Carcinoma papilar tiroideo con invasión locorregional: reporte de caso / Papillary thyroid crcinoma with locoregional invasion: case report

El cáncer diferenciado de tiroides incluye el tipo papilar y folicular que representan más del 80% de los casos y tienen un excelente pronóstico. Existen varios subtipos histológicos y las variantes foliculares son probablemente las más comunes. La incidencia de cáncer papilar variante folicular ha ido en aumento. En un reporte de un solo centro, cerca del 40% de los cánceres papilares eran variantes foliculares1. El subtipo infiltrativo de la variante folicular presenta sectores que invaden el parénquima tiroideo no neoplásico y carece de una cápsula tumoral bien definida. Tiene un comportamiento biológico y un perfil molecular que es más similar al tumor papilar clásico2. Existen características clínicas y patológicas asociadas con riesgo más alto de recurrencia tumoral y mortalidad; entre ellos se describen el tamaño del tumor primario y la presencia de invasión de tejidos blandos3. En la invasión de estructuras adyacentes, los sitios más comprometidos incluyen los músculos pretiroideos, el nervio laríngeo recurrente, el esófago, la faringe, laringe y la tráquea. Además, puede haber otras estructuras involucradas como: la vena yugular interna, la arteria carótida y los nervios vago, frénico y espinal4. El compromiso de los ganglios linfáticos y la incidencia de metástasis ganglionares en adultos depende de la extensión de la cirugía. Entre los que se realizan una disección radical modificada del cuello, hasta el 80% tienen metástasis en los ganglios linfáticos y el 50% de ellas son microscópicas5. Clínicamente los tumores localmente avanzados cursan con disfonía, disfagia, disnea, tos o hemoptisis, pero la ausencia de síntomas no descarta la invasión local. Según las guías de la American Thyroid Association6 son variables de mal pronóstico: la edad del paciente, el tamaño del tumor primario, la extensión extra tiroidea y la resección quirúrgica incompleta.

Differentiated thyroid cancer includes papillary and follicular types that represent more than 80% of cases and have an excellent prognosis. There are several histologic subtypes, and follicular variants are probably the most common. The incidence of papillary follicular variant cancer has been increasing. In a singlecenter report, about 40% of papillary cancers were follicular variants1. The infiltrative subtype of the follicular variant presents sectors that invade the non-neoplastic thyroid parenchyma and lacks a well-defined tumor capsule. It has a biological behavior and a molecular profile that is more similar to the classic papillary tumor2. There are clinical and pathological characteristics associated with a higher risk of tumor recurrence and mortality; These include the size of the primary tumor and the presence of soft tissue invasion3. In the invasion of adjacent structures, the most compromised sites include the pre-thyroid muscles, the recurrent laryngeal nerve, the esophagus, the pharynx, larynx and trachea. In addition, there may be other structures involved such as: the internal jugular vein, the carotid artery and the vagus, phrenic and spinal nerves4. The involvement of the lymph nodes and the incidence of lymph node metastases in adults depends on the extent of the surgery. Among those who undergo a modified radical neck dissection, up to 80% have lymph node metastases and 50% of them are microscopic5. Clinically locally advanced tumors present with dysphonia, dysphagia, dyspnea, cough, or hemoptysis, but the absence of symptoms does not rule out local invasion. According to the American Thyroid Association guidelines6, there are variables with a poor prognosis: the age of the patient, the size of the primary tumor, the extra-thyroid extension, and incomplete surgical resection.

Papel da arquitetura nuclear no manejo do carcinoma de tiroide / Role of nuclear architecture in the management of thyroid carcinoma

One of the biggest dilemmas facing a cytopathology slide is the differential diagnosis of follicular thyroid lesions, grouped as follicular pattern lesions, which include goiter, follicular adenoma and follicular carcinoma, follicular variant of papillary thyroid carcinoma and non-invasive follicular thyroid neoplasm with papillary like nuclear features. Such lesions share many characteristics, which makes the proper identification of malignant follicular lesions a challenge. The cytology obtained through fine needle aspiration puncture is the most effective standard method for diagnosis of thyroid nodules, but its diagnostic efficacy clearly decreases in lesions of thyroid follicular pattern. Thus, a series of auxiliary tools for diagnoses, such as morphometry and nuclear texture analysis, have been increasingly used in the pathologist's practice, as an objective and reproducible tool. These are techniques, which depend on the incorporation of software to digital image analysis and can add accuracy to classical morphological analysis and immunohistochemistry in the evaluation of follicular pattern lesions. In addition to immunocytochemistry and molecular techniques, morphometry allows the estimation of parameters identified in individual cells and represents a tool that, based on quantitative parameters, translates reliable parameters for objective classification of the malignancy. This study aims to review the nuclear characteristics and their role in the diagnosis of follicular thyroid lesions.

Um dos maiores dilemas diante de uma lâmina de citopatologia é o diagnóstico diferencial de lesões foliculares da tiroide agrupadas como lesões de padrão folicular e que incluem; bócio, adenoma e carcinoma foliculares, carcinoma papilífero variante folicular e a neoplasia folicular não invasiva com características nucleares papilares (Uno de los mayores dilemas que presenta una muestra de citopatología es el diagnóstico diferencial de las lesiones foliculares tiroideas reunidas como lesiones de patrón folicular, que incluyen: bocio, adenoma folicular, carcinoma folicular, variante folicular del carcinoma papilar y la neoplasia folicular no invasiva con características nucleares de tipo papilar). Tais lesões compartilham muitas características, o que faz com que a identificação adequada de lesões foliculares malignas represente um desafio. A citologia obtida através de punção aspirativa por agulha fina é o método padrão mais efetivo para diagnóstico em nódulos de tiroide, mas sua eficácia diagnóstica diminui nitidamente em lesões de padrão folicular da tiroide (La citología por punción y aspiración con aguja fina es el método estándar más eficaz para el diagnóstico de los nódulos tiroideos, pero su eficacia diagnóstica se ve notablemente reducida en las lesiones de patrón folicular de la tiroides). Assim, uma série de ferramentas auxiliares ao diagnóstico, como a morfometria e a análise de textura nuclear, têm sido utilizadas cada vez mais na prática do patologista, como ferramenta objetiva e reproduzível. São técnicas que dependem da incorporação de softwares para análise digital de imagens e podem agregar acurácia à análise morfológica clássica e à imunohistoquímica na avaliação de lesões de padrão folicular (para el análisis de imágenes digitales y puede agregar precisión al análisis morfológico clásico y la inmunohistoquímica en la evaluación de lesiones de patrón folicular). Somando-se à imunocitoquímica e às técnicas moleculares, a morfometria permite a estimativa de parâmetros identificados em células individuais e representam uma ferramenta que, a partir de parâmetros quantitativos, traduz parâmetros confiáveis para classificação objetiva de malignidade. O objetivo deste estudo é rever as características nucleares e seu papel no diagnóstico de lesões foliculares da tiroide (es revisar las características nucleares y su papel en el diagnóstico de las lesiones foliculares tiroideas).

Neoplasias foliculares del tiroides. Correlación citopatológica / Follicular thyroid neoplasia. Cytopathological correlations

RESUMEN Introducción: la citología con aguja fina se mantiene como el estudio fundamental ante un nódulo tiroideo, pero el diagnóstico de neoplasia folicular es aún su punto débil para definirlo. Se mantiene como conducta su extirpación quirúrgica para alcanzarlo. Objetivo: determinar la correlación citopatológica en las neoplasias foliculares del tiroides. Materiales y métodos: se realizó un estudio prospectivo y descriptivo que incluyó a 80 pacientes operados con diagnóstico citológico de neoplasia folicular del tiroides, en el Hospital "Comandante Faustino Pérez" de la ciudad de Matanzas, de marzo del 2012 a febrero del 2016. Se evaluaron las variables: edad, sexo, tamaño, localización, número de nódulos y diagnóstico histológico definitivo. Resultados: predominaron las lesiones benignas con 56 para el 70 % dentro de ellas, los bocios multinodulares con 33,75 % y los adenomas foliculares con el 31,25 %. Los tumores malignos ocuparon el 30 %. El carcinoma papilar, variedad folicular con 12 para el 15 %, seguido del carcinoma papilar clásico con 10 para el 12,50 %. Conclusiones: el porcentaje de malignidad de este estudio fue del 30 % con predominio del carcinoma papilar variedad folicular y el carcinoma papilar clásico. Entre las lesiones benignas predominaron los bocios multinodulares y los adenomas foliculares (AU).

ABSTRACT Introduction: fine needle cytology is still the main study against a thyroidal nodule, but the follicular neoplasia diagnosis is still its weak point to define it. The surgical removal keeps being used to reach it. Objective: to determine the cytopathological correlation in follicular thyroid neoplasia. Materials and methods: a prospective, descriptive study was carried out including 80 patient with diagnosis of follicular thyroid neoplasia in the Hospital "Comandante Faustino Pérez" of Matanzas, who underwent a surgery from March 2012 to February 2016. The assessed variables were age, sex, size, location, quantity of nodes and final histological diagnosis. Results: benign lesions predominated, with 56 for 70 %; among them, multinodular goiters with 33.75 % and follicular adenomas with 31.25 %. Malignant tumors were 30 %: papillary carcinoma, follicular variety with 12 for 15 %, followed by the classical papillary carcinoma with 10 for 12.50 % Conclusions: the malignity percent of this study was 30 % with the predominance of the papillary carcinoma, follicular variant and the classic papillary carcinoma. Multinodular goiters and follicular adenomas predominated among the benign lesions (AU).

Resultados del tratamiento del cáncer de tiroides / Thyroid cancer treatment results

El cáncer de tiroides es la neoplasia maligna más frecuente del sistema endocrino, siendo el más frecuente el cáncer bien diferenciado (papilar y folicular). El propósito de este trabajo es recoger nuestra experiencia clínica en el manejo y resultados del cáncer diferenciado de tiroides. Material y métodos: Estudio retrospectivo de 50 casos de pacientes con tumores malignos tiroideos, intervenidos de tiroidectomía total por nuestro servicio durante el periodo de 2015 a 2018. Se han recogido variables clínico-epidemiológicas que han sido procesadas con el programa SPSS versión 25. Se realiza estudio descriptivo y de asociación entre las diferentes variables según el tipo anatomo-patológico de tumor. Se analiza la probabilidad de recidiva del cáncer de tiroides y se utiliza el modelo de Cox para ajustar los efectos sobre la recidiva de diferentes variables en un modelo predictivo. Resultados: El 84% eran carcinoma papilar y 16% eran carcinoma folicular. Al finalizar el periodo de seguimiento (72 meses), el 14% presentaba recidiva, y habían fallecido el 8%. El carcinoma folicular fue el que mostró menor supervivencia. El tiempo medio sin recaída, fue de 129 meses. Las variables que influían en la supervivencia fueron: existencia de complicaciones en el postoperatorio, valor de tiroglobulina y antitiroglobulina y TIRADS. Conclusión: Coincidimos con el resto de autores en los aspectos epidemiológicos y clínicos. El carcinoma papilar es el más frecuente y tiene mejor pronóstico. Entre los factores que influyen en la supervivencia destacan el sexo y el tipo anatomo-patológico. Otros factores a considerar son: la existencia de complicaciones en el postoperatorio, la categoría TIRADS previa al tratamiento, y los valores de tiroglobulina y antitiroglobulina en los controles postoperatorios. (AU)

Thyroid cancer is the most frequent malignant neoplasm of the endocrine system, with well-differentiated cancer (papillary and follicular) being the most frequent. The purpose of this work is to collect our clinical experience in the management and results of well-differentiated thyroid cancer. Material and methods: Retrospective study of 50 cases of patients with malignant thyroid tumors, who underwent total thyroidectomy by our service during the period from 2015 to 2018. Clinical-epidemiological variables were collected and processed using the SPSS version 25 program. We have conducted a descriptive and association study between different variables according to anatomo-pathological tumor type. The probability of recurrence of thyroid cancer is analyzed and Cox model is used to adjust the effects on recurrence of different variables in a predictive model. Results: 84% were papillary carcinoma, and 16% were follicular carcinoma. At the end of the follow-up period (72 months), 14% had recurrence, and 8% had died. Follicular carcinoma showed the lowest survival. The mean time without relapse was 129 months. The variables that influenced survival were existence of postoperative complications, thyroglobulin and antithyroglobulin value, and TIRADS. Conclusion: We agree with the rest of the authors in the epidemiological and clinical aspects. Papillary carcinoma is the most frequent and has a better prognosis. Among the factors that influence survival, sex and anatomo-pathological type stand out. Other factors to consider are the existence of complications in the postoperative period, TIRADS category prior to treatment, and thyroglobulin and antithyroglobulin values in postoperative controls. (AU)

Follicular Lesions with Papillary Nuclear Characteristics: Differences in Chromatin Detected by Computerized Image Analysis

ABSTRACT Objective: Follicular lesions of the thyroid with papillary carcinoma nuclear characteristics are classified as infiltrative follicular variant of papillary thyroid carcinoma-FVPTC (IFVPTC), encapsulated/well demarcated FVPTC with tumour capsular invasion (IEFVPTC), and the newly described category "non-invasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) formerly known as non-invasive encapsulated FVPTC. This study evaluated whether computerized image analysis can detect nuclear differences between these three tumour subtypes. Materials and methods: Slides with histological material from 15 cases of NIFTP and 33 cases of FVPTC subtypes (22 IEFVPTC, and 11 IFVPTC) were analyzed using the Image J image processing program. Tumour cells were compared for both nuclear morphometry and chromatin textural characteristics. Results: Nuclei from NIFTP and IFVPTC tumours differed in terms of chromatin textural features (grey intensity): mean (92.37 ± 21.01 vs 72.99 ± 14.73, p = 0.02), median (84.93 ± 21.17 vs 65.18 ± 17.08, p = 0.02), standard deviation (47.77 ± 9.55 vs 39.39 ± 7.18; p = 0.02), and coefficient of variation of standard deviation (19.96 ± 4.01 vs 24.75 ± 3.31; p = 0.003). No differences were found in relation to IEFVPTC. Conclusion: Computerized image analysis revealed differences in nuclear texture between NIFTP and IFVPTC, but not for IEFVPTC.

Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas

ABSTRACT Objective Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both. Subjetcs and methods Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs). Results Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21. Conclusions Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.

Cáncer diferenciado de tiroides en tiroides lingual, presentación de un caso / Differentiated thyroid cancer in the lingual thyroid, presentation of a case

The lingual thyroid carcinoma is very uncommon neoplasia with an incidence of less than 1 percent. The papillary variant is the most frequent. Cervical MRI helps differentiate muscle from thyroid tissue. The definitive diagnosis is given by histology. Management is similar to that of orthotopic thyroid cancer. We present the case of a 23-year-old woman with hypothyroidism undergoing treatment with dysphagia and sensation of pharyngeal foreign body and malodorous oral bleeding. Nasopharyngoscopy showed a rounded mass at the base of the tongue; the biopsy was compatible with thyroid neoplasia. Image study with ultrasound confirms empty thyroid bed with presence of lingual ectopic thyroid. The team of surgeons performed surgery with Trotter Technique, they removed a tumor of 4 centimeters of diameter. The definitive biopsy concludes minimally invasive follicular carcinoma. The treatment was completed with 100 mCi of radioiodine. Systemic screening at 7 days was negative, as the post-operative thyroglobulin (Tg)

Extremely Well-Differentiated Papillary Thyroid Carcinoma Resembling Adenomatous Hyperplasia Can Metastasize to the Skull: A Case Report

We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study.

The follicular variant of papillary thyroid carcinoma: characteristics of preoperative ultrasonography and cytology

PURPOSE: The goal of this study was to validate the ultrasonography (US) and cytopathological features that are used in the diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) and to characterize the role of BRAF(V600E) mutation analysis in the diagnosis of FVPTC. METHODS: From May 2012 to February 2014, 40 thyroid nodules from 40 patients (mean age, 56.2 years; range, 26 to 81 years) diagnosed with FVPTC were included in this study. The US features of the nodules were analyzed and the nodules were classified as probably benign or suspicious for malignancy. Twenty-three thyroid nodules (57.5%) underwent BRAF(V600E) mutation analysis. Clinical information and histopathologic results were obtained by reviewing the medical records of the patients. RESULTS: Thirty nodules (75.0%) were classified as suspicious for malignancy, while 10 (25.0%) were classified as probably benign. Seven of the eight nodules (87.5%) with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) cytology showed suspicious US features, while one of the two nodules (50.0%) with follicular neoplasm cytology presented suspicious US features. Five of the 23 nodules (21.7%) that underwent BRAF(V600E) mutation analysis had positive results, all of which were diagnosed as suspicious for malignancy or malignant based on cytology. None of the nodules with benign, AUS/FLUS, or follicular neoplasm cytology were positive for the BRAF(V600E) mutation. CONCLUSION: US features allow nodules to be classified as suspicious for malignancy, and the presence of suspicious US features in nodules with ambiguous cytology may aid in the diagnosis of FVPTC. BRAF(V600E) mutation analysis is of limited value in the diagnosis of FVPTC.

Ultrasonographic Characteristics of the Follicular Variant Papillary Thyroid Cancer According to the Tumor Size

Follicular variant papillary thyroid cancer (FVPTC) is the second most common subtype after conventional PTC. We compared ultrasonographic (US) features of FVPTC to those of conventional PTC according to tumor size. We reviewed US findings, pathologic reports, and medical charts of 249 PTC patients with surgically proven disease (83 FVPTCs, 166 conventional PTCs) at our institution from January 2007 to December 2012. FVPTCs were divided into PTC-like and follicular neoplasm (FN)-like based on sonographic characteristics. PTC-like features were defined as having at least one malignant feature (taller-than-wide shape, infiltrative margin, marked hypoechogenicity, and micro-calcifications), whereas FN-like cancers showed oval solid features without malignant features. FVPTCs showed a higher rate of FN-like features than conventional PTCs. Of 166 conventional PTCs, 13 (7.8%) had FN-like features and 153 (92.2%) had PTC-like features, whereas of the 83 FVPTCs, 31 (37.3%) had FN-like features and 52 (62.7%) had PTC-like features. Macro-FVPTCs showed a higher rate of FN-like features than micro-FVPTCs (P < 0.001). Of 21 macro-FVPTCs, 18 (85.7%) had FN-like features and 3 (14.3%) had PTC-like features, whereas of the 62 micro-FVPTCs, 13 (21%) had FN-like features and 49 (79%) had PTC-like features. There were no differences in multifocality, extrathyroidal invasion, and lymph node metastasis between PTC-like FVPTCs and FN-like FVPTCs. FVPTCs showed fewer sonographic malignant features than conventional PTCs. In particular, FVPTCs larger than 1 cm had a more frequent benign sonographic appearance. Therefore, if fine-needle aspiration result is suspicious for PTC in a nodule larger than 1 cm with no suspicious US features, the possibility of FVPTC might be considered.

Utilidad de la citología obtenida mediante aspiración con aguja fina en el diagnóstico de las neoplasias foliculares de la glándula tiroides en la ESE Hospital Universitario del Caribe: un estudio retrospectivo / Utility of the fine needle aspiration cytology in the diagnosis of follicular neoplasms of the thyroid gland at Hospital Universitario del Caribe, Cartagena, Colombia

Introducción. En este estudio se evaluó en forma retrospectiva la utilidad de la citología obtenida mediante aspiración con aguja fina, en el diagnóstico de las neoplasias foliculares de la glándula tiroides. Metodología. Se llevó a cabo una revisión retrospectiva de las historias clínicas de los pacientes con impresión diagnóstica de nódulo tiroideo, durante un periodo de 7 años, de 2007 a 2013, durante los cuales se practicó citología mediante aspiración con aguja fina antes del abordaje quirúrgico. El diagnóstico citológico se comparó con el estudio anatomopatológico, con el objetivo de determinar los parámetros de rendimiento. Resultados. La población de estudio fue de 149 pacientes. Para la citología obtenida mediante aspiración con aguja fina, se calcularon los siguientes parámetros de rendimiento en el diagnóstico de neoplasias foliculares: sensibilidad, 54,5 %; especificidad, 92,9 %; valor diagnóstico positivo, 57,1 %; valor diagnóstico negativo, 92,2 %; precisión diagnóstica, 87,2 %; falsos negativos, 6,9 % y falsos positivos, 6,1 %. Conclusión. La citología obtenida mediante aspiración con aguja fina posee una sensibilidad baja en el diagnóstico de las neoplasias foliculares de la glándula tiroides, comportamiento atribuible a la similitud citológica de este grupo de lesiones con los bocios con cambios adenomatosos.

Introduction: This study evaluates retrospectively the performance of cytology obtained by fine needle aspiration in the diagnosis of follicular neoplasms of the thyroid gland. Methods: A review of medical records of patients with diagnostic impression of thyroid nodule over a period of seven years from 2007 to 2013 was completed, in those patients in which a fine needle aspiration cytology prior to a surgical approach was performed. The cytological diagnosis was compared with pathologic study to determine the performance parameters. Results:The study population included 149 patients. The following performance parameters of the fine needle aspiration cytology were determined in the diagnosis of follicular neoplasms: sensitivity, 54.5%; specificity, 92.9%; positive predictive value, 57.1%; negative predictive value, 92.2%; accurately diagnosed, 87.2%; false negatives and false positives 6.9%, 6.1% Conclusion: Fine needle aspiration cytology has a low sensitivity in the diagnosis of follicular neoplasms of the thyroid gland due to the cytologically similarity presented by this group of lesions with goiters with adenomatous changes.

Horner syndrome as a manifestation of thyroid carcinoma: a rare association / Síndrome de Horner como manifestação clínica de carcinoma da tireoide: uma associação rara

An 82-year-old patient presented a progressively growing hard thyroid nodule, and left ptosis. Additionally, ophthalmologic evaluation revealed ipsilateral miosis, diagnostic findings of Horner syndrome. Computerized tomography revealed a 7.5-cm thyroid mass infiltrating the main neck vessels. Although clinical and imaging data were suggestive of poorly differentiated thyroid carcinoma, fine-needle aspiration led to the diagnosis of papillary carcinoma. Paliative care was proposed to the patient due to the advanced stage of the neoplasm and to significant comorbidities. Horner syndrome is an infrequent manifestation of thyroid disorders and benign etiologies are more often implied. Malignant thyroid neoplasms represent a rare cause of Horner syndrome. However, an appropriate and prompt diagnosis is paramount for timely treatment of rare thyroid malignancies.

Paciente de 82 anos apresentando-se com nódulo tireoidiano de crescimento progressivo e ptose palpebral esquerda. O exame oftalmológico revelou ainda miose ipsilateral e achados diagnósticos de síndrome de Horner. A tomografia computadorizada mostrou massa tireoidiana de 7,5 cm infiltrando os grandes vasos do pescoço. Apesar dos dados clínicos e imagiológicos sugestivos de um carcinoma pouco diferenciado da tireoide, a citologia aspirativa foi diagnóstica de carcinoma papilar. Em função do estádio avançado da neoplasia e das comorbilidades significativas, foi proposta para terapêutica paliativa. A síndrome de Horner é uma manifestação clínica infrequente em tumores tireoidianos, estando as condições benignas maioritariamente implicadas. As neoplasias malignas da tireoide representam uma causa rara de síndrome de Horner. Contudo, um diagnóstico adequado e expedito é fundamental para o tratamento atempado nos raros casos de malignidade da tireoide.

Struma ovarii con un foco de micro-carcinoma papilar variante folicular de tiroides: reporte de caso y revisión de la literatura / Struma ovarii with follicular variant of papillary thyroid carcinoma: report of one case

Struma ovarii is an ovarian teratoma composed mainly of thyroid tissue, which can occasionally develop a malignant thyroid tumor. We report a 61 years old female consulting for a metrorrhagia in whom an ovarian cyst was discovered. The patient was subjected to a hysterectomy and bilateral oophorectomy. The pathological study of the surgical piece revealed a focus of papillary thyroid carcinoma, follicular variety in a right struma ovarii. Three months after surgery, an abdominal CAT scan did not show any abnormality.

Câncer de tireóide no município de São Paulo: análises de tendência e espacial dos dados do Registro de Câncer de Base Populacional / Thyroid cancer in São Paul trend and spatial analysis from the population- based cancer registry data

Introdução: A incidência de câncer de tireóide vem aumentando em todo o mundo e não há um consenso sobre as razões deste fato. O município de São Paulo apresenta altos coeficientes de incidência desta doença, mas ainda não foi analisada sua tendência e nem sua distribuição espacial. Objetivos: Descrever os coeficientes de incidência (1997-2010) e de mortalidade (1981-2010), analisar a tendência dos coeficientes de incidência e mortalidade, segundo sexo, faixa etária, tipo morfológico (incidência), bem como os efeitos da idade, período e coorte, e examinar a distribuição espacial. Métodos: Este é um estudo ecológico. Foram analisados os casos novos de câncer de tireóide diagnosticados no período de 1997 a 2010 fornecidos pelo Registro de Câncer de Base Populacional de São Paulo e os óbitos por câncer de tireóide ocorridos entre 1981 e 2010 fornecidos pelo Sistema de Mortalidade do Ministério da Saúde (SIM-MS) e pelo Programa de Aprimoramento das Informações de Mortalidade (PRO-AIM). Foram calculados os coeficientes bruto e padronizado de incidência e de mortalidade, foi analisada a tendência destes coeficientes através do modelo de regressão, da mudança percentual anual e do modelo idade-período-coorte. Para a análise espacial foram criados mapas temáticos, calculado o índice de Moran e, para as variáveis com padrão cluster foi calculado o índice local de associação espacial (LISA) e estimados modelos de regressão, tendo como variável dependente os coeficientes e como variáveis independentes os indicadores socioeconômicos (IDH, taxa de alfabetização, coeficiente de Gini e número de moradores por domicílio). Resultados: O coeficiente médio de incidência (1997-2010) foi para o sexo feminino de 17,77 por 100.000 e para o sexo masculino 4,46 por 100.000. Ambos apresentaram tendência crescente. O coeficiente médio de mortalidade (1981-2010) foi para o sexo feminino de 0,50 por 100.000 e para o masculino 0,30 por 100.000, ambos apresentaram tendência decrescente. O tipo histológico papilífero apresentou tendência crescente em ambos os sexos. Para incidência (ambos os sexos) e para mortalidade feminina, os efeitos de idade-período e coorte ofereceram o melhor ajuste; para mortalidade apenas a idade. Na análise espacial incidência apresentou padrão cluster para homens e mulheres. Os modelos finais foram explicados pela índice de desenvolvimento humano e pela média de moradores por domicílio. Conclusão: Na cidade de São Paulo há um aumento da incidência do câncer.

Diffuse Follicular Variant of Papillary Thyroid Carcinoma in a 69-Year-old Man with Extensive Extrathyroidal Extension: A Case Report

Diffuse follicular variant papillary thyroid carcinoma (DFVPTC) is a rare variant papillary thyroid carcinoma. DFVPTC typically occurs in young females, extensively involves one lobe or both lobes entirely with frequent nodal metastasis and vascular invasion. In contrast to the other subtypes of follicular variant, DFVPTC has biologically aggressive behavior. We present a case of DFVPTC arising in a 69-yr-old male patient. He presented hoarseness for a few months. Following diagnosis of malignancy on aspiration cytology, total thyroidectomy with neck dissection was performed. The tumor involved both lobes of thyroid, encroaching the surrounding structures including tracheal cartilage and esophagus. Multiple lymph node metastasis and vascular invasion were also found. The patient passed away due to the unexplained bleeding of surgical site.

Role of pro-angiogenic marker galectin-3 in follicular neoplasms of thyroid.

The role of pro-angiogenic marker galectin-3 (GAL-3) was examined in differential diagnosis of follicular neoplasms of thyroid into histological subsets of follicular adenoma (FA), follicular carcinoma (FC) and follicular variant of papillary thyroid carcinoma (FVPTC). The study included 22 cases from January 2006 to June 2011 comprising of FA (n = 12), FC (n = 3) and FVPTC (n = 7). Immunohistochemical evaluation of GAL-3 was performed on representative histologic sections from the resected thyroid specimens. The proportion of stained cells and intensity of staining in tumor blood vessels were evaluated. GAL-3 expression showed that angiogenesis was prominent in malignancy (FC and FVPTC) and negative in non-neoplastic thyroid parenchyma and benign condition (FA). GAL-3 expression was found to differentiate benign from malignant follicular neoplasms. Focal and diffuse positivity for GAL-3 was found to be associated with FC and FVPTC respectively, thus GAL-3 can be used as a immunohistochemical marker in the differential diagnosis of follicular neoplasms of thyroid based on the type of expression. Limitation of this study was relatively less number of cases studied; however, this data need to be corroborated in larger cohort.

Cáncer diferenciado de la tiorides, de la biología molecular a la clínica / Differentiated thyroid cancer, from molecular biology to the clinic

Recent advances in molecular research have made possible to identify intracellular pathways involved in cell proliferation and differentiation processes, and to clarify how functional alterations in these pathways could explain development of differentiated thyroid cancer. This information has direct implications in diagnostic and therapeutic strategies. We present a review of this topic with this integrated vision between molecular findings and clinical management.

Expression of GADD153 in follicular tumors of thyroid and comparison with CK19, Galectin-3 and HBME-1 / 中华病理学杂志

<p><b>OBJECTIVE</b>To study immunohistochemical expression of GADD153 and assess its usefulness as markers in the differential diagnoses in follicular tumors of the thyroid.</p><p><b>METHODS</b>Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue of 34 cases of follicular thyroid adenomas (FTA), 46 cases of follicular thyroid carcinomas (FTC), 29 cases of follicular variant papillary carcinomas (FVPC).</p><p><b>RESULTS</b>(1) GADD153 was expressed in cell nucleus with positive or strong positive expression in FTC, and no or weak expression in FTA and FVPC. The positive expressions of GADD153 were present in 38 of 46(82.6%) in FTC, 11 of 34(32.4%) in FTA and three of 29(10.3%) in FVPC, the positive expression rate in FTC was obviously higher than that in FTA and in FVPC, the differences were statistically significant (χ² = 20.80 and 37.48; P < 0.01). (2) CK19, Galectin-3 (Gal-3) and HBME-1 were all expressed in the cytoplasm, the positive expressions of CK19, Gal-3 and HBME-1 were present in 54.3% (25/46), 67.4% (31/46) and 58.7% (27/46) in FTC; 50.0% (17/34), 29.4% (10/34) and 32.4% (11/34) in FTA; 100% (29/29), 93.1% (27/29) and 89.7% (26/29) in FVPC, the differences were statistically significant as well (χ² = 21.20 and 8.22; P < 0.01). (3) According to the expressions of CK19, Gal-3, HBME-1 and GADD153, we divided the results into low expression group (0 or 1+) and high expression group (2+ or 3+), the sensitivity and the specificity were calculated. in FTA, the sensitivity were 26.5%, 8.8%, 2.9% and 11.8%; the specificity were 50.7%, 52.0%, 54.7% and 58.7%. in FTC, the sensitivity were 19.6%, 26.1%, 23.9% and 65.2%; the specificity were 41.3%, 57.1%, 62.0% and 92.1%. in FVPC, the sensitivity were 96.6%, 82.8%, 79.3% and 3.4%; the specificity were 77.5%, 81.3%, 85.0% and 57.5%.</p><p><b>CONCLUSIONS</b>The sensitivity and the specificity of GADD153 expression are well for diagnosing FTC, and CK19, Gal-3, HBME-1 are well for FVPC. The four markers when used in combination, are better to identify the follicular tumors of the thyroid.</p>

Expression of SMAD proteins, TGF-beta/activin signaling mediators, in human thyroid tissues / Expressão de proteínas SMAD, mediadores da sinalização de TGF-beta/activina, em tecidos de tiroide humana

OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-β/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-β and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-β and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-β/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.

OBJETIVO: Investigar a expressão de proteínas SMAD em tecidos de tiroide humana desde que a inativação dos componentes da sinalização de TGF-β/activina é relatada em diversos tipos de câncer. SMAD 2 e SMAD3 fosforilados (pSMAD2/3) associados com SMAD4 induzem a transmissão do sinal gerado por TGF-β e activina, enquanto SMAD7 inibe essa sinalização intracelular. Embora TGF-β e activina exerçam efeitos antiproliferativos nas células foliculares da tiroide, tumores de tiroide expressam altos níveis dessas proteínas. MATERIAIS E MÉTODOS: A expressão proteica de SMADs foi avaliada em bócio multinodular, adenoma folicular, carcinomas papilífero e folicular por imuno-histoquímica. RESULTADOS: A expressão de pSMAD2/3, SMAD4 e SMAD7 foi observada tanto em tumores benignos como malignos da tiroide. Embora pSMAD2/3, SMAD4 e SMAD7 exibissem alta positividade citoplasmática em carcinomas, a positividade nuclear de pSMAD2/3 não foi diferente entre lesões benignas e malignas da tiroide. CONCLUSÕES: O achado da expressão de SMADs em células tiroidianas e a presença das proteínas pSMAD2/3 e SMAD4 no núcleo de células tumorais indicam propagação da sinalização TGF-β/activina. Contudo, a alta expressão de SMAD7 inibitório, principalmente em tumores malignos, poderia contribuir para atenuação da sinalização antiproliferativa de SMADs em carcinomas de tiroide.