RESUMO
Anaplastic thyroid cancer (ATC) is an infrequent thyroid tumor that usually occurs in elderly patients. There is often a history of previous differentiated thyroid cancer suggesting a biological progression. It is clinically characterized by a locally invasive cervical mass of rapid onset. Metastases are found at diagnosis in 50% of patients. Due to its adverse prognosis, a prompt diagnosis is crucial. In patients with unresectable or metastatic disease, multimodal therapy (chemotherapy and external beam radiotherapy) has yielded poor outcomes with 12-month overall survival of less than 20%. Recently, significant progress has been made in understanding the oncogenic pathways of ATC, leading to the identification of BRAF V600E mutations as the driver oncogene in nearly 40% of cases. The combination of the BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) showed outstanding response rates in BRAF-mutated ATC and is now considered the standard of care in this setting. Recently, it was shown that neoadjuvant use of DT followed by surgery achieved 24-month overall survival rates of 80%. Although these approaches have changed the management of ATC, effective therapies are still needed for patients with BRAF wild-type ATC, and high-quality evidence is lacking for most aspects of this neoplasia. Additionally, in real-world settings, timely access to multidisciplinary care, molecular testing, and targeted therapies continues to be a challenge. Health policies are warranted to ensure specialized treatment for ATC.The expanding knowledge of ATC´s molecular biology, in addition to the ongoing clinical trials provides hope for the development of further therapeutic options.
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Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Idoso , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/uso terapêutico , Neoplasias da Glândula Tireoide/genética , MutaçãoRESUMO
Radioiodine (RAI) refractory differentiated thyroid cancer is an uncommon and challenging situation that requires a multidisciplinary approach to therapeutic strategies. The definition of RAI-refractoriness is usually a clear situation in specialized centers. However, the right moment for initiation of multikinase inhibitors (MKI), the time and availability for genomic testing, and the possibility of prescribing MKI and selective kinase inhibitors differ worldwide.Latin America (LA) refers to the territories of the world that stretch across two regions: North America (including Central America and the Caribbean) and South America, containing 8.5% of the world's population. In this manuscript, we critically review the current standard approach recommended for patients with RAI refractory differentiated thyroid cancer, emphasizing the challenges faced in LA. To achieve this objective, the Latin American Thyroid Society (LATS) convened a panel of experts from Brazil, Argentina, Chile, and Colombia. Access to MKI compounds continues to be a challenge in all LA countries. This is true not only for MKI but also for the new selective tyrosine kinase inhibitor, which will also require genomic testing, that is not widely available. Thus, as precision medicine advances, significant disparities will be made more evident, and despite efforts to improve coverage and reimbursement, molecular-based precision medicine remains inaccessible to most of the LA population. Efforts should be undertaken to alleviate the discrepancies between the current state-of-the-art care for RAI-refractory differentiated thyroid cancer and the present situation in Latin America.
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Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , América Latina , Radioisótopos do Iodo/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , BrasilRESUMO
INTRODUCTION: In patients with history of cancer adrenal metastases can be found in up to 70% of adrenal tumors detected during follow-up. Currently, laparoscopic adrenalectomy (LA) is considered the gold standard approach for benign adrenal tumors but is still controversial in malignant disease. Depending on the patient's oncological status, adrenalectomy might be a possible treatment option. Our objective was to analyze the results of LA for adrenal metastasis from solid tumors in two referral centers. METHODS: Retrospective analysis of 17 patients with non-primary adrenal malignancy treated with LA between 2007 and 2019 was performed. Demographic and primary tumor data, type of metastasis, morbidity, disease recurrence and evolution were evaluated. Patients were compared according to type of metastases: synchronous (< 6 months) vs metachronous (≥ 6 months). RESULTS: 17 patients were included. Median metastatic adrenal tumor size was 4 cm (IQR, 3-5.4). We had one conversion to open surgery. Recurrence was found in 6 patients with one recurring in the adrenal bed. The median OS was 24 (IQR, 10.5-60.5) months and 5-year OS was 61.4% (95%CI: 36.7%-81.4%). Patients with metachronous metastases had better overall survival vs. patients with synchronous metastases (87% vs. 14%, p = 0.0037). CONCLUSION: LA for adrenal metastases is a procedure associated with low morbidity and acceptable oncologic outcomes. Based on our results, seems reasonable to offer this procedure to carefully selected patients, mainly those with metachronous presentation. Indication of LA must be done on a case by case evaluation in the context of a multidisciplinary tumor board.
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Neoplasias das Glândulas Suprarrenais , Laparoscopia , Humanos , Adrenalectomia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgiaRESUMO
Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.
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Terapia Neoadjuvante , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Adulto Jovem , Adolescente , Criança , Tireoidectomia , América Latina , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/terapia , QuinolinasRESUMO
BACKGROUND: In patients with low-risk differentiated thyroid cancer (DTC), remnant ablation with radioiodine (RA) after total thyroidectomy (TT) is controversial. No benefits have been demonstrated in terms of mortality or disease-free survival. Recent evidence found that RA did not improve mid-term outcomes. PURPOSE: To evaluate initial response to treatment and long-term follow-up status in low-risk DTC patients after TT vs. TT + RA with 131I 1.11 GBq (30 mCi). METHODS: Prospective multicenter non-randomized study; 174 low-risk DTC that underwent TT were recruited an divided in two groups according to RA (87 ablated and 87 non-ablated). Response to treatment was evaluated at 6-18 months after thyroidectomy and at the end of follow-up with measurements of thyroglobulin, and anti-thyroglobulin antibodies levels, and neck ultrasonography. RESULTS: Baseline characteristics of both groups were similar. Ablated patients: median age 45.5 years, 84% females, 95.4% papillary thyroid carcinoma (PTC), mean tumor size 16 mm; non-ablated: median age 45 years, 88.5% females, 96.6% PTC, mean tumor size 14 mm. Response to initial treatment was similar between both groups, with < 2% of structural incomplete response. Final status was evaluated in 139 cases (median follow-up of 60 months). Among ablated patients, 82.8% had no evidence of disease (NED), 12% had an indeterminate response (IR) and 5% a biochemical incomplete response (BIR). Non-ablated patients had NED in 90%, IR in 8.7% and BIR in 1.2%. No statistical difference was found between groups (p = 0.29). No patient had evidence of structural disease at the end of follow-up. CONCLUSIONS: Our findings support the recommendation against routine RA in low-risk DTC patients.
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Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Radioisótopos do Iodo/uso terapêutico , Estudos Prospectivos , Seguimentos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
PURPOSE: To present our real-life experience with dabrafenib and trametinib (D-T) treatment in patients with BRAF V600E-mutated ATC in Argentina. PATIENTS Y METHODS: We included five patients from four different hospitals. The median age was 70 years, and 60% were male. The performance status at diagnosis was grade 0 in 60% and grade 2 in 40% of patients. Four patients could undergo total thyroidectomy; in one of them, surgical treatment was amenable due to the indication of D-T as neoadjuvant therapy. From the total cohort, the best response to treatment was complete response in 40%, partial response in 20%, and stable disease in 20%. The median duration of response was 20 weeks, ranging from 16 to 92 weeks. All patients experienced at least one adverse event (AE). Grade ≥3 AEs were observed in two (40%) patients. They were upper gastrointestinal bleeding and subclavian vein thrombosis. The median follow-up was 20 weeks (range: 16 to 92). CONCLUSION: This report contributes to illustrate the feasibility and effectiveness of D-T treatment in five patients with loco-regionally advanced and metastatic BRAF V600E-mutated ATC in a real-life setting. A multidisciplinary approach and rapid molecular-tailored testing are essential to begin this therapeutic option.
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Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Masculino , Idoso , Feminino , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Argentina , Piridonas/uso terapêutico , Piridonas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , MutaçãoRESUMO
INTRODUCTION: Thyroglobulin antibodies (TgAb) trend may be considered a surrogate marker for thyroglobulin in differentiated thyroid carcinoma. The aim of this study is to analyse, in cases with positive TgAb, trend over time and its relationship with response to treatment. MATERIAL AND METHODS: Retrospective and descriptive study of 100 patients with differentiated thyroid carcinoma and positive TgAb (measured by electrochemoluminiscense) after thyroidectomy. Assessment of response to initial treatment was performed 6-24 months after surgery. Status at last follow-up was evaluated. RESULTS: After the first year nearly half of the patients showed a reduction in TgAb levels ≥50%, in 91% of these patients, status at last follow up was excellent response (65%) or indeterminate response due to decreasing TgAb levels (26%). At first assessment, indeterminate responses were found in 49% of cases, without significant differences among initial risk of recurrence category or whether radioiodine ablation was performed. At last evaluation (median 53.5 months), 15% of ablated low-risk patients had an indeterminate response (due to declining TgAb), vs 62% in the non-ablated low-risk group (p 0.03). Median time to negativization for post-surgical TgAb levels<100UI/ml was 11 months [3-94] vs 31 months [8-119] for patients with TgAb≥100UI/ml (p 0.0003). CONCLUSION: A reduction of ≥50% in TgAb levels during the first year correlated with favourable outcomes. Non-ablated patients and patients with higher levels of post-surgical TgAb may need a longer time to achieve negative conversion.
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Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Tireoglobulina , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , TireoidectomiaRESUMO
PURPOSE: 18F-DOPA Positron Emission Tomography/Computed Tomography (18F-DOPA PET/CT) is a sensitive functional imaging method (65-75%) for detecting disease localization in medullary thyroid cancer (MTC). We aimed: (i) to assess the clinical usefulness of 18F-DOPA PET/CT in patients with MTC and elevated calcitonin (Ctn) and CEA levels and, (ii) to evaluate changes in disease management secondary to the findings encountered with this methodology. METHODS: Thirty-six patients with MTC and Ctn levels ≥150 pg/ml were prospectively included. Neck ultrasound, chest contrast-enhanced CT, liver magnetic resonance imaging/abdominal three-phase contrast-enhanced CT and bone scintigraphy were carried out up to 6 months before the 18F DOPA PET/CT. RESULTS: Seventy eight percent of patients were female and 27% had hereditary MTC. Median Ctn level was 1450 pg/ml [150-56620], median CEA level 413 ng/ml [2.9-7436]. Median Ctn DT was 37.5 months [5.7-240]; median CEA DT was 31.8 [4.9-180]. 18F-DOPA PET/CT was positive in 33 patients (91.6%); in 18 (56%) uptake was observed in lymph nodes in the neck or mediastinum, in seven cases (22%) distant metastases were diagnosed, and in eight additional patients (24%) both locoregional and distant sites of disease were found. Ctn and CEA levels were higher in patients with ≥3 foci of distant metastases. In 14 patients (38.8%), findings on 18F-DOPA PET/CT led to changes in management; surgery for locoregional lymph nodes was the most frequent procedure in 8 patients (22%). CONCLUSION: 18F-DOPA PET/CT was useful for the detection of recurrent disease in MTC, providing incremental value over conventional imaging procedures that led to modification in treatment strategies in nearly 40% of patients.
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Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Calcitonina , Antígeno Carcinoembrionário , Carcinoma Neuroendócrino/patologia , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Neoplasias da Glândula Tireoide/patologiaRESUMO
PURPOSE: Non-invasive encapsulated follicular variant of papillary thyroid cancer was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These neoplasms have an extremely low malignant potential. The aim of this study was (1) to assess the prevalence of NIFTP in patients with papillary thyroid carcinoma, (2) to evaluate their outcomes, and (3) to determine their molecular profile. METHODS: Multicenter, descriptive, retrospective study. Patients with papillary thyroid cancer diagnosed from January 2006 to December 2016 from 11 referral centers were included. Diagnosis of NIFTP was based on criteria described by Nikiforov et al. in 2018. At least two pathologists agreed on the diagnosis. Two thousand six hundred and seventy-seven papillary thyroid cancer patients were included; 456 (17%) of them were follicular variant papillary thyroid cancer, and 30 (1.12%) fulfilled diagnostic criteria for NIFTP. RESULTS: Each of the 30 included patients underwent a total thyroidectomy, and 50% were treated with radioiodine (median dose 100 mCi). After a median follow-up of 37 months, 84% of patients had an excellent response, 3% had an indeterminate response and data was missing in the remaining 13%. No metastatic lymph nodes, distant metastases or recurrences were found. RAS mutations were detected in 4 patients (13%). CONCLUSION: The prevalence of NIFTP in our series is amongst the lowest reported. Excellent outcomes of patients underscore their low malignant potential. Molecular findings differ from other series, probably related to environmental or ethnic features of our population and the meticulous criteria for diagnosing NIFTP.
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Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/genética , Argentina/epidemiologia , Humanos , Radioisótopos do Iodo , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genéticaRESUMO
INTRODUCTION: The determination of thyroglobulin (Tg) levels by immunoassay is subject to interference by antithyroglobulin antibodies in up to 30% of cases, suggesting a need to find alternative methods for the follow-up of a significant number of thyroid cancer patients. OBJECTIVES: Assess the sensitivity, specificity, and predictive values of thyroglobulin messenger RNA (Tg-mRNA) levels measured by quantitative Real Time-PCR (qRT-PCR) in the blood of patients followed for differentiated thyroid cancer. METHODS: This is a prospective study of Tg-mRNA levels measured with qRT-PCR. A peripheral blood sample was taken in patients with excellent response (n=69) and with structural incomplete response to treatment (n=23). Results were analysed using the Unity Real-Time program and expressed as fg/µg RNA. A Receiver Operating Characteristic curve was constructed to establish Tg-mRNA cut-off values. RESULTS: Tg-mRNA levels were not significantly different between the group with excellent response [0.10fg/µg RNA (0.08-0.17)] and the group with incomplete structural response [0.133fg/µg RNA (0.07-0.33)] (p<0.06). Test sensitivity was 69.6%, specificity was 59.4%, negative predictive value was 85.4% and positive predictive value was 36.4%. CONCLUSIONS: Our experience shows that this technique could be useful as a rule-out test in selected cases, but its low sensitivity and specificity preclude its usefulness as a first-line test.
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INTRODUCTION: The determination of thyroglobulin levels by immunoassay and imaging studies is subject to interference by antithyroglobulin antibodies in up to 30% of cases, suggesting a need to find alternative methods for the follow-up of a significant number of thyroid cancer patients. OBJECTIVES: Assess the sensitivity, specificity, and predictive values of thyroglobulin messenger RNA levels measured by quantitative Real Time-PCR (qRT-PCR) in the blood of patients followed for differentiated thyroid cancer. METHODS: This is a prospective study of Tg-mRNA levels measured with qRT-PCR. A peripheral blood sample was taken in patients with excellent response (69) and with structural incomplete response to treatment (23). Results were analysed using the Unity Real-Time program and expressed as fg/µg RNA. A Receiver Operating Characteristic curve was constructed to assess Tg-mRNA cut-off values. RESULTS: Tg-mRNA levels were not significantly different between the group with excellent response [0.10â¯fg/µg RNA (0.08-0.17)] and the group with incomplete structural response [0.133â¯fg/µg RNA (0.07-0.33)] (Pâ¯<â¯.06). Test sensitivity was 69.6%, specificity was 59.4%, negative predictive value was 85.4% and positive predictive value 36.4% CONCLUSIONS: Our experience shows that this technique could be useful as a rule-out test in selected cases, but its low sensitivity and specificity preclude its usefulness as a first-line test.
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Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Seguimentos , Humanos , Estudos Prospectivos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Tireoglobulina/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genéticaRESUMO
PURPOSE: To describe the experience with radioiodine-resistant differentiated thyroid cancer (RR-DTC) patients treated with lenvatinib in two university hospitals from Argentina. METHODS: Adult patients with a diagnosis of RR-DTC treated with lenvatinib from April 2017 to February 2020 were registered into a retrospective database. Primary objectives were assessment of progression-free survival (PFS) and tumor response evaluated according to RECIST v 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v5.0. RESULTS: Twenty-two patients were treated with lenvatinib, 13 of whom had previously received one or more multikinase inhibitors. Median duration of treatment was 7.1 months (2.2-24). Best overall response was complete response in one patient (4.5%), partial response in seven (31.8%), stable disease in seven (31.8%), and progressive disease in six (27.3%). Median PFS was 13.7 months (95% CI 3.2-24.2). All patients experienced at least one AE. Grade ≥3 AEs were observed in eight (36.4%) patients. Hypertension was the most frequent AE (63.6%) and the most common grade ≥3 AE (22.7%). Definitive withdrawal was necessary in two patients due to recurrent proteinuria (9%). CONCLUSIONS: Tumor responses and PFS in our study were in line with other real-life clinical data and they seem to be inferior to the reported in the SELECT trial, probably related to the higher number of patients with prior MKI therapy, comorbidities, and poor performance status. Although virtually all patients experienced AEs, most of them were manageable and rarely a definitive withdrawal was necessary.
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Antineoplásicos , Quinolinas , Neoplasias da Glândula Tireoide , Adulto , Antineoplásicos/efeitos adversos , Argentina , Humanos , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/tratamento farmacológicoRESUMO
Los carcinomas de tiroides derivados de células foliculares de alto grado (HGFDTC) son tumores poco frecuentes con un pronóstico intermedio entre carcinomas tiroideos bien diferenciados y anaplásicos. La clasificación de la OMS más reciente identifica dos tipos distintos de HGFDTC: 1) carcinoma de tiroides mal diferenciado (arquitectura sólida, trabecular o insular, falta de características nucleares de núcleos nucleares papilares y contorneados, necrosis mitosis (≥3/2mm2), y 2 ) Diferenciar carcinoma de tiroides de alto grado (recuento mitótico alto (≥5/mm2) y/o necrosis). Estos tumores son frecuentemente refractarios de radioyodo, tienen una alta propensión a metástasis distantes y una mala supervivencia general a largo plazo. Desde un punto de vista molecular, HGFDTC comparten mutaciones del controlador es decir, BRAF) y, con menos frecuencia, las fusiones genéticas (es decir, NTRK, RET) con arcinomas de tiroides diferenciados. A medida que ocurre la desdiferenciación, se adquieren alteraciones secundarias (como el promotor TERT y TP53). En esta revisión, nuestro objetivo es describir las características clínicas, moleculares y patológicas de HGFDTC, así como su gestión e investigación futura
High-grade follicular cell derived thyroid carcinomas (HGFDTC) are infrequent tumors with a prognosis intermediate between well differentiated and anaplastic thyroid carcinomas. The most recent WHO classification identifies two distinct types of HGFDTC: 1) Poorly differentiated thyroid carcinoma (solid, trabecular or insular architecture, lack of nuclear features of papillary nuclear and either convoluted nuclei, necrosis or mitosis (≥3/2mm2), and 2) differentiated high-grade thyroid carcinoma (high mitotic count (≥5/mm2) and/or necrosis). These tumors are frequently radioiodine refractory, have a high propensity for distant metastases, and poor long term overall survival. From a molecular standpoint, HGFDTC share driver mutations (ie BRAF) and, less frequently, gene fusions (ie NTRK, RET) with differentiated thyroid carcinomas. As dedifferentiation occurs, secondary alterations (such as TERT promoter, and TP53) are acquired. In this review, we aim to describe the clinical, molecular and pathological characteristics of HGFDTC, as well as their management and future research
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Humanos , Masculino , Feminino , Neoplasias da Glândula Tireoide/diagnóstico , Adenocarcinoma Folicular/patologia , Carcinoma Anaplásico da Tireoide/patologia , Células Epiteliais da Tireoide/patologiaRESUMO
PURPOSE: Metastases of differentiated thyroid cancer (DTC) in sites different from lungs and bone are unusual (UM); their impact in management and prognosis remains unknown. Our aim was to evaluate the prevalence of UM, to describe their characteristics and to analyze their impact in disease outcome and mortality. METHODS: We retrospectively reviewed the file records from 8 different centers. Those patients with DTC and UM were included. UM were diagnosed by: (i) biopsy/cytology and/or (ii) radioiodine (RAI) uptake associated to elevated thyroglobulin (Tg) levels and/or c) presence of one or more structural lesion/s with 18-FDG uptake in the PET/CT scan and elevated Tg levels. RESULTS: Thirty-six (0.9%) out of a total of 3982 DTC patients were diagnosed with UM; 75% had papillary histology. The most frequent localization was central nervous system (CNS, 31%). UM were metachronous in 75%, symptomatic in 55.6% and fulfilled RAI-refractoriness criteria in 77.8% of cases. Metastatic lesions in lung/bone and/or locoregional disease were present in 34 cases (94.4%). Diagnosis of UM changed the therapeutic approach in 72.2% of patients. After a median follow up of 13 months, 21 (58.3%) patients died from DTC related causes. In 8 of them CNS progression was the immediate cause of death. CONCLUSIONS: Prevalence of UM was low; they were frequently metachronic and RAI-refractory. Although UM were found in patients with widespread disease, their diagnosis usually led to changes in therapy. UM were associated with poor prognosis and high frequency of disease-specific mortality.
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Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/secundário , Carcinoma Papilar/patologia , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/secundário , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/radioterapia , Resultado do TratamentoRESUMO
Objective Bone metastases (BM) from differentiated thyroid cancer (DTC) are associated with poor survival rates. Due to the low frequency of this entity, we performed a multicentric retrospective study that aimed to evaluate the presentation, outcome and causes of death in this population. Subjects and methods We reviewed file records from 10 databases. BM were diagnosed by: i) biopsy and/or ii) radioiodine (RAI) bone uptake + elevated thyroglobulin (Tg) levels and/or c) bone uptake of 18-FDG in the PET-CT scan + elevated Tg levels. Results Fifty-two patients with DTC were included (44% male, mean age 54 years); 58% had papillary histology. BM were synchronous with DTC diagnosis in 46% of the participating cases. BM were symptomatic in 65% of the cases. Multiple BM were present in 65% of patients, while simultaneous metastatic disease in additional sites was found in 69%. Ninety-eight percent of patients received treatment for the BM, which included RAI therapy in 42 patients; 30 of them received cumulative RAI doses that were larger than 600 mCi 131I. The mean follow-up after a BM diagnosis was 34 months. The 2- and 5-year survival rates after diagnosis of the first BM were 64% and 38%, respectively. The status on the last evaluation was DTC-related death in 52% of the patients; 26% of them died from direct complications of BM or their treatments. Conclusion BM are usually radioiodine-refractory and are associated with a short overall survival, although most of the patients died of causes not directly related to the BM.
Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/mortalidade , Fatores de Tempo , Adulto JovemRESUMO
A case of Frey syndrome (FS) secondary to submaxillar gland exeresis is presented and the results of the treatment with botulinum toxin (BTX) type A. FS is a condition of sweating cheek and preauricular area during realtime as a sequel detected in about 20-60% of patients after parotidectomy. The clinical symptoms include swelling, flushing and hyperhidrosis. The treatment choice for this condition is intracutaneous injection of BTX type A which blocks acetylcholine release at the sweat glands. A 30-year-old man, with thyroid medullar carcinoma diagnosed in 2002 received 6 cicles of cisplatin plus doxorubicin previous to the thyroidectomy with anterolateral neck dissection. During surgery the left ramus marginalis mandibulae was damaged. Two years later the patient referred sweating in submaxillar region during meals. CT scan demonstrated the absence of left submaxillar gland. Minor's test disclosed the affected area and BTX type A was injected (2.5 U/cm2/17 points). A twenty-one-day control showed a 95% reduction of the affected skin area. Persistent efficacy was observed up to one year follow-up time when he was reinjected. The FS, also known as "gustatory hyperhidrosis", was probably first reported by M. Duphenix in 1757. Lucja Frey considered its physiopathology as a disorder of both sympathetic and parasympathetic innervation. In our case the FS was caused by a misdirected regeneration of postganglionic parasympathetic nerve fibers that arrised from the nervus lingualis rami ganglionares of the nervus trigeminus. After nerve injury the colinergic parasympathetic fibers seek out colinergic receptors--sympathetic receptors of the skin--innervating sweat glands and small skin vessels. All previous cases were located at masseter region post-parotidectomy. We have not found any description of FS in the submaxillary region. The self-assessed efficacy of the treatment with a hyperhidrosis disease severity scale revealed a very satisfied patient at 20 months follow-up after being injected twice with BTX type A.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Fármacos Neuromusculares/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Glândula Submandibular/cirurgia , Sudorese Gustativa/tratamento farmacológico , Adulto , Humanos , Masculino , Maxila , Esvaziamento Cervical/efeitos adversos , Glândula Parótida/cirurgia , Sudorese Gustativa/etiologia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
ABSTRACT Objective Bone metastases (BM) from differentiated thyroid cancer (DTC) are associated with poor survival rates. Due to the low frequency of this entity, we performed a multicentric retrospective study that aimed to evaluate the presentation, outcome and causes of death in this population. Subjects and methods We reviewed file records from 10 databases. BM were diagnosed by: i) biopsy and/or ii) radioiodine (RAI) bone uptake + elevated thyroglobulin (Tg) levels and/or c) bone uptake of 18-FDG in the PET-CT scan + elevated Tg levels. Results Fifty-two patients with DTC were included (44% male, mean age 54 years); 58% had papillary histology. BM were synchronous with DTC diagnosis in 46% of the participating cases. BM were symptomatic in 65% of the cases. Multiple BM were present in 65% of patients, while simultaneous metastatic disease in additional sites was found in 69%. Ninety-eight percent of patients received treatment for the BM, which included RAI therapy in 42 patients; 30 of them received cumulative RAI doses that were larger than 600 mCi 131I. The mean follow-up after a BM diagnosis was 34 months. The 2- and 5-year survival rates after diagnosis of the first BM were 64% and 38%, respectively. The status on the last evaluation was DTC-related death in 52% of the patients; 26% of them died from direct complications of BM or their treatments. Conclusion BM are usually radioiodine-refractory and are associated with a short overall survival, although most of the patients died of causes not directly related to the BM.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias Ósseas/secundário , Neoplasias da Glândula Tireoide/patologia , Fatores de Tempo , Neoplasias Ósseas/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Estadiamento de NeoplasiasRESUMO
Distant metastases of differentiated thyroid cancer are unusual; lung and bones are the most frequently affected sites. Soft tissue metastases (STM) are extremely rare. We describe two cases of patients with differentiated thyroid cancer metastasizing to soft tissues. Both patients had widespread metastatic disease; clinically asymptomatic soft tissue metastases were found by ¹8-Fluordeoxyglucose positron emission tomography/computed tomography (¹8F FDG PET-CT), and confirmed by cytological and/or histopathological studies. These findings underscore the ability of ¹8F FDG PET-CT in accurately assessing the extent of the disease, as well as the utility of the method to evaluate regions of the body that are not routinely explored.
Assuntos
Fluordesoxiglucose F18 , Imagem Multimodal/métodos , Compostos Radiofarmacêuticos , Neoplasias de Tecidos Moles/secundário , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Papilar/patologia , Adulto , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Neoplasias Musculares/secundário , Metástase Neoplásica , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Cutâneas/secundário , Tomografia Computadorizada por Raios X/métodosRESUMO
Introducción: El objetivo del tratamiento del carcinoma diferenciado de tiroides con invasión traqueal es resecar satisfactoriamente la enfermedad conservando las funciones. Caso clínico: Mujer de 27 años, con masa tiroidea con compromiso traqueal evidenciado por tomografía computarizada. Se efectuó tiroidectomía total, linfadenectomía central y selectiva II-V bilateral, resección segmentaria y anastomosis traqueal. En el postoperatorio presentó dehiscencia de la anastomosis, requiriendo traqueostomía. Posteriormente, se efectuó traqueoplastia con evolución favorable. Discusión: La resección traqueal segmentaria es de elección en casos de compromiso local sin enfermedad a distancia. La traqueoplastia permite obtener un resultado funcional satisfactorio en estos casos en centros de alto volumen.
Introduction: The aim of surgery in well-differentiated thyroid cancer with tracheal invasion is to remove all the tumour while preserving functional structures. Clinical case: A 27 year old female presented with a thyroid mass with tracheal invasion on the computed tomography. She underwent total thyroidectomy, bilateral central compartment and selective II-V neck dissection, and tracheal resection with end-to-end anastomosis. She subsequently had anastomotic dehiscence, which required a tracheostomy. Tracheoplasty was later performed with good functional results. Discussion: Segmentary tracheal resection is the procedure of choice in differentiated thyroid cancer with local invasion and with no distant disease. Tracheoplasty, performed in highvolume centres, leads to a satisfying functional outcome.