Improving Thyroid Cancer Detection in Needle Biopsies

Research aims at improving diagnostics and informing targeted therapies.

Although peak incidence of thyroid cancer occurs in patients aged 50 and older, about two percent of cases occur in patients under the age of 20. After a suspicious nodule is detected in the neck, patients typically undergo fine needle aspiration biopsy. Whereas many cancers have common cellular signposts identified via biopsy, for many thyroid nodules there are no reliable markers to distinguish invasive from benign neoplasms.

“This diagnostic challenge leads to indeterminate biopsies in up to 30 percent of cases,” said Vivian Weiss, M.D., assistant professor of pathology, microbiology and immunology at Vanderbilt University Medical Center. Weiss recently received grants from the V Foundation for Cancer Research and Children’s Cancer Research Fund to investigate pediatric thyroid cancer mutations with a focus on improving diagnostics and revealing pathways for targeted therapies.

“With an atypical biopsy result where we can’t tell if it is benign or malignant, the children go to surgery,” Weiss said. “They lose at least half their thyroid in order to get a diagnosis, which sometimes necessitates lifelong thyroid hormone replacement.”

For children with advanced or metastatic thyroid cancer, surgery and radioactive iodine (RAI) are the mainstays of treatment. RAI treatment can have long-term effects including dry mouth, infertility, and secondary cancers. Among her goals for the research, Weiss hopes that it will spur development of effective radiation-sparing drugs.

Pediatric Thyroid Cancer is Understudied

Removal of the thyroid and RAI are typically curative if the cancer is detected early. Five-year thyroid cancer survival rates are around 98 percent in the general population. Unfortunately, children are more likely than adults to have metastatic thyroid cancer at diagnosis. Add this to the high rate of inconclusive needle biopsies and thyroid excision, and the need for improved diagnostic tools and targeted treatment is clear.

“Pediatric thyroid cancer is not well-studied, despite it being one of the most common solid tumors in children and adolescents,” Weiss said. “The mutations seem to be somewhat different in children and adults. We have evidence that children’s tumors are driven more by gene fusions, while adult cancers are commonly BRAF-driven.”

Since the V Foundation for Cancer Research focuses on older children and the Children’s Cancer Research Fund focuses on children aged 10 and younger, Weiss’ work will help delineate thyroid cancer over a broad age range within pediatrics. “Thyroid cancer is probably different in younger and older children,” Weiss said. “For instance, hormones such as estrogens may not drive thyroid cancer growth in a five- or six-year-old, whereas they might drive it in a 16-year-old or an 18-year-old.”

“Pediatric thyroid cancer is not well-studied, despite it being one of the most common solid tumors in children and adolescents. We need to study the molecular drivers to improve diagnosis and management.”

Improving the Genetic Knowledge Base

The knowledge base on thyroid cancer is partially limited by the fact that some widely used “thyroid cancer” cell lines are redundant, and a few are misidentified and derived from other cancers, muddying understanding of the illness. To work around this flaw, Weiss will use tissue samples collected prospectively for a pediatric thyroid cancer bio-bank to develop her own cell cultures. In addition, she will use 3D organoids, both in vitro and implanted into in animal models, to investigate tumor growth and novel drug treatment.

Weiss hopes genetic sequencing will also reveal diagnostic mutations. This could yield not only improved methods of cancer detection in needle biopsy-derived samples, but new, targeted treatment pathways.

For a child with a suspicious neck nodule, Weiss’s research could mean the difference between a simple needle biopsy and an unnecessary surgery, followed by lifelong hormone replacement therapy. “Through a better understanding of the genetic landscape, we want to improve how we diagnose and treat children with thyroid cancer while sparing those without cancer from unnecessary treatment,” Weiss said.