Metástasis raras de cáncer papilar de tiroides en músculo esquelético: serie de casos / Rare metastases of papillary thyroid cancer in skeletal muscle: case series

Las metástasis del carcinoma papilar de tiroides (CPT) generalmente son a nivel locorregional, la diseminación a distancia es poco habitual, sin embargo la invasión de tejidos blandos aunque inusual puede ocurrir, y afecta negativamente la supervivencia. El presente estudio describe una serie de casos de Metástasis Musculares de CPT. Se realizó un estudio transversal de un solo centro que evaluó diez pacientes con CPT con metástasis en músculo. La edad de los pacientes fue entre 46 a 77 años, siendo la edad promedio de 60 años, 7 de los cuales fueron de sexo masculino que corresponde al 70%, todos con antecedente de CPT con respuesta estructural incompleta, además de las metástasis en músculo presentaron afectación de tres o más órganos, con necesidad de varios tratamientos, cada paciente registró entre 1 a 8 cirugías, recibieron entre 100 a 780mCi de I131 (yodo radiactivo), ocho ameritaron radioterapia, todos tuvieron indicación de tratamiento con ITK, sin embargo solo cuatro pacientes tuvieron acceso a dicho medicamento. La mayoría de las metástasis del CPT en músculo fueron diagnosticadas en los estudios de imagen PET/ CT, después de la tiroidectomía el tiempo de su presentación fue muy variable entre 1 a 18 años, el número de músculos comprometidos se reporta entre uno a cuatro, siendo el glúteo (4 casos) el músculo metastásico más frecuente. La presencia de metástasis musculares empeora el pronóstico en nuestra serie de pacientes.

Metastases of thyroid papillary carcinoma (CPT) are generally at the locoregional level, the dissemination from a distance is unusual, however the invasion of soft tissues, although rare can occur, and it negatively affects survival. The present study describes several Muscular Metastases of CPT cases. A transversal study in one only center was performed and assessed ten patients CPT metastases in muscles.The patients age ranged from 46 to 77, being the average age of 60, and 7 of them were male, corresponding to the 70%, everyone with CPT records with an incomplete structural response. Besides muscular metastases they also presented issues with three or more organs, needing many treatments. Each patient registered between 1 to 8 surgeries, they received between 100 to 780mCi of I131. Eight required radiotherapies, everyone required treatment with ITK, however, just four patients had access to that medication. Most of the CPT metastases in muscles were diagnosed in PET/CT image studies, after the thyroidectomy, the time for its presentation was very variable between 1 to 18 years, the number of compromised muscles is reported between one to four, being the buttock (4 cases) the most frequently muscle with metastases. The presence of muscular metastases aggravates the prognosis in our series of patients.

Guided intraoperative scintigraphic tumor targeting of metastatic cervical lymph nodes in patients with differentiated thyroid cancer: a single-center report

ABSTRACT Objective: Our aim was to present our experiences related to performing neck surgery using the guided intraoperative scintigraphic tumor targeting (GOSTT) procedure for patients who had locally recurrent or persistent differentiated thyroid cancer (DTC) and who had undergone previous thyroid surgery. Subjects and methods: We retrospectively evaluated 11 patients who had locally recurrent or persistent DTC, who had undergone previous surgery, and for whom reoperation was planned for metastatic cervical lymph nodes (LNs). We performed the neck surgery using the GOSTT procedure on all patients and at a single academic institution. Results: The 11 patients had a total of 26 LNs, as marked with a radiotracer, and those LNs' mean size was 14.7 ± 8.2 mm (range: 5-34 mm). Histopathological examinations revealed DTC metastasis in all 26 of the preoperatively marked LNs. Of the 11 patients, only one needed a reoperation in the neck; she had another successful surgery (also using the GOSTT procedure). In the evaluation of the patients' final status, all were disease-free in their necks. There also were no GOSTT-associated postoperative complications. Conclusion: The GOSTT procedure is a useful, successful, inexpensive, and comfortable procedure for marking and mapping metastatic LNs, especially in DTC patients who have undergone previous surgery.

Accuracy of sentinel lymph node mapping in detecting occult neck metastasis in papillary thyroid carcinoma

ABSTRACT Objectives: The objectives of this study were to evaluate the following: 1) the accuracy of sentinel lymph node mapping (SLNM) in detecting metastasis in papillary thyroid carcinoma (PTC), and 2) if SLNM could modify the American Joint Committee on Cancer (AJCC) staging of previous cN0 PTC patients. Subjects and methods: Forty SLNM were performed prospectively in 38 consecutive cN0 PTC patients, with total thyroidectomy and elective compartment neck dissection (CND). The results of SLNM were compared with CND pathological findings to verify the accuracy of sentinel SLNM. Results: The mean patients' follow-up was 36 months. A total of 133 SLN were found at levels VI, II, III and IV. The SLN was identified in 95% of the patients with one false negative, 95% sensitivity, a 94% negative predictive value and 97% accuracy. The SLNM upstaging from cN0 to pN+ was 49%, and to stages III and IVa, it was 21%. Conclusions: For this series of cN0 PTC patients: 1) SLNM accuracy was 97%, and 2) SLNM upstaging from cN0 to pN+ was 49%, whereas to stages III and IVa, it was 21%.

Blood preoperative neutrophil-to-lymphocyte ratio is correlated with TNM stage in patients with papillary thyroid cancer

OBJECTIVE: To predict the American Joint Cancer Committee tumor-node-metastasis stage in patients with papillary thyroid carcinoma by evaluating the relationship between the preoperative neutrophil-to-lymphocyte ratio and the tumor-node-metastasis stage. METHODS: We retrospectively examined 161 patients with a diagnosis of papillary thyroid carcinoma. The Neutrophil-to-Lymphocyte Ratio was calculated according to the absolute neutrophil counts and absolute lymphocyte counts on routine blood tests obtained prior to surgery and patients with a Neutrophil-to-Lymphocyte Ratio of 2.0 or more were classified as the high NLR group, while those with a Neutrophil-to-Lymphocyte Ratio less than 2.0 were classified as the low Neutrophil-to-Lymphocyte Ratio group. Clinicopathological variables, which were stratified by the Neutrophil-to-Lymphocyte Ratio, were analyzed. A multivariate analysis was performed to determine factors that affect the Neutrophil-to-Lymphocyte Ratio. The association between the Neutrophil-to-Lymphocyte Ratio and the TNM stage in patients ≥45 years of age was analyzed using the Spearman rank correlation. RESULTS: Various blood indices, including hemoglobin, platelet and thyroid-stimulating hormone levels in the two groups showed no significant differences. Lymph node metastasis, multifocality and tumor size exhibited significant differences in the two groups (p=0.000, p=0.000 and p=0.035, respectively). Correlation analysis indicated that a higher preoperative Neutrophil-to-Lymphocyte Ratio was observed in patients with lymph node metastasis, larger tumor size and multifocality (r=0.341, p=0.000; r=0.271, p=0.000; and r=0.182, p=0.010, respectively). For patients ≥45 years of age, the number of patients with an advanced TNM stage in the high NLR group was higher than that in the low Neutrophil-to-Lymphocyte Ratio group (p=0.013). A linear regression analysis showed that the preoperative Neutrophil-to-Lymphocyte Ratio was positively correlated with the American Joint Cancer Committee tumor-node-metastasis stage (rho=0.403, p=0.000). CONCLUSION: The preoperative Neutrophil-to-Lymphocyte Ratio was closely related to the stage of papillary thyroid carcinoma. The increase in the preoperative Neutrophil-to-Lymphocyte Ratio contributed to the advanced tumor-node-metastasis stage of papillary thyroid carcinoma patients ≥45 years of age.

Response to sorafenib treatment in advanced metastatic thyroid cancer / Resposta ao tratamento com sorafenibe em pacientes com carcinoma metastático de tireoide

Objective: To investigate the efficacy of sorafenib in progressive radioiodine resistant metastatic thyroid carcinoma.Subjects and methods: Off-label observational study. Sorafenib 400 mg twice daily was evaluated. Therapy duration was 12 ± 3 months (range 6-16 months).Results: Eight patients were included (seven papillary, one insular variant). The eight patients meeting study criteria received sorafenib 400 mg orally twice a day until disease progression or unacceptable toxicity developed. One patient showed a partial response with tumor regression of -35%, six months after the beginning of the treatment; five patients exhibited stable disease and two patients had progressive disease and died. Thyroglobulin decreased within 4 weeks in all patients by 50% ± 23%.Adverse events: one patient had heart failure, and recovered after sorafenib withdrawal. However, she died five months later of sudden death.Conclusion: These data suggest a possible role for sorafenib in the treatment of progressive metastatic DTC. Adverse event are usually manageable, but severe ones may appear and these patients should be strictly controlled.

Objetivo: Investigar a eficácia do sorafenibe no carcinoma de tireoide metastático progressivo e refratário à iodoterapia.Sujeitos e métodos: Estudo observacional do efeito do sorafenibe off-label administrado 400 mg duas vezes ao dia. A duração da terapia foi de 12 ± 3 meses (variação de 6-16 meses).Resultados: Oito pacientes foram incluídos (sete com variante papilífera e um com variante insular). Os oito pacientes que preencheram os critérios do estudo receberam o sorafenibe 400 mg por via oral duas vezes por dia até progressão da doença ou toxicidade inaceitável. Um paciente apresentou uma resposta parcial com regressão tumoral da lesão alvo de 35% seis meses após o início do tratamento; cinco pacientes apresentaram doença estável e dois pacientes progrediram e morreram. A tireoglobulina diminuiu 50% ± 23% em 4 semanas em todos os pacientes.Eventos adversos: um paciente teve insuficiência cardíaca e morreu por morte súbita cinco meses após a retirada do sorafenibe.Conclusão: Esses dados sugerem um possível papel para sorafenibe para o tratamento do CDT metastático progressivo.

Taponamiento cardíaco secundario a carcinoma papilar esclerosante difuso de tiroides / Metastatic cardiac tamponade as initial manifestation of papillary thyroid carcinoma

El carcinoma papilar, variante esclerosante difusa, corresponde al 2% de todos los carcinomas papilares de la tiroides. Se caracteriza por comprometer de manera difusa y bilateral a la glándula tiroides. Clínicamente se manifiesta con metástasis ganglionares y pulmonares, afectando predominantemente a mujeres jóvenes. Se describe un caso de taponamiento cardíaco como presentación inicial de un carcinoma papilar de tiroides variante esclerosante difusa. Una mujer de 32 años concurrió al servicio de emergencias médicas refiriendo epigastralgia y tos seca. Durante el examen físico se constató hipotensión arterial, taquicardia y ruidos cardíacos disminuidos. Se realizó un ecocardiograma, observándose derrame pericárdico. Por medio de una pericardiocentesis se obtuvo líquido pericárdico, cuyo análisis mostró células neoplásicas. Durante la evolución la paciente presentó recurrencia del derrame pericárdico por lo que se realizó una ventana pleuropericárdica, detectándose durante la cirugía una lesión nodular subpleural, la cual fue biopsiada e informada posteriormente como una metástasis de carcinoma papilar vinculable a origen tiroideo. Se realizó una tiroidectomía total con linfadenectomía cervical bilateral. El diagnóstico final fue carcinoma papilar, variante esclerosante difusa. Esta variante infiltra el tejido conectivo de los espacios interfoliculares, simulando una tiroiditis y se caracteriza por una permeación vascular temprana. En oposición a la variante clásica, la esclerosante difusa presenta mayor agresividad y mayor tasa de recurrencia. El carcinoma papilar de tiroides debe tenerse presente como diagnóstico diferencial en nuestro medio, en todas aquellas lesiones neoplásicas papilares metastásicas, más aún si se trata de mujeres jóvenes.

Papillary carcinoma, diffuse sclerosing variant corresponds to 2% of all papillary thyroid carcinomas. It is usually diffuse and bilateral, affecting the entire gland. At the time of diagnosis, patients present lymph node and lung metastasis. It affects mainly young women. This case report describes a cardiac tamponade as the initial manifestation of an unusual variant of papillary thyroid carcinoma. A 32 year-old woman was attended at the emergency room with epigastric pain and dry cough. Physical examination revealed hypotension, tachycardia and decreased heart sounds. An echocardiogram confirmed severe pericardial effusion. Pericardial fluid cytology was positive for malignancy. The patient evolved with recurrent pericardial effusion and a pleuropericardial window was performed. At this procedure, a subpleural nodular lesion was found, which histology corresponded to metastases of papillary carcinoma, probably from thyroid origin. Total thyroidectomy was performed. The final diagnosis was papillary carcinoma, diffuse sclerosing variant. This variant infiltrates the connective tissue of the interfollicular spaces, mimicking thyroiditis and it is associated with early vascular permeation. This tumor, compared to the classic variants of thyroid carcinoma, is more aggressive and it has higher risk of recurrence. Papillary thyroid carcinoma should be considered as differential diagnosis in our population, in all metastatic papillary lesions, and even more in young female patients.

Low risk stage I endometrial carcinoma: Prognostic factors and outcomes.

Objectives: The aim of the study is to evaluate clinical features of patients with low-risk stage I endometrium cancer, who received adjuvant therapy or followed with observation only and to analyse the effects of known prognostic factors in this group of patients. Materials and Methods: A total of 246 patients (median age: 53, range: 31-77) with low-risk stage I endometrial cancer, who were just followed postoperatively (156 patients) or received adjuvant radiotherapy (90 patients) between 1996 and 2007 were reviewed retrospectively. Results: Local recurrence was detected in four patients, distant metastasis occurred in seven patients, and two patients had both local recurrence and distant metastasis. The 83.3% of recurrences were on the vaginal stump. Five- and ten-year local control (LC) and overall survival (OS) rates are 97.6%, 97.6% and 96.4%, 93.5% in the observation and adjuvant therapy groups, respectively, whereas distant control rates are 96.7% and 96.3%. In multivariate analysis, only age and lymphovascular invasion (LVI) were found to affect OS and disease-free survival (DFS). Conclusions: LC and OS rates are high in the low-risk group of patients; however, current adjuvant therapies did not improve the outcomes. Age over 60 years and the presence of LVI have negative effects on outcomes in this group of patients.

Patients with familial non-medullary thyroid cancer have an outcome similar to that of patients with sporadic papillary thyroid tumors / Pacientes com câncer não medular familiar da tiroide têm evolução similar aos portadores de câncer papilífero esporádico

OBJECTIVE:The purpose of this study was to determine whether familial non-medullary thyroid cancer (FNMTC) is more aggressive than sporadic thyroid cancer. SUBJECTS AND METHODS: We compared the clinical behavior and outcome of 16 subjects with FNMTC from 7 unrelated kindred with those observed in 160 subjects with sporadic PTC (SPTC) from our database. RESULTS: The only different baseline characteristics observed between both groups were: bilateral malignancy, 38 percent vs. 24 percent, respectively (p = 0.03), and lymph node metastasis, 56.2 percent vs. 39 percent, respectively (p = 0.01). Considering the outcome, in the FNMTC, 9 (56.2 percent) patients were rendered free of disease, one patient died from thyroid cancer (6 percent), and 6/16 (37.5 percent) had persistent disease. In the SPTC Group, 87 (54 percent) patients were considered free of disease, 11 (7 percent) died due to PTC, and 62 (38 percent) had persistent disease (p = ns). CONCLUSIONS: Despite the higher incidence of lymph node metastasis in FNMTC patients this situation seemed not to alter the compared outcome.

OBJETIVO: O objetivo deste estudo foi determinar se o câncer de tiroide não medular (CNMF) é mais agressivo do que o câncer esporádico de tiroide. SUJEITOS E MÉTODOS: Comparamos o comportamento clínico e a evolução de 16 portadores de CNMF de sete famílias não relacionadas com 160 CP (câncer papilífero) esporádicos de nosso serviço. RESULTADOS: As únicas diferenças nas características basais dos grupos eram: malignidade bilateral 38 por cento vs. 24 por cento, respectivamente (p = 0,03), e metástases linfonodais, 57,1 por cento vs. 39 por cento, respectivamente (p = 0,01). Em relação à evolução, 9 (56,2 por cento) pacientes com CNMF ficaram livres de doença, um paciente faleceu devido ao CP (6 por cento) e 6/16 (37,5 por cento) apresentavam persistência da doença. No grupo de CP esporádicos, 87 (54 por cento) foram considerados livres de doença, 11 (7 por cento) morreram em decorrência do CP e 62 (38 por cento) apresentavam persistência da doença (p = ns). CONCLUSÃO: Apesar da elevada incidência de metástases linfonodais nos pacientes com CNMF, essa situação não parece alterar a evolução dos dois grupos em longo prazo.

Cumulative doses of radioiodine in the treatment of differentiated thyroid carcinoma: knowing when to stop / Doses cumulativas de iodo radioativo no tratamento do carcinoma diferenciado de tireoide: sabendo a hora de parar

OBJECTIVE: Evaluate the efficacy of cumulative doses (CDs) of 131I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). SUBJECTS AND METHODS: The probability of progressive disease according to CDs was evaluated in patients < 45 years old and > 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. RESULTS: At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p < 0.0001), higher TNM stages (p < 0.0001), and follicular carcinomas (p = 0.0034). Probability of disease progression was higher with CDs > 600 mCi in patients > 45 years old and with CDs > 800 mCi in patients < 45 years. CONCLUSION: Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted.

OBJETIVO: Avaliar a eficácia de doses cumulativas (DCs) da terapia com iodeto-131I (RIT) no câncer diferenciado de tiroide (CDT). SUJEITOS E MÉTODOS: A probabilidade de doença em progressão conforme a DC foi calculada em pacientes com idade < 45 e > 45 anos e correlacionada com o TNM, valores de tiroglobulina sérica, tipos histológicos e variantes, idade e tempo de doença. RESULTADOS: Ao final de um seguimento de 69 ± 56 meses, 85 dos 150 pacientes CDT submetidos a doses fixas de RIT não tinham evidência de doença, 47 tinham doença estável e 18, doença progressiva. DCs mais elevadas foram usadas nas variantes agressivas (p < 0,0001), maior estágio TNM (p < 0,0001) e nos carcinomas foliculares (p = 0,0034). A probabilidade de doença em progressão foi maior com DCs > 600 mCi em pacientes > 45 anos e com DCs > 800 mCi em pacientes < 45 anos. CONCLUSÃO: Apesar de alguns pacientes ainda responderem a altas DCs, o impacto de RITs deve ser cuidadosamente avaliado e outras estratégias terapêuticas devem ser consideradas.

Thyroglobulin measurements in washout of fine needle aspirates in cervical lymph nodes for detection of papillary thyroid cancer metastases / Determinação da tireoglobulina no lavado da agulha da punção aspirativa de linfonodos cervicais para detecção de metástases do câncer papilar de tireoide

OBJECTIVE: The aim of this study was to evaluate the accuracy of the measurement of thyroglobulin in washout needle aspiration biopsy (FNAB-Tg) to detect papillary thyroid cancer (PTC) metastases. SUBJECTS AND METHODS: Forty-three patients (51.4 ± 14.6 years) with PTC diagnosis and evidence of enlarged cervical lymph nodes (LN) were included. An ultrasound-guided fine-needle aspiration of suspicious LN was performed, for both cytological examination and measurement of FNAB-Tg. RESULTS: The median values of FNAB-Tg in patients with metastatic LN (n = 5) was 3,419 ng/mL (11.1-25,538), while patients without LN metastasis (n = 38) showed levels of 3.7 ng/mL (0.8-7.4). Considering a 10 ng/mL cutoff value for FNAB-Tg, the sensitivity and specificity was 100 percent. There were no differences on the median of FNAB-Tg measurements between those on (TSH 0.07 mUI/mL) or off levothyroxine (TSH 97.4 mUI/mL) therapy (3.3 vs. 3.8 ng/mL, respectively; P = 0.2). CONCLUSION: The results show that evaluation of FNAB-Tg in cervical LN is a valuable diagnostic tool for PTC metastases that can be used independent of the thyroid status.

OBJETIVO: O objetivo deste estudo foi avaliar a acurácia da dosagem de tireoglobulina no lavado da agulha da punção aspirativa (PAAF-Tg) de linfonodos (LN) cervicais para detecção de metástases do câncer papilar de tireoide (CPT). SUJEITOS E MÉTODOS: Foram incluídos 43 pacientes (51,4 ± 14,6 anos) com diagnóstico de CPT e evidência de LN cervicais aumentados. Os LN suspeitos foram submetidos à punção aspiração com agulha fina guiada por ecografia para análise citológica e dosagem de tireoglobulina (PAAF-Tg). RESULTADOS: A mediana dos valores de PAAF-Tg nos LN metastáticos (n = 5) foi 3.419,0 ng/mL (11,1-25.538), enquanto nos LN não metastáticos (n= 38) a mediana foi de 3,7 ng/mL (0,8-7,4). Utilizando-se o nível de 10 ng/mL como ponto de corte, observaram-se sensibilidade e especificidade de 100 por cento. Os níveis de TSH sérico não interferiram na dosagem de PAAF-Tg (3,3 e 3,8 ng/mL nos grupos com TSH supresso (TSH 0,07 mUI/mL) e hipotireoidismo (TSH 97,4 mUI/mL), respectivamente, P = 0,2). CONCLUSÃO: Os resultados demonstram que a dosagem de PAAF-Tg é uma ferramenta importante no diagnóstico de metástases do CPT, podendo ser utilizada independente do "status" tireoidiano.

Primary hyperparathyroidism and incidental multifocal metastatic papillary thyroid carcinoma in a man / Hiperparatiroidismo primário e carcinoma papilífero metastático, multifocal e incidental da tiroide em paciente do sexo masculino

Co-existence of primary hyperparathyroidism (PHPT) and non-medullary thyroid carcinoma has been previously reported in sporadic case reports and some surgical series, but the majority of cases concerned women with occult papillary carcinomas without cervical lymph node involvement. We present a 71-year man with PHPT and multinodular goiter who was subjected to surgery for single parathyroid adenoma and was found to have synchronous multifocal papillary thyroid carcinoma (PTC) with cervical lymph node involvement. Review of the literature retrieved only a few similar cases. Ultrasonography of both thyroid and parathyroid glands might be considered in patients with hyperparathyroidism. Given that there are no specific guidelines for the management of patients with synchronous PHPT and PTC, they should be managed like the cases of single PTC.

A coexistência de hiperparatiroidismo primário (HPTP) e de carcinoma da tiroide não medular foi descrita anteriormente em relatos de caso esporádicos e em algumas séries cirúrgicas. Entretanto, a maioria dos casos se referiu a mulheres com carcinoma papilífero oculto sem o comprometimento de linfonodos cervicais. Apresentamos um paciente de 71 anos de idade do sexo masculino com HPTP e bócio multinodular que foi submetido a uma cirurgia para adenoma solitário da paratiroide e foi encontrado carcinoma papilífero da tiroide (PTC) multifocal com comprometimento de linfonodos cervicais. Uma revisão da literatura resultou em apenas alguns casos similares. A realização de uma ultrassonografia das glândulas tiroide e paratiroide pode ser considerada em pacientes com hiperparatiroidismo. Como não existe diretriz específica para o tratamento de pacientes com concomitância de HPTP e PTC, eles devem ser tratados como um caso isolado de PTC.

Cisto hepático benigno simulando metástase de carcinoma diferenciado de tireoide / Benign hepatic cyst mimicking thyroid carcinoma metastasis

INTRODUÇÃO: Pesquisa de corpo inteiro após dose terapêutica de (131I) NaI (PCI) associada à tireoglobulina (Tg) sérica, anticorpo antitireoglobulina (anti-Tg) e ultrassom (US) cervical representam os métodos de referência para detecção de carcinoma diferenciado de tireoide (CDT) residual ou metastático. Algumas causas de PCI falsos-positivas, como processos inflamatórios, alguns tumores não tireoidianos e até mesmo cistos renais e sebáceos, são bem conhecidas. MÉTODOS: Neste trabalho, descreveu-se um caso de cisto hepático benigno simulando metástase de carcinoma de tireoide em PCI após dose terapêutica de (131I) NaI. RESULTADOS: Ressalta-se a importância do reconhecimento dos cistos hepáticos benignos como fator complicador do seguimento dos pacientes com câncer de tireoide. CONCLUSÕES: Para minimizar erros de diagnóstico e, consequentemente, na condução dos casos de CDT, é necessário conhecer as possíveis causas de PCI falsos-negativas e positivas.

INTRODUCTION: The follow-up of differentiated thyroid carcinoma (DTC) for detecting persistent or recurrent disease is based on iodine whole body scan (WBS), the evaluation of the tumor marker thyroglobulin (Tg), the anti-thyroglobulin antibody (anti-Tg) and neck ultrasonography (US). Well known false-positive causes of WBS include inflammatory processes, some non-thyroid tumors, kidney or even sebaceous cysts . METHODS: We reported a case of false-positive WBS, after therapeutic dose of (131I) NaI. RESULTS: We enphasize the importance of recognizing benign liver cysts mimicking DTC metastasis. CONCLUSIONS: False-positive and negative results may occur with WBS and must be recognized to avoid mismanagement.

Orbital metastasis as primary clinical manifestation of thyroid carcinoma: case report and literature review / Metástase orbital como manifestação clínica primária de carcinoma de tireóide: relato de caso e revisão de literatura

Capillary thyroid carcinoma (PTC) is the most common neoplasm of thyroid. It usually grows slowly and is clinically indolent, although rare, its aggressive forms with local invasion or distant metastases can occur. Metastatic thyroid carcinoma rarely involves the orbit. We reported an uncommon case of orbital metastasis of PTC. A 66-years-old woman presented proptosis of the right eye. The biopsy of the tumor in orbit revealed metastatic thyroid carcinoma. The ultrasensitive TSH level was 1,34 mUI/L and free T4 level was 1,65 ng/dL. A total thyroidectomy was performed and histopathological analysis of the nodule revealed follicular variant of papillary thyroid carcinoma. Currently, the patient has been receiving palliative chemotherapy with Clodronate Disodium. The importance of the case is due to its unusual presentation, which emerged as a primary clinical manifestation. Although rare, thyroid carcinoma should be suspected in orbit metastasis.

Carcinoma papilífero da tiróide (PTC) é a neoplasia mais comum da tiróide. Geralmente cresce lentamente e é clinicamente indolente, embora raras, as formas agressivas com invasão local ou metástases distantes podem ocorrer. Carcinoma metastático da tiróide raramente envolve a órbita. Relatamos um caso raro de metástase orbital de PTC. Uma mulher de 66 anos apresentou proptose no olho direito. A biópsia do tumor em órbita revelou carcinoma metastático da tiróide. O nível ultra-sensível do TSH foi de 1,34 mUI/L e T4 livre foi de 1,65 ng/dL. A tireoidectomia total foi realizada e a análise histopatológica do nódulo revelou carcinoma papilífero variante folicular da tiróide. Atualmente, a paciente recebe quimioterapia paliativa com clodronato dissódico. A importância do caso é devido à sua apresentação incomum que surgiu como principal manifestação clínica. Embora raro, o carcinoma da tiróide deve ser pensado em metástase orbitária.

Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism / Desfecho Fatal de uma Paciente com Carcinoma Papilífero de Tiróide e Doença de Graves: possível Implicação do Mecanismo de Sinalização Cruzada

A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8 percent (n.v. < 10 percent). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.

Paciente de 29 anos foi encaminhada ao Hospital de Clínicas por causa de convulsões generalizadas. Apresentava hipertiroidismo tratado com metimazol (MMI). A ressonância magnética mostrava quatro lesões metastáticas cerebrais. Possuía bócio com nódulo frio e linfonodo palpável ipsilateral. Usando 5 mg de MMI, a paciente apresentava hipertiroidismo subclínico e TRAb = 47,8 por cento (normal < 10 por cento). A tomografia computadorizada também mostrava metástases pulmonares. A paciente foi submetida a tiroidectomia total com dissecção cervical modificada e recebeu dose acumulada de radioiodo de 700 mCi durante o período de dois anos. Foi analisado o DNA extraído de tecido emblocado em parafina do tumor, do linfonodo metastático e de tecido tiroidiano não-tumoral. Foram encontradas mutações pontuais em dois genes: uma substituição do genótipo selvagem CAA no códon 61 de /N-RAS/ por CAT, substituindo a glicina pela histidina (G61H) e uma substituição da seqüência normal GCC no códon 623 do gene TSHR por TCC, trocando a alanina pela serina (A623S). Não foram encontradas mutações no tecido não-tumoral. Estudos in vitro mostraram ativação constitutiva de TSHR. Já que esta mutação ativadora de TSHR foi incapaz de atingir o final da cascata PKA no tecido tumoral, sugere-se que um mecanismo de cross-signaling possa explicar o desvio da cascata do receptor de TSH para outra mais proliferativa, envolvendo MAPKinase e levando ao comportamento mais agressivo deste câncer papilífero.

Utilidad de la detección de tiroglobulina en el aspirado de punción ganglionar cervical en el seguimiento de pacientes con cancer papilar de tiroides / Thyroglobulin levels in needle lymph node cytology for the detection of papillary thyroid cancer recurrence

Background: During the detection ofneck recurrence in patients with Papillary Thyroid Carcinoma (PTC), sometimes it is difficult to distinguish metastatic from inflammatory neck lymph nodes. The measurement of serum thyroglobulin (sTg) under thyroid hormone suppression therapy the presence of serum thyroglobulin antibodies (sAbTg), the diagnostic whole body sean and cytology can give false negative results. Measurement of thyroglobulin in the washout fluid from fine-needle aspiration biopsy (FNAB) of suspicious neck lymph nodes could improve the diagnostic aecuracy Aim: To evaluate the usefulness of detecting Tg in lymph nodes (LTg) suspicious by ultrasonography (US) and compare it to cytology. Patients and Methods: Between the years 2004 and 2007 we prospectively studied 30 patients with PTC and cervical US findings of suspicious recurrence. LTg was assayed in US guided FNAB used for cytology. Results: Sixteen out of 30 patients underwent surgery using as selective criteria an LTg higher than sTg or a positive cytology. Surgery confirmed the presence of metástasis in all 15 patients with positive LTg (8 with positive cytology) and in 1 patient with negative LTg and positive cytology (a case with undifferentiated thyroid cancer). The sensitivity was 93.7 percent for LTg and 56.2 percent for cytology. We identified byLTg 3 of 6 patients with undetectable sTg and positive sAbTg. Conclusions: The presence of LTg showed a higher sensitivity than cytology for the detection of cervical lymph node metástasis. This method is useful even in the presence ofsAbTg.

Contribuição da tomografia computadorizada em pacientes com metástases pulmonares de carcinoma diferenciado de tireóide não-aparentes na radiografia e tratados com radioiodo / Contribution of computed tomography in patients with lung metastases of differentiated thyroid carcinoma not apparent on plain radiography who were treated with radioiodine

A tomografia computadorizada (TC) de tórax é mais sensível que a radiografia na detecção de metástases pulmonares do carcinoma diferenciado de tireóide (CDT), sendo importante conhecer melhor o valor agregado desse método. Este estudo avaliou a resposta ao tratamento com 131I em pacientes com metástases pulmonares de CDTs não-aparentes na radiografia e o valor da TC nesses casos. Foram avaliados 25 pacientes com metástases pulmonares não-aparentes na radiografia, que receberam inicialmente 100 a 200 mCi de 131I. Naqueles com pesquisa de corpo inteiro (PCI) pós-dose com captação pulmonar, um novo tratamento era realizado após seis a 12 meses, e assim sucessivamente. A chance do encontro de captação pulmonar na PCI pós-dose não foi diferente em pacientes com TC negativa ou positiva (100 por cento versus 91,5 por cento). Os valores médios de tireoglobulina (Tg) sérica foram maiores naqueles com TC positiva (108 ng/mL versus 52 ng/mL). PCI pós-dose negativa foi alcançada em 82 por cento dos pacientes com TC positiva e em 92,3 por cento com TC negativa, e a atividade acumulada de 131I para alcançar essa resposta não foi diferente nos dois grupos (em média, 300 mCi). Quarenta e sete por cento dos pacientes com TC negativa ao final do tratamento apresentaram Tg estimulada indetectável, mas nenhum daqueles que permaneceu com TC positiva apresentou-a. Em pacientes com Tg elevada, o resultado da TC aparentemente não altera a indicação da terapia e a atividade de 131I a ser administrada. Nos casos com metástases pulmonares, a permanência de micronódulos na TC nos pacientes com PCI pós-dose negativa após o tratamento foi associada à persistência de Tg detectável.

Computed tomography (CT or CAT Scan) of the chest is more sensitive than radiography in the detection of lung metastases of differentiated thyroid cancer (DTC), but little information is available regarding the aggregated value of this method. The present study evaluated the response of patients with lung metastases of DTC not apparent on radiography to treatment with 131I and the value of CT in these cases. Twenty-five patients with lung metastases not apparent on radiography, who initially received 100-200 mCi I151, were evaluated and those presenting pulmonary uptake on post-therapy WBS were submitted to a new treatment after 6 to 12 months, and so on. The chance of detection of pulmonary uptake on post-therapy WBS did not differ between patients with negative and positive CT (100 percent versus 91.5 percent). Mean serum Tg levels were higher in patients with positive CT (108 ng/ml versus 52 ng/ml). Negative post-therapy WBS was achieved in 82 percent of patients with positive CT and in 92.3 percent with negative CT and the cumulative I131 activity necessary to achieve this outcome did not differ between the two groups (mean = 300 mCi). Stimulated Tg was undetectable in 47 percent of patients with negative CT at the end of treatment, but in none of the patients whose CT continued to be positive. In patients with elevated Tg, the CT result apparently did not change the indication of therapy or the I131 activity to be administered. In cases with lung metastases, the persistence of micronodules on CT was associated with the persistence of detectable Tg in patients presenting negative post-therapy WBS.

Investigação de linfonodos em pacientes em seguimento por carcinoma diferenciado de tiróide / Cervical lymph nodes metastases in patients with differentiated thyroid cancer

Recorrências regionais dos carcinomas diferenciados de tiróide (CDT) são representadas por linfonodos cervicais em 60-75 por cento dos casos. Com a introdução da ultra-sonografia cervical (USC) no seguimento dos pacientes com carcinoma papilífero de tiróide (CPT) tornou-se freqüente o encontro de pequenos linfonodos (LNs) cervicais. Porém, apesar da USC apresentar alta sensibilidade, o estudo citológico obtido por punção aspirativa (PAAF), e nos últimos anos, a dosagem da tiroglobulina (Tg) no lavado da agulha da PAAF (Tg-PAAF), vêm assumindo papel importante no diagnóstico de LNs cervicais. O objetivo deste estudo é revisar a importância do diagnóstico precoce das metástases em linfonodos cervicais no seguimento dos pacientes com carcinoma de tiróide.

Loco-regional recurrences of the differentiated thyroid cancer have been reported to be located in cervical lymph nodes in 60-75 percent of cases. The widespread use of neck ultrasonography (US) during the follow-up of patients with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this paper is to review the importance of the early diagnosis of lymph node metastases in the follow-up of patients with differentiated thyroid cancer.

Emprego da ultra-sonografia cervical no seguimento de pacientes com carcinoma diferenciado de tireóide / Usefulness of neck ultrasonography in the follow-up of patients with differentiated thyroid cancer

A ultra-sonografia (US) cervical é recomendada na avaliação de todos pacientes com carcinoma de tireóide após a terapia inicial, pois mesmo indivíduos de baixo risco com tireoglobulina (Tg) estimulada indetectável podem apresentar metástases cervicais. Para estas metástases, a US é o método mais sensível, superior à pesquisa de corpo inteiro (PCI) com 131I. Linfonodos cervicais com diâmetro > 5 mm com calcificações finas e/ou degeneração cística quase sempre são de etiologia maligna. Na ausência destas características, o formato arredondado e a ausência do hilo ecogênico são achados "suspeitos", enquanto linfonodos alongados e com hilo ecogênico visível são considerados benignos. A avaliação do fluxo, através do doppler, auxilia no diagnóstico diferencial, usualmente revelando hipervascularização periférica ou mista nos casos malignos. Na presença de linfonodos "suspeitos" na US, a avaliação citológica do material obtido através da punção aspirativa por agulha fina (PAAF) e a dosagem da Tg, obtida do lavado da agulha, são testes úteis e complementares para definir a etiologia, com elevada sensibilidade quando combinados e especificidade de 100 por cento. A US também é útil antes da tiroidectomia, auxiliando e até, em alguns casos, modificando o planejamento cirúrgico; e antes da ablação, para mensuração dos remanescentes tireoidianos e pesquisa de metástases linfonodais persistentes. Outra aplicação desse método de imagem é guiar a injeção de etanol (escleroterapia) ou a introdução de eletrodos para ablação com radiofreqüência em casos selecionados de metástases linfonodais isoladas, como alternativa às terapias convencionais.

Neck ultrasonography (US) is recommended for the assessment of all patients with thyroid carcinoma after initial therapy, since even low-risk patients with undetectable stimulated thyroglobulin (Tg) may present cervical metastases. In the case of these metastases, US is the most sensitive method and is superior to whole-body 131I scanning. Cervical lymph nodes with a diameter > 5 mm presenting thin calcifications and/or cystic degeneration have almost always a malignant etiology. In the absence of these characteristics, a round shape and the absence of an echogenic hilum are "suspicious" findings, whereas elongated lymph nodes with a visible echogenic hilum are considered benign. Doppler flow analysis helps with the differential diagnosis, usually revealing peripheral or mixed hypervascularization in malignant cases. In the presence of "suspicious" lymph nodes upon US, fine-needle aspiration cytology and measurement of Tg in the needle lavage fluid are useful and complementary exams for the definition of the etiology, with the combination of the two methods showing elevated sensitivity and 100 percent specificity. US is also useful before thyroidectomy, even contributing in some cases to modify the surgical planning, and before ablation for the measurement of thyroid remnants and detection of persistent lymph node metastases. Another application of this imaging method is to guide the injection of ethanol (sclerotherapy) or the introduction of electrodes for radiofrequency ablation in selected cases of isolated lymph node metastases as an alternative to traditional therapies.

Tiroglobulina y sus limitaciones en el seguimiento del carcinoma diferenciado del tiroides: Report of two cases / Recurrence of differentiated thyroid carcinoma without concomitant elevation of serum thyroglobulin

Thyroid carcinoma is the most prevalent endocrine tumor, and the papillary carcinoma (PC) is the most common histological type. In the follow-up, after thyroidectomy serum thyroglobulin (s-Tg) is used as a marker to evaluate recurrence of thyroid carcinoma. In most cases, this parameter allows an adequate diagnosis, but occasionally s-Tg may miss the detection of a recurrence. We report a 57 year-old female and a 36 year-old male sujected to a total thyroidectomy for a papillary thyroid carcinoma with intermediate and high-risk of recurrence. Both had a cervical recurrence without a concomitant increase in s-Tg levels. In both, Tg staining was positive in the tumor cells. These cases confirm that in these patients, the follow-up must be done with measurement of s-Tg and complementary diagnostic tests.

Diagnóstico de metástases de carcinoma papilífero de tiróide através da dosagem de tiroglobulina no líquido obtido da lavagem da agulha utilizada na punção aspirativa / Diagnosis of metastases in patients with papillary thyroid cancer by the measurement of thyroglobulin in fine needle aspirate

Com a introdução da ultra-sonografia cervical (USC) no seguimento dos pacientes com carcinoma papilífero de tiróide (CPT), tornou-se freqüente o encontro de pequenos linfonodos (LNs) cervicais. Porém, apesar de a USC apresentar alta sensibilidade, o estudo citológico obtido por punção aspirativa (PAAF) e, nos últimos anos, a dosagem da tiroglobulina (Tg) no lavado da agulha da PAAF (Tg-PAAF) vêm assumindo papel importante no diagnóstico de LNs cervicais. O objetivo deste estudo é verificar a acurácia da combinação da USC, citologia e Tg-PAAF em LNs suspeitos. Estudamos 32 pacientes que apresentavam 44 LNs à USC, classificados como "inflamatórios" (19) ou "suspeitos" (25). Dos 25 LNs suspeitos, 15 apresentavam Tg-PAAF elevada (13 com citologia compatível com metástases e 2 com citologia não-diagnóstica). Esses 15 LNs (11 pacientes) foram confirmados como metástase de CP pelo exame histopatológico. Os 19 LNs "inflamatórios" e os 10/25 LNs "suspeitos" apresentaram citologia negativa e Tg-PAAF indetectável. Concluímos que a USC apresenta alta sensibilidade na detecção de linfonodos cervicais, porém citologia e dosagem de Tg-PAAF são fundamentais para o diagnóstico. A associação USC, citologia e Tg-PAAF pode ser considerada a abordagem mais sensível e específica na detecção de LNs metastáticos em pacientes com CPT.

The widespread use of neck ultrasonography (US) during the follow-up of patients with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this study is to determine the sensitivity of the combined use of neck US, FNA biopsy and FNA-Tg for diagnosis of cervical lymph nodes. We have studied 32 patients with 44 LN detected by US, 19 classified as inflammatory and 25 as suspicious. 15 of those 25 suspicious LN had high FNA-Tg (13 of the 15 had positive cytology and 2 indeterminate). All of these 15 LN (11 patients) were proven to be PTC metastasis by histopathology. All 19 inflammatory LN and those 10/25 suspicious LN, had cytology negative for malignancy and undetectable FNA-Tg. We conclude that fine needle aspiration biopsy and FNA-Tg combined with neck US are essential for detecting positive cervical lymph nodes due to its high sensitivity and specificity and it should be considered the standard for investigating locally recurrent disease in patients with PTC.