Evidence map›Paper›PMID 41982771›Full record

Observational studyFrontiers in endocrinology2026

When cytology misses and ultrasound warns: the predictive role of BRAFV600E mutation in thyroid nodules.

Liu Jie, Cai Wenqing, Zhang Guang, Li Shijie, Fu Qingfeng, Li Kangping, Yu Yuexin, Chen Zhuo, Carla Colombo, Francesco Brucchi and 2 more

Abstract readObservational Study
In one paragraph

Observational study in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Liu JieDepartment of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Treatment, Changchun, China.
Cai WenqingDepartment of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Treatment, Changchun, China.
Zhang GuangDepartment of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Treatment, Changchun, China.
Li ShijieDepartment of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Treatment, Changchun, China.
Fu QingfengDepartment of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Treatment, Changchun, China.
Li KangpingDepartment of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Treatment, Changchun, China.
Yu YuexinDepartment of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Treatment, Changchun, China.
Chen ZhuoDepartment of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Treatment, Changchun, China.
Carla ColomboDepartment of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Francesco BrucchiDepartment of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Gianlorenzo DionigiDepartment of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Liu XiaoliDepartment of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and Treatment, Changchun, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Thyroid nodules with high-suspicion ultrasound features but benign cytologic findings remain a diagnostic challenge due to potential false-negative fine-needle aspiration (FNA) results. The BRAFV600E mutation, a hallmark of papillary thyroid carcinoma (PTC), may improve malignancy risk stratification. This study prospectively evaluated the diagnostic performance of BRAFV600E mutation testing in ultrasound-high-suspicion thyroid nodules with non-malignant cytology. Methods: A prospective observational study was conducted at the China-Japan Union Hospital of Jilin University between January 2019 and July 2024, enrolling 562 ultrasound-high-suspicion thyroid nodules with non-malignant or indeterminate cytology (Bethesda II-III). Preoperative BRAFV600E analysis was performed using PCR-based methods, and all nodules subsequently underwent surgical excision with definitive histopathology. Associations between mutation status, sonographic patterns, and final diagnoses were assessed through univariate and multivariable logistic regression. Results: Among 562 nodules, 280 (49.8%) harbored the BRAFV600E mutation. Final pathology confirmed 390 PTCs (69.4%) and 172 benign lesions (30.6%). The BRAFV600E mutation was strongly associated with malignancy (66.2% vs. 12.8%, P < 0.001). On multivariable analysis, BRAFV600E positivity independently predicted PTC (OR = 10.36, 95% CI = 6.18-17.35, P < 0.001). The test showed a sensitivity of 66.2%, specificity of 87.2%, positive predictive value of 92.1%, and overall accuracy of 72.6%. Conclusion: BRAFV600E mutation testing is a valuable molecular tool for evaluating high-suspicion thyroid nodules with cytologically benign or indeterminate findings. Its strong predictive value enables earlier identification of papillary thyroid carcinoma (PTC), but results should always be interpreted alongside clinicopathologic and imaging assessments to guide optimal diagnostic decisions. In this highly selected cohort, BRAFV600E testing added diagnostic value beyond high-suspicion ultrasound features, improving the distinction between true malignancy and benign mimics in a population with a 69.4% baseline cancer prevalence.

Indexed as

MutationProto-Oncogene Proteins B-rafThyroid Cancer, PapillaryThyroid NeoplasmsThyroid NoduleAdultAgedBiopsy, Fine-NeedleFemaleHumansMaleMiddle AgedPredictive Value of TestsProspective StudiesUltrasonographyBRAF protein, humanProto-Oncogene Proteins B-rafBRAFV600E mutationfine-needle aspirationmolecular diagnosticspapillary thyroid carcinomathyroid nodules

Identifiers

PMID41982771
PMCPMC13070763

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.