Cytologic and Surgical Correlation of TERT-Mutated Indeterminate Thyroid Nodules - A Case Series

Sep 22, 2026

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The study investigates TERT promoter mutations in cytologically indeterminate thyroid nodules and correlates molecular findings with cytology, surgical pathology, and clinical outcomes. A retrospective review identified Bethesda III and IV specimens referred for ThyroSeq testing between 2019 and 2022 that carried TERT mutations. Among 567 specimens tested, 12 (2%) harbored TERT, often with additional molecular alterations. Eight patients had surgical follow-up with malignancy in 50%, and clinical follow-up showed no recurrences or metastases at last contact.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages6

Reading Time15 min

AccessFree to download

Abstract

Introduction

Methods

Results

Conclusion

Cytologic and Surgical Correlation of TERT-Mutated Indeterminate Thyroid Nodules: A Case Series International Journal of Surgical Pathology 2026, Vol. 34(7) 1800-1805 © The Author(s) 2026 Article reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions)[ ](sagepub.com/journals-permissions)[DOI:](DOI: 10.1177/10668969261448578)[ 1](DOI: 10.1177/10668969261448578)[0.](DOI: 10.1177/10668969261448578)[11](DOI: 10.1177/10668969261448578)[77/](DOI: 10.1177/10668969261448578)[1](DOI: 10.1177/10668969261448578)[066896926](DOI: 10.1177/10668969261448578)[1](DOI: 10.1177/10668969261448578)[448578](DOI: 10.1177/10668969261448578)[ ](DOI: 10.1177/10668969261448578)[journals.sagepub.com/home/ijs](journals.sagepub.com/home/ijs) Saroja Devi Geetha, MD1 , Neha Seth, MD1 , Karen Chau, CT1, and Kasturi Das, MD1 Abstract Introduction: Telomerase reverse transcriptase (TERT) promoter mutations is a relatively novel mutation that has been linked with thyroid cancers. This study examines the frequency, cytology and histo-morphologic features, and clinical outcomes of TERT-mutated indeterminate thyroid nodules. Methods: A retrospective review of Bethesda III and IV thyroid cytology specimen sent for ThyroSeq® testing (2019- 2022) was performed, selecting those with TERT mutations. Demographics, cytologic features, surgical diagnoses, and follow-up data were analyzed. Results: Among 567 specimens tested, 12 (2%) harbored TERT mutations; 4 had TERT alone, and 8 had additional mutations. Average age of patients was 69 years (92%>50 years). Eight had surgical follow-up: 50% were malignant, 25% were benign and 25% were of uncertain malignant potential. Additionally, 62% were oncocytic nodules. Clinical follow-up showed all evaluated patients were alive without recurrences or metastases at last contact. Conclusion: In our cohort, TERT promoter mutations were rare in indeterminate thyroid nodules (2%) and frequently accompanied by additional molecular changes. It is more frequently detected in older patients. Unlike prior reports describing TERT mutations exclusively in malignant thyroid tumors, our ﬁndings encompassed a broader histological spectrum, including benign, uncertain malignant potential and malignant lesions. Keywords Telomerase reverse transcriptase-mutated thyroid nodules, follicular adenoma, Bethesda III, Bethesda IV, thyroid cytology, oncocytic thyroid nodules Introduction Thyroid cancers have been known to harbor various molecular alterations. Telomerase reverse transcriptase (TERT) promoter mutations is a relatively novel mutation that has been linked with thyroid cancers such as papillary thyroid carcinoma (PTC), follicular thyroid carcinomas (FTC), poorly differentiated thyroid carcinoma, and anaplastic thyroid cancers but not in medullary thyroid carcinoma.1 The most common TERT promoter mutations are C228T and C250T, with C228T being more common in thyroid cancers. Clinically, TERT-mutated thyroid cancers tend to have poor outcomes and aggressive disease courses, including tumor metastasis, recurrences, and early mortality.2,3 TERT promoter mutations may be seen with other gene mutations, particularly BRAF V600E and RAS mutations, with studies showing a higher incidence of TERT mutation in BRAF-mutated lesions compared to BRAF-wild type.4 There have been reports ofTERTpromoter mutations being associated with increased mortality in patients with differentiated thyroid cancer independently.5 Additionally, few studies have shown that TERT promoter mutations, especially in PTC, have been known to be associated with extrathyroidal extension,6 vascular invasion,7 lymph node metastasis,8 and distant metastasis.9 TERT promoter mutations have also been associated with advanced TNM stages 1Department of Pathology and Laboratory Medicine, North Shore University Hospital and Long Island Jewish Medical Center, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, New Yo

FAQs

What is the main purpose of this case series?

To determine how often TERT promoter mutations occur in Bethesda III and IV indeterminate thyroid nodules and to describe associated cytologic, histologic, and clinical outcomes.

How were patients selected for the study?

Thyroid cytology specimens categorized as Bethesda III or IV that were reflexed to ThyroSeq testing between 2019 and 2022 were reviewed, and only those with TERT mutations were selected.

What proportion of indeterminate thyroid cytology specimens showed TERT mutations?

Among 567 specimens tested, 12 (2%) harbored TERT mutations.

What did follow-up show for patients with TERT-mutated nodules?

In surgical follow-up, malignant, benign, and uncertain malignant potential outcomes were reported, and clinical follow-up indicated all evaluated patients were alive without recurrences or metastases at last contact.

Sep 22, 2026

Uploaded by acoobca