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

Wong, Kristine; Dong, Fei; Telatar, Milhan; Lorch, Jochen H.; Alexander, Erik K.; Marqusee, Ellen; Cho, Nancy L.; Nehs, Matthew A.; Doherty, Gerard M.; Afkhami, Michelle; Barletta, Justine A.

doi:10.1089/thy.2020.0668

Cited by 59 publications

(46 citation statements)

References 27 publications

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“…Based on a mitotic count of five or more per 10 HPF and/or tumour necrosis, six (75%) tumours met criteria for PTC with high-grade features. 18 Most CCV in our study pursued an aggressive clinical course. At last follow-up, five (56%) patients had died of disease and two (22%) had persistent or recurrent disease (median follow-up time of 18 months; range = 7-55 months); only two patients had no evidence of recurrent or residual disease at last follow-up (follow-up for these two patients was 35 and 47 months).…”

Section: Resultsmentioning

confidence: 95%

Genomic profile of columnar cell variant of papillary thyroid carcinoma

et al. 2021

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Genomic profile of columnar cell variant of papillary thyroid carcinomaBackground and aims: Columnar cell variant (CCV) is a rare papillary thyroid carcinoma subtype. The majority of CCV occur in older patients and are large, invasive tumours that pursue an aggressive clinical course. Rare well-circumscribed CCV occur in younger female patients and are comparatively indolent. Methods and results: We retrospectively identified CCV with material available to perform targeted nextgeneration sequencing and correlated molecular results with clinicopathological features and outcome. Our cohort was comprised of nine CCV. Nearly all were aggressive tumours; however, one was predominantly well-circumscribed and arose in a thyroglossal duct cyst of a 26-year-old woman who had no evidence of disease at last follow-up. Seven (78%) cases demonstrated activating oncogenic driver alterations in BRAF, including BRAF V600E, an activating N486_P490del deletion, and BRAF-AGK fusions. Activating RAS mutations were seen in two (22%) cases. Additionally, three (33%) cases had TERT promoter mutations, four (44%) had loss of the tumour suppressor CDKN2A and one (11%) case had a loss of function TP53 mutation. Most cases (89%) also demonstrated copy number alterations, including recurrent gain of chromosome 1q (five cases) and losses of chromosome 9p (three cases) and 22q (four cases). The one case without secondary pathogenic mutations or copy number alterations was the tumour in the 26-year-old woman. Conclusions: We found that CCV is primarily a BRAF-driven tumour, with most also harbouring secondary oncogenic mutations and multiple chromosomal gains and losses. Moreover, our findings suggest that molecular analysis could potentially be used to help risk stratify CCV.

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Section: Resultsmentioning

confidence: 95%

Genomic profile of columnar cell variant of papillary thyroid carcinoma

et al. 2021

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“…For further analysis, we compared the genetic profiles of frequently altered driver mutations, TERT promotor mutations, and other related mutations in aggressive variants of PTC with those of PTC from The Cancer Genome Atlas (TCGA) data, as well as those of poor differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) from Memorial Sloan Kettering Cancer Center (MSKCC) data analyzed by the MSK-IMPACT panel [ 8 , 18 ]. In addition, we compared the genetic profiles to 526 advanced PTC patients from four recent studies [ 17 , 19 , 20 , 21 ]. Genes encoding three functional groups including HMTs, SWI/SNF chromatin remodeling complex, and the PI3K/AKT/mTOR pathway were evaluated between different types of thyroid cancers [ 8 , 20 ].…”

Section: Methodsmentioning

confidence: 99%

“… Comparison of BRAF, RAS, TERT promoter, and TP53 mutations: ( A ) papillary thyroid carcinoma (PTC) from The Cancer Genome Atlas (TCGA); ( B ) aggressive variants of PTC in current study; ( C ) poorly differentiated carcinoma (PDTC) and ( D ) anaplastic thyroid carcinoma (ATC) from the Memorial Sloan Kettering Cancer Center (MSKCC) group; ( E ) advanced PTCs from other studies [ 17 , 19 , 20 , 21 ]. …”

Section: Figurementioning

confidence: 99%

Genetic Profiles of Aggressive Variants of Papillary Thyroid Carcinomas

Jin

Song

Ahn

et al. 2021

Cancers

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Aggressive variants of papillary thyroid carcinoma (PTC) have been described with increasing frequency and are associated with unfavorable clinical outcomes. However, limited data exist on the comprehensive genetic profile of these variants. We performed targeted next-generation sequencing in 36 patients with aggressive variants of PTC and compared it to PTC from The Cancer Genome Atlas (TCGA) project and poorly differentiated thyroid cancers (PDTCs)/anaplastic thyroid cancers (ATCs) from the Memorial Sloan Kettering Cancer Center (MSKCC). BRAF mutation was the most prevalent (89%) in aggressive variants of PTC compared to that in other thyroid cancers. RAS mutation was identified in one patient (3%), which was less frequent than in others. TERT promoter mutation (17%) ranged between that of PTCs (9%) and PDTCs (40%). Tumor suppressor genes, ZFHX3, TP53, and CHEK2, were mutated in 14%, 3%, and 6% of aggressive variants of PTC, respectively. The mutation rate of TP53 (3%) was significantly higher than that of PTCs (0.7%) and lower than that of ATCs (73%). Mutations in three functional groups, histone methyl transferases, SWI/SNF chromatin remodeling complex, and the PI3K/AKT/mTOR pathway, were present in 11%, 14%, and 11% of samples, respectively. In conclusion, aggressive variants of PTC had higher BRAF and lower NRAS mutation prevalence than other thyroid cancers. The prevalence of mutations in the TERT promoter, TP53, and genes encoding three functional groups ranged between that of PTCs and PDTCs/ATCs.

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“…For further analysis, we compared the genetic profiles of frequently altered driver mutations, TERT promotor mutations, and other related mutations in aggressive variants of PTC with those of PTC from The Cancer Genome Atlas (TCGA) data, as well as those of poor differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) from Memorial Sloan Kettering Cancer Center (MSKCC) data analyzed by the MSK-IMPACT panel [8,18]. In addition, we compared the genetic profiles to 526 advanced PTC patients from four recent studies [17,[19][20][21]. Genes encoding three functional groups including HMTs, SWI/SNF chromatin remodeling complex, and the PI3K/AKT/mTOR pathway were evaluated between different types of thyroid cancers [8,20].…”

Section: Analysis Processmentioning

confidence: 99%