Riesgo de recurrencia dinámico en pacientes con microcarcinoma de tiroides con y sin ablación con Yodo-131 / Dynamic risk of recurrence in patients with thyroid microcarcinoma with and without iodine-131 ablation

Introducción: El cáncer diferenciado de tiroides ha incrementado su incidencia en las últimas 3 décadas debido al sobrediagnóstico de tumores pequeños o microcarcinomas, las nuevas tendencias en su manejo hacen de la cirugía y la terapia con iodo radioactivo el tratamiento de elección para casos seleccionados. El manejo actual de microcarcinoma de tiroides se basa en el riesgo de recurrencia inicial y su seguimiento en el tiempo con el riesgo de recurrencia dinámico. Objetivo: El presente trabajo se enfocó en analizar el riesgo de recurrencia dinámico en pacientes con microcarcinoma de tiroides que recibieron o no terapia ablativa con Iodo 131 posterior a tratamiento quirúrgico en el Hospital Teodoro Maldonado Carbo durante los años 2016 ­ 2018. Métodos: Se realizó un estudio ambispectivo, no experimental, descriptivo, analítico, transversal y correlacional. Se analizaron 51 pacientes atendidos en la unidad técnica de endocrinología. Resultados: De un total de 51 casos de microcarcinoma, el 60% fue tratado con terapia ablativa, la respuesta inicial fue excelente en el 53.3% de pacientes ablacionados y en el 66.7% de los casos no ablacionados. El riesgo de recurrencia inicial fue significativamente más bajo en el grupo no tratado mediante ablación (100%), mientras que en el tratado con ablación fue bajo, intermedio y alto en 16 (53.3%), 7 (23.3) y 7 (23.3), respectivamente. Conclusiones: Existe un riesgo bajo de recurrencia dinámico, independientemente de la indicación de terapia ablativa con I131, la estratificación del riesgo de recurrencia constituye una herramienta útil para seleccionar aquellos pacientes que deben recibir iodo radioactivo.

Introduction: Differentiated thyroid cancer has increased its incidence in the last 3 decades due to overdiagnosis of small tumors or microcarcinomas; new trends in its management make surgery and radioactive iodine therapy the treatment of choice for selected cases. The current management of thyroid microcarcinoma is based on the initial risk of recurrence and its follow-up over time with the dynamic risk of recurrence. Objective: The present work focused on analyzing the risk of dynamic recurrence in patients with thyroid microcarcinoma who received or did not receive ablative therapy with Iodine 131 after surgical treatment at the Teodoro Maldonado Carbo Hospital during the years 2016 - 2018. Methods: An ambispective, non-experimental, descriptive, analytical, cross-sectional, and correlational study was carried out. Fifty-one patients treated at the endocrinology technical unit were analyzed. Results: Of 51 cases of microcarcinoma, 60% were treated with ablative therapy, and the initial response was excellent in 53.3% of ablated patients and 66.7% of non-ablated cases. The initial recurrence risk was significantly lower in the group not treated by ablation (100%). In contrast, in the group treated with ablation, it was low, intermediate, and high in 16 (53.3%), 7 (23.3), and 7 (23.3), respectively. Conclusions: There is a low risk of dynamic recurrence, regardless of the indication for ablative therapy with I131; a recurrence risk stratification is a helpful tool for selecting those patients who should receive radioactive iodine.

Clinical characteristics and prognosis of anaplastic thyroid carcinoma: a 20-year single-center retrospective study / 中华耳鼻咽喉头颈外科杂志

Objectives: To investigate the clinical characteristics and prognoses of patients with anaplastic thyroid carcinoma(ATC), and to explore the value of multi-modality treatment in improving overall survival(OS) of ATC patients. Methods: Medical records including clinicopathological data of patients diagnosed with ATC at Cancer Hospital, Chinese Academy of Medical Sciences between 2001 and 2020 were retrospectively analyzed. The cohort were divided into surgery-only and multi-modality subgroups, and the latter included patients treated with surgery plus radiotherapy and/or medical therapy(including chemotherapy, target therapy and immunotherapy). Univariate survival analysis was conducted through Kaplan-Meier method, and multivariate survival analysis was performed using Cox proportional hazard model. Results: A total of 47 patients were included in the study, including 24 males and 23 females, with a median age of 63 years. After a median follow-up duration of 3.37 months, 42 patients died due to tumor recurrence or progression. The median OS of the cohort was 4.33 months. Univariate survival analysis demonstrated that symptoms of recurrent laryngeal nerve(RLN) involvement, distant metastasis, leukocyte elevation, and treatment modality were significantly associated with OS (P values all<0.05). Multivariate analysis showed that symptoms of RLN involvement(HR=2.49, 95%CI: 1.16-5.32, P=0.019), distant metastasis(HR=2.33, 95%CI: 1.06-5.16, P=0.036), and leukocyte elevation(HR=2.50, 95%CI: 1.16-5.40, P=0.020) were all independent risk factors for OS, while multi-modality therapy significantly prolonged OS compared with surgery alone(HR=0.22, 95%CI: 0.10-0.47, P<0.001). Conclusions: Among ATC patients, absence of symptoms of RLN invasion, normal leukocyte level and absence of distant metastasis at initial diagnosis are all independent protective factors for OS and multi-modality treatment can help to improve the prognosis.

Carcinoma Anaplásico de Tireoide em uma Paciente Jovem: Relato de Caso / Anaplastic Thyroid Carcinoma in a Young Woman: Case Report / Carcinoma Anaplásico de Tiroides en una Mujer Joven: Reporte de Caso

Introdução: O carcinoma anaplásico da tireoide é um tumor raro e agressivo, que afeta principalmente mulheres com idade acima de 60 anos, sendo menos comum em pessoas mais jovens. Acredita-se que esse tumor surja em razão da perda de diferenciação em carcinomas bem diferenciados de tireoide. Uma baixa ingestão de iodo também foi sugerida. Apesar das tentativas de intervenção multimodal, o prognóstico é ruim. Relato do caso: Paciente do sexo feminino, 41 anos, submetida à tireoidectomia total, por causa do rápido crescimento de massa tireoidiana, associada à suspeita radiológica de malignidade. A avaliação macroscópica mostrou que o tumor apresentava formato lobulado, áreas necróticas e hemorrágicas e margens mal definidas. Os achados microscópicos confirmaram um carcinoma anaplásico de tireoide, caracterizado pela proliferação de células multinucleadas fusiformes e osteoclásticas, associadas a um carcinoma papilar de tireoide bem diferenciado. Conclusão: Apesar de sua raridade, o carcinoma anaplásico deve ser considerado uma possibilidade na avaliação de uma neoplasia tireoidiana, e o diagnóstico diferencial deve ser levado em conta com cautela, pois pode ser confundido com outros tumores, como linfomas e sarcomas. Além disso, é importante ressaltar a necessidade de considerá-la mesmo quando o paciente não pertence ao grupo epidemiológico usual

Introduction: The anaplastic thyroid carcinoma is a rare, aggressive tumor, and it affects mainly women over the age of 60 years, being less common in younger people. It is believed that this tumor appears due to the loss of differentiation in well differentiated thyroid carcinomas. Low iodine ingestion has also been suggested. Despite multimodal intervention attempts, prognosis is poor. Case report: A 41 year-old female patient underwent a total thyroidectomy because of to the rapid growth of a thyroid mass, associated with radiological suspicion of malignancy. The macroscopic evaluation showed that the tumor had a lobulated shape, necrotic and hemorrhagic areas, and poorly-defined margins. Microscopic findings confirmed an anaplastic thyroid carcinoma, characterized by the proliferation of spindle and osteoclast-like multinucleated cells, associated with a well differentiated papillary thyroid carcinoma. Conclusion: Despite its rarity, the anaplastic carcinoma should be thought as a possibility when evaluating a thyroid neoplasia, and differential diagnosis must be considered cautiously, since it can be misleading for other tumors, such as lymphomas and sarcomas. In addition, it is important to point out the necessity to admit it even when the patient does not belong to the typical epidemiological group

Introducción: El carcinoma anaplásico de tiroides es un tumor agresivo poco común y afecta principalmente a mujeres mayores de 60 años, siendo menos común en adultos más jóvenes. Se cree que este tumor surge debido a la pérdida de diferenciación en carcinomas tiroideos bien diferenciados. También se ha implicado una baja ingestión de yodo. A pesar de los intentos de intervención multimodal, el pronóstico es malo. Reporte del caso: Paciente de 41 años fue sometida a tiroidectomía total por rápido crecimiento de una masa tiroidea, asociada a sospecha radiológica de malignidad. La evaluación macroscópica mostró que un tumor voluminoso con áreas necróticas y hemorrágicas y márgenes mal definidos. Los hallazgos microscópicos confirmaron un carcinoma anaplásico de tiroides, caracterizado por la proliferación de células multinucleadas fusiformes y similares a los osteoclastos, asociado con un carcinoma papilar de tiroides bien diferenciado. Conclusión: A pesar de su rareza, el carcinoma anaplásico debe considerarse una posibilidad al evaluar la neoplasia tiroidea. Se deben considerar cuidadosamente los diferentes diagnósticos, ya que pueden confundirse con otros cánceres, como linfomas y sarcomas. Además, es importante señalar la necesidad de considerarlo incluso cuando el paciente no pertenece al grupo epidemiológico habitual

Mutação do promotor TERT no carcinoma anaplásico da tireoide: um relato de caso / TERT promoter mutation in anaplastic thyroid carcinoma: a case report

Introdução: o gene TERT codifica a subunidade catalítica da telomerase responsável pelo alongamento dos telômeros no final dos cromossomos. Mutações na região promotora do gene TERT resultam em superexpressão da subunidade catalítica e promovem aumento da atividade da telomerase, fatos que levam ao aumento da incidência do câncer. No carcinoma anaplásico da tireoide, essas mutações são preditores de pior prognóstico e estão associadas a comportamento clínico agressivo, incluindo alta frequência de recidivas, metástases a distância e morte específica pela doença. Objetivo: relatar o caso de uma paciente idosa portadora de carcinoma anaplásico da tireoide, cujo teste de sequenciamento genético revelou a mutação do promotor TERT C228T. Caso clínico: mulher idosa, 66 anos, diagnosticada inicialmente com nódulo tireoidiano, o qual cresceu rapidamente em um curto período de tempo. Diante da suspeita de neoplasia maligna, a paciente foi submetida a tireoidectomia total, com realização de esvaziamento cervical. Os estudos anatomopatológico e imuno-histoquímico do tumor confirmaram o carcinoma. Estudos moleculares realizados a partir da tecnologia do sequenciamento de nova geração negaram a presença de fusões gênicas, porém detectaram a mutação TERT C228T. Discussão: a identificação da mutação no promotor TERT C288T reforça a hipótese de que mutações TERT são frequentes em tumores tireoidianos mais agressivos, como é o caso do carcinoma anaplásico da tireoide. Conclusão: os dados apresentados neste estudo reforçam a premissa de que mutações no promotor TERT são preditores de pior prognóstico e de comportamento clínico mais agressivo.

Introduction: the TERT gene encodes the catalytic telomerase subunit responsible for elongating telomeres at the end of chromosomes. Mutations in the promoter region of the TERT gene result in overexpression of the catalytic subunit and promote increased telomerase activity, facts that lead to an increased incidence of cancer. In anaplastic thyroid carcinoma, these mutations are predictors of worse prognosis and are associated with aggressive clinical behavior, including a high frequency of relapses, distant metastases, and diseasespecific death. Objective: to report the case of an elderly patient with anaplastic thyroid carcinoma, whose gene sequencing test revealed a TERT C228T promoter mutation. Case report: Elderly woman, 66 years old, initially diagnosed with a thyroid nodule, which grew rapidly in a short period of time. Given the suspicion of malignant neoplasm, the patient underwent total thyroidectomy, with neck dissection. The anatomopathological and immunohistochemical studies of the tumor confirmed the carcinoma. Molecular studies performed using next-generation sequencing technology denied the presence of gene fusions, but detected the TERT C228T mutation. Discussion: identification of the mutation in the TERT C288T promoter reinforces the hypothesis that TERT mutations are frequent in more aggressive thyroid tumors, such as anaplastic thyroid carcinoma. Conclusion: data presented in this study reinforce the premise that mutations in the TERT promoter are predictors of worse prognosis and more aggressive clinical behavior.

Metástasis cardíaca de carcinoma anaplásico de tiroides / Cardiac metastasis from primary anaplastic thyroid carcinoma

Resumen Las neoplasias cardíacas son entidades poco frecuentes en la práctica clínica cardiológica y dentro de éstas, la afectación metastásica es 20 a 40 veces más frecuente que la forma primaria, corres pondiendo al 95% de todos los tumores cardíacos; no obstante, debido a las características clínicas y oncológicas del tumor primario, los tumores cardíacos metastásicos son habitualmente subdiagnosticados. En este trabajo se presentan dos casos de pacientes con carcinoma anaplásico de tiroides, una mujer de 69 años con metástasis en ventrículo derecho y un varón de 61 años con metástasis en aurícula derecha. Ambos pacientes fallecieron durante la internación y a uno de ellos se le realizó autopsia.

Abstract Cardiac neoplasms are rare entities in the clinical practice. Cardiac metastatic involvement is 20 to 40 times more frequent than the primary form, representing 95% of all cardiac tumors; however, they are frequently underdiagnosed because of their clinical and oncologic features. In this report, we present two cases of cardiac metastasis from primary anaplastic thyroid carcinoma: a 69-years-old woman with right ventricular metastasis and a 61-years-old man with right atrial metastasis. Both patients died during their hospitalization and one of them underwent an autopsy.

Dramatic clinical response to dabrafenib plus trametinib in anaplastic thyroid carcinoma and the challenges faced during the COVID-19 pandemic

SUMMARY Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.

Small bowel perforation and death caused by anaplastic thyroid carcinoma metastasis in a patient with concomitant colonic and bilateral breast carcinoma

Undifferentiated or anaplastic thyroid carcinoma (ATC) is rare and one of the most aggressive human malignancies. The tumor is usually voluminous and fast-growing and mostly affects older women. The most common sites of distant metastases are the lungs, brain, and bones. Herein, we describe the case of a 66-year-old woman with a history of bilateral breast carcinoma and ATC, who presented with an acute abdomen and subsequently died. At autopsy, an isolated metastasis of ATC in the small intestine leading to bowel perforation was found. Moreover, there was adenocarcinoma in the descending colon. The review of extra-abdominal malignancies metastasizing to bowel and coincidence of breast and thyroid carcinoma is included.

El Rol de la Radioterapia en el Cáncer Diferenciado de Tiroides: Serie de Casos y Revisión de Literatura / The Role of Radiotherapy in the Different Cancer of Tiroides: Case Series and Literature Review

Introducción: El manejo inicial del cáncer diferenciado de tiroides (CDT) usualmente comprende la cirugía que puede acompañarse según el riesgo de recurrencia de la administración del yodo radioactivo (I-131); sin embargo, existe un pequeño grupo de pacientes que se catalogan como refractarios al I131, lo cual incide directamente en su pronóstico y expectativa de vida, siendo necesario evaluar opciones locales de tratamiento antes de avanzar a las terapias sistémicas y en estas condiciones la radioterapia (RTP) representa una opción local con fines de tratamiento primario o paliativo Métodos:Se realizó un estudio epidemiológico, descriptivo, retrospectivo, de centro único, que involucra a 49 pacientes con CDT e indicación de radioterapia. Resultados:En el 80% de los casos la edad fue mayor de 45 años, con predominio 74% en el sexo femenino, todos con diagnóstico de CDT sometidos a cirugía, 88%con variante no agresiva, 57% con un tamaño tumoral entre 1 a 4cm, 71% con extensión extratiroidea, 71% con metástasis ganglionares cervicales, 45% estadio TNM I y el 71% con alto riesgo de recurrencia. El 96% recibió I-131, con necesidad de reintervenciones quirúrgicas hasta por 5 o más ocasiones (8%). Recibieron RTP 57%con fines curativos y 43% paliativos. La técnica de radioterapia utilizada en el 69% de los pacientes fue IMRT/VMAT, y la dosis más frecuentemente empleada fue ≥ 60Gy en región cervical (61%). De los 49 pacientes, el 90% tiene respuesta estructural incompleta y 12% falleció por CDT. Conclusiones:La radioterapia debe considerarse en enfermedad avanzada localmente con extensión extratiroidea, enfermedad residual macroscópica y tumor irresecable o recurrente que falla a la terapia convencional del CDT. Palabras clave:Neoplasias de la Tiroides, Carcinoma Anaplásico de Tiroides, Tiroidectomía, Recurrencia Local de Neoplasia, recurrencia, /radioterapia

Introduction:The initial management of differentiated thyroid cancer (DTC) usually includes surgery that can be accompanied according to the risk of recurrence of the administration of radioactive iodine (I-131). However, there is a small group of patients who are classified as refractory to I-131, which directly affects their prognosis and life expectancy, making it necessary to evaluate local treatment options before advancing to systemic therapies and, in these conditions, radiotherapy (RTP) represents a local option for primary or palliative treatment purposes. Methods:An epidemiological, descriptive, retrospective, single-center study was carried out, involving 49 patients with DTC and indication for radiotherapy. Results:In 80% of the cases the age was over 45 years, with a 74% predominance in the female sex, all with a diagnosis of DTC undergoing surgery, 88% with a non-aggressive variant, 57% with a tumor size between 1 at 4cm, 71% with extrathyroid extension, 71% with cervical lymph node metastases, 45% TNM stage I, and 71% with a high risk of recurrence. 96% received I-131, requiring reoperations for up to 5 or more occasions (8%). 57% received RTP for curative purposes and 43% palliative. The radiotherapy techniqueused in 69% of the patients was IMRT / VMAT, and the most frequently used dose was ≥60Gy in the cervical region (61%). Of the 49 patients, 90% had an incomplete structural response and 12% died from DTC. Conclusions:Radiation therapy should be consideredin locally advanced disease with extrathyroid extension, macroscopic residual disease and unresectable or recurrent tumor that fails conventional therapy for DTC. Keywords:Thyroid Neoplasms; Thyroid Carcinoma,Anaplastic;Thyroidectomy;Neoplasm Recurrence, Local;/radiotherapy

Carcinoma anaplásico de tireoide: relato de caso tratado com cirurgia e radioterapia adjuvante / Anaplastic thyroid cancer: a case report treated with surgery and adjuvant radiotherapy

Introdução: o Carcinoma Anaplásico de Tireoide (CAT) está entre as mais letais malignidades humanas, sendo a taxa de sobrevida estimada em 10-20% em 01 ano e menor que 5% em 10 anos. Diante da raridade do CAT e desfecho consideravelmente desfavorável da doença, este relato discute as modalidades terapêuticas utilizadas no tratamento do CAT e as características da doença possivelmente relacionadas a um melhor desfecho clínico. Objetivo: relatar o caso de um paciente idoso portador de CAT com resposta completa loco-regional após tratamento combinado com cirurgia e radioterapia (RT) adjuvante. Neste estudo, a literatura a respeito das características da patologia da neoplasia indiferenciada da tireoide e modalidades de tratamento no controle oncológico desta doença é revisada e discutida. Caso clínico: trata-se de um paciente masculino de 88 anos submetido a Tireoidectomia Total (TT) cujo estudo imuno-histoquímico evidenciou neoplasia maligna indiferenciada da tireoide. O paciente realizou tratamento adjuvante com RT na dose total de 66 Gy em leito operatório. Em tempo de seguimento de 18 meses, o paciente encontra-se vivo sem doença detectável em atividade. Conclusão: neste relato, descreveu-se um raro caso de uma evolução favorável de um paciente idoso portador de CAT com longa sobrevida livre de doença quando comparada ao prognóstico reservado dessa neoplasia. Este relato destaca a importância de uma terapia multimodal no manejo desta doença.

Backgroud: anaplastic thyroid cancer (ATC) ranks among the most lethal of all human malignancies, and the estimated survival rate ranges from 10 to 20% in 01 year and is less than 5% in 10 years. In view of the rarity of ATC and considerably unfavorable outcome of the disease, this report makes it possible to discuss the therapeutic modalities in the treatment of the ATC and the features of the disease possibly related to a better clinical outcome. Objective: the objective of the present study is to report the case of an elderly patient with ATC with locoregional complete response after combined treatment with surgery and adjuvant radiotherapy (RT.) In this study, the literature regarding the pathological features of the undifferentiated thyroid cancer and treatment modalities on oncologic outcome is reviewed and discussed. Case presentation: this is a case of a 88 year old male patient, who underwent total thyroidectomy (TT) for thyroid cancer treatment whose cytological analysis was compatible with anaplastic thyroid cancer. The immunohistochemical study showed undifferentiated malignancy of the thyroid. The patient underwent adjuvant treatment with RT at the total dose of 66 Gy in operative bed. In a follow-up period of 18 months, the patient is alive with no detectable disease in activity. Conclusions: in this report, is described a rare case of a favorable evolution of an elderly patient with ATC relatively long disease-free survival compared to the reserved prognosis of this neoplasm. This case underlines the importance of a multimodal therapy in the management of this disease.

Unmet Clinical Needs in the Treatment of Patients with Thyroid Cancer

The increased incidence of thyroid cancer is a worldwide phenomenon; however, the issue of overdiagnosis has been most prominent in South Korea. The age-standardized mortality rate of thyroid cancer in Korea steeply increased from 1985 to 2004 (from 0.17 per 100,000 to 0.85 per 100,000), and then decreased until 2015 to 0.42 per 100,000, suggesting that early detection reduced mortality. However, early detection of thyroid cancer may be cost-ineffective, considering its very high prevalence and indolent course. Therefore, risk stratification and tailored management are vitally important, but many prognostic markers can only be evaluated postoperatively. Discovery of preoperative marker(s), especially for small cancers, is the most important unmet clinical need for thyroid cancer. Herein, we discuss some such factors that we recently discovered. Another unmet clinical need is better treatment of radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) and undifferentiated cancers. Although sorafenib and lenvatinib are available, better drugs are needed. We found that phosphoglycerate dehydrogenase, a critical enzyme for serine biosynthesis, could be a novel therapeutic target, and that the lymphocyte-to-monocyte ratio is a prognostic marker of survival in patients with anaplastic thyroid carcinoma or RAIR DTC. Deeper insights are needed into tumor-host interactions in thyroid cancer to improve treatment.

Recent Improvements in Genomic and Transcriptomic Understanding of Anaplastic and Poorly Differentiated Thyroid Cancers

Anaplastic thyroid cancer (ATC) is a lethal human cancer with a 5-year survival rate of less than 10%. Recently, its genomic and transcriptomic characteristics have been extensively elucidated over 5 years owing to advance in high throughput sequencing. These efforts have extended molecular understandings into the progression mechanisms and therapeutic vulnerabilities of aggressive thyroid cancers. In this review, we provide an overview of genomic and transcriptomic alterations in ATC and poorly-differentiated thyroid cancer, which are distinguished from differentiated thyroid cancers. Clinically relevant genomic alterations and deregulated signaling pathways will be able to shed light on more effective prevention and stratified therapeutic interventions for affected patients.

Prognostic value of thyroidectomy and tracheostomy in anaplastic thyroid carcinoma

@#<p><strong>OBJECTIVE:</strong> To determine the prognostic value of surgical interventions done among patients with anaplastic thyroid carcinoma (ATC)</p><p><strong>METHODS:</strong> A five-year retrospective chart review of 25 patients was done and baseline characteristics determined. Patients discharged alive as of the time of last chart entry were followed up by phone interview or personal visit. Overall survival was the main outcome measure which was plotted as Kaplan-Meier estimates and compared via log-rank test. The incidence of complications surrounding tracheostomy and thyroidectomy were also noted.</p><p><strong>Methods: </strong></p><p><strong>Design:</strong> Ambispective Cohort Study</p><p><strong>Setting:</strong> Tertiary National University Hospital</p><p><strong>Participants:</strong> All private and public (charity) patients seen at the wards or clinics diagnosed with ATC via fine needle cytology or tissue histopathology.</p><p><strong>RESULTS:</strong> All patients presented with either stage IV-B or stage IV-C disease. A significant difference in survival curves was noted when comparing between the two stages (p<.05). Subgroup analysis per stage revealed no significant difference in overall survival when comparing patients who did not undergo surgery, those who underwent tracheostomy or those who underwent thyroidectomy for both IV-B (p=.244) or IV-C (p=.165) disease. The incidence of complications for tracheostomy was 60%, the most common being mucus plugging. For thyroidectomy, the incidence of complications was 80% with hypocalcemia being the most common.</p><p><strong>CONCLUSION:</strong> The current available data fails to demonstrate any significant survival advantage of tracheostomy or thyroidectomy when performed among similarly staged patients.</p>

Expression of NF2 Modulates the Progression of BRAFV600E Mutated Thyroid Cancer Cells

BACKGROUND: We previously reported the frequent neurofibromatosis 2 (NF2) gene mutations in anaplastic thyroid cancers in association with the BRAF V600E mutation. We aimed to investigate the role of NF2 in thyroid cancer with BRAF mutation. METHODS: To identify the function of NF2 in thyroid cancers, we investigated the changes in cell proliferation, colon formation, migration and invasion of thyroid cancer cells (8505C, BHT101, and KTC-1) with BRAF V600E mutation after overexpression and knock-down of NF2. We also examined how cell proliferation changed when NF2 was mutagenized. Human NF2 expression in papillary thyroid carcinoma (PTC) was analyzed using the The Cancer Genome Atlas (TCGA) data. RESULTS: First, NF2 was overexpressed in 8505C and KTC-1 cells. Compared to control, NF2 overexpressed group of both thyroid cancer cells showed significant inhibition in cell proliferation and colony formation. These results were also confirmed by cell migration and invasion assay. After knock-down of NF2 in 8505C cells, there were no significant changes in cell proliferation and colony formation, compared with the control group. However, after mutagenized S288* and Q470* sites of NF2 gene, the cell proliferation increased compared to NF2 overexpression group. In the analysis of TCGA data, the mRNA expression of NF2 was significantly decreased in PTCs with lateral cervical lymph node (LN) metastasis compared with PTCs without LN metastasis. CONCLUSION: Our study suggests that NF2 might play a role as a tumor suppressor in thyroid cancer with BRAF mutation. More studies are needed to elucidate the mechanism how NF2 acts in thyroid cancer with BRAF mutation.

Anti-cancer Activity of Paclitaxel, Lenvatinib and Radiation Combination Therapy on Anaplastic Thyroid Cancer in Vitro and in Vivo / 대한두경부종양학회지

BACKGROUND/OBJECTIVES: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%. The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways.MATERIALS #SPCHAR_X0026; METHODS: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo.RESULTS: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts.CONCLUSION: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.

Facteurs prédictifs de malignité des tumeurs oncocytaires de la thyroïde

INTRODUCTION : Les tumeurs oncocytaires (TO) de la thyroïde regroupent les adénomes et les carcinomes. La distinction entre malignité et bénignité constitue une difficulté de taille sur le plan histologique. De cet aspect découlent des contraintes dans l'attitude thérapeutique à adopter. L'objectif du travail était de déterminer les particularités cliniques, pathologiques et pronostiques des TO de la thyroïde et dégager les facteurs prédictifs de malignité. MÉTHODES : Etude descriptive, rétrospective portant sur 35 cas de TO de la thyroïde opérés entre 2007 et 2015. Les prélèvements ont été étudiés au service d'anatomopathologie. Une étude statistique a été réalisée à la recherche des facteurs prédictifs de mali¬gnité.RÉSULTATS : L'âge moyen des patients était de 53 ans. Le sex-ratio a été de 0,09. Le traitement était chirurgical dans tous les cas. L'examen anatomopathologique définitif a confirmé le diagnostic de 26 adénomes oncocytaires, six carcinomes papillaires on-cocytaires et trois carcinomes vésiculaires oncocytaires. La taille moyenne de la tumeur était de 38,1 mm (10-120). Une irathérapie post-opératoire a été proposée pour les carcinomes. En analyse univariée, les facteurs prédictifs de malignité étaient : l'âge supé¬rieur à 55 ans, la consistance dure, les limites floues, la double vascularisation anarchique, le caractère hypoéchogène du nodule, les microcalcifications, la colloïde sombre et dense, la capsule épaisse et la thyroïdite associée. En analyse multivariée, aucun de ces facteurs n'était prédictif de malignité.CONCLUSION : Les tumeurs oncocytaires de la thyroïde représentent une entité anatomo-clinique distincte. La détermination des facteurs prédictifs de malignité est essentielle pour adapter la prise en charge thérapeutique

Treatment outcomes of radiotherapy for anaplastic thyroid cancer

PURPOSE: Anaplastic thyroid cancer (ATC) is a rare tumor with a lethal clinical course despite aggressive multimodal therapy. Intensity-modulated radiotherapy (IMRT) may achieve a good therapeutic outcome in ATC patients, and the role of IMRT should be assessed. We retrospectively reviewed outcomes for ATC treated with three-dimensional conformal radiotherapy (3D-CRT) or IMRT to determine the optimal treatment option and explore the role of radiotherapy (RT). MATERIALS AND METHODS: Between December 2000 and December 2015, 41 patients with pathologically proven ATC received RT with a sufficient dose of ≥40 Gy. Among them, 21 patients (51%) underwent surgery before RT. Twenty-eight patients received IMRT, and 13 received 3D-CRT. Overall survival (OS) and progression-free survival (PFS), patterns of failure, and toxicity were examined. RESULTS: The median follow-up time for survivors was 38.0 months. The median and 1-year OS and PFS rates were 7.2 months and 29%, 4.5 months and 15%, respectively. Surgery significantly improved the prognosis (median OS: 10.7 vs. 3.9 months, p = 0.001; median PFS: 5.9 vs. 2.5 months, p = 0.007). IMRT showed significantly better PFS and OS than 3D-CRT, even in multivariate analysis (OS: hazard ratio [HR] = 0.30, p = 0.005; PFS: HR = 0.33, p = 0.005). Significantly higher radiation dose could be delivered with IMRT than 3D-CRT (EQD210 66 vs. 60 Gy, p = 0.005). Only 2 patients had grade III dermatitis after IMRT. No other severe toxicity ≥grade III occurred. CONCLUSION: Patients with ATC showed better prognosis through multimodal treatment. Furthermore, IMRT could achieve favorable survival rates by safely delivering higher dose than 3D-CRT.

Detection of Solitary Axillary Lymph Node Metastases from Hürthle Cell Carcinoma of the Thyroid on ¹⁸F-FDG PET/CT / 대한핵의학회잡지

Thyroid carcinoma is the most common neoplasm of endocrine malignancies. Differentiated thyroid carcinoma (DTC) constitutes 90% of the thyroid carcinomas, rest being medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC). Distant metastases occur in up to 10% of patients with DTC. Metastases to axillary lymph nodes (ALN) are very rare. As per literature, only 25 cases have been reported. We report an unusual case of 47-year-old male with Hürthle cell carcinoma of the thyroid presenting with a solitary axillary lymph node metastasis 17 years after thyroidectomy, along with review of literature.

Identification of key pathways and drug repurposing for anaplastic thyroid carcinoma by integrated bioinformatics analysis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To identify hub genes and key pathways associated with anaplastic thyroid carcinoma (ATC), and to explore possible intervention strategy.</p><p><b>METHODS</b>The differentially expressed genes (DEGs) in ATC were identified by Gene Expression Omnibus (GEO) combined with using R language; the pathway enrichment of DEGs were performed by using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The protein-protein interaction (PPI) network of DEGs was constructed by STRING database and visualized by Cytoscape. Furthermore, the hub genes and key nodes were calculated by MCODE. Finally, the drug repurposing was performed by L1000CDS.</p><p><b>RESULTS</b>A total of 2087 DEGs were identified. The DEGs were clustered based on functions and pathways with significant enrichment analysis, among which PI3K-Akt signaling pathway, p53 signaling pathway, inflammatory response, extracellular matrix organization were significantly upregulated. The PPI network was constructed and the most significant three modules and nine genes were filtered. Twenty-two potential compounds were repurposed for ATC treatment.</p><p><b>CONCLUSIONS</b>Using integrated bioinformatics analysis, we have identified hub genes and key pathways in ATC, and provide novel strategy for the treatment of ATC.</p>

Combined Effects of Baicalein and Docetaxel on Apoptosis in 8505c Anaplastic Thyroid Cancer Cells via Downregulation of the ERK and Akt/mTOR Pathways

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells. METHODS: The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis. RESULTS: The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt. CONCLUSION: The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.

Hipercalcemia paraneoplásica de carcinoma anaplásico da tireoide / Paraneoplastic hypercalcemia of anaplastic thyroid carcinoma: case report

A hipercalcemia deve ser considerada no diagnóstico diferencial de alterações neuropsiquiátricas agudas. Em 90% dos casos, a etiologia corresponde a hiperparatireoidismo primário ou neoplasias. Valores séricos superiores a 14mg/dL e sintomáticos são frequentemente tradutores de causa maligna. O carcinoma anaplásico da tireoide consiste em um tumor indiferenciado, com progressão rápida e prognóstico reservado, que evolui, em alguns casos, a partir de lesões tireóideas preexistentes, benignas ou malignas (desdiferenciação). Embora a apresentação clínica mais frequente destes tumores consista no desenvolvimento de massa cervical, eles podem ser diagnosticados no esclarecimento etiológico de metástases ou síndromes paraneoplásicos. A hipercalcemia, associada à neoplasia, pode ocorrer em contexto de metástases ósseas, com libertação de citocinas, ou por mecanismo humoral, mediada pela proteína relacionada ao hormônio hormônio paratireóideo (PTHrP). Os autores descrevem o caso de uma mulher de 85 anos, com antecedentes de bócio multinodular benigno, internada para esclarecimento etiológico de hipercalcemia grave, com manifestações neuropsiquiátricas, diagnosticando-se, após avaliação, carcinoma anaplásico da tireoide. O caso foi abordado em reunião multidisciplinar, optando-se por limitação terapêutica a cuidados paliativos. A doente faleceu 3 meses após o diagnóstico.(AU)

Hypercalcaemia should be considered in the differential diagnosis of acute neuropsychiatric disorders. In 90% of the cases, the etiology corresponds to primary hyperparathyroidism or neoplasms. Serum values above 14mg/dL and symptomatic are often indicative of a malignant cause. The anaplastic thyroid carcinoma consists of an undifferentiated tumor, with rapid progression and poor prognosis, which in some cases progresses from pre-existing benign or malignant thyroid diseases (dedifferentiation). Although the most frequent clinical presentation of these tumors consists of the development of a cervical mass, they can be diagnosed in the etiological clarification of metastases or paraneoplastic syndromes. Neoplasm-associated hypercalcaemia may occur in the context of bone metastasis, with release of cytokines, or through a humoral mechanism, mediated by the parathyroid hormone (PTHrP)-related protein. The authors describe the case of an 85-year-old woman with a history of multinodular benign goiter, hospitalized for etiological elucidation of severe hypercalcaemia with neuropsychiatric manifestations, with a final diagnosis of anaplastic thyroid carcinoma, after the diagnostic evaluation. The case was approached in a multidisciplinary meeting, and the therapeutic limitation to palliative care was chosen. The patient died 3 months after the diagnosis.(AU)