Two recent studies have demonstrated the benefits of molecular testing in pediatric cases of thyroid lesions.

Pediatric thyroid lesions tend to be cancerous more often than those found in adults, but detecting thyroid nodules, found in 1–2% of children, can be difficult. Even with the aid of cytologic evaluation, 10–40% of pediatric thyroid lesion (TL) diagnoses are inconclusive.

Many times children with these undetermined diagnoses are treated with hemithyroidectomy, and, if cancer is found, completion thyroidectomy. Having multiple surgeries increases both the cost and risk of complications as a result of treatment.

Researchers tested 27 thyroid carcinomas from patients aged 10 to 19 years for alterations common in adult TL, including BRAF V600E mutation, RET fusions, and TERT promoter mutations.1 They searched for additional targets in mutation-negative cases by using a next-generation sequencing (NGS) mutation panel. Results showed 12 classic papillary thyroid carcinomas, 13 follicular variant PTCs, one medullary thyroid carcinoma, and one follicular carcinoma, with 14 showing lymph node involvement, and 13 showing lymphovascular invasion. Ten cases showed the BRAF V600E mutation, and six showed RET fusions. The team concluded that molecular abnormalities are common in pediatric TLs, ultimately showing a need for increased molecular testing in these cases.

“Thyroid nodules are often diagnosed in children; however, our understanding of the underlying genetic alterations of pediatric thyroid lesions and how they compare to those seen in adults, is limited,” says Dolores López-Terrada, MD, PhD, director of the molecular oncology laboratory at Texas Children’s Cancer Center. “The study specifically demonstrates the utility of molecular testing of fine needle aspiration biopsies, and how this information may improve clinical management and avoid surgical procedures in cases showing atypia of uncertain significance.”

She continues, “Characterization of the genetic defects underlying thyroid lesions diagnosed in children might also be prognostically relevant, such as in tumors seen in adults carrying specific mutations associated with higher recurrence rates, and even be indicated for the selection of targeted therapies in some patients.”

Another recent study sought to determine whether a 60-gene DNA/RNA NGS assay could identify more genetic markers, such as gene fusions in sporadic pediatric differentiated thyroid carcinomas, than standard testing alone.2

The study showed that the ThyroSeq v2 NGS assay from CBLPath, Rye Brook, NY, increased the identification rate of molecular alterations by 27%, compared to standard testing. This testing could be highly beneficial for efficiency in pediatric TL cases.

Jennifer Picarsic, MD, Children’s Hospital of Pittsburgh of UPMC.

Jennifer Picarsic, MD, Children’s Hospital of Pittsburgh of UPMC.

“Children identified with thyroid lumps are typically biopsied with a fine needle,” says study author Jennifer Picarsic, MD, pediatric pathologist at the Children’s Hospital of Pittsburgh of UPMC. “In most cases, the cells viewed under the microscope are benign or malignant. However, in cases where the result is indeterminate or inconclusive, the patient may need a repeat biopsy or have the lump surgically removed in the operating room. If the lump is cancerous, then the child has to go back to the operating room to remove the other thyroid lobe.”

An additional upfront test like the ThyroSeq panel can benefit certain pediatric patients. “Children with indeterminate nodules may benefit from having a more personalized treatment plan and prevent additional procedures,” Picarsic says. “Our findings support the use of broader genetic testing in pediatric thyroid nodule evaluation, which may aid future management recommendations and better insight into the natural history and basic biology of sporadic pediatric thyroid cancer.”

Thyroid cancer in children is generally rare, Picarsic says, but pediatric patients diagnosed with thyroid lumps and nodules may face a greater risk of malignancy, as compared to adults. “Pediatric thyroid cancer was once thought to have lower rates of molecular alterations as compared to adult thyroid cancer,” she says. “However, this may not be entirely accurate. We investigated pediatric thyroid cancers using a new NGS test called ThyroSeq that looks at a larger number of cancer-associated mutations. We found previously unrecognized genetic changes in a small cohort of pediatric thyroid cancer patients.”


  1. Ballester LY, Sarabia SF, Sayeed H, et al. Integrating molecular testing in the diagnosis and management of children with thyroid lesions. Pediatr Dev Pathol. 2016;19(2):94–100; doi: 10.2350/15-05-1638-OA.1.
  1. Picarsic JL, Buryk MA, Ozolek J, et al. Molecular characterization of sporadic pediatric thyroid carcinoma with the DNA/RNA ThyroSeq v2 next-generation sequencing assay. Pediatr Dev Pathol. 2016;19(2):115–122; doi: 10.2350/15-07-1667-OA.1.