{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:31:37Z","timestamp":1790796697519,"version":"4.1.0"},"reference-count":32,"publisher":"Scientific Scholar","content-domain":{"domain":["cytojournal.com"],"crossmark-restriction":true},"short-container-title":["Cytojournal"],"abstract":"\n Objective:<\/jats:title>\n Oncocytic thyroid follicular neoplasms (ONs), including oncocytic adenoma (OA) and oncocytic carcinoma (OC), are distinct follicular cell-derived tumors with unique molecular profiles. Oncocytic changes can also occur in other situations, such as papillary thyroid carcinoma (PTC) and thyroiditis. Due to overlapping cytological features, distinguishing benign from malignant ONs preoperatively remains challenging. This study examines cytological patterns and genetic alterations in ONs and aims to enhance diagnostic accuracy.<\/jats:p>\n <\/jats:sec>\n \n Material and Methods:<\/jats:title>\n We retrospectively analyzed ON and oncocytic PTC (OPTC) cases from January 2018 to March 2025 at Cooper University Hospital, identifying 119 surgical resections (55 malignant, 62 benign, and two oncocytic non-invasive follicular thyroid neoplasms with papillary-like nuclear features. Sixty-five cases had fine-needle aspiration biopsy results categorized using The Bethesda System for Reporting Thyroid Cytopathology. Molecular examinations were performed in Afirma, ThyroSeq, or ThyGeNEXT\/ThyraMIR. Statistical analyses included Wilcoxon Rank Sum tests, logistic regression, and Fisher\u2019s exact tests.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n No significant differences were observed between benign and malignant groups in terms of patient sex or tumor size; however, younger patient age was associated with malignant neoplasm within the cytology tested samples (\n P<\/jats:italic>\n = 0.0300). Molecular analysis showed that 3.6% (1\/28) of malignant cases were negative for tested alterations, while 33.3% (12\/36) of benign cases were negative (\n P<\/jats:italic>\n = 0.0035). Common mutations included eukaryotic translation initiation factor 1A X-linked (EIF1AX) (27.3%) in OCs and Harvey rat sarcoma viral oncogene homolog (HRAS) Q61R (41.2%) in OPTCs. In contrast, OA exhibited a higher frequency of chromosomal copy number alterations (33.3%) and variable other genetic changes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n ONs pose diagnostic challenges due to significant cytological and molecular overlap between benign and malignant cases. Current thyroid molecular testing reveals a broad range of genetic alterations in ONs but lack sufficient specificity to reliably distinguish benign from malignancy in most instances. In this study, genetic alterations were detected in 66.6% (24\/36) of OAs, and telomerase reverse transcriptase (TERT) mutations \u2013 typically associated with malignancy \u2013 were identified in two OAs. However, notably, certain mutations were exclusive to specific groups, such as B-Raf proto-oncogene, serine\/threonine kinase (BRAF), anaplastic lymphoma kinase\/echinoderm microtubule-associated protein-like 4 (ALK\/EML4), and paired box 8 \u2014 peroxisome proliferator activator receptor gamma (PAX8-PPARG) in OPTCs or EIF1AX in OCs. Importantly, only 3.6% (1\/28) of malignant OPTC\/ONs were tested negative on molecular analysis, suggesting that ONs with negative molecular test results are more likely to be benign than malignant.<\/jats:p>\n <\/jats:sec>","DOI":"10.25259\/cytojournal_84_2025","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:32:52Z","timestamp":1765006372000},"page":"100","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Various genetic alterations observed in both benign and malignant oncocytic (H\u00fcrthle cell) neoplasms of the thyroid"],"prefix":"10.25259","volume":"22","author":[{"given":"Chiara Jean","family":"Cocelli","sequence":"first","affiliation":[{"name":"Cooper Medical School of Rowan University, Camden, United States,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cooper University Hospital, Camden, United States,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyue","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cooper University Hospital, Camden, United States,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10894","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"10.25259\/Cytojournal_84_2025\/ref-1","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/S2213-8587(17)30325-X","article-title":"Follicular thyroid cancer and H\u00fcrthle cell carcinoma: Challenges in diagnosis, treatment, and clinical management","volume":"6","author":"Grani","year":"2018","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10.25259\/Cytojournal_84_2025\/ref-2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s12022-022-09707-3","article-title":"Overview of the 2022 WHO classification of thyroid 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