Pediatric Thyroid Nodules: Malignancy Linked to Radiation Exposure

Crop of child lying on bed, during ultrasound of thyroid. Little girl, wearing in dress, courteously follows instructions of female doctor with ultrasound probe in hand and scanning her neck.
Researchers evaluated the utility of ultrasound characteristics for refining malignancy risk to inform the management of cytologically indeterminate pediatric thyroid nodules.

Malignancy among pediatric thyroid nodules with indeterminate cytology was found to be associated with increased thyroid radiation exposure and not with sonographic features, according to results of a retrospective cohort study published in the European Journal of Endocrinology.

Medical records of pediatric patients (n=395) who underwent ultrasound-guided fine-needle aspiration (FNA) at Brigham and Women’s Hospital and Boston Children’s Hospital between 2004 and 2019 were retrospectively reviewed. Nodules with indeterminate cytologic findings were assessed for malignancy.

Of 499 thyroid nodules, 17.8% were cytologically indeterminate. The 87 indeterminate nodules were found among 76 patients with a median age of 15.8 (range, 8.3-18.9) years at FNA, and 74% of these patients were girls or women. A history of thyroid irradiation was reported by 8 patients, 4 patients had phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome, and 1 patient had both radiation exposure and a genetic predisposition.

Cytology determined 64% of these nodules had a rating of Bethesda III, 12% had Bethesda IV, and 22% had Bethesda V. The final diagnoses were malignant (53%) and benign (47%) nodules. Malignancy increased with Bethesda grading from 41% among Bethesda III to 75% for Bethesda IV to 79% for Bethesda V.

Among the malignant nodules, 76% were papillary carcinoma and 24% were follicular carcinoma. Among the papillary carcinomas, 16 were classical, 12 were follicular, 4 were diffuse sclerosing, and 3 were solid variants.

Indeterminant cytologic findings were more likely among nodules with irregular or poorly defined margins (P <.001) or with calcifications (P =.002), in solitary nodules (P =.004), and among patients with high thyroid radiation exposure (P =.006) or abnormal lymph nodes (P =.06). Nodules with a grading of Bethesda V were more likely among nodules that were solid (P =.001) and in those with irregular or poorly defined margins (P =.03).

Among patients with Bethesda III nodules, no significant differences in demographic or sonographic features were observed between the benign and indeterminate cohorts (all P >.05).

This study may not be generalizable because these data were collected from a tertiary referral center and may be skewed toward a more high-risk patient population.

These data indicate that sonographic features have a limited role in determining malignancy among thyroid nodules with undetermined cytology. Increased thyroid radiation risk is associated with malignant nodules.


Richman DM, Cherella CE, Smith JR, et al. Clinical utility of sonographic features in indeterminate pediatric thyroid nodules. Eur J Endocrinol. 2021;184(5):657-665. doi:10.1530/EJE-20-1480