Impact of molecular testing on detecting mimics of oncocytic neoplasms in thyroid fine‐needle aspirates diagnosed as follicular neoplasm of Hürthle cell (oncocytic) type. Issue 10 (26th April 2021)

• Record Type: Journal Article
• Authors: Landau, Michael S.; Nikiforov, Yuri E.; Ohori, N. Paul; Chiosea, Simion I.
• Is Part Of: Cancer cytopathology. Volume 129:Issue 10(2021)
• Page Start: 788
• Page End: 797
• Publication Date: 2021-04-26
• Subjects: autonomously functioning thyroid nodule -- biopsy -- DNA copy‐number alterations -- EZH1 -- fine‐needle aspiration -- follicular adenoma thyroid cancer -- follicular oncocytic -- papillary -- PAX8‐GLIS3 -- RAS -- THSR -- thyroid neoplasms; Cancer -- Cytopathology -- Periodicals; Pathology, Cellular -- Periodicals; Cytology -- Technique -- Periodicals; 611.01815
• DOI: 10.1002/cncy.22439
• Languages: English
• ISSNs: 1934-662X

Abstract

Abstract : Background: Some thyroid nodules cytologically presenting as follicular neoplasm, Hürthle cell (Oncocytic) type (FNHCT), are not oncocytic tumors and represent autonomously functioning thyroid nodules (AFTNs) with TSHR, GNAS, and EZH1 mutations or oncocytic metaplasia. A to be defined subset of FNHCT harbors genome haploidisation‐type DNA copy number alterations (GH‐CNA). Molecular profiling of FNHCT may distinguish oncocytic neoplasms from its mimics. Methods: Consecutive fine‐needle aspirates of 180 thyroid nodules over 37 months diagnosed as FNHCT and tested by ThyroSeq v3 were identified. Histologic follow‐up was available for 79 of 180 nodules (44%). Results: No molecular alterations were found in 76 of 180 nodules (42%), of which 15 were resected (oncocytic metaplasia, n = 7; follicular oncocytic adenoma, n = 8). Of nodules followed without surgery, 17 of 101 (17%) showed TSHR, EZH1, and GNAS mutations of AFTNs. Papillary thyroid carcinoma was identified by BRAF V600E (n = 2) and hyalinizing trabecular adenoma by PAX8‐GLIS3 (n = 1). GH‐CNA alone was detected in 42 of 180 FNHCT nodules (23%), of which 29 were resected and histologically diagnosed as follicular oncocytic neoplasms. All remaining resected nodules were histologically proven oncocytic neoplasms: 1) RAS ‐like alterations without GH‐CNA (n = 25) and 2) TERT and/or TP53 mutations co‐occurring with GH‐CNA (n = 6), including anaplastic thyroid carcinoma arising from follicular oncocytic carcinoma with TP53, TERT mutations with GH‐CNA (n = 2). Conclusions: A proportion of FNHCT nodules are AFTNs and oncocytic metaplasias, which can be suspected based on characteristic mutations or lack of alterations on molecular testing. Among resected FNHCTs, GH‐CNAs characterize approximately half of histologically confirmed follicular oncocytic neoplasms. Abstract : Thyroid nodules with cytologic diagnosis of follicular neoplasm, Hürthle cell (oncocytic) type (FNHCT) include cases of oncocytic metaplasia, autonomously functioning thyroid nodules (with TSHR, EZH1, or GNAS mutations), conventional papillary thyroid carcinoma (with BRAF V600E mutation), and hyalinizing trabecular adenoma (with PAX8‐GLIS3 fusion). Among resected FNHCT thyroid nodules, genome haploidisation‐type DNA copy‐number alterations identify approximately half of histologically confirmed follicular oncocytic neoplasms, including follicular oncocytic adenomas and excluding oncocytic metaplasia.