ABSTRACT Objectives: To assess the molecular profile of follicular cell-derived thyroid carcinomas (FCDTCs) and correlate the identified mutations with the clinical and pathological features of the affected patients. Materials and methods: Cross-sectional study of tumor samples from 100 adult patients diagnosed with FCDTC between 2010 and 2019. The patients’ clinical and pathological data were collected. Genomic DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumors using the ReliaPrep FFPE gDNA Miniprep System. Genotyping of target genomic regions (KRAS, NRAS, BRAF, EGFR, and PIK3CA) was performed using the AmpliSeq panel, while sequencing was performed on the iSeq 100 platform. Results: The patients’ mean age was 39 years. In all, 82% of the tumors were classic papillary thyroid carcinomas. Overall, 54 (54%) tumor samples yielded satisfactory results on next-generation sequencing (NGS), of which 31 harbored mutations. BRAF gene mutations were the most frequent, with the BRAFV600E mutation present in 10 tumors. Seven tumors had BRAFNON-V600E mutations not previously described in FCDTCs (G464E, G464R, G466E, S467L, G469E, G596D, and the T599Ifs*10 deletion) but described in other types of cancer (i.e., skin/melanoma, lung, colorectal, and others). One tumor had a previously reported BRAFA598V mutation. EGFR gene mutations were found in 16 (29%) and KRAS or NRAS alterations in 8 (14%) of the 54 tumors analyzed. Conclusion: We described herein seven non-hotspot/novel variants in the BRAF gene, highlighting their potential role in expanding our understanding of FCDTC genetics.

RESUMO Introdução: O carcinoma medular da tireoide é um câncer raro que se origina nas células C parafoliculares e pode ser esporádico ou hereditário. Tanto as doenças esporádicas quanto as hereditárias são causadas principalmente por mutações no proto-oncogene RET. Objetivo: Investigar variantes germinativas patogênicas do gene RET em uma coorte de pacientes com carcinoma medular da tireoide no Estado da Bahia. Método: Estudo transversal, descritivo, envolvendo pacientes com diagnóstico histopatológico de carcinoma medular da tireoide, encaminhados para testes moleculares de 2020 a 2022. Dados clínicos e patológicos foram coletados de dados médicos. O DNA genômico foi extraído do sangue periférico. Os éxons 10, 11, 13, 14 e 15 do RET foram amplificados usando a técnica de reação em cadeia da polimerase e posteriormente sequenciados usando o método de Sanger. Resultados: O estudo incluiu 29 pacientes (82,8% mulheres). A idade média no diagnóstico foi de 46,5 ± 13,1 anos, e o tamanho médio do tumor foi de 2,1 ± 1,4 cm. De acordo com a classificação TNM, 38% dos tumores foram estadiados como T1a, 27,6% como T1b, 24,1% como T2 e 10,3% como T3. Metástase linfonodal regional (N1) esteve presente em 44,8% dos casos. Metástase a distância (M1) para o mediastino foi observada em um caso (3,4%). Variantes do RET foram identificadas em 55,2% dos pacientes. A variante patogênica C634R foi identificada em um paciente (3,4%). Conclusão: Este estudo conseguiu descrever o perfil clínico e molecular de pacientes com carcinoma medular de tireoide no Estado da Bahia.

ABSTRACT Introduction: Medullary thyroid carcinoma is a rare cancer that originates in parafollicular C cells and can be sporadic or hereditary. Both sporadic and hereditary diseases are primarily caused by mutations in the RET proto-oncogene. Objective: To investigate RET gene pathogenic germline variants in a cohort of patients with medullary thyroid carcinoma in the State of Bahia. Method: Cross-sectional, descriptive study involving patients with histopathological diagnosis of medullary thyroid carcinoma, referred for molecular testing from 2020 to 2022. Clinical and pathological data were collected from medical charts. Genomic DNA was extracted from peripheral blood. Exons 10, 11, 13, 14, and 15 of RET were amplified using polymerase chain reaction technique and subsequently sequenced using the Sanger method. Results: The study included 29 patients (82.8% women). The mean age at diagnosis was 46.5 ± 13.1 years, and the mean tumor size was 2.1 ± 1.4 cm. According to the TNM classification, 38% of tumors were staged as T1a, 27.6% as T1b, 24.1% as T2, and 10.3% as T3. Regional lymph node metastasis (N1) was present in 44.8% of the cases. Distant metastasis (M1) to the mediastinum was observed in one case (3.4%). Variants of RET were identified in 55.2% of the patients. The C634R pathogenic variant was identified in one patient (3.4%). Conclusion: This study managed to describe the clinical and molecular profile of patients with medullary thyroid carcinoma in the State of Bahia.

RESUMEN Introducción: El carcinoma medular de tiroides es un cáncer poco común que se origina en las células C parafoliculares y puede ser esporádico o hereditario. Tanto las enfermedades esporádicas como las hereditarias son causadas principalmente por mutaciones en el protooncogén RET. Objetivo: Investigar variantes patogénicas de la línea germinal del gen RET en una cohorte de pacientes con carcinoma medular de tiroides en el estado de Bahía. Método: Estudio descriptivo transversal que involucró a pacientes con diagnóstico histopatológico de carcinoma medular de tiroides, remitidos para pruebas moleculares del 2020 al 2022. Las informaciones clínicas y patológicas se recolectaron a partir de datos médicos. El ADN genómico se extrajo de sangre periférica. Los exones 10, 11, 13, 14 y 15 del RET se amplificaron mediante la técnica de reacción en cadena de la polimerasa y posteriormente se secuenciaron mediante el método de Sanger. Resultados: Se incluyeron 29 pacientes (82,8% mujeres). La edad promedio al diagnóstico fue de 46,5 ± 13,1 años y el tamaño promedio del tumor fue de 2,1 ± 1,4 cm. Según la clasificación TNM, el 38% de los tumores se estadificaron como T1a, el 27,6% como T1b, el 24,1% como T2 y el 10,3% como T3. La metástasis a los ganglios linfáticos regionales (N1) estuvo presente en el 44,8% de los casos. En un caso (3,4%) se observó metástasis a distancia (M1) al mediastino. Se identificaron variantes del RET en el 55,2% de los pacientes. La variante patogénica C634R se identificó en un paciente (3,4%). Conclusión: Este estudio logró describir el perfil clínico y molecular de los pacientes con carcinoma medular de tiroides en el estado de Bahía.

Abstract Objectives: This study aims to investigate if a sampling method using virtual networks is feasible to survey AS adoption among this “hard-to-reach” population of Brazilian doctors. Methods: An online piloted 11-point structured survey questionnaire (designed using Googleforms®) probed the actual treatment patterns for adult patients with PTMCs, including treatment decision-making nonoperative options, was undertaken between 10 November and 30 November 2020. Participants were reached by the mobile phone Application (APP) and a snowball sampling strategy was used to recruit a total of 4783 members (maximum number of potential reach), which is the total of doctors of the all 21 social media WhatsApp® groups. Results: From a total of 4783 members (maximum number of potential reach), there were 657 (13.7%) doctors (actual reach) who clicked the web link of the questionnaire, out of whom 512 (10.7%) fully completed the online survey. Among the survey respondents, 361 were endocrinologists (70.5%) and 151 were surgeons (29.5%). Overall, for low-risk PTMCs in an elderly patient, 118 responders (23%) recommend AS, while 390 (76%) recommend immediate surgery as the management, including lobectomy (18.5%) and Total Thyroidectomy (58.2%). The present responders tended to recommend surgery for PTMCs that were located adjacent to the dorsal surface of the thyroid, were multiple, or raised the size during the follow-up. Conclusion: Using snowball sampling strategy as an innovative route to conduct surveys was feasible and applicable but the rate of response was still very low. Our data also suggests the need to investigate if AS is embraced by Brazilian doctors. Objectives hardtoreach hard reach “hard-to-reach Methods 11point point 11 designed Googleforms® Googleforms decisionmaking decision making options 1 3 2020 APP (APP 478 maximum reach, , 2 WhatsApp groups Results 65 13.7% 137 13 7 (13.7% 51 10.7% 107 (10.7% respondents 36 70.5% 705 70 5 (70.5% 15 29.5%. 295 29.5% . 29 (29.5%) Overall lowrisk low risk patient 23% 23 (23% 39 76% 76 (76% management 18.5% 185 18 (18.5% 58.2%. 582 58.2% 58 (58.2%) thyroid multiple followup. followup follow up. up follow-up Conclusion 202 47 6 13.7 (13.7 10.7 (10.7 70.5 (70.5 29.5 (29.5% (23 (76 18.5 (18.5 58.2 (58.2% 20 4 13. (13. 10. (10. 70. (70. 29. (29.5 (2 (7 18. (18. 58. (58.2 (13 (10 (70 (29. ( (18 (58. (1 (29 (58 (5

Resumo O objetivo desse artigo é oferecer uma leitura latino-americana feminista a respeito de representações de gênero que constituem o discurso de guerra às drogas dos EUA para a América Latina. Baseando-se na literatura feminista sobre segurança internacional, esse artigo visa explorar algumas nuances do discurso de guerra às drogas dos EUA quando isso se trata de gênero. Ele argumenta que, embora um discurso genderizado esteja constantemente presente no discurso oficial dos EUA, ele tem visivelmente mudado de caráter à medida que as políticas antidrogas dos EUA se tornaram cada vez mais internacionalizadas, militarizadas e orientadas por uma ‘abordagem do lado da oferta.’ Uma vez implantado através da feminização do consumo de droga como uma degradação moral do corpo social da nação, o discurso dos EUA de guerra às drogas mudou perceptivelmente para abranger um processo de hiper-masculinização da figura do guerreiro antidrogas, apoiada por masculinidades e feminidades representadas pelo subalterno, feminizados guerreiros antidrogas Latino Americanos, e os senhores das drogas implacáveis e hiperagressivos. Em última análise, as cartografias genderizadas do discurso de guerra às drogas dos EUA funcionam como condições de possibilidade para enquadrar a guerra às drogas como única ‘solução’ para o ‘problema da droga’ e reafirmam a busca incessante por soberania que tem como último objetivo o controle total, dominação, e vigilância da interação humana com substâncias psicoativas, atributos de uma masculinidade de um estado hegemônico por excelência. Através de performances de (in)segurança de gênero, o Estado defende não apenas suas fronteiras ‘físicas’ de ameaças externas, mas também suas próprias fronteiras de possibilidade.

Abstract This paper aims to offer a feminist, Latin-American reading on the gender representations that constitute the discourse on the US war on drugs in Latin America. Drawing upon the feminist literature on international security, this article explores some of the nuances of the US war-on-drugs discourse when it comes to gender. It argues that, although a gendered discourse has been constantly present in US official discourse, it has visibly changed in character as the USA’s antidrug policies became increasingly internationalized, militarized, and oriented by a ‘supply-side approach.’ Once deployed through the feminization of drug consumption as a moral degradation of the nation’s social body, US war-on-drugs discourse perceptibly changed to encompass a process of hyper-masculinization of the figure of the US drug warrior, supported by subordinate masculinities and femininities represented by the subaltern, feminized Latin American drug warriors, and the ruthless, hyper-aggressive drug lords. Ultimately, the gender(ed) cartographies of the USA’s war-on-drugs discourse work as conditions of possibility for framing the war on drugs as the only ‘solution’ to the ‘drug problem’ and reaffirm the incessant search for sovereignty that has as its ultimate goal the total control, domination and vigilance of human interaction with psychoactive substances: attributes of a hegemonic state masculinity par excellence. Through gendered (in)security performances, the state defends not only its ‘physical’ borders from external threats, but also its own frontiers of possibility.