Papillary Thyroid Carcinoma with High-Grade Features Versus Poorly Differentiated Thyroid Carcinoma: An Analysis of
Kristine S Wong1, Fei Dong1, Milhan Telatar2
1Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Abstract:
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 World Health Organization (WHO) definition of PDTC based on maintained nuclear features of PTC. 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 as per the WHO criteria) were identified. Clinicopathologic characteristics, follow-up data, and targeted next-generation sequencing results were compared between groups. 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 was worse for patients with PTC HGF compared with 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 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. 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 a distinct group from PDTC.
