Clinicopathological and genetic characteristics of diffuse sclerosing papillary thyroid carcinoma

Diffuse sclerosing papillary thyroid carcinoma (DS-PTC) is a rare subtype of PTC with distinct clinical, histological and molecular characteristics compared to classic PTC. Due to its rarity, studies have been limited. In this study we performed comprehensive genotype-phenotype correlation on 48 resected DS-PTC. We found gene rearrangements involving RET, NTRK3, NTRK1, ALK or BRAF were present in 75% of cases, and BRAFV600E mutations were found in the remaining 25%. All paediatric cases were gene-rearranged tumours (p= 0.04). Histologically, gene-rearranged tumours were characterised by RAS-like nuclei (p= 0.001), diffuse psammoma bodies (p= 0.019), follicular predominant architecture (p=0.031), lymphovascular invasion (p=0.012), and nodal disease at the time of diagnosis (p=0.008). Gene-rearranged tumours were not associated with worse disease recurrence or survival. Features associated with poor outcome included de-differentiation (p <0.0001), macroscopic extrathyroidal extension (p <0.001), metastasis at initial presentation (p=0.003), and Stage 2 disease (p=0.004). In conclusion, DS-PTC has unique clinicopathological characteristics and is enriched for common gene rearrangements. This may have therapeutic implications when radioactive iodine resistance or de-differentiation develops during the clinical course of the disease.