Papillary Thyroid Carcinoma with High-Grade Features Versus Poorly Differentiated Thyroid Carcinoma: An Analysis of Clinicopathologic and Molecular Features and Outcome.

BACKGROUND Similar to poorly differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma with high-grade features (PTC HGF) demonstrates increased mitotic activity and/or necrosis; however, PTC HGF is excluded from the WHO definition of PDTC based on maintained nuclear features of PTC. METHODS Consecutive tumors that met criteria for PTC HGF, defined as tumors with maintained nuclear features of PTC and mitoses numbering 5 or more per 10 contiguous high power fields and/or tumor necrosis, and PDTC (defined per WHO criteria) were identified. Clinicopathologic characteristics, follow-up data, and targeted next generation sequencing results were compared between groups. RESULTS There were 15 PTC HGF and 47 PDTC. PTC HGF was associated with a higher rate of pT4 disease (53% vs. 13%, p=0.0027) and lymph node metastases (73% vs. 38%, p=0.049). The disease-specific survival (DSS) was worse for patients with PTC HGF compared to those with PDTC using Kaplan-Meier estimation (p=<0.001) and was worse in subgroup analysis evaluating patients with widely invasive PDTC (i.e. those with a similar rate of pT4 disease) and PTC HGF (p=0.040). PTC HGF had a higher BRAF V600E mutation rate (42% vs. 3%; p=0.003), a trend toward more gene fusions (25% vs. 3%; p=0.052), and a higher rate of relative gain of 1q (67% vs. 15%; p=0.002) than PDTC. CONCLUSIONS Our results demonstrate that PTC HGF are important to recognize based on their aggressive behavior. The molecular differences between PTC HGF and PDTC suggest that PTC HGF should be considered as a distinct group from PDTC.