SUMMARY Most papillary thyroid carcinomas (PTC) harbor excellent prognosis. Although rare, distant metastases normally occur in lungs and/or bones. Here we describe a rare case of pancreatic metastasis presenting with rapid onset cholestatic syndrome. A literature review was also performed. A 73-year-old man with a high risk PTC was submitted to total thyroidectomy (TT) followed by radioiodine therapy. After initial therapy, he persisted with progressive rising serum thyroglobulin levels but with no evidence of structural disease. Recently, the patient presented with a rapid onset and progressive cholestatic syndrome. A 4 cm lesion in pancreas was identified, with echoendoscopy fine-needle aspiration biopsy (FNAB) confirming a pancreatic metastasis from PTC. The patient was submitted to a successful pancreaticoduodenectomy. Pancreatic metastases of PTC are rare and few long-term follow-up data are available to guide management. Fourteen cases were former reported, mean age was 65.7 years-old with mean time between PTC and pancreatic metastasis diagnosis of 7.9 years. Nine of them had another distant metastasis, nine were diagnosed by FNAB and just two received sorafenib.

Abstract Pathological parameters have been indicated as tumor prognostic factors in oral carcinoma. Objective: The objective of this study was to investigate the impact of pathological parameters on prognosis of patients affected only by tongue and/or floor of the mouth squamous cell carcinoma (SCC). Methodology: In total, 380 patients treated in the Brazilian National Cancer Institute (INCA) from 1999 to 2006 were included. These patients underwent radical resection followed by neck dissection. The clinical and pathological characteristics were recorded. The Kaplan-Meier method and Cox proportional hazards model were used in survival analysis. Overall survival (OS), cancer-specific survival (CSS) and disease-free interval (DFI) were estimated. Cox residuals were evaluated using the R software version 3.5.2. Worst OS, CSS and DFI were observed in patients with tumors in advanced pathological stages (p<0.001), with the presence of perineural invasion (p<0.001) and vascular invasion (p=0.005). Results: Advanced pathological stage and the presence of a poorly differentiated tumor were independent prognostic factors for OS and CSS. However, advanced pathological stage and perineural invasion were independent predictors of a shorter OS, DFI and CSS. Conclusion: Pathological stage and perineural invasion were the most significant pathological variables in survival analysis in tongue and/or floor of the mouth SCC.

Introdução:O gene TP53 (proteína tumoral p53) é alvo constante de investigação na patogênese do câncer. A imuno-histoquímica fornece dados limitados na análise de p53 no processo da carcinogênese bucal e o sequenciamento de TP53 pode contribuir nessa investigação. Contudo, a obtenção de ácido desoxirribonucleico (DNA) com qualidade para amplificação e livre de contaminação pode constituir uma tarefa difícil na utilização de material parafinado.Objetivo:Padronizar as técnicas de extração de DNA, amplificação por reação em cadeia da polimerase (PCR) e sequenciamento para a análise de mutações em TP53.Material e métodos:Foram selecionados 39 casos de carcinomas de células escamosas bucal da Divisão de Patologia do Instituto Nacional de Câncer (Inca). O DNA foi extraído utilizando o sistema comercial QIAamp® DNA minikit®. Após quantificação do DNA por espectrofotometria, 250 ng de amostra foram amplificados pela técnica de PCR para o éxon 2 e por nested PCR para o éxon 6 do gene TP53. Da amostra total, 11 casos foram selecionados para a padronização da reação de sequenciamento do éxon 2.Resultados:As amostras de DNA apresentaram concentração média de 119,74 ng/µl ± 88,86 (28,9-556,4 ng/µl) e pureza de 1,69 ± 0,18 (1-1,9). Do total das amostras analisadas, 33 (84,6%) foram amplificadas para o éxon 2, e todas (39/100%), para o éxon 6. No sequenciamento do éxon 2 obtiveram-se sequências passíveis de leitura em 10 (90,9%) casos.Conclusão:A otimização das condições para o sequenciamento de TP53 foi obtida, o que facilitará a análise de mutações em tecidos parafinados, permitindo a realização de estudos moleculares retrospectivos.

Introduction:The tumor protein p53 gene (TP53) is a constant target of investigation in cancer pathogenesis. Analysis by immunohistochemistry provides limited data about p53 in oral carcinogenesis, and TP53sequencing can contribute to this analysis. However, obtaining high-quality and contamination-free deoxyribonucleic acid (DNA) for a proper amplification can be a difficult task when using paraffin-embedded tissues.Objective:Standardize DNA extraction, polymerase chain reaction (PCR) amplification and DNA sequencing techniques for TP53 mutation analysis.Material and methods:Thirty-nine cases of oral squamous cell carcinoma (OSCC) were selected from the Pathology Division of Instituto Nacional de Câncer (Inca). The DNA extraction method used was the QIAamp® DNA minikit® system. After DNA quantification by spectrophotometry, 250 ng of genetic material obtained from TP53 gene were amplified by PCR for exon 2 and by nested PCR for exon 6. Out of the total sample, 11 cases were selected for exon 2 sequencing. Results: The DNA samples presented mean concentration of 119.74 ± 88.86 ng/µl (28.9-556.4) and purity of 1.69 ± 0.18 (1-1.9). Thirty-three (84.6%) samples were amplified for exon 2, and all samples for exon 6 (39/100%). Readable sequencing data were obtained in 10 (90.9%) cases.Conclusion:Optimization of conditions for TP53 sequencing was obtained, and this will facilitate the analysis of mutations in paraffin-embedded tissues, allowing molecular retrospective studies.

RESUMO Objetivo: Avaliar a importância da reatividade linfonodal na recidiva e mortalidade em pacientes com carcinoma epidermoide de laringe estagiados como pT3 ou pT4 pN0 M0. Métodos: Entre 2002 e 2005, foram selecionados 105 pacientes matriculados na Seção de Cirurgia de Cabeça e Pescoço do Instituto Nacional de Câncer (INCA) com o diagnóstico de carcinoma epidermoide de laringe, com estágio III ou IV. A radioterapia foi indicada em 69 casos. Todos os pacientes foram estagiados como pT3 ou pT4 e pN0. Todos os linfonodos ressecados foram analisados e classificados conforme os quatro padrões de reatividade linfonodal: hiperplasia folicular associada à resposta imune humoral, hiperplasia paracortical associada à resposta imune celular, histiocitose sinusal sem relação com resposta imune específica, e linfonodo normal. Os dois primeiros padrões são definidos como linfonodos estimulados e os dois últimos como linfonodos não-estimulados. O padrão linfonodal mais frequente em cada paciente foi considerado para a análise da relação com a recidiva e mortalidade. Resultados: Foi analisado um total de 3.648 linfonodos, com média de 34,7 linfonodos por paciente. O padrão de reatividade mais frequente foi a histiocitose sinusal (50 casos), seguido da hiperplasia paracortical (35 casos) e da hiperplasia folicular (20 casos), sendo esses padrões sem relação com a recidiva (p = 0,98) ou mortalidade (p = 0,49). No entanto, o estímulo da imunidade celular relacionada à hiperplasia paracervical apresentou relação com significância estatística com melhor sobrevida global em cinco anos (76 versus 60%; log-rank = 0,05). Conclusões: houve correlação positiva entre o padrão de estímulo da imunidade celular e o aumento da sobrevida em cinco anos em paciente pN0 com carcinoma epidermoide de laringe sugerindo a indicação de tratamento adjuvante em casos que apresentarem diminuição da imunidade celular mesmo na ausência de metástases patológicas detectadas pelos métodos habituais.

ABSTRACT Objective: To evaluate the influence of lymph node reactivity on recurrence and survival rates in a population of pT3 or pT4 pN0 patients with laryngeal squamous cell carcinoma. Methods: Between 2002 and 2005, 105 patients with LSSC underwent total laryngectomy with bilateral selective neck dissection including levels II, III and IV. Most (69) received PO radiotherapy. All pathological specimens were either pT3 or pT4, and all necks were pN0. All lymph nodes were analyzed and their reactivity status were classified as the following four patterns: follicular hyperplasia associated with humoral response, paracortical hyperplasia associated with cellular response, sinus histiocytosis with no association with specific immune response, or normal lymph node. Only the first two patterns were considered stimulated, whereas the last two were considered non-stimulated. The most prevalent pattern in a particular neck specimen was considered for the analysis of recurrence and survival. Results: The total number of lymph nodes studied was 3,648, with an average of 34.7 lymph nodes/neck specimens. The most frequent lymph node reactivity patterns were sinusal histiocytosis (50 cases), paracortical hyperplasia (35 cases), and follicular hyperplasia (20 cases). There was no statistical association of these individual patterns with recurrence rate (p = 0.98) or mortality (p = 0.49). However, there was a statistically significant association between paracortical hyperplasia pattern (related to cellular lymph node immunity) and improved five-year survival (76 versus 60%; log-rank = 0.05). Conclusions: There was a positive correlation between stimulated cellular lymph node pattern and improved 5-year survival rate in patients with pN0 laryngeal squamous cell carcinoma, suggesting the indication of adjuvant treatment for those individuals with decreased immune response, even in the absence of pathologic metastases detected by the usual methods.

O carcinoma de células escamosas de boca compreende cerca de 90 a 95% de todas as neoplasias malignas da boca e é um dos tipos de câncer mais frequentes no Brasil. O índice de sobrevida em 5 anos é baixo e permaneceu estável nas últimas décadas, apesar dos avanços nas terapias. O objetivo deste estudo foi analisar o perfil e a sobrevida global dos pacientes diagnosticados com carcinoma de células escamosas de boca no ano de 1999 no Instituto Nacional de Câncer. Dos 320 pacientes incluídos no estudo, 79,4% eram homens. A idade média foi de 56,7 anos, e 82,2% deles fumavam e/ou bebiam. A língua, seguida do assoalho de boca foram os locais mais acometidos. A maioria (68,9%) dos pacientes foi diagnosticada em estádios tardios e submetida à radioterapia exclusiva (53,6%). A sobrevida média no período do estudo foi de 29,4 meses. Os pacientes dos estádios iniciais apresentaram maior sobrevida, assim como aqueles submetidos apenas à cirurgia como forma de tratamento e os que não apresentaram linfonodos acometidos ao diagnóstico. Tumores localizados em palato duro e mucosa jugal apresentaram pior prognóstico. Foram fatores preditivos independentes de melhor sobrevida os tumores T1 ou T2 (p=0,001), sem acometimento de linfonodos (p=0,012) e não localizados em mucosa jugal (p=0,021). O diagnóstico do câncer oral ainda se faz em estádios tardios, o que influencia negativamente a sobrevida global dos pacientes. Maior ênfase deve ser dada à capacitação dos profissionais para o reconhecimento precoce do câncer e à conscientização da população de risco.

Oral squamous cell carcinoma accounts for 90 to 95% of all malignant neoplasms of the mouth and it is one of most common cancers in Brazil. Five-year survival rates remain low and have not improved over the past decades, despite advances in therapy. The purpose of this study was to analyze the features and overall survival of patients diagnosed with oral squamous cell carcinoma in 1999 at the National Institute of Cancer. Male patients (79.4%) with a medium age of 56.7 years, with smoking or drinking habits (82.2%) comprised most of the sample. Tongue and floor of the mouth were the most prevalent sites of occurrence. Patients were diagnosed mainly at advanced stages of the disease (68.9% stages III and IV) and were treated with radiation therapy alone (53.6 %). Mean survival was 29.4 months, and patients diagnosed in early stages had better survival rates, as well as those who were surgically treated and those who did not show cervical node metastasis at diagnosis. Tumors located in the palate or in the buccal mucosa presented the worst prognosis. Cox regression analysis showed that T1 or T2 lesions (p=0.001), with no neck metastasis (p=0.012) and anatomic site other than buccal mucosa (p=0.021) were independent predictive factors of a better survival rate. Oral cancer diagnosis still occurs in advanced stages, and it negatively influences overall survival, so there should be efforts to prepare and train professionals to recognize lesions at early stages and to make the population at greatest risk aware of the disease.

O carcinoma de células escamosas de boca compreende cerca de 90 a 95% de todas as neoplasias malignas da boca e é um dos tipos de câncer mais frequentes no Brasil. O índice de sobrevida em 5 anos é baixo e permaneceu estável nas últimas décadas, apesar dos avanços nas terapias. O objetivo deste estudo foi analisar o perfil e a sobrevida global dos pacientes diagnosticados com carcinoma de células escamosas de boca no ano de 1999 no Instituto Nacional de Câncer. Dos 320 pacientes incluídos no estudo, 79,4% eram homens. A idade média foi de 56,7 anos, e 82,2% deles fumavam e/ou bebiam. A língua, seguida do assoalho de boca foram os locais mais acometidos. A maioria (68,9%) dos pacientes foi diagnosticada em estádios tardios e submetida à radioterapia exclusiva (53,6%). A sobrevida média no período do estudo foi de 29,4 meses. Os pacientes dos estádios iniciais apresentaram maior sobrevida, assim como aqueles submetidos apenas à cirurgia como forma de tratamento e os que não apresentaram linfonodos acometidos ao diagnóstico. Tumores localizados em palato duro e mucosa jugal apresentaram pior prognóstico. Foram fatores preditivos independentes de melhor sobrevida os tumores T1 ou T2 (p=0,001), sem acometimento de linfonodos (p=0,012) e não localizados em mucosa jugal (p=0,021). O diagnóstico do câncer oral ainda se faz em estádios tardios, o que influencia negativamente a sobrevida global dos pacientes. Maior ênfase deve ser dada à capacitação dos profissionais para o reconhecimento precoce do câncer e à conscientização da população de risco.

Oral squamous cell carcinoma accounts for 90 to 95% of all malignant neoplasms of the mouth and it is one of most common cancers in Brazil. Five-year survival rates remain low and have not improved over the past decades, despite advances in therapy. The purpose of this study was to analyze the features and overall survival of patients diagnosed with oral squamous cell carcinoma in 1999 at the National Institute of Cancer. Male patients (79.4%) with a medium age of 56.7 years, with smoking or drinking habits (82.2%) comprised most of the sample. Tongue and floor of the mouth were the most prevalent sites of occurrence. Patients were diagnosed mainly at advanced stages of the disease (68.9% stages III and IV) and were treated with radiation therapy alone (53.6 %). Mean survival was 29.4 months, and patients diagnosed in early stages had better survival rates, as well as those who were surgically treated and those who did not show cervical node metastasis at diagnosis. Tumors located in the palate or in the buccal mucosa presented the worst prognosis. Cox regression analysis showed that T1 or T2 lesions (p=0.001), with no neck metastasis (p=0.012) and anatomic site other than buccal mucosa (p=0.021) were independent predictive factors of a better survival rate. Oral cancer diagnosis still occurs in advanced stages, and it negatively influences overall survival, so there should be efforts to prepare and train professionals to recognize lesions at early stages and to make the population at greatest risk aware of the disease.