Bilateral follicular variant of papillary thyroid cancer with different RAS mutations detected with next-generation sequencing: Report of an unusual case and literature review

Multifocality in papillary thyroid carcinoma (PTC) is a common finding, but the clonal relationship between individual tumors remains uncertain. While multiple synchronous tumor foci of PTC may develop through permeation of intraglandular lymph vessels of a single malignant clone, they can also arise from independent progenitor clones sustained by different genetic events. We report the case of a 37-year-old man who underwent total thyroidectomy after fine-needle aspiration of two bilateral thyroid nodules that yielded cytological findings consistent with atypia of undetermined significance/follicular lesion of undetermined significance. By next-generation sequencing of a large panel of thyroid carcinoma related genes, we found that the larger tumor harbored a mutation of the NRAS gene, while the contralateral tumor harbored a different mutation in the HRAS gene. Final pathology of the surgical specimen showed two encapsulated follicular variant papillary thyroid carcinomas of 16 and 6 mm in the right and the left lobes, respectively. To the best of our knowledge, this is the fourth case of multifocal PTC showing different HRAS and NRAS mutations, and highlights that mutational heterogeneity is also present in non-BRAF, non-RET genes, supporting the hypothesis that independent progenitor clones may explain multifocality in papillary thyroid carcinoma.