Kristine S Wong1, Fei Dong1, Milhan Telatar2, Jochen H Lorch3, Erik K Alexander4, Ellen Marqusee4, Nancy L Cho4, Matthew A Nehs5, Gerard M Doherty5, Michelle Afkhami2, Justine A Barletta1. 1. Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA. 2. Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, California, USA. 3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. 4. Division of Endocrinology, Harvard Medical School, Boston, Massachusetts, USA. 5. Department of Surgery; Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
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 World Health Organization (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 as per the 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 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 BRAFV600E 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 a distinct group from PDTC.
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 World Health Organization (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 as per the 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 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 BRAFV600E 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 a distinct group from PDTC.
Authors: Zubair W Baloch; Sylvia L Asa; Justine A Barletta; Ronald A Ghossein; C Christofer Juhlin; Chan Kwon Jung; Virginia A LiVolsi; Mauro G Papotti; Manuel Sobrinho-Simões; Giovanni Tallini; Ozgur Mete Journal: Endocr Pathol Date: 2022-03-14 Impact factor: 3.943
Authors: Bin Xu; Julia David; Snjezana Dogan; Iñigo Landa; Nora Katabi; Maelle Saliba; Anjanie Khimraj; Eric J Sherman; Robert Michael Tuttle; Giovanni Tallini; Ian Ganly; James A Fagin; Ronald A Ghossein Journal: Histopathology Date: 2021-10-07 Impact factor: 7.778