Thyroid carcinomas (TC) are rare in the pediatric population; however, they constitute the most common endocrine malignancy. Despite some similarities with adult carcinomas, they have distinct clinical behavior and responses to therapy due to their unique pathology and molecular characteristics. The age cut-off used for defining the pediatric age group has been variable across different studies, and the universally accepted recommendations influence accurate interpretation of the available data. Moreover, factors such as radiation exposure and germline mutations have greater impact in children than in adults. Papillary TC is the most common and the most evaluated pediatric TC. Others, including follicular, poorly differentiated and medullary carcinomas, are rarer and have limited available literature. Most studies are from the West. Asian studies are primarily from Japan, with few from China, India, Saudi Arabia and Republic of Korea. This review provides a comprehensive account of the well-established and novel biomarkers in the field, including point mutations, fusions, miRNA, and thyroid differentiation genes. Familial and syndromic associations are also discussed. Current management guidelines for pediatric patients are largely derived from those for adults. An awareness of the molecular landscape is essential to acknowledge the uniqueness of these tumors and establish specific diagnostic and therapeutic guidelines.

Aims: The 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends subclassification of atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) into six subcategories. The present study evaluates the risk of malignancy (ROM) and risk of neoplasm (RON) among these. Methods: All thyroid aspirates reported as AUS/FLUS over a 4.5-year period, with available histology, were reviewed and subclassified as per TBSRTC. ROM and RON were calculated and compared. Results: Of 2554 thyroid aspirates, 281 (11.0%) were AUS/FLUS. Eighty-one with available histology were evaluated. ROM was 51.8%. Cytologic and architectural atypia (AUS-C&A) was the most prevalent (62.9%), followed by Hürthle cell type (19.6%), AUS-A (11.1%), AUS-not otherwise specified (NOS) (7.4%), cytologic atypia (AUS-C) (4.9%) and atypical lymphoid cells (1.2%). Papillary thyroid carcinoma (PTC) and adenomatous goitre (AG) were the most common histological diagnoses (27% each). On histology, AUS-C had 2/4 PTC and 2/4 AG on histology. AUS-A had 4/9 follicular neoplasm (FN) and 2/9 non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) while AUS C&A had 18/51 PTC, 13/51 AG, 11/51 NIFTP and 5/51 FN. ROM and RON were similar across subcategories, ROM was the highest for AUS-C&A (58.8%), AUS-C (50%) and AUS-NOS (50%). NIFTP reclassification as non-malignant reduced ROM to 35.8% (absolute reduction of 16% and a relative decrease of 31%) with the greatest relative decrease seen in AUS-A (50%), followed by AUS-C&A (37%), and none in others. Conclusions: AUS/FLUS subcategorisation helped to indicate risk for the more likely neoplasm, whether PTC or FN. ROM was the highest for cases with cytological atypia but did not differ significantly across different subcategories. NIFTP changed the ROM of AUS-A and AUS-C&A, since both NIFTP and FN have microfollicles.