{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:46:30Z","timestamp":1791521190816,"version":"4.3.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2025,10]]},"abstract":"\n Background:<\/jats:title>\n \n Mutations in the promoter region of\n TERT<\/jats:italic>\n (\n TERTp<\/jats:italic>\n ) in thyroid nodules with indeterminate cytology are quoted to confer a high (\u223c80\u201395%) probability for thyroid carcinoma when detected on genomic classifier (GC) ThyroSeq.\n TERTp<\/jats:italic>\n mutations may also occur in benign and low-risk thyroid neoplasms, and the risk of malignancy (ROM) in nodules harboring\n TERTp<\/jats:italic>\n mutations without\n \n BRAF\n V600E<\/jats:sup>\n <\/jats:italic>\n is unknown. We analyzed the ROM and the surgical diagnosis in a retrospective cohort of thyroid nodules with\n TERTp<\/jats:italic>\n treated at two academic medical centers.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n From 2323 patients with ThyroSeq GC performed on preoperative fine needle aspiration samples, 52 cases (2.3%) were identified harboring\n TERTp<\/jats:italic>\n mutations without coexisting\n \n BRAF\n V600E<\/jats:sup>\n <\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The surgical diagnosis was obtained from resection (\n n<\/jats:italic>\n = 51) or biopsy (\n n<\/jats:italic>\n = 1, anaplastic thyroid carcinoma). The ROM was 65%. The reviewed diagnoses were benign\/low-risk neoplasms in 18 (35%), carcinoma-American Thyroid Association (ATA) low\/intermediate-risk in 14 (27%), and carcinoma-ATA high-risk in 20 (38.5%). All 18 benign or low-risk neoplasms had their tumor capsule submitted entirely, and 78% underwent total thyroidectomy. The molecular alterations were substratified into four groups:\n TERTp<\/jats:italic>\n alone (\n n<\/jats:italic>\n = 21, 40%),\n TERTp<\/jats:italic>\n +\n RAS<\/jats:italic>\n (\n n<\/jats:italic>\n = 18, 35%),\n TERTp<\/jats:italic>\n + other non-\n RAS<\/jats:italic>\n mutation (\n n<\/jats:italic>\n = 8, 15%), and\n TERTp<\/jats:italic>\n +\n RAS<\/jats:italic>\n + other alterations (\n n<\/jats:italic>\n = 5, 10%), and the ROM for each group was 57%, 78%, 50%, and 80%, respectively. The frequency of a high-risk malignancy, which would often lead to a recommendation for total thyroidectomy, was 9.5%, 44.5%, 37.5%, and 80%, respectively. The frequency of high-risk carcinomas was significantly higher when a nodule harbored\n TERTp<\/jats:italic>\n and other concomitant alterations (48%) compared with\n TERTp<\/jats:italic>\n alone (9.5%;\n p<\/jats:italic>\n = 0.006).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n Thirty five percent of\n TERTp<\/jats:italic>\n nodules without\n \n BRAF\n V600E<\/jats:sup>\n <\/jats:italic>\n are benign\/low-risk thyroid neoplasms, leading to their overtreatment. The incidence of high-risk carcinomas increases in\n TERTp<\/jats:italic>\n -mutated nodules with the presence of additional mutations. If the indolent histology found in these lesions is confirmed at the behavior level, lobectomy may be sufficient for the initial management of\n TERTp<\/jats:italic>\n thyroid nodules without\n \n BRAF\n V600E<\/jats:sup>\n <\/jats:italic>\n as long as there is no aggressive clinical or imaging feature. This will spare many patients from the side effects of total thyroidectomy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/10507256251363450","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T18:52:36Z","timestamp":1759949556000},"page":"1145-1152","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Pathological Diagnosis of Thyroid Nodules with Preoperatively Detected\n TERT<\/i>\n Promoter Mutations in the Absence of\n \n BRAF\n V600E<\/sup>\n <\/i>\n : A Bi-Center Series of 52 Cases"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5628-6384","authenticated-orcid":false,"given":"Bayan A.","family":"Alzumaili","sequence":"first","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Instrum","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5338-2944","authenticated-orcid":false,"given":"Anas","family":"Alabkaa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1036-6367","authenticated-orcid":false,"given":"Peter M.","family":"Sadow","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Tuttle","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-9835","authenticated-orcid":false,"given":"Bin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc G.T.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald A.","family":"Ghossein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010073"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-016-0324-x"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-13-0210"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2383"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-016-2027-5"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14567"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0350"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.4616"},{"key":"e_1_3_7_10_2","unstructured":"USA SH. 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