Papillary Thyroid Carcinoma With 5 Unique Point Mutations and Typical Behavior

The frequency and impact of multiple driver mutations have not been extensively explored in papillary thyroid carcinoma (PTC), in which driver mutations are most commonly solitary. We present a case of a 62-year-old female who was found to have a 2.6-cm classical, nonaggressive-appearing PTC. A next-generation sequencing panel assessed the tumor for mutations. Five unique single nucleotide sequence variants, none of which was seen in The Cancer Genome Atlas study on PTC, were found: <i>BRAF D594N, NRAS Q61H, PIK3CA G1007R, PTEN R335*</i>, and <i>PTEN Y225*</i>. We believe that 5 pathogenic variants are the highest reported number for a primary PTC resection specimen to date. The observed typical PTC behavior may be due to a weaker strength of the individual pathogenic variants to drive oncogenic processes. In this case, the high number of genetic alterations did not translate into aggressive histopathology or clinical course.