Pediatric Thyroid Nodules: Malignancy Linked to Radiation Exposure

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

The 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 undetermined cytologic findings were assessed for malignancy.

Of the 499 thyroid nodules, 17.8% were cytologically indeterminate. The 87 indeterminate nodules were found in 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 in 8 patients, 4 patients had phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome, and 1 patient had both radiation exposure and a genetic predisposition.

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

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

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

In patients with Bethesda III nodules, no significant differences in demographic or ultrasound characteristics were observed between the benign and indeterminate cohorts (all P > 0.05).

This study may not be generalizable because this data was collected at a tertiary referral center and may be skewed toward a more at-risk patient population.

These data indicate that ultrasound features play a limited role in determining malignancy in thyroid nodules of undetermined cytology. An increased risk of thyroid radiation is associated with malignant nodules.


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

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