Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study.

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.

Recurrence and mortality prognostic factors in childhood adrenocortical tumors: Analysis from the Brazilian National Institute of Cancer experience.

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.

Thyroid Lobectomy Is Associated with Excellent Clinical Outcomes in Properly Selected Differentiated Thyroid Cancer Patients with Primary Tumors Greater Than 1 cm.

Background and Objective. An individualized risk-based approach to the treatment of thyroid cancer is being extensively discussed in the recent literature. However, controversies about the ideal surgical approach remain an important issue with regard to the impact on prognosis and follow-up strategies. This study was designed to describe clinical outcomes in a cohort of low and intermediate risk thyroid cancer patients treated with thyroid lobectomy. Methods. Retrospective review of 70 patients who underwent lobectomy. Results. After a median follow-up of 11 years, 5 patients (5/70, 7.1%) recurred and 5 had a completion for benign lesions, while 60 patients (86%) continued to be observed without evidence for disease recurrence. Suspicious ultrasound findings were significantly more common in patients that had structural disease recurrence (100% versus 4.3%, P < 0.001). Furthermore, a rising suppressed Tg value over time was also associated with structural disease recurrence (80% versus 21.5%, P = 0.01). After additional therapy, 99% of the patients had no evidence of disease. Conclusions. Properly selected thyroid cancer patients can be treated with lobectomy with excellent clinical outcomes.

Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy.

OBJECTIVE: 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.

Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): case report and review.

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.

Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): case report and review / Tumor epitelial de células fusiformes com diferenciação thymus-like da tireoide (SETTLE): relato de caso e revisão da literatura

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.