The Complex Cyto-Molecular Landscape of Thyroid Nodules in Pediatrics

Abstract

Thyroid fine-needle aspiration (FNA) is a commonly used diagnostic cytological procedure in pediatric patients for the evaluation of thyroid nodules, triaging them for the detection of thyroid cancer. In recent years, greater attention has been paid to thyroid FNA in this setting, including the use of updated ultrasound score algorithms to improve accuracy and yield, especially considering the theoretically higher risk of malignancy of these lesions compared with the adult population, as well as to minimize patient discomfort. Moreover, molecular genetic testing for thyroid disease is an expanding field of research that could aid in distinguishing benign from cancerous nodules and assist in determining their clinical management. Finally, artificial intelligence tools can help in this task by performing a comprehensive analysis of all the obtained data. These advancements have led to greater reliance on FNA as a first-line diagnostic tool for pediatric thyroid disease. This review article provides an overview of these recent developments and their impact on the diagnosis and management of thyroid nodules in children.

Keywords: fine-needle aspiration; molecular pathology; pediatrics; thyroid nodule; ultrasound.

Figure 1

Example of US, cytological and molecular assessment of a thyroid nodule in a 17-year-old female patient with multinodular goiter without clinical risk factors. (A) Nodular thyroid lesion of the right lobe, 17 mm in diameter (red line), isoechoic, with a mixed composition and smooth margins, no microcalcifications, deserving FNA according to ATA guidelines (≥1 cm partly solid nodule), but not deserving it according to ACR TI-RADS (class 2) (B) FNA shows a blood-rich background with fluid colloid, rare foamy histiocytes and numerous groups of thyroid cells mainly arranged in sheets and microfollicular structures, sometimes with oxyphilic appearance (class IV sec. TBSRTC, Papanicolau stained smear, ×40). (C) Molecular test (real time PCR) was performed, since the indeterminate cytology, starting from the needle wash, revealing the NRAS p.Q61X mutation (blue line mutated allele, green line wild type allele), a low-risk mutation group, which confirms the clonality of the lesion and its likely low biological aggressiveness. (D,E) Accordingly, a hemi-thyroidectomy was performed, revealing a partly cystic nodule composed of oncocytic thyrocytes, with pushing borders and a thin fibrotic capsule without invasion or lymphovascular infiltration, leading to the final histological diagnosis of NRAS-mutant oncocytic follicular adenoma (H & E, 10× and 40×).

Figure 2

Putative future combined approach for correct identification of malignant thyroid nodules.