Molecular Genetics Augment Cytopathologic Evaluation and Surgical Planning of Pediatric Thyroid Nodules.

Purpose: Molecular genetic testing in conjunction with cytopathology may improve prediction of malignancy in thyroid nodules, particularly those with indeterminate cytology (Bethesda III/IV). Though now commonplace in adults, pediatric data are limited. This study examines molecular genetics of pediatric nodules with correlation to cytologic and histologic classification at time of surgery and the distribution of mutations.

Differences in the management of thyroid nodules in children and adolescents as compared to adults.

Purpose Of Review: To describe recent advances in the diagnosis and management of thyroid nodules in both children and adults, highlighting differences between the two groups.

Recent Findings: Thyroid nodules are less common in children than adults but the risk of malignancy is higher. Screening recommendations for patients with certain genetic syndromes or specific risk factors for thyroid nodules and cancer continue to evolve ultrasound is the most appropriate imaging modality for evaluating thyroid nodules in all patients, but radiographic risk stratification systems validated in adults have not been extensively studied in children.

Treatment of hypothyroidism in infants, children and adolescents.

In 2014, treatment guidelines from the American Thyroid Association reflected the general consensus that levothyroxine (LT4), adjusted to maintain a normal thyrotropin (TSH) level, is the preferred method for treatment of hypothyroidism. Although this is generally applicable to children, there are subsets of children for whom the diagnosis and treatment of hypothyroidism are problematic. These include children with congenital hypothyroidism (CH), low birth weight (LBW) and very low birth weight (VLBW), Down syndrome (DS), subclinical hypothyroidism, and obesity.

Management of Pediatric Graves Disease: A Review.

Importance: The incidence of Graves disease (GD) is rising in children, and adequate care of these patients requires a multidisciplinary approach. Whether patients are seen in the context of endocrinology, nuclear medicine, or surgery, it is important to know the nuances of the therapeutic options in children.

Observations: Given the rarity of GD in children, it is important to recognize its various clinical presenting signs and symptoms, as well as the tests that may be important for diagnosis.

Cytomorphologic features of thyroid disease in patients with DICER1 mutations: A report of cytology-histopathology correlation in 7 patients.

Background: Germline and somatic mutations of DICER1 have been identified in various types of neoplastic lesions, with germline DICER1 mutation being linked to autosomal dominant hereditary pleiotropic tumor syndrome (DICER1 syndrome). Patients with DICER1 syndrome are at increased risk of developing thyroid disease, including thyroid cancer. The goal of this study was to identify diagnostic cytologic features in thyroid fine-needle aspiration (FNA) samples from patients with DICER1 mutation.

Large-scale second-hit AIP deletion causing a pediatric growth hormone-secreting pituitary adenoma: Case report and review of literature.

Gigantism (early-onset acromegaly) is a rare pediatric disorder caused by a growth hormone (GH)-secreting pituitary adenoma. Approximately 50% patients of gigantism have a germline mutation, most commonly an inactivating mutation in the aryl-hydrocarbon interacting receptor protein (AIP) gene on chromosome 11q13.2.

Recurrence and Complications in Pediatric and Adolescent Papillary Thyroid Cancer in a High-Volume Practice.

Background: Treatment approaches for pediatric papillary thyroid cancer (PTC) are historically extrapolated from adult experience. However, pediatric PTC demonstrates a greater propensity for lymph node involvement, early metastases, and recurrence, highlighting the need for pediatric-specific treatment paradigms.

Materials And Methods: A retrospective review included patients with PTC aged ≤21 y, with ≥18 mo of follow-up, treated between 2002 and 2015.

Lymph node ratio predicts recurrence in pediatric papillary thyroid cancer.

Background: Regional lymph node (LN) metastasis at the time of presentation plays a significant role in predicting recurrence in patients with papillary thyroid cancer (PTC). Multiple studies in the adult population have demonstrated that the lymph node ratio (LNR) in both the central and lateral neck can improve the accuracy of recurrence prediction, but this ratio has not been studied in the pediatric population. In this study, we sought to investigate the LNR in the central and lateral compartments as a prognostic predictor for recurrence in pediatric patients with PTC.

Pathologic Characteristics, Natural History, and Prognostic Implications of BRAF Mutation in Pediatric Papillary Thyroid Carcinoma.

The BRAF mutation is the most common genetic aberration in papillary thyroid cancer (PTC), found in up to 68% of PTC in adults where it is associated with aggressive features. The incidence of this mutation in pediatric PTC is less frequent, reported as 0%-20% in the past and up to 63% in one recent series. Data suggest the mutation is not associated with an aggressive course in children; however, there are limited numbers of reported case series, so the prognostic implications remain poorly understood.

NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States.

Background: An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children.

Methods: The histopathology of 28 consecutive PTCs from the northeast United States was reviewed. None of the patients (ages 6-18 years; 20 females, 8 males) had significant exposure to radiation.

C-Cell Neoplasia in Asymptomatic Carriers of RET Mutation in Extracellular Cysteine-Rich and Intracellular Tyrosine Kinase Domain.

Germline mutations in RET proto-oncogene associated with multiple endocrine neoplasia type 2 (MEN2) may affect codons for the extracellular cysteine-rich (ECR) or the intracellular tyrosine kinase (ITK) domain of the transmembrane receptor tyrosine kinase protein. We compared C-cell pathology in asymptomatic carriers of RET mutation affecting the 2 domains. Twenty-two asymptomatic carriers (median age, 9.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment.

The treatment of differentiated thyroid cancer in children: emphasis on surgical approach and radioactive iodine therapy.

Pediatric thyroid cancer is a rare disease with an excellent prognosis. Compared with adults, epithelial-derived differentiated thyroid cancer (DTC), which includes papillary and follicular thyroid cancer, presents at more advanced stages in children and is associated with higher rates of recurrence. Because of its uncommon occurrence, randomized trials have not been applied to test best-care options in children.

Adverse events associated with methimazole therapy of graves' disease in children.

Objective. Graves' disease is the most common cause of hyperthyroidism in the pediatric population. Antithyroid medications used in children and adults include propylthiouracil (PTU) and methimazole (MMI).

Differentiated thyroid cancer in children: diagnosis and management.

Purpose Of Review: Differentiated thyroid cancer is the most common endocrine malignancy in children. In 2006, the American Thyroid Association Guidelines Taskforce released detailed management recommendations for differentiated thyroid cancer, which primarily addressed the approach for treating adult patients. Children with differentiated thyroid cancer present with more advanced disease and yet have a more favorable outcome than adults.

Thyroid cancer in children.

In 1996, the authors were asked to review the subject of thyroid cancer in children. Over the subsequent decade, much has been learned about the treatment and outcome of these uncommon tumors. We now recognize quantitative and perhaps qualitative differences in genetic mutations and growth factor expression patterns in childhood thyroid cancers compared with those of adults.

An optimal treatment for pediatric Graves' disease is radioiodine.

Context: Antithyroid medications, surgery, and radioactive iodine have been used for more than five decades for the treatment of hyperthyroidism due to Graves' disease in children, adolescents, and adults. Despite the widespread use of these different approaches, controversy still exists relative to the merits of each treatment, especially regarding the use of radioactive iodine.

Objective: The objective of the study was to address the risk and benefits of (131)I therapy, as compared with other treatment approaches.

The MACIS score predicts the clinical course of papillary thyroid carcinoma in children and adolescents.

MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores are employed to predict mortality for papillary thyroid carcinoma (PTC) in adults. However, this system has not been validated in children and adolescents. We hypothesized that MACIS scores would correlate with recurrent and persistent disease in children.

Treatment of recurrent papillary thyroid carcinoma in children and adolescents.

Mortality for children with papillary thyroid carcinoma (PTC) is low (< or = 10%), but recurrence is frequent (20%). In adults, recurrent PTC has a poor prognosis (50% remission) and a high mortality (16-63%). We hypothesized that treatment of recurrent PTC would be more effective in children than in adults.

Tumor size and extent of disease at diagnosis predict the response to initial therapy for papillary thyroid carcinoma in children and adolescents.

Treatment of papillary thyroid carcinoma (PTC) in children and adolescents is controversial. We previously showed that large tumor size, multifocal disease, and extensive disease at diagnosis predict recurrence. We examined 47 patients with PTC to determine whether these features predict response to treatment.

Differentiated thyroid carcinoma that express sodium-iodide symporter have a lower risk of recurrence for children and adolescents.

The sodium-iodide symporter (NIS) is expressed by papillary (PTC) and follicular (FTC) thyroid carcinoma, and is essential for iodine uptake. We hypothesized that PTC and FTC with detectable NIS immunostaining would be more amenable to radioactive iodine ((131)I) treatment and follow a more benevolent course. To test this, we determined NIS expression by immunohistochemistry in 23 PTC, 9 FTC, and 12 benign thyroid lesions from children and adolescents.

Intense expression of the b7-2 antigen presentation coactivator is an unfavorable prognostic indicator for differentiated thyroid carcinoma of children and adolescents.

Previous observations suggest that an immune response against thyroid carcinoma could be important for long-term survival. We recently found that infiltration of thyroid carcinoma by proliferating lymphocytes is associated with improved disease-free survival, but the factors that control lymphocytic infiltration and proliferation are largely unknown. We hypothesized that the antigen presentation coactivators (B7-1 and B7-2), which are important in other immune-mediated thyroid diseases, might be important in lymphocytic infiltration of thyroid carcinoma.