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Prognostic markers that can help identifying precocious risk of unfavorable outcomes in patients with childhood adrenocortical tumors (ACTs) are still unclear. This observational and retrospective study aimed to identify clinical and pathology prognostic factors of recurrence and death in a tertiary cancer center population. Clinical, pathology, demographic, staging, and therapy data from patients with childhood ACT (median age: 3.6 years) treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed. Univariate and bivariate analyses were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Twenty-seven patients were included. Complete tumor resection was performed in 21 cases. The median tumor size was 8.2 cm. Mitotane was the most common adjuvant/palliative therapy (n = 13). Recurrence occurred in 6 patients, after a median time of 7.2 months, and was more common among those with larger tumors (P =.008), higher Weiss score (P =.001), and microscopic tumoral necrosis (P =.002). Ten patients died from the disease. Older age (P =.04), larger tumor size (P =.002), metastatic disease (P =.003), previous recurrence (P =.003), incomplete resection (P =.002), intraoperative tumor spillage (P =.005), higher Weiss score (P =.03), microscopic necrosis (P =.005), and capsular invasion (P =.02) were all associated with increased death risk. Even though complete tumor resection was performed in most cases, a considerable number of cases of childhood ACT resulted in recurrence and death. Early identification of unfavorable outcomes is essential to determine ideal therapy and appropriate surveillance.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.

Medullary thyroid cancer (MTC) is a rare but potentially life-threatening disease with limited therapeutic options. As a neuroendocrine tumor, MTC expresses somatostatin receptors, and therefore, somatostatin-labeled radiopharmaceuticals could be used to treat patients with MTC.The aims of this study were to evaluate tumor shrinkage after Lu-DOTATATE treatment, to analyze the impact on quality of life as accessed by the SF-36 questionnaire, and to demonstrate a possible prognostic role for In-DTPA-octreotide uptake in patients with MTC.Patients with progressive MTC underwent evaluation using In-DTPA-octreotide. Patients who demonstrated In-DTPA-octreotide uptake were treated with 4 cycles of 200 mCi of Lu-DOTATATE and were evaluated using CT scans over 8 to 12 months of treatment.Of the 16 patients initially enrolled, 9 (56.25%) had lesions that were observed in the In-DTPA-octreotide scans and were eligible for therapy with Lu-DOTATATE. Three patients had a partial response, 3 patients were classified as having stable disease and, 1 patient had a progressive disease. All responders indicated improvement in quality of life 6 to 12 months after therapy.Treatment with Lu-DOTATATE seems to be an alternative therapy for somatostatin receptor-positive tumors, with very mild adverse effects and quality-of-life improvement, at least during a short-term period. Further studies are needed to determine long-term benefits and to identify which patients are more likely to respond to this modality of therapy.

Aim To evaluate the impact of genetic polymorphisms in uridine 5′-glucuronosylytansferases UGT1A1 and UGT1A3 and iodothyronine-deiodinases types 1 and 2 on levothyroxine (T4; 3,5,3′,5′-triiodo-L-thyronine) dose requirement for suppression of thyrotropin (TSH) secretion in patients with differentiated thyroid cancer (DTC). Methods Patients (n = 268) submitted to total thyroidectomy and ablation by 131I, under T4 therapy for at least 6 months were recruited in three public institutions in Brazil. Multivariate regression modelling was applied to assess the association of T4 dosing with polymorphisms in UGT1A1 (rs8175347), UGT1A3 (rs3806596 and rs1983023), DIO1 (rs11206244 and rs2235544) and DIO2 (rs225014 and rs12885300), demographic and clinical variables. Results A regression model including UGT1A haplotypes, age, gender, body weight and serum TSH concentration accounted for 39% of the inter-individual variation in the T4 dosage. The association of T4 dose with UGT1A haplotype is attributed to reduced UGT1A1 expression and T4 glucuronidation in liver of carriers of low expression UGT1A1 rs8175347 alleles. The DIO1 and DIO2 genotypes had no influence of T4 dosage. Conclusion UGT1A haplotypes associate with T4 dosage in DTC patients, but the effect accounts for only 2% of the total variability and recommendation of pre-emptive UGT1A genotyping is not warranted.

SummaryObjective To validate the American Thyroid Association (ATA) initial risk of recurrence scheme and the Memorial Sloan Kettering Cancer Center (MSKCC) response to therapy re-stratification approach in a large cohort of patients with differentiated thyroid cancer (DTC) treated outside of the United States. Design Retrospective chart review. Patients Five hundred and six patients with DTC followed for a median of 10 years after total thyroidectomy and RAI remnant ablation at a major cancer centre in Brazil. Measurements Final clinical outcomes were assessed based on American Joint Cancer Committee (AJCC)/Union Internationale Contre le Cancer (UICC) staging, ATA risk stratification and response to therapy assessment (excellent, acceptable, biochemical incomplete and structural incomplete). Results The AJCC/UICC staging system did not adequately stratify patients with regard to the risk of recurrence/persistent disease. However, the ATA system demonstrated a 13% risk of recurrent/persistent disease in low-risk patients, 36% in intermediate risk patients, and 68% in high-risk patients. Furthermore, an excellent response to therapy decreased the risk of recurrent/persistent disease to 1·4%. At the time of final follow-up, 34% of the biochemical incomplete response patients had been re-classified as having no evidence of disease (NED) without having received any additional therapy beyond continue levothyroxine suppression. Conversely, even after additional therapies, only 9% of the patients with an incomplete structural response were eventually re-classified as NED. Conclusions These data validate the ATA risk classification as an excellent initial predictor of recurrent/persistent disease and confirm the clinical utility of the MSKCC dynamic risk assessment system in a cohort of patients evaluated and treated outside the United States.

Spindle epithelial tumor with thymus-like element (SETTLE) is a rare malignant neoplasm of the thyroid, occurring predominantly in children, adolescents, and young adults. SETTLE usually presents itself as a thyroid mass, without metastases at diagnosis. It is believed to derive from branchial pouch or thymic remnant tissue showing primitive thymic differentiation. This article reports the clinical, cytological, histological and immunohistochemical features of a SETTLE in a 3-year-old girl. Microscopic exam revealed a nodular, highly cellular neoplasm displayed in the classic biphasic pattern, with mixture of prominent spindle cell component and a minor glandular component lined by mucinous or respiratory-type epithelium. The immunohistochemical study showed strong and diffuse positivity for pan-CK, vimentin and smooth muscle actin. The present case is the first SETTLE case reported in Brazil. To date, the patient described remains without evidence of recurrence or metastasis 5 years after surgery. O tumor epitelial de células fusiformes com elemento thymus-like é uma rara neoplasia maligna da tireoide, ocorrendo predominantemente em crianças, adolescentes e adultos jovens. Habitualmente, esse tumor se apresenta como massa tireoideana, sem metástases ao diagnóstico. Acredita-se derivar de arco branquial ou tecido remanescente tímico, apresentando diferenciação tímica primitiva. Este artigo descreve os aspectos clínicos, citológicos, histológicos e imuno-histoquímicos de um caso de SETTLE diagnosticado em uma menina de 3 anos de idade. O aspecto microscópico encontrado no tumor foi de uma lesão nodular, hipercelular, disposta em aspecto bifásico clássico, com componente de células fusiformes, e de tecido glandular acompanhado por epitélio mucinoso e respiratório. O estudo imuno-histoquímico foi positivo para pan-CK, vimentina e actina de músculo liso. Esse caso é o primeiro relato de SETTLE no Brasil. A paciente descrita permanece sem evidência de doença em atividade cinco anos após o tratamento cirúrgico.

Medullary thyroid cancer is a rare tumor driven from neuroendocrine cells. In the last decade there has been important discoveries regarding its genetics and relationship between genotype and phenotype on familial cases. However remains unknown the best approach for patient with maintained high levels of tumor markers such as calcitonin. Most available imaging techniques are able to accurately find metastatic lesions only in advanced disease. Traditionaly, nuclear medicine images are able to find metastatic suspicious lesions before they reach the size to be considered suspicious in conventional studies such as computed tomography scans or magnetic resonance imaging. However in patients with medullary thyroid cancer the ideal radiopharmaceutical for this purpose is yet to be found. Based on the biology of the tumor, some radiopharmaceuticals have been studied for diagnosis and also for therapy in those patients. The aim of this review is to describe the radiopharmaceuticals used for diagnosis and treatment until today and the role of each of them in medical care. In conclusion, the medullary thyroid cancer is a rare tumor and the review shows that despite all studies there is still no consensus on the importance of nuclear medicine in the diagnosis and treatment of these patients. Further studies are still needed.

There is a considerable interindividual variation in L-thyroxine [3,5,3',5'-tetraiodo-l-thyronine (T 4 )] dose required for thyrotropin (thyroid-stimulating hormone) suppression in patients with differentiated thyroid cancer. To investigate whether uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)-mediated T 4 glucuronidation in liver affects T 4 dose, we genotyped 101 patients for the common UG1A1-53(TA) n polymorphism and compared T 4 doses among patients having zero (5/6 and 6/6 genotypes), one (6/7 genotype), or two (7/7 and 7/8 genotypes) copies of the low-expression (TA) 7 and (TA) 8 alleles. A significant trend for decreasing T 4 dose with increasing number of copies of (TA) 7 and (TA) 8 (P=0.037) and significant difference in T 4 dose across the UGT1A1-53(TA) n genotypes (P=0 . 0 48 ) were observed, despite considerable overlap of T 4 doses among different genotypes. These results are consistent with reduced T 4 glucuronidation in patients with low-expression (TA) 7 and (TA) 8 alleles and provide the first evidence for association between UGT1A1-53(TA)n and T 4 -dose requirement for thyroid-stimulating hormone suppression in a natural clinical setting.

A 30-year-old man diagnosed with follicular thyroid carcinoma treated previously with total thyroidectomy was referred to radioiodine treatment. Post-therapy scan performed 10 days after a 150 mCi 131NaI revealed radioiodine uptake in left temporal region. To elucidate the abnormal head uptake, Tc-99m MDP bone scan and head magnetic resonance image was performed. No anomalous uptake was observed in the bone scan. Head magnetic resonance image found a well-circumscribed lesion in temporal was compatible with a vascular malformation. Angioresonance confirmed the diagnosis of cavernous angioma, a benign vascular tumor.