Journal of Pathology and Translational Medicine

Newsletter

What’s new in thyroid pathology 2024: updates from the new WHO classification and Bethesda system: Andrey Bychkov, Chan Kwon Jung; J Pathol Transl Med. 2024;58(2):98-101. Published online March 13, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.06

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Abstract PDF: In line with the release of the 5th edition WHO Classification of Tumors of Endocrine Organs (2022) and the 3rd edition of the Bethesda System for Reporting Thyroid Cytopathology (2023), the field of thyroid pathology and cytopathology has witnessed key transformations. This digest brings to the fore the refined terminologies, newly introduced categories, and contentious methodological considerations pivotal to the updated classification.

Review

The Asian Thyroid Working Group, from 2017 to 2023: Kennichi Kakudo, Chan Kwon Jung, Zhiyan Liu, Mitsuyoshi Hirokawa, Andrey Bychkov, Huy Gia Vuong, Somboon Keelawat, Radhika Srinivasan, Jen-Fan Hang, Chiung-Ru Lai; J Pathol Transl Med. 2023;57(6):289-304. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.04

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Abstract PDF Supplementary Material: The Asian Thyroid Working Group was founded in 2017 at the 12th Asia Oceania Thyroid Association (AOTA) Congress in Busan, Korea. This group activity aims to characterize Asian thyroid nodule practice and establish strict diagnostic criteria for thyroid carcinomas, a reporting system for thyroid fine needle aspiration cytology without the aid of gene panel tests, and new clinical guidelines appropriate to conservative Asian thyroid nodule practice based on scientific evidence obtained from Asian patient cohorts. Asian thyroid nodule practice is usually designed for patient-centered clinical practice, which is based on the Hippocratic Oath, “First do not harm patients,” and an oriental filial piety “Do not harm one’s own body because it is a precious gift from parents,” which is remote from defensive medical practice in the West where physicians, including pathologists, suffer from severe malpractice climate. Furthermore, Asian practice emphasizes the importance of resource management in navigating the overdiagnosis of low-risk thyroid carcinomas. This article summarizes the Asian Thyroid Working Group activities in the past 7 years, from 2017 to 2023, highlighting the diversity of thyroid nodule practice between Asia and the West and the background reasons why Asian clinicians and pathologists modified Western systems significantly.

Case Study

Diagnostic conundrums of schwannomas: two cases highlighting morphological extremes and diagnostic challenges in biopsy specimens of soft tissue tumors: Chankyung Kim, Yang-Guk Chung, Chan Kwon Jung; J Pathol Transl Med. 2023;57(5):278-283. Published online August 24, 2023; DOI: https://doi.org/10.4132/jptm.2023.07.13

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Abstract PDF: Schwannomas are benign, slow-growing peripheral nerve sheath tumors commonly occurring in the head, neck, and flexor regions of the extremities. Although most schwannomas are easily diagnosable, their variable morphology can occasionally create difficulty in diagnosis. Reporting pathologists should be aware that schwannomas can exhibit a broad spectrum of morphological patterns. Clinical and radiological examinations can show correlation and should be performed, in conjunction with ancillary tests, when appropriate. Furthermore, deferring a definitive diagnosis until excision may be necessary for small biopsy specimens and frozen sections. This report underscores these challenges through examination of two unique schwannoma cases, one predominantly cellular and the other myxoid, both of which posed significant challenges in histological interpretation.

Reviews

Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy: Chan Kwon Jung; J Pathol Transl Med. 2023;57(4):208-216. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.20

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Abstract PDF

As the application of core needle biopsy (CNB) in evaluating thyroid nodules rises in clinical practice, the 2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules have officially recognized its value for the first time. CNB procures tissue samples preserving both histologic structure and cytologic detail, thereby supplying substantial material for an accurate diagnosis and reducing the necessity for repeated biopsies or subsequent surgical interventions. The current review introduces the risk of malignancy within distinct diagnostic categories, emphasizing the implications of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on these malignancy risks. Prior research has indicated diagnostic challenges associated with follicular-patterned lesions, resulting in notable variation within indeterminate diagnostic categories. The utilization of mutation-specific immunostaining in CNB enhances the accuracy of lesion classification. This review underlines the essential role of a multidisciplinary approach in diagnosing follicular-patterned lesions and the potential of mutation-specific immunostaining to strengthen diagnostic consensus and inform patient management decisions.

Citations

Citations to this article as recorded by

Diagnostic implication of thyroid spherules for cytological diagnosis of thyroid nodules
Heeseung Sohn, Kennichi Kakudo, Chan Kwon Jung
Cytopathology.2024; 35(3): 383. CrossRef
A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules
Eun Kyung Lee, Young Joo Park, Chan Kwon Jung, Dong Gyu Na
Endocrinology and Metabolism.2024; 39(1): 61. CrossRef

Recommendations for pathologic practice using digital pathology: consensus report of the Korean Society of Pathologists: Yosep Chong, Dae Cheol Kim, Chan Kwon Jung, Dong-chul Kim, Sang Yong Song, Hee Jae Joo, Sang-Yeop Yi; J Pathol Transl Med. 2020;54(6):437-452. Published online October 8, 2020; DOI: https://doi.org/10.4132/jptm.2020.08.27

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Abstract PDF Supplementary Material

Digital pathology (DP) using whole slide imaging (WSI) is becoming a fundamental issue in pathology with recent advances and the rapid development of associated technologies. However, the available evidence on its diagnostic uses and practical advice for pathologists on implementing DP remains insufficient, particularly in light of the exponential growth of this industry. To inform DP implementation in Korea, we developed relevant and timely recommendations. We first performed a literature review of DP guidelines, recommendations, and position papers from major countries, as well as a review of relevant studies validating WSI. Based on that information, we prepared a draft. After several revisions, we released this draft to the public and the members of the Korean Society of Pathologists through our homepage and held an open forum for interested parties. Through that process, this final manuscript has been prepared. This recommendation contains an overview describing the background, objectives, scope of application, and basic terminology; guidelines and considerations for the hardware and software used in DP systems and the validation required for DP implementation; conclusions; and references and appendices, including literature on DP from major countries and WSI validation studies.

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Original Article

Highly prevalent BRAF V600E and low-frequency TERT promoter mutations underlie papillary thyroid carcinoma in Koreans: Sue Youn Kim, Taeeun Kim, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Chan Kwon Jung; J Pathol Transl Med. 2020;54(4):310-317. Published online June 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.05.12

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Abstract PDF

Background
The presence of telomerase reverse transcriptase (TERT) promoter mutations have been associated with a poor prognosis in patients with papillary thyroid carcinomas (PTC). The frequency of TERT promoter mutations varies widely depending on the population and the nature of the study.
Methods
Data were prospectively collected in 724 consecutive patients who underwent thyroidectomy for PTC from 2018 to 2019. Molecular testing for BRAF V600E and TERT promoter mutations was performed in all cases.
Results
TERT promoter alterations in two hotspots (C228T and C250T) and C216T were found in 16 (2.2%) and 4 (0.6%) of all PTCs, respectively. The hotspot mutations were significantly associated with older age at diagnosis, larger tumor size, extrathyroidal extension, higher pathologic T category, lateral lymph node metastasis, and higher American Thyroid Association recurrence risk. The patients with C216T variant were younger and had a lower American Thyroid Association recurrence risk than those with hotspot mutations. Concurrent BRAF V600E was found in 19 of 20 cases with TERT promoter mutations. Of 518 microcarcinomas measuring ≤1.0 cm in size, hotspot mutations and C216T variants were detected in five (1.0%) and three (0.6%) cases, respectively.
Conclusions
Our study indicates a low frequency of TERT promoter mutations in Korean patients with PTC and supports previous findings that TERT promoter mutations are more common in older patients with unfavorable clinicopathologic features and BRAF V600E. TERT promoter mutations in patients with microcarcinoma are uncommon and may have a limited role in risk stratification. The C216T variant seems to have no clinicopathologic effect on PTC.

Citations

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Active surveillance for adult low-risk papillary thyroid microcarcinoma—a review focused on the 30-year experience of Kuma Hospital—
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Diagnostic utilities of washout CYFRA 21-1 combined with washout thyroglobulin for metastatic lymph nodes in thyroid cancer: a prospective study
Joonseon Park, Solji An, Kwangsoon Kim, Jeong Soo Kim, Chan Kwon Jung, Ja Seong Bae
Scientific Reports.2024;[Epub] CrossRef
2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules
Young Joo Park, Eun Kyung Lee, Young Shin Song, Soo Hwan Kang, Bon Seok Koo, Sun Wook Kim, Dong Gyu Na, Seung-Kuk Baek, So Won Oh, Min Kyoung Lee, Sang-Woo Lee, Young Ah Lee, Yong Sang Lee, Ji Ye Lee, Dong-Jun Lim, Leehi Joo, Yuh-Seog Jung, Chan Kwon Jung
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Identification of NIFTP-Specific mRNA Markers for Reliable Molecular Diagnosis of Thyroid Tumors
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Editorial

New insights into classification and risk stratification of encapsulated thyroid tumors with a predominantly papillary architecture: Chan Kwon Jung, So Yeon Park, Jang-Hee Kim, Kennichi Kakudo; J Pathol Transl Med. 2020;54(3):197-203. Published online May 14, 2020; DOI: https://doi.org/10.4132/jptm.2020.04.29

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PDF

Citations

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The Asian Thyroid Working Group, from 2017 to 2023
Kennichi Kakudo, Chan Kwon Jung, Zhiyan Liu, Mitsuyoshi Hirokawa, Andrey Bychkov, Huy Gia Vuong, Somboon Keelawat, Radhika Srinivasan, Jen-Fan Hang, Chiung-Ru Lai
Journal of Pathology and Translational Medicine.2023; 57(6): 289. CrossRef
Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification
Yanhua Bai, Kennichi Kakudo, Chan Kwon Jung
Endocrinology and Metabolism.2020; 35(4): 696. CrossRef

Review

Introduction to digital pathology and computer-aided pathology: Soojeong Nam, Yosep Chong, Chan Kwon Jung, Tae-Yeong Kwak, Ji Youl Lee, Jihwan Park, Mi Jung Rho, Heounjeong Go; J Pathol Transl Med. 2020;54(2):125-134. Published online February 13, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.31

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Abstract PDF

Digital pathology (DP) is no longer an unfamiliar term for pathologists, but it is still difficult for many pathologists to understand the engineering and mathematics concepts involved in DP. Computer-aided pathology (CAP) aids pathologists in diagnosis. However, some consider CAP a threat to the existence of pathologists and are skeptical of its clinical utility. Implementation of DP is very burdensome for pathologists because technical factors, impact on workflow, and information technology infrastructure must be considered. In this paper, various terms related to DP and computer-aided pathologic diagnosis are defined, current applications of DP are discussed, and various issues related to implementation of DP are outlined. The development of computer-aided pathologic diagnostic tools and their limitations are also discussed.

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Editorial

Papillary thyroid carcinoma variants with tall columnar cells: Chan Kwon Jung; J Pathol Transl Med. 2020;54(1):123-123. Published online January 15, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.18

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Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification
Yanhua Bai, Kennichi Kakudo, Chan Kwon Jung
Endocrinology and Metabolism.2020; 35(4): 696. CrossRef

Review

2019 Practice guidelines for thyroid core needle biopsy: a report of the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association: Chan Kwon Jung, Jung Hwan Baek, Dong Gyu Na, Young Lyun Oh, Ka Hee Yi, Ho-Cheol Kang; J Pathol Transl Med. 2020;54(1):64-86. Published online January 15, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.04

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Abstract PDF

Ultrasound-guided core needle biopsy (CNB) has been increasingly used for the pre-operative diagnosis of thyroid nodules. Since the Korean Society of the Thyroid Radiology published the ‘Consensus Statement and Recommendations for Thyroid CNB’ in 2017 and the Korean Endocrine Pathology Thyroid CNB Study Group published ‘Pathology Reporting of Thyroid Core Needle Biopsy’ in 2015, advances have occurred rapidly not only in the management guidelines for thyroid nodules but also in the diagnostic terminology and classification schemes. The Clinical Practice Guidelines Development Committee of the Korean Thyroid Association (KTA) reviewed publications on thyroid CNB from 1995 to September 2019 and updated the recommendations and statements for the diagnosis and management of thyroid nodules using CNB. Recommendations for the resolution of clinical controversies regarding the use of CNB were based on expert opinion. These practical guidelines include recommendations and statements regarding indications for CNB, patient preparation, CNB technique, biopsy-related complications, biopsy specimen preparation and processing, and pathology interpretation and reporting of thyroid CNB.

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Original Article

A Multi-institutional Study of Prevalence and Clinicopathologic Features of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) in Korea: Ja Yeong Seo, Ji Hyun Park, Ju Yeon Pyo, Yoon Jin Cha, Chan Kwon Jung, Dong Eun Song, Jeong Ja Kwak, So Yeon Park, Hee Young Na, Jang-Hee Kim, Jae Yeon Seok, Hee Sung Kim, Soon Won Hong; J Pathol Transl Med. 2019;53(6):378-385. Published online October 21, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.18

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Abstract PDF

Background
In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC).
Methods
Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases.
Results
The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAF^V600E mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27).
Conclusions
The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.

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Reviews

Artificial Intelligence in Pathology: Hye Yoon Chang, Chan Kwon Jung, Junwoo Isaac Woo, Sanghun Lee, Joonyoung Cho, Sun Woo Kim, Tae-Yeong Kwak; J Pathol Transl Med. 2019;53(1):1-12. Published online December 28, 2018; DOI: https://doi.org/10.4132/jptm.2018.12.16

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As in other domains, artificial intelligence is becoming increasingly important in medicine. In particular,deep learning-based pattern recognition methods can advance the field of pathology byincorporating clinical, radiologic, and genomic data to accurately diagnose diseases and predictpatient prognoses. In this review, we present an overview of artificial intelligence, the brief historyof artificial intelligence in the medical domain, recent advances in artificial intelligence applied topathology, and future prospects of pathology driven by artificial intelligence.

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The Use of Fine-Needle Aspiration (FNA) Cytology in Patients with Thyroid Nodules in Asia: A Brief Overview of Studies from the Working Group of Asian Thyroid FNA Cytology: Chan Kwon Jung, SoonWon Hong, Andrey Bychkov, Kennichi Kakudo; J Pathol Transl Med. 2017;51(6):571-578. Published online October 27, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.19

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Abstract PDF

Ultrasound-guided fine-needle aspiration (FNA) cytology is the most widely used screening and diagnostic method for thyroid nodules. Although Western guidelines for managing thyroid nodules and the Bethesda System for Reporting Thyroid Cytopathology are widely available throughout Asia, the clinical practices in Asia vary from those of Western countries. Accordingly, the Working Group of Asian Thyroid FNA Cytology encouraged group members to publish their works jointly with the same topic. The articles in this special issue focused on the history of thyroid FNA, FNA performers and interpreters, training programs of cytopathologists and cytotechnicians, staining methods, the reporting system of thyroid FNA, quality assurance programs, ancillary testing, and literature review of their own country’s products. Herein, we provide a brief overview of thyroid FNA practices in China, India, Japan, Korea, the Philippines, Taiwan, and Thailand.

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Cytological evaluation of thyroid nodules in children and young adults: a multi-institutional experience
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Endocrine.2023; 80(3): 580. CrossRef
The Asian Thyroid Working Group, from 2017 to 2023
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Core Needle Biopsy in Suspicious Malignant Thyroid Nodules with Repeated Nondiagnostic Fine Needle Aspiration
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The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology
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Original Articles

Current Cytology Practices in Korea: A Nationwide Survey by the Korean Society for Cytopathology: Eun Ji Oh, Chan Kwon Jung, Dong-Hoon Kim, Han Kyeom Kim, Wan Seop Kim, So-Young Jin, Hye Kyoung Yoon; J Pathol Transl Med. 2017;51(6):579-587. Published online September 27, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.11

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Abstract PDF

Background
Limited data are available on the current status of cytology practices in Korea. This nationwide study presents Korean cytology statistics from 2015.
Methods
A nationwide survey was conducted in 2016 as a part of the mandatory quality-control program by the Korean Society for Cytopathology. The questionnaire was sent to 208 medical institutions performing cytopathologic examinations in Korea. Individual institutions were asked to submit their annual cytology statistical reports and gynecologic cytology-histology correlation data for 2015.
Results
Responses were obtained from 206 medical institutions including 83 university hospitals, 87 general hospitals, and 36 commercial laboratories. A total of 8,284,952 cytologic examinations were performed in 2015, primarily in commercial laboratories (74.9%). The most common cytology specimens were gynecologic samples (81.3%). Conventional smears and liquid-based cytology were performed in 6,190,526 (74.7%) and 2,094,426 (25.3%) cases, respectively. The overall diagnostic concordance rate between cytologic and histologic diagnoses of uterine cervical samples was 70.5%. Discordant cases were classified into three categories: category A (minimal clinical impact, 17.4%), category B (moderate clinical impact, 10.2%), and category C (major clinical impact, 1.9%). The ratio of atypical squamous cells of undetermined significance to squamous intraepithelial lesion was 1.6 in university hospitals, 2.9 in general hospitals, and 4.9 in commercial laboratories.
Conclusions
This survey reveals the current status and trend of cytology practices in Korea. The results of this study can serve as basic data for the establishment of nationwide cytopathology policies and quality improvement guidelines in Korean medical institutions.

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Thyroid Fine-Needle Aspiration Cytology Practice in Korea
Yoon Jin Cha, Ju Yeon Pyo, SoonWon Hong, Jae Yeon Seok, Kyung-Ju Kim, Jee-Young Han, Jeong Mo Bae, Hyeong Ju Kwon, Yeejeong Kim, Kyueng-Whan Min, Soonae Oak, Sunhee Chang
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The Use of the Bethesda System for Reporting Thyroid Cytopathology in Korea: A Nationwide Multicenter Survey by the Korean Society of Endocrine Pathologists: Mimi Kim, Hyo Jin Park, Hye Sook Min, Hyeong Ju Kwon, Chan Kwon Jung, Seoung Wan Chae, Hyun Ju Yoo, Yoo Duk Choi, Mi Ja Lee, Jeong Ja Kwak, Dong Eun Song, Dong Hoon Kim, Hye Kyung Lee, Ji Yeon Kim, Sook Hee Hong, Jang Sihn Sohn, Hyun Seung Lee, So Yeon Park, Soon Won Hong, Mi Kyung Shin; J Pathol Transl Med. 2017;51(4):410-417. Published online June 14, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.05

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Abstract PDF

Background
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has standardized the reporting of thyroid cytology specimens. The objective of the current study was to evaluate the nationwide usage of TBSRTC and assess the malignancy rates in each category of TBSRTC in Korea.
Methods
Questionnaire surveys were used for data collection on the fine needle aspiration (FNA) of thyroid nodules at 74 institutes in 2012. The incidences and follow-up malignancy rates of each category diagnosed from January to December, 2011, in each institute were also collected and analyzed.
Results
Sixty out of 74 institutes answering the surveys reported the results of thyroid FNA in accordance with TBSRTC. The average malignancy rates for resected cases in 15 institutes were as follows: nondiagnostic, 45.6%; benign, 16.5%; atypical of undetermined significance, 68.8%; suspicious for follicular neoplasm (SFN), 30.2%; suspicious for malignancy, 97.5%; malignancy, 99.7%.
Conclusions
More than 80% of Korean institutes were using TBSRTC as of 2012. All malignancy rates other than the SFN and malignancy categories were higher than those reported by other countries. Therefore, the guidelines for treating patients with thyroid nodules in Korea should be revisited based on the malignancy rates reported in this study.

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