Janovitz Tyler, Williamson Drew F K, Wong Kristine S, Dong Fei, Barletta Justine A
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Histopathology. 2021 Oct;79(4):491-498. doi: 10.1111/his.14374. Epub 2021 Jun 15.
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.
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.
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.
柱状细胞变体（CCV）是一种罕见的甲状腺乳头状癌亚型。大多数CCV发生于老年患者，肿瘤体积大且具有侵袭性，临床病程呈侵袭性。罕见的边界清晰的CCV发生于年轻女性患者，病情相对惰性。
我们回顾性鉴定了可用于进行靶向二代测序的CCV样本，并将分子结果与临床病理特征及预后相关联。我们的队列包括9例CCV。几乎所有肿瘤都具有侵袭性；然而，有1例主要边界清晰，发生于一名26岁女性的甲状舌管囊肿中，最后一次随访时无疾病证据。7例（78%）病例显示BRAF基因存在激活的致癌驱动改变，包括BRAF V600E、激活的N486_P490del缺失以及BRAF-AGK融合。2例（22%）病例存在激活的RAS突变。此外，3例（33%）病例有TERT启动子突变，4例（44%）存在肿瘤抑制基因CDKN2A缺失，1例（11%）病例存在功能缺失的TP53突变。大多数病例（89%）还显示出拷贝数改变，包括1号染色体q臂的反复增益（5例）以及9号染色体p臂（3例）和22号染色体q臂（4例）的缺失。没有继发致病突变或拷贝数改变的1例是那名26岁女性的肿瘤。
我们发现CCV主要是一种由BRAF驱动的肿瘤，大多数还伴有继发致癌突变以及多条染色体的增减。此外，我们的研究结果表明分子分析可能有助于对CCV进行风险分层。
