Background: Aberrations involving the ROS1 gene have not been reported in thyroid cancer. Here, a case of ROS1-associated thyroid cancer with unique and aggressive characteristics is presented.
Patient findings: A 24-year-old athlete presented with a 3.5 cm left paramedian upper neck mass. Open biopsy demonstrated a papillary thyroid carcinoma arising in the pyramidal lobe. Additional imaging revealed involvement of her cricothyroid membrane, thyroid laryngeal cartilage, and left vocal cord. Complete en bloc surgical resection of the thyroid with cricothyroid membrane and endolarynx was performed with negative surgical margins. Microscopically, the tumor was largely solid with microfollicular architecture with focal cytoplasmic clearing and nodular invasion with rare true papillae, extending posteriorly through the cricothyroid membrane into the deep soft tissue of the left anterior vocal cord (pT4a). Metastases were present in 5/11 lateral neck and pretracheal lymph nodes with a size up to 0.4 cm (pN1b) with perinodal lymphatic involvement. She was staged according to her age (<45 years) as stage I. The solid-variant histology and locally aggressive behavior triggered oncologic genotyping, which was performed using massive parallel sequencing and anchored multiplexed next-generation sequencing for gene fusion detection on formalin-fixed paraffin embedded tissue. Targeted genotyping did not reveal a panel-specific point mutation. However, gene fusion assessment demonstrated a gene fusion involving ROS1. Mapping of the fusion and sequence analysis identified CCDC30 as the ROS1 fusion partner. Sequence-based prediction of the fusion product revealed the coiled-coil domain 30 (CCDC30) gene fused to the N-terminal ROS1 kinase domain, with CCDC30 as the postulated driver of ROS1-kinase constitutive activation. ROS1 rearrangement was confirmed using fluorescent in situ hybridization as an orthogonal method. A review of all currently reported ROS1 fusions in >7000 samples (The Cancer Genome Atlas) showed no prior report of ROS1-CCDC30, ROS1 fusions, or presence of ROS1 aberrations in thyroid cancer.
Summary: Herein, the first case of a ROS1 rearrangement in a papillary thyroid carcinoma with a locally aggressive presentation is reported.
Conclusion: A review of additional patients with solid-variant papillary thyroid carcinoma and similar clinical characteristics with undetermined tumor genetics is needed, especially in light of the availability of ROS1-targeted therapeutics.