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Preoperative Risk Stratification of Follicular-patterned Thyroid Lesions on Core Needle Biopsy by Histologic Subtyping and RAS Variant-specific Immunohistochemistry

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Abstract

Follicular-patterned lesions often have indeterminate results (diagnostic category III or IV) by core needle biopsy (CNB) and fine needle aspiration (FNA). However, CNB diagnoses follicular neoplasm (category IV) more frequently than FNA. Therefore, we aimed to develop a risk stratification system for CNB samples with category III/IV using immunohistochemistry (IHC). The specificity of the RAS Q61R antibody was validated on 58 thyroid nodules with six different types of RAS genetic variants and 40 cases of RAS wild-type. We then applied IHC analysis of RAS Q61R to 207 CNB samples with category III/IV in which all patients underwent surgical resection. RAS Q61R IHC had 98% sensitivity and 98% specificity for detecting the RAS p.Q16R variant. In an independent dataset, the positive rate of RAS Q61R was significantly higher in NIFTP (48%) and malignancies (45%) than in benign tumors (19%). The risk of NIFTP/malignancy was highest in the group with nuclear atypia and RAS Q61R expression (86%) and lowest in the group without both parameters (32%). The high-risk group with either nuclear atypia or RAS Q61R had 67.3% sensitivity, 73.4% specificity, 75.2% positive predictive value, and 65.1% negative predictive value for identifying NIFTP/malignancy. We conclude that RAS Q61R IHC can be a rule-in diagnostic test for NIFTP/malignancy in CNB category III/IV results. Combining of the histologic parameter (nuclear atypia) with RAS Q61R IHC results can further stratify CNB category III/IV into a high-risk group, which is sufficient for a surgical referral, and a low-risk group sufficient for observation.

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Funding

This research was supported by a grant (HI21C0940) from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea. This research was also supported by a grant (NRF-2020R1F1A1070028) from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT.

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Authors and Affiliations

  1. Department of Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Meejeong Kim & Chan Kwon Jung

  2. College of Medicine, Cancer Research Institute, The Catholic University of Korea, Seoul, Korea

    Sora Jeon & Chan Kwon Jung

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Contributions

Conceptualization, C.K.J.; Methodology, M.K. and S.J.; Validation, C.K.J; Data Analysis, M.K., S.J., and C.K.J; Investigation, M.K. and C.K.J; Resources, C.K.J.; Data Curation, M.K. and C.K.J.; Writing – Original Draft Preparation; M.K. and C.K.J; Writing – Review & Editing, M.K., S.J., and C.K.J.; Supervision, C.K.J. All authors have read and agreed to the submitted version.

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Correspondence to Chan Kwon Jung.

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This study was conducted according to the guidelines of the Declaration of Helsinki, and was approved by the Institutional Review Board of Seoul St. Mary’s Hospital of the Catholic University of Korea (KC20TISI0766).

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Kim, M., Jeon, S. & Jung, C.K. Preoperative Risk Stratification of Follicular-patterned Thyroid Lesions on Core Needle Biopsy by Histologic Subtyping and RAS Variant-specific Immunohistochemistry. Endocr Pathol 34, 247–256 (2023). https://doi.org/10.1007/s12022-023-09763-3

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