Puberty and sex in pediatric thyroid cancer: could expression of estrogen and progesterone receptors affect prognosis?

Objective: A sharp increase in pediatric thyroid cancer incidence is observed during adolescence, driven mainly by girls. Differences in disease presentation across sexual maturity stages raise the question of whether sex steroids have a role in the heterogeneity. The aims of this study were to analyze the influence of puberty and sex on clinical presentation and prognosis and to evaluate the correlation between the expression of sex hormone receptors. Design and methods: Clinical records and immunohistochemical of specimens from 79 patients were analyzed. Puberty was analyzed by two criteria: end of puberty and beginning, in which the age of 10 was the cutoff. Results: Postpubertal were more frequently classified as having low-risk disease and a lower frequency of persistent disease, especially when the completion of puberty was used as the criteria. Male sex was associated with a higher risk of persistent disease at the end of the observation period. Estrogen receptor α positivity was low in the entire sample, while progesterone receptor positivity was positive in 30% of the cases. Female hormone receptor expression was not associated with sex, American Thyroid Association risk score, persistent structural disease, or pubertal status. Conclusion: Our study showed that the completion of puberty correlated best with the clinical behaviour of pediatric thyroid cancer. It was also shown that postpubertal patients have a less aggressive initial presentation and better outcomes. However, this observation could not be explained by the expression of estrogen and progesterone receptors in the primary tumors.

Pregnancy has no significant impact on the prognosis of differentiated thyroid cancer.

OBJECTIVE: To evaluate the impact of pregnancy on differentiated thyroid carcinomas (DTC) behavior. METHODS: Retrospective study of patients diagnosed with DTC before or during pregnancy and treated with standard therapy. In women diagnosed with DTC before pregnancy, we evaluated the occurrence of progression according to categories of response to therapy based on imaging and non-stimulated thyroglobulin (TG) levels. RESULTS: Of 96 analyzed patients, 76 became pregnant after DTC treatment and 20 were diagnosed with DTC during pregnancy. Among women who became pregnant after a DTC diagnosis, no difference was observed regarding response to therapy before and after pregnancy. Disease progression after pregnancy was documented in six of these patients, while seven of them presented progression before pregnancy but were only treated after delivery. Patients with DTC diagnosed during pregnancy had a higher rate of distant metastases at diagnosis (30%) compared with the patients who became pregnant after DTC diagnosis (9.2%, p = 0.01). CONCLUSION: Pregnancy had no impact on the natural course of DTC. Disease progression after pregnancy was limited and probably related to more aggressive disease and higher risk stratification at diagnosis. Still, mild disease progression may have occurred asymptomatically in some patients.

High thyroglobulin and negative whole-body scan: no long-term benefit of empiric radioiodine therapy.

PURPOSE: Around 10-27% of patients will present elevated thyroglobulin (Tg) levels and negative diagnostic whole-body scan (dxWBS) during differentiated thyroid cancer (DTC) follow-up. Empiric radioactive iodine (RAI) therapy in this context is controversial due to the lack of good quality studies in the context. The main purpose of this study is to compare long-term response to therapy status and overall survival between empiric RAI treated and untreated DTC patients. METHODS: A retrospective study comparing differentiated thyroid cancer patients with negative diagnostic whole-body scan and elevated thyroglobulin levels submitted or not to empiric radioactive iodine therapy in a thyroid cancer referral center. The main outcome measures were ATA Response to Therapy Stratification at 6-12 months after RAI ablative dose, at 6-18 months after negative dxWBS and last follow-up visits. RESULTS: Overall, 120 DTC patients with stimulated Tg >10 ng/ml and negative dxWBS were included in this study. Overall, 53 patients were submitted to empiric RAI and 67 were in the control group. No difference was observed in ATA Response to Therapy Stratification after RAI ablation or at the end of follow-up between groups. Also, no difference was found in terms of Tg changes response. After more than 10 years of follow-up, 17 patients died (13 from treated and 4 from untreated group). CONCLUSIONS: Empiric RAI treatment was not associated with better long-term ATA response to therapy status or overall survival.

AGK-BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma.

BACKGROUND: The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen-activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiation-exposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC. PROCEDURE: In this study, we investigated the prevalence of BRAF alterations (AGK-BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK-BRAF fusion was investigated by RT-PCR and confirmed by FISH break-apart. The BRAF V600E mutation was screened using Sanger sequencing. RESULTS: AGK-BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size. CONCLUSION: Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.

Prognostic Factors for Early and Long-Term Remission in Pediatric Differentiated Thyroid Carcinoma: The Role of Sex, Age, Clinical Presentation, and the Newly Proposed American Thyroid Association Risk Stratification System.

BACKGROUND: The incidence of pediatric differentiated thyroid carcinoma (DTC) has been rising in recent years, and the main risk factors for recurrence are lymph node and distant metastasis at diagnosis. Other clinical features remain unclear, such as the impact of age, sex, and puberty. Furthermore, until now, this population has been treated using the same strategies used to treat adults. In 2015, the American Thyroid Association (ATA) published the first guidelines targeted at this age group. The aims of this study were to investigate the prognostic factors for early and long-term remission and also to validate the ATA risk stratification proposal in a population outside the United States. METHODS: Clinical records from 118 patients <18 years old followed in two referral centers were reviewed. The median age was 12 years (range 4-18 years), and 20.3% (24 patients) were <10 years old at diagnosis. The median follow-up was 9.1 years. The majority were female (72%) and received total thyroidectomy and radioiodine therapy (RAI), and 61.8% were treated with more than one dose of RAI. The majority were classified as high risk (48.3%) by the new ATA pediatric guidelines due to distant metastasis (30 patients) or extensive lymph node involvement (27 patients). The remained were classified as low risk (31.3%) and intermediate risk (20.4%). RESULTS: Females with no lymph node or distant metastasis and low ATA pediatric risk were more likely to have no evidence of disease (p < 0.05) within the first year and also in the long term. In this study, age did not significantly predict outcomes. Furthermore, patients also benefitted from multiple doses of RAI, but when the cumulative activity was >400 mCi, this benefit was diminished. CONCLUSIONS: This study shows that the ATA risk stratification proposal for pediatric patients is useful in predicting early and long-term outcomes in pediatric patients with DTC. In addition, it shows that sex and metastatic disease are important prognostic factors in pediatric populations.