Journal of Pathology and Translational Medicine

Reviews

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.

A stepwise approach to fine needle aspiration cytology of lymph nodes: Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee; J Pathol Transl Med. 2023;57(4):196-207. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.12

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The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

Citations

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Immunocytochemical markers, molecular testing and digital cytopathology for aspiration cytology of metastatic breast carcinoma
Joshua J. X. Li, Gary M. Tse
Cytopathology.2024; 35(2): 218. CrossRef
Response to comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee
Journal of Pathology and Translational Medicine.2024; 58(1): 43. CrossRef
Comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
Elisabetta Maffei, Valeria Ciliberti, Pio Zeppa, Alessandro Caputo
Journal of Pathology and Translational Medicine.2024; 58(1): 40. CrossRef

Pathologic interpretation of endoscopic ultrasound–guided fine needle aspiration cytology/biopsy for pancreatic lesions: Haeryoung Kim, Kee-Taek Jang; J Pathol Transl Med. 2020;54(5):367-377. Published online August 31, 2020; DOI: https://doi.org/10.4132/jptm.2020.07.21

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Abstract PDF

Pathologic interpretation of endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) cytology/biopsy specimens is one of the most challenging tasks in cytology and surgical pathology practice, as the procedure often yields minimal amounts of diagnostic material and contains contaminants, such as blood cells and normal intestinal mucosa. EUS-FNA cytology/biopsy will nevertheless become a more popular procedure for evaluation of various pancreatic lesions because they are difficult to approach with conventional endoscopic procedures. Pathologists should understand the structural differences and limitations of EUS-FNA that make pathologic diagnosis difficult. Ancillary tests are available for differential diagnosis of EUS-FNA for various pancreatic lesions. Immunostains are the most commonly used ancillary tests, and pathologists should able to choose the necessary panel for differential diagnosis. Pathologists should review clinical history and radiologic and/or EUS findings before selecting an immunostain panel and making a pathologic diagnosis. In addition, one’s threshold of malignancy should be adjusted according to the appropriate clinical setting to avoid under-evaluation of pathologic diagnoses. Clinico-pathologic correlation is essential in pathologic evaluation of EUS-FNA for pancreatic lesions. Pathologists can reduce errors by correlating clinical and radiologic findings when evaluating EUS-FNA. Some molecular tests can be applied in differential diagnosis of pancreatic neoplastic and cystic lesions. Molecular data should be used as supportive evidence of a specific disease entity, rather than direct evidence, and should be correlated with clinico-pathologic findings to avoid errors in pathologic diagnosis.

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A prospective randomized noninferiority trial comparing conventional smears and SurePathTM liquid-based cytology in endoscopic ultrasound-guided sampling of esophageal, gastric, and duodenal lesions
Jae Chang Jun, Sang Hyub Lee, Han Myung Lee, Sang Gyun Kim, Hyunsoo Chung, Joo Seong Kim, Namyoung Park, Jin Ho Choi, Yoonjin Kwak, Soo-Jeong Cho
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Double Ki-67 and synaptophysin labeling in pancreatic neuroendocrine tumor biopsies
Bokyung Ahn, Jin Kying Jung, HaeSung Jung, Yeon-Mi Ryu, Yeon Wook Kim, Tae Jun Song, Do Hyun Park, Dae wook Hwang, HyungJun Cho, Sang-Yeob Kim, Seung-Mo Hong
Pancreatology.2022; 22(3): 427. CrossRef
Comparison of Endoscopic Ultrasound-Guided Fine Needle Aspiration with 19-Gauge and 22-Gauge Needles for Solid Pancreatic Lesions
Changjuan Li, Jianwei Mi, Fulai Gao, Xinying Zhu, Miao Su, Xiaoli Xie, Dongqiang Zhao
International Journal of General Medicine.2021; Volume 14: 10439. CrossRef

Original Article

Cytological Features That Differentiate Follicular Neoplasm from Mimicking Lesions: Kanghee Han, Hwa-Jeong Ha, Joon Seog Kong, Jung-Soon Kim, Jae Kyung Myung, Jae Soo Koh, Sunhoo Park, Myung-Soon Shin, Woo-Tack Song, Hye Sil Seol, Seung-Sook Lee; J Pathol Transl Med. 2018;52(2):110-120. Published online January 29, 2018; DOI: https://doi.org/10.4132/jptm.2018.01.17

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Abstract PDF

Background
It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions. The aim of this study was to identify the cytological features that differentiate FNs from mimicking lesions.
Methods
We included the cytological slides from 116 cases of thyroid FN diagnosed on FNAC, and included their subsequent histological diagnoses. We evaluated the cytological architectural pattern and nuclear features of the lesions according to their histological groups.
Results
The final histological diagnoses of the 116 cases varied, and included 51 FNs (44%), 47 papillary thyroid carcinomas (40%) including follicular variant, and seventeen cellular nodular hyperplasias (15%). Regardless of the final histological diagnosis, microfollicular pattern was observed in most cases. On the other hand, trabecular pattern was identified in 34% of FNs, but not in any other lesions. Additionally, elongated nuclei and ground glass chromatin were found in only some papillary thyroid carcinomas.
Conclusions
This study shows that the trabecular pattern is a representative cytological feature of FNs that can be used to distinguish FNs from mimicking lesions. In addition, nuclear shape and chromatin pattern can be used to further confirm the diagnosis of FNs from mimicking lesions through FNAC.

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Wai-Kin Chan, Jui-Hung Sun, Miaw-Jene Liou, Yan-Rong Li, Wei-Yu Chou, Feng-Hsuan Liu, Szu-Tah Chen, Syu-Jyun Peng
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The Role of Fine Needle Aspiration Biopsy with Bethesda System in the Evaluation of Thyroid Nodules
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Comprehensive DNA Methylation Profiling Identifies Novel Diagnostic Biomarkers for Thyroid Cancer
Jong-Lyul Park, Sora Jeon, Eun-Hye Seo, Dong Hyuck Bae, Young Mun Jeong, Yourha Kim, Ja Seong Bae, Seon-Kyu Kim, Chan Kwon Jung, Yong Sung Kim
Thyroid.2020; 30(2): 192. CrossRef
Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses
Hee Young Na, Jae Hoon Moon, June Young Choi, Hyeong Won Yu, Woo-Jin Jeong, Yeo Koon Kim, Ji-Young Choe, So Yeon Park, Paula Soares
PLOS ONE.2020; 15(11): e0241597. CrossRef

Reviews

History and Practice of Thyroid Fine-Needle Aspiration in China, Based on Retrospective Study of the Practice in Shandong University Qilu Hospital: Zhiyan Liu, Dongge Liu, Bowen Ma, Xiaofang Zhang, Peng Su, Li Chen, Qingdong Zeng; J Pathol Transl Med. 2017;51(6):528-532. Published online October 19, 2017; DOI: https://doi.org/10.4132/jptm.2017.09.12

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Abstract PDF

Cytology in China developed from nothing and underwent a long journey from gynecologic cytology to that of all organs, laying a solid foundation for new developments in the 21st century. Thyroid fine-needle aspiration (FNA) was primarily developed in an endocrinology department and then in the clinical laboratory department or pathology department in the 1970–80s. Wrights staining is popular in endocrine and clinical laboratory departments, while hematoxylin and eosin staining is common in pathology. Liquid based cytology is not common in thyroid FNA cytology, while BRAFV600E mutation analysis has been the most popular molecular test. The history and practice of thyroid FNA practice in China were reviewed based on retrospective study of the practice in Qilu Hospital of Shandong University.

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Deep learning to predict cervical lymph node metastasis from intraoperative frozen section of tumour in papillary thyroid carcinoma: a multicentre diagnostic study
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Comparative Study of C-TIRADS, ACR-TIRADS, and EU-TIRADS for Diagnosis and Management of Thyroid Nodules
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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
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A multicenter, prospective study to observe the initial management of patients with differentiated thyroid cancer in China (DTCC study)
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Differences in surgical resection rate and risk of malignancy in thyroid cytopathology practice between Western and Asian countries: A systematic review and meta‐analysis
Huy Gia Vuong, Hanh Thi Tuyet Ngo, Andrey Bychkov, Chan Kwon Jung, Trang Huyen Vu, Kim Bach Lu, Kennichi Kakudo, Tetsuo Kondo
Cancer Cytopathology.2020; 128(4): 238. CrossRef
Thyroid FNA cytology in Asian practice—Active surveillance for indeterminate thyroid nodules reduces overtreatment of thyroid carcinomas
K. Kakudo, M. Higuchi, M. Hirokawa, S. Satoh, C. K. Jung, A. Bychkov
Cytopathology.2017; 28(6): 455. CrossRef
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
Journal of Pathology and Translational Medicine.2017; 51(6): 571. CrossRef

Thyroid Cytology: The Japanese System and Experience at Yamashita Thyroid Hospital: Shinya Satoh, Hiroyuki Yamashita, Kennichi Kakudo; J Pathol Transl Med. 2017;51(6):548-554. Published online October 11, 2017; DOI: https://doi.org/10.4132/jptm.2017.09.29

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Abstract PDF

In Japan, fine-needle aspiration (FNA) cytology is the most important diagnostic modality for triaging patients with thyroid nodules. A clinician (endocrinologist, endocrine surgeon, or head and neck surgeon) generally performs FNA cytology at the outpatient clinic, and ultrasound (US)-guided FNA is widespread because US is extremely common and most clinicians are familiar with it. Although almost all FNA thyroid samples are examined by certified cytopathologists and pathologists, some clinicians assess cytological specimens themselves. In Japan, there are two clinical guidelines regarding the management of thyroid nodules. One is the General Rules for the Description of Thyroid Cancer (GRDTC) published by the Japanese Society of Thyroid Surgery (JSTS) in 2005, and the other is the national reporting system for thyroid FNA cytology published by the Japan Thyroid Association in 2013 (Japanese system). Although the Bethesda System for Reporting Thyroid Cytopathology (Bethesda system) is rarely used in Japan, both the GRDTC and Japanese system tried to incorporate the Bethesda system so that the cytological diagnoses would be compatible with each other. The essential point of the Japanese system is stratification of follicular neoplasm (FN) into three subgroups based on cytological features in order to reduce unnecessary diagnostic thyroidectomy, and this system has been successful in stratifying the risk of malignancy in FN patients at several high-volume thyroid surgery centers. In Japan, the measurement of thyroglobulin and/or calcitonin in FNA needle washings is often used as an adjunct for diagnosis of possible cervical lymph node metastasis when FNA cytology is performed.

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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
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Chanchal Rana, Huy Gia Vuong, Thu Quynh Nguyen, Hoang Cong Nguyen, Chan Kwon Jung, Kennichi Kakudo, Andrey Bychkov
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Huy Gia Vuong, Thao T.K. Tran, Andre y. Bychkov, Chan Kwon Jung, Tadao Nakazawa, Kennichi Kakudo, R yohei Katoh, Tetsuo Kondo
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Hyunseo Cha, Ju Yeon Pyo, Soon Won Hong
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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
Journal of Pathology and Translational Medicine.2017; 51(6): 571. CrossRef

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; J Pathol Transl Med. 2017;51(6):521-527. Published online October 11, 2017; DOI: https://doi.org/10.4132/jptm.2017.09.26

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Abstract PDF

We reviewed the current status of thyroid fine-needle aspiration cytology (FNAC) in Korea. Thyroid aspiration biopsy was first introduced in Korea in 1977. Currently, radiologists aspirate the thyroid nodule under the guidance of ultrasonography, and cytologic interpretation is only legally approved when a cytopathologist makes the diagnosis. In 2008, eight thyroid-related societies came together to form the Korean Thyroid Association. The Korean Society for Cytopathology and the endocrine pathology study group of the Korean Society for Pathologists have been updating the cytologic diagnostic guidelines. The Bethesda System for Reporting Thyroid Cytopathology was first introduced in 2009, and has been used by up to 94% of institutions by 2016. The average diagnosis rates are as follows for each category: I (12.4%), II (57.9%), III (10.4%), IV (2.9%), V (3.7%), and VI (12.7%). The malignancy rates in surgical cases are as follows for each category: I (28.7%), II (27.8%), III (50.6%), IV (52.3%), V (90.7%), and VI (100.0%). Liquid-based cytology has been used since 2010, and it was utilized by 68% of institutions in 2016. The categorization of thyroid lesions into “atypia of undetermined significance” or “follicular lesion of undetermined significance” is necessary to draw consensus in our society. Immunocytochemistry for galectin-3 and BRAF is used. Additionally, a molecular test for BRAF in thyroid FNACs is actively used. Core biopsies were performed in only 44% of institutions. Even the institutions that perform core biopsies only perform them for less than 3% of all FNACs. However, only 5% of institutions performed core biopsies up to three times more than FNAC.

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Journal of Pathology and Translational Medicine.2023; 57(6): 289. CrossRef
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BRAFV600E Mutation is a Strong Preoperative Indicator for Predicting Malignancy in Thyroid Nodule Patients with Atypia of Undetermined Significance Identified by Fine Needle Aspiration
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The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology
Hyunseo Cha, Ju Yeon Pyo, Soon Won Hong
Journal of Pathology and Translational Medicine.2018; 52(6): 404. CrossRef
Thyroid FNA cytology in Asian practice—Active surveillance for indeterminate thyroid nodules reduces overtreatment of thyroid carcinomas
K. Kakudo, M. Higuchi, M. Hirokawa, S. Satoh, C. K. Jung, A. Bychkov
Cytopathology.2017; 28(6): 455. CrossRef
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
Journal of Pathology and Translational Medicine.2017; 51(6): 571. CrossRef

Original Articles

Image-Guided Fine Needle Cytology with Aspiration Versus Non-Aspiration in Retroperitoneal Masses: Is Aspiration Necessary?: Rajiv Kumar Misra, Shaila Mitra, Rishav Kumar Jain, Shilpa Vahikar, Archana Bundela, Purak Misra; J Pathol Transl Med. 2015;49(2):129-135. Published online March 12, 2015; DOI: https://doi.org/10.4132/jptm.2015.01.28

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Abstract PDF

Background
Although using fine needle cytology with aspiration (FNC-A) for establishing diagnoses in the retroperitoneal region has shown promise, there is scant literature supporting a role of non-aspiration cytology (FNC-NA) for this region. We assessed the accuracy and reliability of FNC-A and FNC-NA as tools for preoperative diagnosis of retroperitoneal masses and compared the results of both techniques with each other and with histopathology. Methods: Fifty-seven patients with retroperitoneal masses were subjected to FNC-A and FNC-NA. Smears were stained with May-Grunwald Giemsa and hematoxylin and eosin stain. An individual slide was objectively analysed using a point scoring system to enable comparison between FNC-A and FNC-NA. Results: By FNC-A, 91.7% accuracy was obtained in cases of retroperitoneal lymph node lesions followed by renal masses (83.3%). The diagnostic accuracy of other sites by FNC-A varied from 75.0%–81.9%. By FNC-NA, 93.4% diagnostically accurate results were obtained in the kidney, followed by 75.0% in adrenal masses. The diagnostic accuracy of other sites by FNC-NA varied from 66.7%–72.8%. Conclusions: Although both techniques have their own advantages and disadvantages, FNC-NA may be a more efficient adjuvant method of sampling in retroperitoneal lesions.

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Diagnostic Accuracy of Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology of Pancreatic Lesions: Hae Woon Baek, Min Jee Park, Ye-Young Rhee, Kyoung Bun Lee, Min A Kim, In Ae Park; J Pathol Transl Med. 2015;49(1):52-60. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.26

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Background
Endoscopic ultrasound–guided fine needle aspiration cytology (EUS-FNAC) is currently the most commonly used procedure for obtaining cytologic specimens of the pancreas. It is accurate, minimally invasive, safe and cost-effective. However, there is discrepancy between cytological and surgical diagnoses. This study was aimed at evaluating the diagnostic accuracy of EUS-FNAC of the pancreas. Methods: We performed a retrospective review of 191 cases of pancreatic lesions initially diagnosed by EUS-FNAC with subsequent histological diagnosis between 2010 and 2012 in the Department of Pathology, Seoul National University Hospital. Cytologic and surgical diagnoses were categorized into five groups: negative, benign, atypical, malignant, and insufficient for diagnosis. Subsequently, 167 cases with satisfactory yield in both surgical and cytology specimens were statistically analyzed to determine correlations with diagnosis. Results: In comparison to surgical diagnoses, cytologic diagnoses were true-positive in 103 cases (61.7%), true-negative in 28 cases (16.8%), false-positive in 9 cases (5.4%), and false-negative in 27 cases (16.1%). The diagnostic accuracy was 78.4%, sensitivity was 79.2%, and specificity was 75.7%. The positive predictive value was 92.0%, and negative predictive value was 50.9%. Conclusions: EUS-FNAC has high accuracy, sensitivity, specificity and positive predictive value. Overcoming the limitations of EUS-FNAC will make it a useful and reliable diagnostic tool for accurate evaluation of pancreatic lesions.

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