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Genomic profile of columnar cell variant of papillary thyroid carcinoma
Author(s) -
Janovitz Tyler,
Williamson Drew F K,
Wong Kristine S,
Dong Fei,
Barletta Justine A
Publication year - 2021
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.14374
Subject(s) - cdkn2a , thyroid carcinoma , v600e , cancer research , biology , carcinoma , pathology , chromosome , comparative genomic hybridization , thyroid , mutation , copy number variation , kras , medicine , cancer , gene , genetics , genome
Background 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 next‐generation 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.