A Dissertation submitted to the Faculty of Health Sciences of University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Medicine in Surgery. Johannesburg, 2017 / Background: Hurthle cell neoplasms (HCN) are considered a variant of follicular thyroid neoplasms, and accounts for 3-10% of neoplasms of the thyroid gland. They include Hurthle cell adenomas (HCA) and carcinomas (HCC). Differentiating HCA from HCC preoperatively is currently not possible. We retrospectively searched for demographic and histopathological factors which can be used to predict the risk of malignancy in HCN. Aim: To determine the prevalence of HCC and its demographic factors and histopathological features that can be used to predict the risk of malignancy in HCN. Methods: Records of all patients who underwent thyroidectomy at Academic Hospitals associated with University of the Witwatersrand from January 2001 to October 2015 were reviewed. Patients’ demographic data and the final histology of HCN were further analyzed including pre-operative fine needle aspiration cytology (FNAC) results. Data collected included patients’ demographic, final histology, tumor size and preoperative FNAC result. Data was entered into Excel Spreadsheet and analyzed using STATICA 13.1 program. Results: At total of 2641 records of thyroidectomies were found of which 25.6% (676/2641) were for thyroid neoplasms. Only 15.8% (107/676) of the neoplasms were HCNs and 25.2% (27/107) of HCNs were HCCs. Hurthle cell carcinoma made up 5.6% (27/481) of thyroid carcinomas. 70.4% (19/27) of HCCs were incidentally found following thyroidectomy for multinodular goiter (MNG). The mean tumor size was significantly greater for carcinomas than for adenomas (4.9 cm vs. 3.5 cm; p = 0.016). The risk of malignancy increased from 11.1% when the size was less or equal to 1cm, through 33.3% for size of 1-4cm to 51.8% when the size was greater than 4cm in diameter. A total of 58 FNACs results of 107 HCNs were available for further analysis. Thirty one (53.4%: 31/58) of FNAC results were suspicious for HCN (Bethesda IV), seven (12.1%: 7/58) suspicious of papillary carcinoma (Bethesda V) and eight (13.8%: 8/58) were reported as benign (Bethesda II). Around 10.3% (6/58) were non-diagnostic (Bethesda I) whereas 8.6% (5/58) were reported as atypia of unknown significance (Bethesda III). Both HCA and HCC were more prevalent in females, 88.7% (71/80) and 77.8% (21/27); respectively. The mean age of the patients who had HCA and HCC in years was 52.3+/- 15.6 SD and 55.0 +/- 15.0 SD, respectively. Conclusion: Majority of HCCs are diagnosed following thyroidectomy for benign disease. Close to a quarter of HCNs are malignant and the risk of malignancy increases with size. Age and gender are not useful to predict malignancy in HCNs. We recommend total thyroidectomy for thyroid nodule greater than 4cm in diameter if FNAC result is suggestive of HCN as the risk of malignancy is above 50%. / MT2017

Orientadores: Laura Sterian Ward, André Lopes Carvalho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-17T23:05:53Z (GMT). No. of bitstreams: 1 Marcello_MarjoryAlana_M.pdf: 3980107 bytes, checksum: f475ed1f2cf3e67afbfdbc6216680195 (MD5) Previous issue date: 2011 / Resumo: Nódulos de tiróide são palpados em cerca de 10% da população e diagnosticados em mais de 50% da população usando-se a ultrassonografia. No entanto, apenas 0,01% são câncer. Por outro lado, o Câncer Diferenciado da Tiróide (CDT) é a neoplasia endócrina mais comum e suas taxas de incidência vem crescendo pelo mundo. Urge, portanto, estabelecer marcadores capazes de identificar malignidade em nódulos na população. Objetivamos, neste trabalho, investigar a utilidade clínica de BRAF, TPO, GAL-3, VEGF e VEGF-C como marcadores para o CDT. Foram utilizados 165 pacientes com CDT; 31 pacientes com nódulos Benignos e 216 Controles. Utilizamos ensaios de PCR-RFLP para a pesquisa da mutação de BRAF, RT-PCRq para dosar TPO e ELISA para dosar VEGF, VEGF-C e Galectina-3 circulantes. A identificação da mutação de BRAF em células tiroidianas circulantes não foi possível com a metodologia por nós empregada. Não encontramos expressão de TPO em sangue periférico de pacientes com CDT. O nível sérico de Gal-3 diferiu entre os grupos CDT, Benigno e Controles, mas não diferenciou nódulos benignos de malignos (p=0, 884). O nível sérico de VEGF pôde diferenciar os pacientes com CDT de pacientes com nódulos Benignos (p=0, 041), assim como diferenciou CDT dos controles (p=0.015), embora não tenha grande poder como marcador único. Os níveis séricos de VEGF-C distinguem pacientes com nódulos Benignos, Malignos e Controles (p=0, 025). Dentre estes, distinguem pacientes com CDT dos Controles (p=0, 046), porém não dos nódulos Benignos (p=0.242). Os níveis séricos de Gal-3, VEGF e VEGF-C parecem discriminar alguns grupos em relação a variáveis clínico-patologicas, porem não há indicação de que possam ser usados como marcadores para o CDT, uma vez que seus poderes preditivos positivo e negativo não são bons. Concluímos que, embora possam auxiliar no diagnóstico, nenhum dos marcadores estudados é promissor do ponto de vista clínico / Abstract: Thyroid nodules may be diagnosed in about 10% of the population and half of the population if they're examined through ultrasonography. However, only 0.1% of those nodules are cancer. On the other hand, Differentiated Thyroid Cancer (DTC) is the most common endocrine malignancy and its incidence rate is increasing worldwide. This fact creates an urgent need for new markers that might be used in a large scale to diagnose thyroid nodules malignancy. We aimed to investigate the clinical utility of BRAF, TPO, Gal-3, VEGF and VEGF-C as markers for the CDT. We studied 165 patients with DTC, 31 patients with benign tumors and 216 controls. We used PCR-RFLP to investigate the presence of BRAF mutation, RT-PCRq to quantify TPO mRNA and ELISA to quantify VEGF, VEGF-C and Gal-3 in circulation. The identification of BRAF mutation in thyroid cells was not possible with the methodology employed. We didn't find any expression of TPO in peripheral blood of patients with DTC. The serum levels of Gal-3 differed among groups DTC, Benign and Controls, but did not differentiate benign and malignant tumors (p = 0.884). The serum levels of VEGF could differentiate patients with DTC from patients with benign nodules (p = 0.041) and DTC differed from controls (p = 0.015), although this test didn't have a great predictive power as a single marker. Serum levels of VEGF-C distinguished patients with benign nodules, malignant tumors and controls (p = 0.025). It distinguished patients with DTC from Controls (p = 0.046) but not from the benign tumors (p = 0242). Serum levels of Gal-3, VEGF and VEGF-C seem to discriminate some groups in what concerns clinical and pathological variables, but there is no indication that they can be used as markers for the CDT, as its positive and negative predictive powers are not high. We conclude that, although they might support the diagnosis, none of the markers studied is promising in a clinical perspective / Mestrado / Ciencias Basicas / Mestre em Clinica Medica