T4). Materiais e Métodos: Sessenta e três pacientes com CCP foram avaliados no pré-operatório. A TC foi utilizada para avaliar a massa muscular de L3, assim como as secções transversais de C3 e T4. Resultados: A maioria dos pacientes (73,0%) tinha baixa massa muscular analisada pela TC de L3, mas índice de massa corpórea normal (50,8%). Também foi observada forte correlação entre as áreas e o índice de massa muscular (IMM) de L3 com C3 (área: r = 0,831, p < 0,001; IMM: r = 0,781, p < 0,001) e T4 (área: r = 0,763, p < 0,001; IMM: r = 0,715, p < 0,001). Conclusão: A baixa massa muscular é altamente prevalente em pacientes com CCP. As análises de TC em C3 e T4 podem representar opção para avaliar a massa muscular em pacientes com CCP.

Abstract Objective The outbreak of the COVID-19 pandemic had a considerable impact on the healthcare access, treatment, and follow-up of oncologic patients. The aim of this study was to evaluate how the COVID-19 pandemic has affected consultation and follow-up demand as well as treatment volume at Brazilian Head and Neck Surgery centers. Methods An anonymous online questionnaire was used for collection of data across all Brazilian Head and Neck Surgery Centers across a 3-month period (April‒June 2021). This information included the characteristics of each center, and the perceived self-reported impact of the COVID-19 pandemic on academic activities, residency training, and the diagnosis, treatment, and follow-up of patients with Head and Neck diseases between 2019 and 2020. Results The response rate across the 40 registered Brazilian Head and Neck Surgery Centers was 47.5% (n = 19). The data showed a significant reduction in the total number of consultations (24.8%) and number of attending patients (20.2%) between 2019 and 2020. The total number of diagnostic exams (31.6%) and surgical procedures (13.0%) conducted over this period also decreased significantly. Conclusions The COVID-19 pandemic had a significant national impact on Brazilian Head and Neck Surgery Centers. Future studies should examine the long-term effects of the pandemic on cancer treatment. Level of evidence Evidence from a single descriptive study.

Resumo Objetivo: Avaliar e comparar a massa muscular de pacientes com câncer de cabeça e pescoço (CCP) durante o período pré-operatório com tomografia computadorizada (TC), por meio da análise das áreas transversais no nível da terceira vértebra lombar (L3) em comparação com níveis cervical (C3) e torácico (T4). Materiais e Métodos: Sessenta e três pacientes com CCP foram avaliados no pré-operatório. A TC foi utilizada para avaliar a massa muscular de L3, assim como as secções transversais de C3 e T4. Resultados: A maioria dos pacientes (73,0%) tinha baixa massa muscular analisada pela TC de L3, mas índice de massa corpórea normal (50,8%). Também foi observada forte correlação entre as áreas e o índice de massa muscular (IMM) de L3 com C3 (área: r = 0,831, p < 0,001; IMM: r = 0,781, p < 0,001) e T4 (área: r = 0,763, p < 0,001; IMM: r = 0,715, p < 0,001). Conclusão: A baixa massa muscular é altamente prevalente em pacientes com CCP. As análises de TC em C3 e T4 podem representar opção para avaliar a massa muscular em pacientes com CCP.

Abstract Objective: To evaluate the preoperative muscle mass of patients with head and neck cancer (HNC) with computed tomography (CT), comparing the results obtained through analysis of cross-sectional areas at the level of the third lumbar vertebra (L3) with those obtained through analysis of cross-sectional areas at the levels of the third cervical and fourth thoracic vertebrae (C3 and T4, respectively). Materials and Methods: A total of 63 patients with HNC were evaluated preoperatively. Using CT, we assessed muscle mass at L3, as well as at C3 and T4. Results: Most (73.0%) of the patients had low muscle mass at L3, whereas 50.8% had a normal body mass index. The cross-sectional area at L3 correlated strongly with those at C3 and T4 (r = 0.831 and r = 0.763, respectively; p < 0.001 for both). In addition, the muscle mass index at L3 correlated strongly with those at C3 and T4 (r = 0.781 and r = 0.715, respectively; p < 0.001 for both). Conclusion: Low muscle mass appears to be highly prevalent in patients with HNC. Measurements at C3 and T4 could represent alternative means of assessing muscle mass in such patients.

ABSTRACT Objective: The purpose of these guidelines is to provide specific recommendations for the surgical treatment of neck metastases in patients with papillary, follicular, and medullary thyroid carcinomas. Materials and methods: Recommendations were developed based on research of scientific articles (preferentially meta-analyses) and guidelines issued by international medical specialty societies. The American College of Physicians’ Guideline Grading System was used to determine the levels of evidence and grades of recommendations. The following questions were answered: A) Is elective neck dissection indicated in the treatment of papillary, follicular, and medullary thyroid carcinoma? B) When should central, lateral, and modified radical neck dissection be performed? C) Could molecular tests guide the extent of the neck dissection? Results/conclusion: Recommendation 1: Elective central neck dissection is not indicated in patients with cN0 well-differentiated thyroid carcinoma or in those with noninvasive T1 and T2 tumors but may be considered in T3-T4 tumors or in the presence of metastases in the lateral neck compartments. Recommendation 2: Elective central neck dissection is recommended in medullary thyroid carcinoma. Recommendation 3: Selective neck dissection of levels II–V should be indicated to treat neck metastases in papillary thyroid cancer, an approach that decreases the risk of recurrence and mortality. Recommendation 4: Compartmental neck dissection is indicated in the treatment of lymph node recurrence after elective or therapeutic neck dissection; “berry node picking” is not recommended. Recommendation 5: There are currently no recommendations regarding the use of molecular tests in guiding the extent of neck dissection in thyroid cancer.

Abstract The objective of this study was to assess the remodeling-associated gene expression in the mandible of patients diagnosed with oral squamous cell carcinoma (OSCC), investigating the cortical microarchitecture, and their influence on disease-free survival (DFS) and overall survival (OS) rates. A total of twenty-four patients who underwent mandibulectomy for OSCC treatment had two bone fragments harvested from the mandible for gene expression (RANK, RANKL, OPG, and SOST), and microarchitecture analysis, including bone volume, surface, mineral density, degree of anisotropy, and fractal dimension. The prognosis of the patients was assessed. The results revealed that RANK, RANKL, and SOST were predominantly downregulated, while OPG was completely downregulated. Tumors located adjacent to the posterior region of the mandible (p = 0.02), with a bone mineral density below 1.03 g/cm3 HA (p = 0.001), and a bone volume less than 86.47% (p = 0.03) were associated with poor outcomes. In conclusion, bone-remodeling-associated genes exhibited downregulation in the cortex of the mandible in OSCC patients. Additionally, the tumor’s location within the mandible, bone volume, and cortical bone mineral density were identified as factors impacting DFS.

Abstract Objective: The aim of the present study was to analyze the prognostic relationship of weight loss and preoperative hematological indexes in patients surgically treated for pT4a squamous cell carcinoma of the oral cavity. Methods: A retrospective cohort study. Results: Percent weight loss greater than 10% was identified in 49 patients (28.2%), and any weight loss in relation to the usual weight occurred in 140 patients (78.7%). Percent weight loss greater than 10% (HR = 1.679), Red cell distribution width (RDW) values greater than 14.3% (HR = 2.210) and extracapsular spread (HR = 1.677) were independent variables associated with risk of death. Conclusion: Patients with advanced squamous cell carcinoma of the oral cavity present significant weight loss and as significantly immunocompromised. Increased values of RDW and higher percentages of weight loss in relation to the individual’s usual weight, together with extracapsular spread of metastatic lymph nodes, were risk factors for lower survival, regardless of other clinical and anatomopathological characteristics. Level of evidence: 3.

Abstract Introduction Treatment of stage III laryngeal cancer suffered a major paradigm change with surgery being substituted by radiation therapy with chemotherapy. Objective To evaluate the oncological outcome of different treatment modalities for stage III laryngeal cancer using a population database. Methods A population database representing patients treated in the state of São Paulo, Brazil, was analyzed. Demographic, clinical and treatment variables were included, and the outcomes of interest were disease-specific and overall survival. Propensity score with nearest neighbor matching was used to compensate for imbalances in treatment groups. Results We retrieved data from 1,804 patients. In multivariate analysis, age, female gender, payment source, clinical N stage (cN) stages, and treatment modality were significant for disease-specific and overall survival. Patients submitted to surgery treatment had a significantly better disease-specific (p < 0.001) and overall survival (p <0.001) compared with chemoradiation. Propensity score matching was based on cN stage, gender, age, topography, and payment modality, and allowed the pairing of 685 patients from each treatment modality. There was a significant difference in disease-specific survival favoring surgery-based treatment (p = 0.017). Conclusion The treatment choice has a significant impact on survival in patients with stage III laryngeal cancer with surgery-based treatment being superior to chemoradiotherapy (CRT).

Resumo Introdução: O carcinoma papilífero de tireoide é a neoplasia endócrina mais frequente e sua incidência triplicou nos últimos 35 anos. Embora o carcinoma papilífero de tireoide tenha um bom prognóstico, 1% a 30% dos pacientes desenvolvem recorrência e metástase. Algumas características clínicas e genéticas estão associadas a um pior prognóstico. A mutação mais frequente é a BRAF p.V600E, a qual tem sido associada a muitas características clínicas de pior prognóstico. No entanto, muitos estudos apresentam resultados controversos, sem qualquer associação entre a mutação em BRAF e características clinicopatológicas de pior prognóstico. Objetivo: Uma vez que o valor prognóstico das mutações em BRAF permanece controverso, investigar a importância dessa mutação em decisões terapêuticas para o carcinoma papilífero de tireoide. Método: Foi avaliada a associação da mutação em BRAF com características de pior prognóstico em 85 pacientes com carcinoma papilífero de tireoide acima de 45 anos tratados no A.C. Camargo Cancer Center, de 1980 a 2007. A mutação em BRAF foi avaliada por pirossequenciamento. A análise estatística foi feita com o software SPSS. Resultados: A média de idade dos pacientes foi de 54 anos (variação de 45 - 77), 73 eram mulheres (85,8%) e 12 eram homens (14,2%). Entre eles, 39 casos (45,9%) apresentaram extensão extratireoidiana e 11, doença recorrente. A mutação em BRAF foi detectada em 57 (67%) pacientes. Não foi observada associação significante entre mutação em BRAF e sexo (p = 0,743), idade (p = 0,236), estágio N (p = 0,423), infiltração vascular e perineural (p = 0,085) ou multi-focalidade (p = 1,0). Apesar de não apresentar associação estatística, a maioria dos pacientes com doença recorrente foi positiva para BRAF (9 em 11) (p = 0,325). Os pacientes afetados pela mutação em BRAF estão associados a tumores maiores do que 1 cm (p = 0,034) e com extensão extratireoidiana (p = 0,033). Conclusão: Embora a mutação em BRAF seja amplamente avaliada, não há dados consistentes que demonstrem uma melhor sobrevida ou benefício clínico ao incorporá-la à decisão terapêutica para o câncer de tireoide.

Abstract Introduction: Papillary thyroid carcinoma is the most frequent endocrine neoplasia and its incidence has tripled over the past 35years. Although papillary thyroid carcinoma carries a good prognosis, 10%–30% of patients still develop recurrence and metastasis. Some clinical and genetic features are associated with worse prognosis. The most frequent mutation is the BRAF p.V600E, which has been associated with many clinical features of poor prognosis. However, many studies have produced controversial results without any association between BRAF mutation and clinicopathological features of poor prognosis. Objective: Since the prognostic value of BRAF mutations remains controversial, this study aims to investigate the importance of this mutation in therapeutic decisions for papillary thyroid carcinoma. Methods: Therefore, we evaluated whether the presence of BRAF mutation is associated with features of poor prognosis in 85 patients with papillary thyroid carcinoma older than 45years treated at A.C. Camargo Cancer Center, from 1980 to 2007. BRAF mutation was evaluated by pyrosequencing. Statistical analysis was performed using SPSS. Results: The mean age of patients was 54 years (range: 45 - 77 years), 73 were women (85.8%) and 12 were men (14.2%). Among them, 39 cases (45.9%) presented extrathyroidal extension and 11 cases had recurrent disease. BRAF mutation was detected in 57 (67%) patients. No significant association was observed between BRAF mutation and gender (p =0.743), age (p = 0.236), N-stage (p =0.423), vascular and perineural infiltration (p =0.085 or multifocality (p = 1.0). Although not statistically significant, the majority of patients with recurrent disease were BRAF positive (9 out of 11) (p =0.325). Patients affected by BRAF mutation are associated with tumors larger than 1 cm (p =0.034) and with extrathyroidal extension (p =0.033). Conclusion: Although BRAF testing is widely available, there are no consistent data to support improvement in outcomes from incorporating it into therapeutic decision for thyroid cancer.

Resumo Introdução O carcinoma epidermoide de laringe é o segundo mais prevalente entre os tumores de cabeça e pescoço e o tratamento dos pacientes com doença em estádio I ou II pode ser feito com cirurgia ou radioterapia. Estudos populacionais nacionais que descrevem os resultados terapêuticos e compararam essas modalidades são poucos frequentes, mas podem ser muito importantes para orientar diretrizes de tratamento. Objetivo Avaliar os resultados de sobrevida dos pacientes com carcinoma epidermoide de laringe em estádios clínicos I ou II de acordo com as principais modalidades terapêuticas usadas. Método Estudo transversal de base populacional com a base de dados da Fundação Oncocentro de São Paulo de janeiro de 2000 a março de 2019. Os critérios de inclusão foram pacientes com carcinoma epidermoide de laringe em estádios clínicos cT1-2N0. Para compensar pela alocação não randômica dos pacientes e pelo desequilíbrio entre variáveis confundidoras entre os grupos, usamos a metodologia do escore de propensão. Resultados Preencheram os critérios de inclusão 3.786 pacientes. Em relação ao estádio cT, houve 2.171 pacientes (57,3%) com tumores cT1. Os pacientes do sistema único de saúde (SUS) apresentaram um maior tempo entre o diagnóstico e o tratamento (p < 0,001). A análise por escore de propensão mostrou que os pacientes submetidos a cirurgia apresentaram uma tendência de melhor sobrevida doença específica (p = 0,012). Comparando-se radioterapia isolada versus combinação com radioquimioterapia, o tratamento isolado demonstrou tendência a melhor taxa de sobrevida (p< 0,001). Conclusão A análise por escore de propensão identificou melhores resultados de sobrevida doença específica em pacientes com carcinoma epidermoide de laringe estádios clínicos I e II tratados por cirurgia quando comparados a radioterapia.

Abstract Introduction Laryngeal squamous cell carcinoma is the second most prevalent malignancy among head and neck tumors, and the treatment of patients with stage I or II disease can be performed with surgery or radiation therapy. National population studies describing therapeutic results comparing these modalities are unusual, but they can be very important to direct treatment guidelines. Objective To evaluate the survival results of patients with laryngeal squamous cell carcinoma at clinical stages I or II, according to the main therapeutic modalities used. Methods Cross-sectional, population-based study using the database of Fundação Oncocentro de São Paulo from January 2000 to March 2019. Inclusion criteria were patients with laryngeal squamous cell carcinoma in clinical stages cT1-2N0. To compensate for the non-random allocation of patients and the imbalance between confounding variables between groups, we used the propensity score methodology. Results A total of 3786 patients met the inclusion criteria. Regarding the cT stage, there were 2171 patients (57.3%) with cT1 tumors. Patients in the public health system had a longer time between diagnosis and treatment (p< 0.001). The analysis by propensity score showed that patients treated with surgery had a tendency towards better disease-specific survival (p = 0.012). Comparing radiotherapy alone versus its combination with radiochemotherapy, radiotherapy alone showed a tendency towards a better survival rate (p< 0.001). Conclusion Analysis by propensity score identified better results for disease-specific survival in patients with laryngeal squamous cell carcinoma at clinical stages I and II treated by surgery when compared to radiotherapy.

SUMMARY We report a rare case of Cushing’s syndrome in a 37-year-old female who initially presented with localized acinic cell carcinoma of the parotid gland. In January 2014, she underwent a right parotidectomy with facial nerve preservation and adjuvant radiotherapy. In August 2018, she presented a histologically-proven local regional relapse. The patient was considered for salvage surgery with facial nerve sacrifice and remained with no evidence of disease. One year later the patient developed pulmonary dissemination and started to gain weight and developed facial plethora and acne on the face and upper trunk. In a physical examination, the patient presented moon face, buffalo hump, acne and stage 2 hypertension. Biochemical evaluation confirmed ACTH-dependent Cushing’s syndrome. IHC for ACTH in the lung biopsy revealed strong positive staining for ACTH confirming a diagnosis of ectopic ACTH secretion by a metastatic parotid acinic cell carcinoma. Ketoconazole (600 mg/d) was started to treat the CS. In addition, as chemotherapy was initiated to treat the metastatic disease. After the fifth cycle of chemotherapy, ketoconazole was suspended and the patient remained in remission of CS for four months, when CS recurred. A unique feature of this case is related to the clinical CS relapse associated with disease progression, which needed prompt treatment with ketoconazole, resulting in a significant improvement in the patient’s condition. Although rare, should be attentive for possible CS features in patients with high-grade salivary gland carcinomas, since the diagnosis of ectopic secretion of ACTH may significantly impact their management and outcomes.

Abstract Objective To investigate Incidental Thyroid Carcinoma (ITC) by comparing the results of Fine Needle Aspiration Biopsy (FNAB) cytology and the postoperative pathological findings. Methods Data of 1479 patients who underwent total thyroidectomy were retrieved. Three hundred eighty-six patients were excluded due to insufficient data. Each surgical specimen studied received two histopathological diagnoses: the local diagnosis ‒ for the same area in which the FNAB was performed; and the final diagnosis, which includes a study of the entire surgical specimen. Results A thousand and ninety-three patients were investigated. FNAB result was malignant in 187 patients, benign in 204, suspicious or indeterminate in 668 cases, and inconclusive in 34 cases. The prevalence of ITC was 15.1%. Most of the ITC in this series was less than 0.5 cm. The incidence of ITC was higher in Bethesda III (17.5% ITC) and IV (19% ITC) than in Bethesda II cases (1.5% false negatives and 9% ITC). Conclusion Although the incidence of false-negative results in Bethesda II nodules is only 1.5%, 9% of these patients had ITC in the thyroid parenchyma outside the nodule that underwent preoperative FNAB. The incidence of ITC in the same scenario was even higher in Bethesda III (17.5%) and Bethesda IV cases (19%). Ultrasonography-guided FNAB is an excellent method for the assessment of thyroid nodules. However, biopsy sites should be carefully selected. Despite the high incidence of incidentalomas, total thyroidectomy should not always be the treatment of choice due to its rare but potentially serious complications. The findings of the present study can assist future clinical decisions towards active surveillance strategies for the management of papillary thyroid carcinoma.

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer. Objective: To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection. Methodology: CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018). Results: There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004). Conclusion: Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.

Abstract Introduction The incidence of papillary thyroid microcarcinoma (PTMC) has increased, and its treatment remains controversial. Objective To identify the clinical and pathological factors predictive of tumor recurrence. Methods We retrospectively analyzed 2,538 consecutive patients treated for PTMC, most submitted to total thyroidectomy (98%) followed by radioactive iodine (RAI) ablation (51.7%) at a cancer center from 1996 to 2015. The patients were stratified according to the AmericanThyroid Association (ATA) risk categories (low, intermediate, or high), and the clinicopathological features were evaluated by multivariate Cox regression analysis to identify independent prognostic factors for recurrence. Results After a mean follow-up of 58 months (range: 3 to 236.5 months), tumor recurrence was diagnosed in 63 (2.5%) patients, mostly in the lymph nodes. Distant metastasis occurred in 2 (0.1%) patients. There were no cancer-related deaths. The multivariate analysis showed that age < 55 years (p = 0.049; hazard ratio [HR]: 2.54; 95% confidence interval [95%CI]: 0.95 to 0.99), multifocality (p = 0.032; HR: 1.76; 95% CI: 1.05 to 2.96), and the presence of lymph-node metastasis (p < 0.001; HR: 3.69; 95% CI: 2.07–6.57) were independent risk factors for recurrence. Recurrence was observed in 29 (1.5%) out of 1,940 low-risk patients, 32 (5.4%) out of 590 intermediate-risk patients, and in 2 (25%) out of 8 high-risk patients. Conclusions The prognosis of PTMC is excellent, favoring a conservative treatment for most patients. Age <55 years, multifocality, and node metastasis at diagnosis, as well the ATA staging system effectively predict the risk of recurrence. The presence of these risk factors can help identify patients who should be considered for more aggressive management and more frequent follow-up.