Carcinoma medular esporádico de tiroides / Sporadic Medullary Thyroid Carcinoma

Introducción: El carcinoma medular de tiroides, representa aproximadamente entre el 5 - 10 por ciento de todos los carcinomas tiroideos, aparece con más frecuencia entre los 25 y 60 años y en el sexo femenino. Se distinguen dos tipos: el esporádico (no hereditario) y el familiar (hereditario). La localización más frecuente es la unión del tercio superior de lóbulo tiroideo con el tercio medio, que es la zona de mayor concentración de células C. Objetivo: Presentar el caso de paciente masculino operado de carcinoma medular de tiroides, tipo esporádico, en la provincia de Cienfuegos. Caso clínico: Paciente masculino de 60 años de edad, piel blanca, que acudió a la consulta; refiere aumento de volumen del cuello acompañado de disfonía y disfagia a los alimentos sólidos. Al examen físico se constató la presencia del nódulo tiroideo. Se le realizó ultrasonido que corrobora la presencia de un nódulo en el lóbulo derecho del tiroides. La biopsia por aspiración con aguja fina informó el nódulo como sospechoso de malignidad. Se le realizó tiroidectomía total, informándose por la biopsia por parafina de la pieza como un carcinoma medular del tiroides. En la actualidad lleva 6 meses de operado con evolución favorable. Conclusiones: El carcinoma medular de tiroides constituye una entidad rara y agresiva más frecuente en los pacientes mayores de 45 años, cuyo tratamiento de elección es la cirugía(AU)

Introduction: Medullary thyroid carcinoma accounts for approximately 5-10 percent of all thyroid carcinomas. It appears more frequently at ages 25-60 years and in females. Two types are distinguished: sporadic (nonhereditary) and familial (hereditary). The most common location is the union of the upper third of the thyroid lobe to the middle third, the area with the highest concentration of C cells. Objective: To present the case of a male patient operated on for medullary thyroid carcinoma, of sporadic type, in the Cienfuegos Province. Clinical case: A 60-year-old male patient of white skin attended consultation. He reported an increase in neck volume accompanied by dysphonia and dysphagia for solid food. The physical examination revealed the presence of the thyroid nodule. Ultrasound was performed, which confirmed the presence of a nodule in the right lobe of the thyroid. Fine needle aspiration biopsy reported the nodule as suspicious for malignancy. A total thyroidectomy was performed, after which, paraffin biopsy of the specimen permitted to report a medullary carcinoma of the thyroid. At present, he has been operating for six months, with favorable evolution. Conclusions: Medullary thyroid carcinoma is a rare and aggressive entity, more frequent in patients over 45 years of age, whose treatment of choice is surgery(AU)

Neoplasia endócrina múltipla tipo 2A: relato de caso / Multiple endocrine neoplasia type 2A: a case report / Neoplasia endocrina múltiple tipo 2A: reporte de caso

As neoplasias endócrinas múltiplas (NEM) são síndromes genéticas autossômicas dominantes implicadas no desenvolvimento de neoplasias benignas ou malignas, envolvendo ao menos duas glândulas endócrinas. Entre seus subtipos, está a NEM2A, que consiste em carcinoma medular de tireoide (CMT), feocromocitoma e hiperparatireoidismo. Este texto apresente o relato de caso de um paciente de 40 anos, previamente hígido, que passou a apresentar episódios de cefaleia associada a sudorese profusa, vômitos e taquicardia. Evoluiu com distensão abdominal intensa após alimentação por via oral, perda ponderal, desnutrição, astenia, obstipação, humor deprimido e picos pressóricos. Exames laboratoriais evidenciaram alterações dos hormônios tireoidianos, PTH e hormônios da adrenal. Foi levantada a suspeita clínica de NEM2A, posteriormente corroborada pelos diagnósticos anatomopatológicos de feocromocitoma e CMT, associados à presença de hiperparatireoidismo. Foi possível concluir que, a despeito de sua baixa prevalência na população geral, a NEM é uma síndrome clínica de grande relevância, tendo em vista os impactos para os pacientes e famílias acometidas. Dessa forma, é necessário que os profissionais de saúde tenham conhecimento acerca da síndrome e que o Sistema Único de Saúde (SUS) esteja apto a assistir aos pacientes portadores de NEM, possibilitando diagnóstico precoce e tratamento adequado.

Multiple endocrine neoplasias (MEN) are dominant autosomal genetic syndromes involved in the development of benign or malignant tumors in at least two endocrine glands. MEN2A is one of its subtypes, which consists of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. This study reports the case of a healthy 40-year-old male patient presenting with episodes of headache associated with profuse sweating, vomiting, and tachycardia. The patient evolved with severe abdominal distension after oral feeding, weight loss, malnutrition, asthenia, constipation, depressed mood, and pressure peaks. Laboratory tests showed abnormalities in thyroid, parathyroid (PTH), and adrenal hormones ­ thus raising the hypothesis of MEN2A, which was later corroborated by the histological diagnosis of pheochromocytoma and MTC, associated with hyperparathyroidism. The results indicate that, despite its low prevalence in the general population, MEN has a great impact on affected patients and families, thus being a relevant clinical syndrome. For enabling early diagnosis and adequate treatment, health professionals must be familiarized with such a condition, and the Brazilian Unified Health System (SUS) must be able to assist affected patients.

Las neoplasias endocrinas múltiples (NEM) son síndromes genéticos autosómicos dominantes involucrados en el desarrollo de neoplasias benignas o malignas, que afectan al menos dos glándulas endocrinas. Entre sus subtipos se encuentra NEM2A, que consiste en carcinoma medular de tiroides (CMT), feocromocitoma e hiperparatiroidismo. Este es un reporte de caso de un paciente de 40 años de edad, previamente sano, que comenzó a presentar episodios de cefalea asociada a sudoración profusa, vómitos y taquicardia. Evolucionó con distensión abdominal severa después de alimentarse, pérdida de peso, desnutrición, astenia, estreñimiento, estado de ánimo deprimido y picos de presión. Las pruebas de laboratorio mostraron alteraciones en las hormonas tiroideas, PTH y hormonas suprarrenales. Se planteó la hipótesis de MEN2A, posteriormente corroborada por el diagnóstico anatomopatológico de feocromocitoma y CMT, asociado a hiperparatiroidismo. Se pudo concluir que, a pesar de su baja prevalencia en la población general, el NEM es un síndrome clínico de gran relevancia, dado el impacto que tiene en los pacientes y familiares afectados. Por tanto, es necesario que los profesionales sanitarios tengan conocimiento sobre el síndrome y que el Sistema Único de Salud (SUS) sea capaz de asistir a los pacientes con NEM, posibilitándoles diagnóstico precoz y tratamiento adecuado.

Concurrent Medullary Thyroid Carcinoma and Primary Thyroid Lymphoma (Diffuse Large B Cell Lymphoma): the First Case Report

Cases of simultaneously occurring medullary thyroid carcinoma (MTC) and lymphoma are extremely rare. An 84-year-old woman visited the hospital due to dyspnea, resulting from rapidly aggravated enlarged neck mass. Ultrasonography revealed two lesions in the thyroid and they were diagnosed as concurrent medullary thyroid carcinoma and diffuse large B cell lymphoma after total thyroidectomy. A few cases simultaneously diagnosed with MTC and systemic lymphoma have been reported. However, the coexistence of MTC and primary thyroid lymphoma is extremely rare.

Rare breast malignancy subtypes: A cytological, histological, and immunohistochemical correlation

Background: Breast malignancies encompass various subtypes which differ in their clinical presentations, outcomes, and response to the treatment regimens. Thus, a proper histological diagnosis and a special mention of the rare histologic subtypes are required to formulate clear recommendations of their treatment protocols. Materials and Methods: This is a 1-year retrospective study highlighting the rarely encountered subtypes on the mastectomy specimens received. Results: We encountered only 11 rare cases out of the total 153 mastectomy specimens received. The rare subtypes were as follows mucinous cystadenocarcinoma (0.6%), mucinous carcinoma (0.6%), dermatofibrosarcoma protuberans (0.6%), Squamous cell carcinoma (0.6%), papillary carcinoma (2.6%), medullary carcinoma (0.6%), and malignant mesenchymal tumor (1.3%). Conclusion: Our data suggest that these variants are distinct clinicopathological entities with a unique hormonal receptor status. Scant information is available on the rare breast tumor subtypes

Rare complications of multikinase inhibitor treatment

ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.

Estudio patológico intraoperatorio en la cirugía tiroidea: ¿cuánto contribuye a la estrategia quirúrgica? / Intraoperative pathologic evaluation in thyroid surgery: how much does it contribute to surgical strategy?

Antecedentes: el papel del estudio patológico intraoperatorio (EPI) en cirugía tiroidea ha sido discutido largamente y es todavía motivo de controversia. Objetivo: estimar los resultados del EPI en el diagnóstico de malignidad, su relación con la biopsia por punción-aspiración preoperatoria con aguja fina (PAAF) y el estudio patológico diferido (EPD), así como su contribución al cambio en la estrategia quirúrgica en cirugía tiroidea. Material y métodos: revisión retrospectiva de las historias clínicas de 773 pacientes operados por patología tiroidea entre enero de 2014 y diciembre de 2015. En todos se efectuó EPI y EPD; a 686 (89%) pacientes también se les efectuó la biopsia por PAAF preoperatoria. Resultados: los resultados del EPI fueron benigno en 215 pacientes (27,8%), maligno en 419 (54,2%) y no definitivo en 139 (18,0%). Cuando estos resultados fueron comparados con la EPD se encontraron 19 casos (8,8%) de falsos negativos y 4 (0,95%) de falsos positivos. Considerando solo los resultados definitivos, el EPI tuvo sensibilidad 95%, especificidad 98%, valor predictivo positivo 99%, valor predictivo negativo 91% y exactitud 91%. Cuando se comparó el EPI con la PAAF preoperatoria, los valores de sensibilidad más bajos (44%) correspondieron a las categorías de Bethesda III y IV. El EPI influyó en la estrategia quirúrgica en 95 pacientes (12,28%): en 53 (6,8%), la hemitiroidectomía cambió a tiroidectomía total; en 37 (4,8%), el diagnóstico de metástasis ganglionares permitió realizar un vaciamiento modificado de cuello, y en 5 (0,6%) ocurrieron ambas situaciones. Conclusión: el EPI tuvo altos valores de utilidad diagnóstica cuando se compararon con el EPD. También se correlacionó con la PAAF preoperatoria, pero tuvo menos utilidad en las categorías Bethesda III y IV. El EPI contribuyó a cambiar la decisión de técnica quirúrgica en un grupo de pacientes y evitar una segunda operación.

Background: the role of intraoperative pathologic evaluation (IPE) in thyroid surgery has largely been discussed and it is still controversial. Objective: to estimate the results of IPE in diagnosis of malignancy, its correlation with preoperative fine needle aspiration (FNA) biopsy and permanent pathologic evaluation (PPE), and its contribution to change surgical strategy in thyroid surgery. Materials and methods: retrospective chart review of 773 patients operated on for thyroid disease between January 2014 and December 2015. All patients underwent IPE and PPE; 686 (89%) patients had also preoperative FNA biopsy. Results: IPE resulted benign in 215 patients (27.8%), malignant in 419 (54.2%) and non definitive in 139 (18.0%). When these results were compared with PPE, 19 cases were false negative (8.8%) and 4 false positive (0.95). Considering only definitive results, IPE had sensitivity 95%, specificity 98%, positive predictive value 99%, negative predictive value 91% and accuracy 91%. When IPE was compared with preoperative FNA biopsy, lowest values of sensitivity (44%) corresponded with Bethesda categories III and IV. IPE influenced surgical strategy in 95 patients (12.28%): in 53 (6.8%) hemithyroidectomy changed to total thyroidectomy, in 37 (4.8%) lymph node metastases diagnosis allowed to perform modified neck dissection, and in 5 (0.6%) both situations occurred. Conclusion: IPE had high values of diagnostic utility when compared with PPE. It also correlated with preoperative FNA biopsy, but had less utility in Bethesda categories III and IV. IPE contributed to change surgical technical decision in a subset of patients and avoid a second operation.

Genetic and epigenetic of medullary thyroid cancer

Medullary thyroid carcinoma [MTC] is an infrequent calcitonin-producing neuroendocrine tumor that initiates from the parafollicular C cells of the thyroid gland. Several genetic and epigenetic alterations are collaterally responsible for medullary thyroid carcinogenesis. In this review article, we shed light on all the genetic and epigenetic hallmarks of MTC. From the genetic perspective, RET, HRAS, and KRAS are the most important genes that are characterized in MTC. From the epigenetic perspective, Ras-association domain family member 1A, telomerase reverse transcriptase promoter methylations, overexpression of histone methyltransferases, EZH2 and SMYD3, and wide ranging increase and decrease in non-coding RNAs can be responsible for medullary thyroid carcinogenesis

Cirugía profiláctica en cáncer medular de tiroides hereditario / Prophylactic surgery in hereditary medullary thyroid cancer

Introducción: Se estima que del total de los cánceres, el 5-10% tendría una base genética. Actualmente es posible identificar a los individuos con predisposición genética en algunos cánceres como manera de intervenir precozmente en el desarrollo de esta enfermedad. Objetivos: Evaluar la utilidad de la cirugía profiláctica en el cáncer medular de tiroides hereditario. Material y métodos: Este trabajo es una revisión de literatura de diferentes estudios extraídos de bibliotecas electrónicas como Scientific Electronic Library Online (SciELO), MedLine-PubMed y UpToDate, mediante la construcción de preguntas clínicas y términos MeSH enfocados principalmente en la búsqueda específica de información sobre el cáncer medular de tiroides hereditario. Resultados: Los estudios revisados demuestran que la tiroidectomía profiláctica con resección linfática cervical representa el único tratamiento eficaz en el caso del cáncer medular de tiroides hereditario. Conclusiones: La cirugía profiláctica ha demostrado una importante disminución del riesgo de cáncer de tiroides y se considera una conducta de rigor en portadores del gen RET en el cáncer medular de tiroides.

Introduction: Approximately 5-10% of global cancer has a genetic base. Nowadays it is possible to identify those who have a genetic predisposition for some cancers, so they can be treated in short term. Objectives: Evaluate how useful is prophylactic surgery on hereditary Medullary Thyroid Cancer. Materials and methods: This investigation is a literature review of different research papers from electronic databases such as Scientific Electronic Library Online (SciELO), MedLine-PubMed and UpToDate. The research was made with clinical queries and MeSH terms, specially focused on hereditary Medullary Thyroid Cancer. Results: This research shows that prophylactic Thyroidectomy with cervical lymph node resection is the only effective and curative treatment for hereditary Medullary Thyroid Cancer. Conclusions: Prophylactic surgery has proof an important role decreasing the risk on Hereditary Thyroid cancer Syndrome and in RET carriers surgery is considered a must.

Guía práctica para el manejo de efectos adversos por inhibidores multicinasas (sorafenib y vandetanib) en pacientes con cáncer de tiroides avanzado / Practice guidelines for the management of adverse effects due to multikinase inhibitors (sorafenib and vandetanib) in patients with advanced thyroid cancer

El advenimiento de la terapia con inhibidores multicinasas (IMK) representó un cambio radical en el tratamiento de pacientes con carcinoma avanzado de tiroides. Hasta la fecha, 2 fármacos se encuentran aprobados por la Asociación Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) en Argentina: sorafenib, para pacientes con carcinoma diferenciado de tiroides radiorresistente, y vandetanib, para aquellos con carcinoma medular de tiroides (enfermedad progresiva y/o sintomática). Los estudios de fase III han demostrado que estos fármacos aumentan significativamente la supervivencia libre de progresión en este grupo de pacientes. Si bien tienen una indicación precisa, su manejo requiere de un equipo multidisciplinario en contacto estrecho con un paciente involucrado en su tratamiento. Los efectos adversos de sorafenib y vandetanib son frecuentes, sin embargo, muchos de ellos disminuyen con el tiempo y la mayoría puede manejarse a menudo sin disminuir la dosis ni suspender el fármaco. El conocimiento del correcto manejo de los efectos adversos por parte del equipo tratante constituye una herramienta fundamental para poder educar al paciente y, consecuentemente, poder prevenirlos o minimizarlos, y de esta manera evitar complicaciones severas. El objetivo de esta publicación es brindar una guía para el diagnóstico y tratamiento de los efectos adversos de estos IMK y, por otro lado, presentar la iniciativa del Hospital de Clínicas de la Universidad de Buenos Aires en cuanto a la implementación de la misma.

The advent of multikinase inhibitors therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The ANMAT (the Argentinian regulatory health agency) has currently approved sorafenib for patients with radioiodine resistant differentiated thyroid carcinoma, and vandetanib for patients with medullary thyroid carcinoma (progressive and/or symptomatic disease). It has been demonstrated by phase III clinical trials that these drugs improve progression free survival in this group of patients. Although they have a precise indication, an interdisciplinary team in close contact with a committed patient, are required for their effective management. The adverse events of these drugs are common, but many of them may ameliorate over time, and most of them are manageable, even without the need for dose reduction or drug withdrawal. Knowledge of the correct management of the adverse events is a fundamental tool for the medical team and for the patient to prevent or minimise them, to avoid serious complications and to obtain better patient compliance. The primary objective of this article is to provide a guideline for the diagnosis and treatment of the adverse events produced by the multikinase inhibitors, and to present the initiative of the Hospital de Clinicas in order to implement these guidelines.

Clinical features and mutations of RET proto-oncogene in a pedigree affected with type 2A multiple endocrine neoplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical features and mutations of RET proto-oncogene in a pedigree affected with multiple endocrine neoplasia type 2A (MEN2A).</p><p><b>METHODS</b>Clinical data of the family members was collected. Genomic DNA from peripheral blood leukocytes were extracted and subjected to PCR amplification. Exons 8, 10, 11, 13, 14, 15, 16 of the RET gene was sequenced.</p><p><b>RESULTS</b>A missense mutation p.C634W was detected in 8 members from the family. Among them, 3 were diagnosed with pheochromocytoma, 1 with medullary thyroid carcinoma, 1 with medullary thyroid carcinoma and pheochromocytoma, 1 with medullary thyroid carcinoma and hyperparathyroidism. One member was found with thyroid enlargement but refused further examination, and another one was identified as carrier of the RET gene mutation.</p><p><b>CONCLUSION</b>A p.C634W mutation has been detected in a family affected with MEN2A, in which most carriers have developed clinical symptoms. RET mutation detection should be routinely performed for families affected with MEN2A.</p>

Uso de inhibidores de tirosina quinasa en carcinoma medular de tiroides. Experiencia Institucional / Use of tyrosine kinase inhibitors in medullary thyroid carcinoma. Institutional Experience

El cáncer medular de tiroides (CMT) correspondeal 5% de los tumores de la glándula tiroides. El único tratamiento curativo es la cirugía. En pacientes con compromiso locorregional o a distancia, la enfermedad puede evolucionar en forma indolente o bien con una rápida progresión de síntomas, requiriendo tratamiento sistémico. Si bien el CMT se caracteriza por tener escasa respuesta a la quimioterapia (QT), la evidencia actual en estudios aleatorizados demostró que los inhibidores de tirosina quinasa (ITQ) han demostrado beneficio en supervivencia libre de progresión (SLP). Se analizaron 6 pacientes con un seguimiento mediano de 29 meses. Todos presentaron más de dos sitios metastásicos. Dos requirieron tratamientos locorregionales (quimioembolización y RT). Los ITQ más utilizados fueron: vandetanib (3), sorafenib (2) y sunitinib (1). Un 50% inició tratamiento con dosis plenas y 3 requirieron reducción de dosis debido a toxicidad G3-G4. El intervalo libre de progresión (ILP) mediano, luego del inicio con ITQ, fue de 4.1 meses (AU)

Medullary thyroid cancer (CMT) accounts for 5% of thyroid tumors. The only curative treatment is surgery. In patients with locally or distal involvement, the disease may evolve indolently or with rapid progression of symptoms, requiring systemic treatment. Although CMT is characterized by a poor response to chemotherapy, current evidence in randomized trials has shown that tyrosine kinase inhibitors (ITKs) have demonstrated benefit in progressionfree survival. Six patients with a median follow-up of 29 months were analyzed. All had more than two metastatic sites. Two patients required locoregional treatments (chemoembolization and radio therapy). The most commonly used ITKs were: vandetanib (3), sorafenib (2) and sunitinib (1). The 50% initiated treatment with full dose and 3 required reduction of the dose due to G3- G4 toxicity. The median progression-free interval after initiation with ITK was 4.1 months (AU)

Histopathological pattern of thyroid diseases among patients in Hadhramout-Yemen

Objective: To determine the histopathological pattern of thyroid diseases among patients in Hadhramout Province, Yemen

Methods: A descriptive retrospective study was conducted at Ibn Sina Central Teaching Hospital, in Mukalla city, Hadhramout, Yemen between January 2007 and December 2012. Eight hundred and seventeen patients with thyropathy were included in this study diagnosed histologically by experienced pathologists using fine needle aspiration cytology. This was followed-up by postoperative pathological thyroid specimen study. The patients in the study were treated medically and surgically by authors

Results: 817 patients with thyropathy were included in the study. There were 716 [87.6%] females and 101 [12.4%] males, with a female to male ratio of 7: 1. The age of the patients ranged from 5 to 80 years, with a mean age of 37.7 +/- 12.2 years. Median age was 35. More than half of the patients aged between 21-40 years. The majority of the thyroid lesions were non neoplastic = 703 [86%]. The most common lesion was simple colloid goiter = 578 [82%] followed by thyroid Hashimoto = 75 [10.7%]. The minority were granulomatous [subacute] thyroiditis, hyperplastic nodule and thyroglossal cyst, 5 [0.7%], 6 [0.9%], 8 [1.1%] respectively. 114 [14%] patients have neoplastic lesions. 61 [7.5%] patients have benign adenoma, 2 [1.75%] patients have Hurthel cell adenoma. 43 [5.3%] patients have papillary carcinoma while 3 [2.63%] patients have anaplastic carcinoma. The less common malignant neoplastic thyroid lesions were primary lymphoma, follicular and medullary carcinoma, and mucoepidermoid carcinoma, 2 [1.75%], 1 [0.9%], 1 [0.9%], and 1 [0.9%] respectively

Conclusion: The most common non-neoplastic thyroid disorder reported in this study is a simple colloid goiter. Adenoma was found to be the most common benign tumor while papillary carcinoma was found to be the most common malignant one. Most cancerous lesions were found within the age groups in the third and the fourth decade, mostly females

A Calcitonin-Negative Neuroendocrine Tumor Derived from Follicular Lesions of the Thyroid

Neuroendocrine lesions of the thyroid are rare. The most common types are medullary thyroid carcinomas (MTCs) and C-cell hyperplasia. MTCs originate from thyroid parafollicular cells that secrete calcitonin which serves as a serum marker of MTCs. Here, the rare case of a calcitonin-negative neuroendocrine tumor (NET) derived from follicular lesions of the thyroid is described. A 34-year-old man presented at our hospital for the surgical management of an incidental thyroid nodule that was observed on an ultrasound sonography (USG) of the neck. Initially, USG-guided aspiration cytology was performed, and a MTC was suspected. The expressions of thyroglobulin and thyroid transcription factor-1, which are thyroid follicular cell markers, and synaptophysin and chromogranin A, which are neuroendocrine markers, was confirmed following surgical pathology. However, the staining of calcitonin, a marker of MTCs, was not observed. A nonmedullary NET of the thyroid is uncommon, and the distinction between calcitonin-negative NETs and MTCs of the thyroid may be important due to differences in their clinical courses and management.

Synchronous Intra-Thyroid Paraganglioma with Carotid Body Tumor / 대한이비인후과학회지

Paraganglioma is an uncommon and slowly-growing benign neuro-endocrine tumor originating from the extra-adrenal paraganglia. The most common site of head and neck paraganglioma is the carotid body. Paraganglioma of thyroid gland is a rare disease, and is hard to diagnose preoperatively since the pathologic features are similar to thyroid neoplasm, especially to medullary carcinoma. Occasionally, multiple paragangliomas can be found in the body. To our knowledge, there are two cases of synchronous carotid body tumor with thyroid paraganglioma that have been reported to date. We report a case of 34-year-old female with carotid body paraganglioma synchronous with intra-thyroid paragangloma, which was misdiagnosed as papillary thyroid carcinoma in the preoperative evaluation. After the tumors were successfully excised, there were no signs of complications and the patient has survived the 2-year-follow-up period without recurrence.

Granular Cell Tumor of the Thyroid Gland: A Case Report and Review of the Literature / 대한내분비외과학회지

Granular cell tumor (GCT) is a rare tumor of Schwann cell origin. While this tumor can occur anywhere in the body, GCT of the thyroid gland is very rare. This tumor is benign, despite showing grossly and histologically malignant features, and should be differentiated from oncocytic/Hurthle cell neoplasm and medullary carcinoma of thyroid. Immunohistochemistry can confirm the final diagnosis and differentiate from other tumors and cell types. We report on a GCT of thyroid in a 46-year-old woman with medical history of right breast cancer and review of literatures.

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia / Diagnosis, treatment, and follow-up of medullary thyroid carcinoma: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism

Introdução O carcinoma medular de tireoide (CMT) origina-se das células parafoliculares da tireoide e corresponde a 3-4% das neoplasias malignas da glândula. Aproximadamente 25% dos casos de CMT são hereditários e decorrentes de mutações ativadoras no proto-oncogene RET (REarranged during Transfection). O CMT é uma neoplasia de curso indolente, com taxas de sobrevida dependentes do estádio tumoral ao diagnóstico. Este artigo descreve diretrizes baseadas em evidências clínicas para o diagnóstico, tratamento e seguimento do CMT. Objetivo O presente consenso, elaborado por especialistas brasileiros e patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia, visa abordar o diagnóstico, tratamento e seguimento dos pacientes com CMT, de acordo com as evidências mais recentes da literatura. Materiais e métodos: Após estruturação das questões clínicas, foi realizada busca das evidências disponíveis na literatura, inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO – Lilacs. A força das evidências, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão. Resultados Foram definidas 11 questões sobre o diagnóstico, 8 sobre o tratamento cirúrgico e 13 questões abordando o seguimento do CMT, totalizando 32 recomendações. Como um todo, o artigo aborda o diagnóstico clínico e molecular, o tratamento cirúrgico inicial, o manejo pós-operatório e as opções terapêuticas para a doença metastática. Conclusões O diagnóstico de CMT deve ser suspeitado na presença de nódulo tireoidiano e história ...

Introduction Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. Objective The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. Materials and methods: After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. Results Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. Conclusions 7 .

Effects of CD147 gene silencing on protein expression of ANXA2, MMP-2 and TIMP-2 by thyroid medullary carcinoma TT cells and biologic characteristics / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the influence of CD147 gene silencing on the expression of ANXA2, MMP-2 and TIMP-2 of thyroid medullary carcinoma TT cells and related biological characteristics.</p><p><b>METHODS</b>Protein expression of CD147, ANXA2, MMP-2 and TIMP-2 was detected by immunocytochemistry.RNAi technology was used to identify the specific siRNA sequences and the optimal time point of effective inhibition of CD147 gene. The expression of ANXA2, MMP-2 and TIMP-2 at mRNA and protein levels was detected with RT-PCR and Western blot, respectively. MTT method was used to detect the proliferation of the TT cells, flow cytometry (FCM) to detect the cell cycle and apoptosis changes of TT cells and transwell chamber assays to document the influence of CD147 gene silencing on migration and invasion of the TT cells.</p><p><b>RESULTS</b>The protein expression of CD147, ANXA2, MMP-2 and TIMP-2 proteins was variable in the TT cells. Two siRNA sequences were identified to effectively silence CD147 gene in the TT cells, in which relative expression of MMP-2 was reduced at both mRNA and protein levels; although the expression of ANXA2 mRNA and protein did not change significantly. TIMP-2 protein expression markedly decreased in an absence of its mRNA expression. The proliferation of the TT cells was inhibited upon the CD147 gene silencing along with a significant increase of G(0)/G(1) phase cells and a decrease of G(2)/M phase cells.However, the proportion of the apoptotic cells in all experimental groups did not change. The number of the penetrating cells through the membrane filters did not show significant changes in all experimental groups in the Transwell chamber assays.</p><p><b>CONCLUSIONS</b>Through RNAi technology, two CD147 siRNA sequences are identified and shown to effectively inhibit CD147 gene expression of the TT cells. CD147 gene silencing leads to growth inhibition of the TT cells and alteration of the cell cycle. However, silencing CD147 does not significantly affect the apoptosis, migration and invasion of the TT cells.</p>

Metastasis of Colon Cancer to Medullary Thyroid Carcinoma: A Case Report

Metastasis to the primary thyroid carcinoma is extremely rare. We report here a case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53-yr old man with a history of colon cancer. He showed a nodular lesion, suggesting malignancy in the thyroid gland, in a follow-up examination after colon cancer surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The patient underwent a total thyroidectomy. Using several specific immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma metastasis to MTC. To the best of our knowledge, the present patient is the first case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor metastasis to primary thyroid carcinoma is very rare, we still should consider metastasis to the thyroid gland, when a patient with a history of other malignancy presents with a new thyroid finding.

Translocation Renal Cell Carcinoma t(6;11)(p21;q12) and Sickle Cell Anemia: First Report and Review of the Literature

Translocation renal cell carcinoma (RCC) is a family of rare tumors recently identified in the pediatric and young adult population. We report the first case of a young woman from French West Indies with sickle cell anemia who developed a translocation RCC t(6;11)(p21;q12). Usually people with the sickle cell condition are known to develop renal medullary carcinoma (RMC). To our knowledge, this is the first case described in the literature of a translocation RCC associated with sickle cell disease. Here we discuss the relation between translocation RCC, RMC, and sickle cell disease.