Journal of Pathology and Translational Medicine

Original Article

Spectrum of thyroiditis types: clinical, cytomorphological, and radiological findings: Anam Singh, Indrajeet Kundu; J Pathol Transl Med. 2025;59(6):421-433. Published online November 6, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.13

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Abstract PDF: Background
Thyroiditis encompasses a range of inflammatory conditions affecting the thyroid gland. Lymphocytic thyroiditis (LT) is a common form of thyroiditis, with acute suppuration of the thyroid, while tuberculous thyroiditis is relatively rare. Fine-needle aspiration cytology (FNAC) remains a safe and cost-effective tool for diagnosing thyroid-related diseases, especially when paired with ultrasound (US) and clinical examination. Methods: This is a cross-sectional study including 21 cases. The cases were reported as thyroiditis on US and FNAC, and the findings were correlated with patient clinical history, symptoms during presentation, and serological profiles. Results: The cases of thyroiditis encompassed the more common forms, LT and subacute granulomatous thyroiditis (SAT), as well as relatively rare forms like tuberculous thyroiditis and thyroid abscess. Cases of follicular neoplasms (FN) arising in the context of LT also are included in this study. The case of tuberculous thyroiditis presented as a bulky thyroid gland that appeared heterogeneous on US with extensive necrosis on FNAC. The cases of thyroid abscess and SAT presented with painful neck swellings, with granulomas in the latter cases. US features of LT showed an array of appearances ranging from pseudonodular to an atrophic thyroid gland. All cases of FN showed a lymphocytic background. Conclusions: Thyroiditis is a commonly encountered condition that needs to be sub-categorized accurately into acute, subacute, and chronic types for appropriate clinical management, as they can sometimes show overlapping features. Though rare, acute suppurative and tuberculous thyroiditis are often encountered and warrant immediate care and treatment.

Review Article

Recent topics on thyroid cytopathology: reporting systems and ancillary studies: Mitsuyoshi Hirokawa, Ayana Suzuki; J Pathol Transl Med. 2025;59(4):214-224. Published online June 30, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.18

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Abstract PDF: As fine-needle aspiration techniques and diagnostic methodologies for thyroid nodules have continued to evolve and reporting systems have been updated accordingly, we need to be up to date with the latest information to achieve accurate diagnoses. However, the diagnostic approaches and therapeutic strategies for thyroid nodules vary across laboratories and institutions. Several differences exist between Western and Eastern practices regarding thyroid fine-needle aspiration. This review describes the reporting systems for thyroid cytopathology and ancillary studies. Updated reporting systems enhance the accuracy, consistency, and clarity of cytology reporting, leading to improved patient outcomes and management strategies. Although a single global reporting system is optimal, reporting systems tailored to each country is acceptable. In such cases, compatibility must be ensured to facilitate data sharing. Ancillary methods include liquid-based cytology, immunocytochemistry, biochemical measurements, flow cytometry, molecular testing, and artificial intelligence, all of which improve diagnostic accuracy. These methods continue to evolve, and cytopathologists should actively adopt the latest methods and information to achieve more accurate diagnoses. We believe this review will be useful to practitioners of routine thyroid cytology.

Original Articles

Diagnostic yield of fine needle aspiration with simultaneous core needle biopsy for thyroid nodules: Mohammad Ali Hasannia, Ramin Pourghorban, Hoda Asefi, Amir Aria, Elham Nazar, Hojat Ebrahiminik, Alireza Mohamadian; J Pathol Transl Med. 2025;59(3):180-187. Published online April 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.03.04

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Abstract PDF: Background
Fine needle aspiration (FNA) is a widely utilized technique for assessing thyroid nodules; however, its inherent non-diagnostic rate poses diagnostic challenges. The present study aimed to evaluate and compare the diagnostic efficacy of FNA, core needle biopsy (CNB), and their combined application in the assessment of thyroid nodules.
Methods
A total of 56 nodules from 50 patients was analyzed using both FNA and simultaneous CNB. The ultrasound characteristics were categorized according to the American College of Radiology Thyroid Imaging Reporting and Data Systems classification system. The study compared the sensitivity, specificity, and accuracy of FNA, CNB, and the combination of the two techniques.
Results
The concordance between FNA and CNB was notably high, with a kappa coefficient of 0.837. The sensitivity for detecting thyroid malignancy was found to be 25.0% for FNA, 66.7% for CNB, and 83.3% for the combined FNA/CNB approach, with corresponding specificities of 84.6%, 97.4%, and 97.4%. The accuracy of the FNA/CNB combination was the highest at 94.1%.
Conclusions
The findings of this study indicate that both CNB and the FNA/CNB combination offer greater diagnostic accuracy for thyroid malignancy compared to FNA alone, with no significant complications reported. Integrating CNB with FNA findings may enhance management strategies and treatment outcomes for patients with thyroid nodules.

Characteristics of RET gene mutations in Vietnamese medullary thyroid carcinoma patients: a single-center analysis: Van Hung Pham, Quoc Thang Pham, Minh Nguyen, Hoa Nhat Ngo, Thao Thi Thu Luu, Nha Dao Thi Minh, Trâm Đặng, Anh Tu Thai, Hoang Anh Vu, Dat Quoc Ngo; J Pathol Transl Med. 2025;59(2):125-132. Published online March 14, 2025; DOI: https://doi.org/10.4132/jptm.2025.01.18

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Abstract PDF Supplementary Material: Background
The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

Low Ki-67 labeling index is a clinically useful predictive factor for recurrence-free survival in patients with papillary thyroid carcinoma: Takashi Masui, Katsunari Yane, Ichiro Ota, Kennichi Kakudo, Tomoko Wakasa, Satoru Koike, Hirotaka Kinugawa, Ryuji Yasumatsu, Tadashi Kitahara; J Pathol Transl Med. 2025;59(2):115-124. Published online February 18, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.08

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Abstract PDF

Background
We report a new risk stratification of invasive stage papillary thyroid carcinomas (PTCs) by combining invasive status, using extrathyroid invasion (Ex) status, and tumor growth speed using the Ki-67 labeling index (LI). Methods: We examined tumor recurrence in 167 patients with PTC who were surgically treated at the Kindai University Nara Hospital between 2010 and 2022. The patients were classified according to the degree of invasion [negative (Ex0) or positive (Ex1, Ex2, and Ex3)] and tumor growth speed expressed with Ki-67 LI, as low (<5%) or high (>5%). This study confirmed previous findings that the disease-free survival (DFS) rate in PTCs significantly differed between patients with a high and low Ki-67 index. Results: When combining Ex status (negative or positive) and Ki-67 proliferation status (low or high), the DFS rate of invasion in the negative, low Ki-67 LI group was only 1.1%, while that of invasion in the positive, high Ki-67 LI was 44.1%. This study reports for the first time that recurrence risks can be stratified accurately when combining carcinoma’s essential two features of extrathyroid invasion status and tumor growth speed. Conclusions: We believe the evidence for low tumor recurrence risk may contribute to use of more conservative treatment options for invasive-stage PTCs and help alleviate patient anxiety about tumor recurrence and death.

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Research Progress on the Correlation between Three Biomarkers, Ki-67, CAIX and VEGF and Clear Cell Renal Cell Carcinoma
锦容马
Advances in Clinical Medicine.2025; 15(09): 326. CrossRef
Immunophenotypic Panel for Comprehensive Characterization of Aggressive Thyroid Carcinomas
Mihail Ceausu, Mihai Alin Publik, Dana Terzea, Carmen Adina Cristea, Dumitru Ioachim, Dana Manda, Sorina Schipor
Cells.2025; 14(19): 1554. CrossRef
High Ki-67 labeling index correlates with aggressive clinicopathological features in papillary thyroid carcinoma: a retrospective study
Defi Nurlia Erdian, Maria Francisca Ham, Dina Khoirunnisa, Agnes Stephanie Harahap
Thyroid Research.2025;[Epub] CrossRef

Fine needle aspiration cytology diagnoses of follicular thyroid carcinoma: results from a multicenter study in Asia: Hee Young Na, Miyoko Higuchi, Shinya Satoh, Kaori Kameyama, Chan Kwon Jung, Su-Jin Shin, Shipra Agarwal, Jen-Fan Hang, Yun Zhu, Zhiyan Liu, Andrey Bychkov, Kennichi Kakudo, So Yeon Park; J Pathol Transl Med. 2024;58(6):331-340. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.12

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Abstract PDF Supplementary Material

Background
This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.

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Misdiagnosed follicular adenoma with 11 year postoperative liver and lung metastases a case report and literature review
Kai-Li Yang, Heng-Tong Han, Shou-Hua Li, Xiao-Xiao Li, Ze Yang, Li-Bin Ma, Yong-Xun Zhao
Discover Oncology.2025;[Epub] CrossRef

Review

Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes: Agnes Stephanie Harahap, Chan Kwon Jung; J Pathol Transl Med. 2024;58(6):265-282. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.11

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Abstract PDF

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, characterized by a range of subtypes that differ in their cytologic features, clinical behavior, and prognosis. Accurate cytologic evaluation of PTC using fine-needle aspiration is essential but can be challenging due to the morphologic diversity among subtypes. This review focuses on the distinct cytologic characteristics of various PTC subtypes, including the classic type, follicular variant, tall cell, columnar cell, hobnail, diffuse sclerosing, Warthin-like, solid/trabecular, and oncocytic PTCs. Each subtype demonstrates unique nuclear features, architectural patterns, and background elements essential for diagnosis and differentiation from other thyroid lesions. Recognizing these distinct cytologic patterns is essential for identifying aggressive subtypes like tall cell, hobnail, and columnar cell PTCs, which have a higher risk of recurrence, metastasis, and poorer clinical outcomes. Additionally, rare subtypes such as diffuse sclerosing and Warthin-like PTCs present unique cytologic profiles that must be carefully interpreted to avoid diagnostic errors. The review also highlights the cytologic indicators of lymph node metastasis and high-grade features, such as differentiated high-grade thyroid carcinoma. The integration of molecular testing can further refine subtype diagnosis by identifying specific genetic mutations. A thorough understanding of these subtype-specific cytologic features and molecular profiles is vital for accurate diagnosis, risk stratification, and personalized management of PTC patients. Future improvements in diagnostic techniques and standardization are needed to enhance cytologic evaluation and clinical decision-making in thyroid cancer.

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Oncocytic Thyroid Tumours With Pathogenic FLCN Mutations Mimic Oncocytic Papillary Thyroid Carcinoma on Fine‐Needle Aspiration
Adeel M. Ashraf, Faisal Hassan, Adrian A. Dawkins, Julie C. Dueber, Derek B. Allison, Thèrése J. Bocklage
Cytopathology.2026; 37(1): 108. CrossRef
Using a new type of visible light-based emission fluorescence microscope to identify the benign and malignant nature of thyroid tissue during the surgical process: Analysis of diagnostic results
Yu Miao, Liu Xiaowei, Li Muyang, Gao Jian, Chen Lu
Photodiagnosis and Photodynamic Therapy.2026; 57: 105324. CrossRef
Nuclear pseudoinclusion is associated with BRAFV600E mutation: Analysis of nuclear features in papillary thyroid carcinoma
Agnes Stephanie Harahap, Dina Khoirunnisa, Salinah, Maria Francisca Ham
Annals of Diagnostic Pathology.2025; 75: 152434. CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shin Je Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyo
International Journal of Thyroidology.2025; 18(1): 30. CrossRef
Structure-based molecular screening and dynamic simulation of phytocompounds targeting VEGFR-2: a novel therapeutic approach for papillary thyroid carcinoma
Shuai Wang, Lingqian Zhang, Wenjun Zhang, Xiong Zeng, Jie Mei, Weidong Xiao, Lijie Yang
Frontiers in Pharmacology.2025;[Epub] CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shinje Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyon
Endocrinology and Metabolism.2025; 40(3): 307. CrossRef
A Case of Warthin-Like Variant of Papillary Thyroid Cancer
Amy Chow, Israa Laklouk
Cureus.2025;[Epub] CrossRef
Propensity score-matched analysis of the ‘2+2’ parathyroid strategy in total thyroidectomy with central neck dissection
Hao Gong, Simei Yao, Tianyuchen Jiang, Yi Yang, Yuhan Jiang, Zhujuan Wu, Anping Su
Frontiers in Endocrinology.2025;[Epub] CrossRef

Original Articles

Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning: Truong Phan-Xuan Nguyen, Minh-Khang Le, Sittiruk Roytrakul, Shanop Shuangshoti, Nakarin Kitkumthorn, Somboon Keelawat; J Pathol Transl Med. 2025;59(1):39-49. Published online October 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.14

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Abstract PDF Supplementary Material

Background
Although the criteria for follicular-pattern thyroid tumors are well-established, diagnosing these lesions remains challenging in some cases. In the recent World Health Organization Classification of Endocrine and Neuroendocrine Tumors (5th edition), the invasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as its own entity. It is crucial to differentiate this variant of papillary thyroid carcinoma from low-risk follicular pattern tumors due to their shared morphological characteristics. Proteomics holds significant promise for detecting and quantifying protein biomarkers. We investigated the potential value of a protein biomarker panel defined by machine learning for identifying the invasive encapsulated follicular variant of papillary thyroid carcinoma, initially using formalin- fixed paraffin-embedded samples.
Methods
We developed a supervised machine-learning model and tested its performance using proteomics data from 46 thyroid tissue samples.
Results
We applied a random forest classifier utilizing five protein biomarkers (ZEB1, NUP98, C2C2L, NPAP1, and KCNJ3). This classifier achieved areas under the curve (AUCs) of 1.00 and accuracy rates of 1.00 in training samples for distinguishing the invasive encapsulated follicular variant of papillary thyroid carcinoma from non-malignant samples. Additionally, we analyzed the performance of single-protein/gene receiver operating characteristic in differentiating the invasive encapsulated follicular variant of papillary thyroid carcinoma from others within The Cancer Genome Atlas projects, which yielded an AUC >0.5.
Conclusions
We demonstrated that integration of high-throughput proteomics with machine learning can effectively differentiate the invasive encapsulated follicular variant of papillary thyroid carcinoma from other follicular pattern thyroid tumors.

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Misdiagnosed follicular adenoma with 11 year postoperative liver and lung metastases a case report and literature review
Kai-Li Yang, Heng-Tong Han, Shou-Hua Li, Xiao-Xiao Li, Ze Yang, Li-Bin Ma, Yong-Xun Zhao
Discover Oncology.2025;[Epub] CrossRef

TERT mutations and aggressive histopathologic characteristics of radioiodine-refractory papillary thyroid cancer: Ju Yeon Pyo, Yoon Jin Cha, SoonWon Hong; J Pathol Transl Med. 2024;58(6):310-320. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.29

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Abstract PDF

Background
Radioiodine (RI) ablation following thyroid-stimulating hormone suppression is an effective treatment for papillary thyroid cancer (PTC), typically leading to favorable outcomes. However, RI-refractory tumors exhibit aggressive behavior and poor prognoses. Recent studies highlight the role of genetic abnormalities in PTC signaling pathways, including the activation of telomerase reverse transcriptase (TERT), and the correlation of mutations with adverse outcomes.
Methods
This study analyzed mutations in BRAF V600E and the TERT-promoter genes, comparing clinicopathological features between RI-refractory and RI-responsive PTCs. Among 82 RI-refractory patients, formalin-fixed, paraffin-embedded tissues from initial surgeries were available for 26. Another 89 without distant metastasis over 5 years formed a matched RI-responsive control group.
Results
Histopathologically, RI-refractory PTCs showed increased frequencies of small tumor clusters without fibrovascular cores, hobnail features, and a high height-to-width ratio of tumor cells. These tumors were more likely to exhibit necrosis, mitosis, lymph node metastasis, extrathyroidal extension, and involvement of resection margins. TERT-promoter mutations were statistically significantly associated with these aggressive clinicopathologic features. Immunohistochemically, decreased expression of sodium iodide symporter and thyroglobulin stimulating hormone receptor proteins was common in RI-refractory PTCs, along with lower levels of oncogenic proteins such as vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells. Total loss of PTEN expression was occasionally observed. In contrast, all cases tested positive for cytoplasmic β-catenin.
Conclusions
RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.

Citations

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Characterizing thyroid carcinomas in the elderly: Histological subtypes and TERT promoter mutation analysis based on the latest WHO classification
Myoung Ju Koh, Songmi Noh, Jin Kyong Kim, Gi Jeong Kim
Annals of Diagnostic Pathology.2026; 80: 152578. CrossRef
The ability of anexelekto (AXL) expression and TERT promoter mutation to predict radioiodine-refractory differentiated thyroid carcinoma
Hasrayati Agustina, Tutik Nur Ayni, Yohana Azhar, Erwin Affandi Soeriadi, Bethy Suryawathy Hernowo
Diagnostic Pathology.2025;[Epub] CrossRef
Clinicopathologic characteristics of papillary thyroid carcinoma, tall cell subtype and subtype with tall cell features, an institutional experience
Xueting Jin, Shunsuke Koga, Xiao Zhou, Niaz Z. Khan, Zubair W. Baloch
Human Pathology.2025; 161: 105867. CrossRef
Calcifying nested stromal-epithelial tumor of the liver: Report of two cases revealing novel WT1 mutation and distinct epigenetic features
Andrea Strakova-Peterikova, Franco Fedeli, Boris Rychly, Jiri Soukup, Michael Michal, Petr Martinek, Marian Grendar, Elaheh Mosaieby, Nikola Ptakova, Maryna Slisarenko, Michal Michal, Kvetoslava Michalova
Virchows Archiv.2025;[Epub] CrossRef
Insulin resistance and metabolic dysfunction in thyroid nodules and differentiated thyroid cancer
Stefano Iuliano, Maria Mirabelli, Stefania Giuliano, Antonio Brunetti
Current Opinion in Oncology.2025;[Epub] CrossRef

Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study: Agnes Stephanie Harahap, Mutiah Mutmainnah, Maria Francisca Ham, Dina Khoirunnisa, Abdillah Hasbi Assadyk, Husni Cangara, Aswiyanti Asri, Diah Prabawati Retnani, Fairuz Quzwain, Hasrayati Agustina, Hermawan Istiadi, Indri Windarti, Krisna Murti, Muhammad Takbir, Ni Made Mahastuti, Nila Kurniasari, Nungki Anggorowati, Pamela Abineno, Yulita Pundewi Setyorini, Kennichi Kakudo; J Pathol Transl Med. 2024;58(6):299-309. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.25; Correction in: J Pathol Transl Med 2025;59(3):201

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Abstract PDF Supplementary Material

Background
The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms.
Methods
This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test.
Results
Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = –0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001).
Conclusions
The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.

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Nuclear pseudoinclusion is associated with BRAFV600E mutation: Analysis of nuclear features in papillary thyroid carcinoma
Agnes Stephanie Harahap, Dina Khoirunnisa, Salinah, Maria Francisca Ham
Annals of Diagnostic Pathology.2025; 75: 152434. CrossRef

Educational exchange in thyroid core needle biopsy diagnosis: enhancing pathological interpretation through guideline integration and peer learning: Agnes Stephanie Harahap, Chan Kwon Jung; J Pathol Transl Med. 2024;58(5):205-213. Published online July 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.06.24

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Abstract PDF

Background
While fine needle aspiration cytology (FNAC) plays an essential role in the screening of thyroid nodules, core needle biopsy (CNB) acts as an alternative method to address FNAC limitations. However, diagnosing thyroid CNB samples can be challenging due to variations in background and levels of experience. Effective training is indispensable to mitigate this challenge. We aim to evaluate the impact of an educational program on improving the accuracy of CNB diagnostics.
Methods
The 2-week observational program included a host mentor pathologist with extensive experience and a visiting pathologist. The CNB classification by The Practice Guidelines Committee of the Korean Thyroid Association was used for the report. Two rounds of reviewing the case were carried out, and the level of agreement between the reviewers was analyzed.
Results
The first-round assessment showed a concordance between two pathologists for 247 thyroid CNB specimens by 84.2%, with a kappa coefficient of 0.74 (indicating substantial agreement). This finding was attributed to the discordance in the use of categories III and V. After peer learning, the two pathologists evaluated 30 new cases, which showed an overall improvement in the level of agreement. The percentage of agreement between pathologists on thyroid CNB diagnosis was 86.7%, as measured by kappa coefficient of 0.80.
Conclusions
This educational program, consisting of guided mentorship and peer learning, can substantially enhance the diagnostic accuracy of thyroid CNB. It is useful in promoting consistent diagnostic standards and contributes to the ongoing development of global pathology practices.

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Lessons learned from the first 2 years of experience with thyroid core needle biopsy at an Indonesian national referral hospital
Agnes Stephanie Harahap, Maria Francisca Ham, Retno Asti Werdhani, Erwin Danil Julian, Rafi Ilmansyah, Chloe Indira Arfelita Mangunkusumso, Tri Juli Edi Tarigan
Journal of Pathology and Translational Medicine.2025; 59(3): 149. CrossRef

Review

Welcoming the new, revisiting the old: a brief glance at cytopathology reporting systems for lung, pancreas, and thyroid: Rita Luis, Balamurugan Thirunavukkarasu, Deepali Jain, Sule Canberk; J Pathol Transl Med. 2024;58(4):165-173. Published online July 15, 2024; DOI: https://doi.org/10.4132/jptm.2024.06.11

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Abstract PDF

This review addresses new reporting systems for lung and pancreatobiliary cytopathology as well as the most recent edition of The Bethesda Reporting System for Thyroid Cytopathology. The review spans past, present, and future aspects within the context of the intricate interplay between traditional morphological assessments and cutting-edge molecular diagnostics. For lung and pancreas, the authors discuss the evolution of reporting systems, emphasizing the bridge between past directives and more recent collaborative efforts of the International Academy of Cytology and the World Health Organization in shaping universal reporting systems. The review offers a brief overview of the structure of these novel systems, highlighting their strengths and pinpointing areas that require further refinement. For thyroid, the authors primarily focus on the third edition of The Bethesda System for Reporting Thyroid Cytopathology, also considering the two preceding editions. This review serves as an invaluable resource for cytopathologists, offering a panoramic view of the evolving landscape of cytopathology reporting and pointing out the integrative role of the cytopathologist in an era of rapid diagnostic and therapeutic advancements.

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WHO Reporting System for Lung Cytopathology: Insights Into the Insufficient/Inadequate/Non‐Diagnostic, Atypical and Suspicious for Malignancy Categories and How to Use Them
Zahra Maleki, Sule Canberk, Andrew Field
Cytopathology.2025; 36(5): 434. CrossRef
Reproducibility of the Bethesda system for reporting thyroid cytopathology (TBSRTC): An observational study of 100 patients
Kishori Moni Panda, Reena Naik, Mohd Ghouse Mohiddin
Indian Journal of Pathology and Oncology.2024; 11(4): 385. CrossRef

Original Articles

Revisiting the utility of identifying nuclear grooves as unique nuclear changes by an object detector model: Pedro R. F. Rende, Joel Machado Pires, Kátia Sakimi Nakadaira, Sara Lopes, João Vale, Fabio Hecht, Fabyan E. L. Beltrão, Gabriel J. R. Machado, Edna T. Kimura, Catarina Eloy, Helton E. Ramos; J Pathol Transl Med. 2024;58(3):117-126. Published online April 30, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.07

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Abstract PDF: Background
Among other structures, nuclear grooves are vastly found in papillary thyroid carcinoma (PTC). Considering that the application of artificial intelligence in thyroid cytology has potential for diagnostic routine, our goal was to develop a new supervised convolutional neural network capable of identifying nuclear grooves in Diff-Quik stained whole-slide images (WSI) obtained from thyroid fineneedle aspiration.
Methods
We selected 22 Diff-Quik stained cytological slides with cytological diagnosis of PTC and concordant histological diagnosis. Each of the slides was scanned, forming a WSI. Images that contained the region of interest were obtained, followed by pre-formatting, annotation of the nuclear grooves and data augmentation techniques. The final dataset was divided into training and validation groups in a 7:3 ratio.
Results
This is the first artificial intelligence model based on object detection applied to nuclear structures in thyroid cytopathology. A total of 7,255 images were obtained from 22 WSI, totaling 7,242 annotated nuclear grooves. The best model was obtained after it was submitted 15 times with the train dataset (14th epoch), with 67% true positives, 49.8% for sensitivity and 43.1% for predictive positive value.
Conclusions
The model was able to develop a structure predictor rule, indicating that the application of an artificial intelligence model based on object detection in the identification of nuclear grooves is feasible. Associated with a reduction in interobserver variability and in time per slide, this demonstrates that nuclear evaluation constitutes one of the possibilities for refining the diagnosis through computational models.

Identification of invasive subpopulations using spatial transcriptome analysis in thyroid follicular tumors: Ayana Suzuki, Satoshi Nojima, Shinichiro Tahara, Daisuke Motooka, Masaharu Kohara, Daisuke Okuzaki, Mitsuyoshi Hirokawa, Eiichi Morii; J Pathol Transl Med. 2024;58(1):22-28. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.21

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Abstract PDF

Background
Follicular tumors include follicular thyroid adenomas and carcinomas; however, it is difficult to distinguish between the two when the cytology or biopsy material is obtained from a portion of the tumor. The presence or absence of invasion in the resected material is used to differentiate between adenomas and carcinomas, which often results in the unnecessary removal of the adenomas. If nodules that may be follicular thyroid carcinomas are identified preoperatively, active surveillance of other nodules as adenomas is possible, which reduces the risk of surgical complications and the expenses incurred during medical treatment. Therefore, we aimed to identify biomarkers in the invasive subpopulation of follicular tumor cells.
Methods
We performed a spatial transcriptome analysis of a case of follicular thyroid carcinoma and examined the dynamics of CD74 expression in 36 cases.
Results
We identified a subpopulation in a region close to the invasive area, and this subpopulation expressed high levels of CD74. Immunohistochemically, CD74 was highly expressed in the invasive and peripheral areas of the tumor.
Conclusions
Although high CD74 expression has been reported in papillary and anaplastic thyroid carcinomas, it has not been analyzed in follicular thyroid carcinomas. Furthermore, the heterogeneity of CD74 expression in thyroid tumors has not yet been reported. The CD74-positive subpopulation identified in this study may be useful in predicting invasion of follicular thyroid carcinomas.

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Biomedicine & Pharmacotherapy.2026; 194: 118945. CrossRef
Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning
Truong Phan-Xuan Nguyen, Minh-Khang Le, Sittiruk Roytrakul, Shanop Shuangshoti, Nakarin Kitkumthorn, Somboon Keelawat
Journal of Pathology and Translational Medicine.2025; 59(1): 39. CrossRef
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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.

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Dorota Słowińska-Klencka, Bożena Popowicz, Joanna Duda-Szymańska, Mariusz Klencki
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Hee Young Na, Miyoko Higuchi, Shinya Satoh, Kaori Kameyama, Chan Kwon Jung, Su-Jin Shin, Shipra Agarwal, Jen-Fan Hang, Yun Zhu, Zhiyan Liu, Andrey Bychkov, Kennichi Kakudo, So Yeon Park
Journal of Pathology and Translational Medicine.2024; 58(6): 331. CrossRef

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.

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Journal of Pathology and Translational Medicine.2025; 59(3): 149. CrossRef
Risk Stratification of Thyroid Nodules Diagnosed as Follicular Neoplasm on Core Needle Biopsy
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Core needle biopsy for thyroid nodules assessment-a new horizon?
David D Dolidze, Serghei Covantsev, Grigorii M Chechenin, Natalia V Pichugina, Anastasia V Bedina, Anna Bumbu
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Case Studies

Intrathyroidal metastasis of tonsillar squamous cell carcinoma masquerading as a primary thyroid tumor: Jai-Hyang Go; J Pathol Transl Med. 2023;57(4):242-245. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.16

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Abstract PDF

Intrathyroidal metastasis of tonsillar squamous cell carcinoma is rare. To date, only six cases have been reported in the literature. This case was unusual and presented with thyromegaly before the diagnosis of the primary tumor. A 55-year-old male patient was suspected to have a primary thyroid tumor with nodal metastasis. The thyroid gland was diffusely enlarged, with no discernible mass. Histologically, the thyroid parenchyma revealed extensive endolymphatic tumor emboli, which were positive for p40 and p16 in a background of chronic lymphocytic thyroiditis. Positron emission tomography–computed tomography revealed hypermetabolic activity in the right tonsillar region. Tonsillar biopsy revealed human papillomavirus–positive squamous cell carcinoma. The present case is the first reported case of intrathyroidal metastasis of tonsillar squamous cell carcinoma with an initial clinical presentation of thyroid enlargement before the primary tumor of tonsillar cancer was diagnosed.

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Metastasis to Thyroid from Recurrent Head and Neck Squamous Cell Carcinoma: A Case Series and Review of Literature
Avneet Kaur, Rohit Nayyar, Harit Kumar Chaturvedi, Akshat Malik
Indian Journal of Surgical Oncology.2025; 16(1): 122. CrossRef
Metastatic oropharyngeal squamous cell carcinoma to the thyroid: A case report and review of literature
Hannah Walker, Jed Speers, Milena Fabry, Sameep Kadakia
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Thyroid pathology, a clue to PTEN hamartoma tumor syndrome: Yurimi Lee, Young Lyun Oh; J Pathol Transl Med. 2023;57(3):178-183. Published online March 30, 2023; DOI: https://doi.org/10.4132/jptm.2023.03.04

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Abstract PDF

Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline inactivating mutations in the PTEN tumor suppressor gene. As a type of PHTS, Cowden syndrome is associated with abnormalities of the thyroid, breast, uterus, and gastrointestinal tract. A 52-year-old-woman visited the outpatient clinic of our endocrinology clinic with multiple thyroid nodules and Hashimoto's thyroiditis. Computed tomography imaging revealed a multinodular mass measuring up to 3.5 cm in the left thyroid lobe, causing laryngotracheal airway displacement. The total thyroidectomy specimen revealed multiple follicular adenomas and adenomatous nodules with lymphocytic thyroiditis and lipomatous metaplasia in the background. The patient was suspected of PTHS based on her thyroid pathology, family history, and numerous hamartomatous lesions of the breast, uterus, and skin. Her diagnosis was confirmed through molecular testing. This case demonstrates that pathologists must be well acquainted with thyroid pathology in PHTS.

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A clinical case of papillary thyroid cancer associated with a PTEN gene defect
R. A. Atanesyan, L. Ja. Klimov, T. M. Vdovina, G. A. Saneeva, E. I. Andreeva, I. A. Stremenkova, R. I. Arakelyan, I. K. Gasparyan
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Review

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy: Hee Young Na, So Yeon Park; J Pathol Transl Med. 2022;56(6):319-325. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.09.29

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Abstract PDF

Due to the extremely indolent behavior, a subset of noninvasive encapsulated follicular variant papillary thyroid carcinomas has been classified as “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)” since 2016 and is no longer considered carcinoma. Since the introduction of this new terminology, changes and refinements have been made in diagnostic criteria. Initially, the incidence of NIFTP was estimated substantial. However, the reported incidence of NIFTP varies greatly among studies and regions, with higher incidence in North American and European countries than in Asian countries. Thus, the changes in the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) differ inevitably among regions. Because more conservative surgery is recommended for NIFTPs, distinguishing NIFTPs from papillary thyroid carcinomas in preoperative fine-needle aspiration cytology became one of the major concerns. This review will provide comprehensive overview of updates on diagnostic criteria, actual incidence and preoperative cytologic diagnoses of NIFTP, and its impact on the ROM in TBSRTC.

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Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning
Truong Phan-Xuan Nguyen, Minh-Khang Le, Sittiruk Roytrakul, Shanop Shuangshoti, Nakarin Kitkumthorn, Somboon Keelawat
Journal of Pathology and Translational Medicine.2025; 59(1): 39. CrossRef
Papillae, psammoma bodies, and/or many nuclear pseudoinclusions are helpful criteria but should not be required for a definitive cytologic diagnosis of papillary thyroid carcinoma: An institutional experience of 207 cases with surgical follow up
Tarik M. Elsheikh, Matthew Thomas, Jennifer Brainard, Jessica Di Marco, Erica Manosky, Bridgette Springer, Dawn Underwood, Deborah J. Chute
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Oncocytic Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Case Report
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Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes
Agnes Stephanie Harahap, Chan Kwon Jung
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Preoperative evaluation of thyroid nodules – Diagnosis and management strategies
Tapoi Dana Antonia, Lambrescu Ioana Maria, Gheorghisan-Galateanu Ancuta-Augustina
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Chan Kwon Jung
Journal of Pathology and Translational Medicine.2023; 57(4): 208. CrossRef
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Deepika Yadav, Pramod Kumar Sharma, Rishabha Malviya, Prem Shankar Mishra
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Case Study

Papillary and medullary thyroid carcinomas coexisting in the same lobe, first suspected based on fine-needle aspiration cytology: a case report: Hyun Hee Koh, Young Lyun Oh; J Pathol Transl Med. 2022;56(5):301-308. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.03

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Abstract PDF

Because different types of thyroid malignancies have distinct embryological origins, coexisting tumors are rarely observed. We describe a coexisting papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) first suspected by fine-needle aspiration cytology (FNAC). A 57-year-old female presented with an irregular mass in the right thyroid lobe. The cytopathologic findings of fine-needle aspiration showed two components: a papillary-like arrangement consisting of cells with pale enlarged nuclei indicative of PTC and loose clusters comprised of oval cells with granular chromatin indicative of MTC. The diagnosis of a coexisting PTC and MTC was initially confirmed by calcitonin immunocytochemistry and later after total thyroidectomy. Although some surgical case reports of PTC and MTC coexisting in either the same or different lobes have been documented, a case suspected by FNAC before the surgery has rarely been reported. Because appropriate treatment and prognosis of PTC and MTC are different, cytopathologists should be aware of this rare entity.

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Evaluation of Diagnostic Accuracy of Medullary Thyroid Carcinoma Using Fine‐Needle Aspiration Cytology—Based on a Single Tertiary Centre Experience
Si‐Yi Chen, Dong‐Mei Gu
Cytopathology.2026;[Epub] CrossRef
Synchronous papillary and medullary thyroid carcinoma with distinct genetic mutations: A case report
Huanyu Jiang, Lijuan Zhou, Gang Zou, Haidong Zhang, Zhenkun Yu
Oral Oncology.2025; 161: 107191. CrossRef
Coexisting papillary and medullary thyroid carcinomas in a 60 year old male: a case report
Allahdad Khan, Anam Malik, Abdul Ahad Riaz, Muhammad Hussnain Sadiq, Muhammad Shahzaib Arshad, Alka Rani, Ibrahim Nagmeldin Hassan
Annals of Medicine & Surgery.2025; 87(10): 6740. CrossRef
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Suyeon Kim, Hyunsik Bae, Hyun-Soo Kim
Diagnostics.2024; 14(2): 160. CrossRef
Coexisting Medullary and Papillary Thyroid Carcinomas: A Case of Dual Neoplasia With a High Risk of Misdiagnosis
Santiago Sierra Castillo, Maria A Henao Rincón, David Aristizabal Colorado, David Alexander Vernaza Trujillo, Alin Abreu Lomba
Cureus.2024;[Epub] CrossRef

Original Article

Correlation between myoferlin expression and lymph node metastasis in papillary thyroid carcinoma: Ji Min Na, Dong Chul Kim, Dae Hyun Song, Hyo Jung An, Hyun Min Koh, Jeong-Hee Lee, Jong Sil Lee, Jung Wook Yang, Min Hye Kim; J Pathol Transl Med. 2022;56(4):199-204. Published online May 11, 2022; DOI: https://doi.org/10.4132/jptm.2022.03.19

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Abstract PDF: Background
Myoferlin is a multifunctional protein expressed in various normal and cancer cells, with novel oncogenic roles being newly discovered. Recently, correlations have been found between myoferlin expression and unfavorable prognosis in various carcinomas. This study investigated the prognostic role of myoferlin expression in papillary thyroid carcinoma (PTC), specifically that associated with nodal metastasis.
Methods
We collected clinicopathological data and PTC tissues from 116 patients who had been admitted to Gyeongsang National University Hospital in 2010. Immunohistochemical analysis was performed on surgical specimen-derived tissue microarray blocks. Myoferlin expression was graded, and the relationship between expression level and pathological features of tumors based on the American Joint Committee on Cancer staging system was evaluated.
Results
Of the 116 patient samples, 100 cases exhibited positive myoferlin expression. Higher grade of myoferlin expression was correlated with lower T category group (p = .010). Presence of lymph node metastasis was determined to be significantly correlated with low-grade myoferlin expression (p = .019), with no significant difference between pN1a and pN1b tumors.
Conclusions
Our study revealed an adverse correlation between myoferlin expression and pathological features of PTC, evidence of the potential prognostic role of myoferlin in PTC lymph node metastasis.

Case Studies

TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma: Anurag Mehta, Himanshi Diwan, Divya Bansal, Manoj Gupta; J Pathol Transl Med. 2022;56(1):53-56. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.16

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Abstract PDF

SMARCA4/BRG1-deficient lung adenocarcinoma (SD-LUAD) is being recognized as a distinct subtype based on subtle differences in its clinical, morphological, and immunophenotypic attributes compared to other non–small cell lung carcinomas. We present here a case of SD-LUAD with curious thyroid transcription factor 1 (TTF1) expression in a morphologically heterogenous lung adenocarcinoma. The better differentiated area showed preservation of TTF1 expression, and a poorly differentiated tumor had loss of TTF1 expression with universal BRG1 loss.

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SMARCA4-deficient Non–small Cell Lung Cancer on 18F-FDG PET/CT
Tao Liu, Hengshan Ji, Siyuan Jiang, Rongxin Qi, Xiaodie Zhou, Jingjing Sun, Jiang Wu
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Current Problems in Cancer: Case Reports.2022; 8: 100205. CrossRef

Metastatic leiomyosarcoma of the thyroid gland: cytologic findings and differential diagnosis: Jiyeon Lee, Yunjoo Cho, Kyue Hee Choi, Inwoo Hwang, Young Lyun Oh; J Pathol Transl Med. 2021;55(5):360-365. Published online August 13, 2021; DOI: https://doi.org/10.4132/jptm.2021.06.23

5,454 View
102 Download
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Abstract PDF

Metastatic leiomyosarcoma to the thyroid is an extremely rare occurrence, and only 18 cases have been reported. Here, we report a case of a 37-year-old woman who presented with multiple masses on the scalp. Excisional biopsy was done and the mass revealed fascicles of smooth muscle fibers which showed positive staining for smooth muscle actin, thus confirming the diagnosis of leiomyosarcoma. The patient was also found to have a 0.9 cm mass within the left thyroid. Fine-needle aspiration was done and the cytological smear showed hypercellular spindle cell clusters with hyperchromatic and large nuclei. Normal thyroid follicular cells were found within or around tumor cells. In this report, we present the cytologic findings of metastatic leiomyosarcoma to the thyroid and offer differential diagnoses of the aspirated spindle cells.

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Original Articles

Proto-oncogene Pokemon in thyroid cancer: a potential promoter of tumorigenesis in papillary thyroid carcinoma: Kyungseek Chang, Sung-Im Do, Kyungeun Kim, Seoung Wan Chae, In-gu Do, Hyun Joo Lee, Dong Hoon Kim, Jin Hee Sohn; J Pathol Transl Med. 2021;55(5):317-323. Published online August 9, 2021; DOI: https://doi.org/10.4132/jptm.2021.06.28

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Abstract PDF Supplementary Material

Background
Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters.
Methods
Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed.
Results
Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006).
Conclusions
Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

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Systems biology approach delineates critical pathways associated with papillary thyroid cancer: a multi-omics data analysis
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Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma: Tripti Nakra, Varsha Singh, Aruna Nambirajan, Prabhat Singh Malik, Anant Mohan, Deepali Jain; J Pathol Transl Med. 2021;55(4):279-288. Published online July 8, 2021; DOI: https://doi.org/10.4132/jptm.2021.05.10

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Abstract PDF

Background
Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort.
Methods
This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the
results
were analyzed. Results: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed.
Conclusions
Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

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Review

Thyroid fine-needle aspiration cytology in Taiwan: a nationwide survey and literature update: Chien-Chin Chen, Jen-Fan Hang, Chih-Yi Liu, Yeh-Han Wang, Chiung-Ru Lai; J Pathol Transl Med. 2020;54(5):361-366. Published online August 31, 2020; DOI: https://doi.org/10.4132/jptm.2020.07.17

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Abstract PDF

In Taiwan, thyroid fine-needle aspiration cytology is easily accessible and reliable for evaluating thyroid nodules. The sonographic pattern plays a major role and is the deciding factor for aspiration. We conducted a nationwide survey in 2017 and it revealed that 31% of laboratories had adopted The Bethesda System for Reporting Thyroid Cytopathology. There was a relatively high unsatisfactory rate (24.04%) and low rates of indeterminate diagnoses, including atypia of undetermined significance/follicular lesions of undetermined significance: 4.87%, and follicular neoplasm/suspicious for a follicular neoplasm: 0.35%. Moreover, the risks of malignancy in benign, atypia of undetermined significance, and suspicious for a follicular neoplasm were relatively high. These may reflect strict diagnostic criteria for indeterminate categories and better patient selection for surgery. Improvements in specimen sampling and continuing education programs are crucial. Newly-developed thyroid cytology technologies, such as immunocytochemistry, molecular testing, and computerized cytomorphometry, may further facilitate cytology diagnoses.

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Original Articles

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.

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Contribution of cytologic examination to diagnosis of poorly differentiated thyroid carcinoma: Na Rae Kim, Jae Yeon Seok, Yoo Seung Chung, Joon Hyop Lee, Dong Hae Chung; J Pathol Transl Med. 2020;54(2):171-178. Published online February 5, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.03

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Abstract PDF

Background
The cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) is difficult because it lacks salient cytologic findings and shares cytologic features with more commonly encountered neoplasms. Due to diverse cytologic findings and paucicellularity of PDTC, standardization of cytologic diagnostic criteria is limited. The purpose of this study is to investigate and recognize diverse thyroid findings of fine needle aspiration (FNA) cytology and frozen smear cytology in diagnosis of this rare but aggressive carcinoma.
Methods
The present study included six cases of FNA cytology and frozen smears of histologically diagnosed PDTCs.
Results
PDTC showed cytologic overlap with well-differentiated thyroid carcinomas (WDTCs). Five of six cases showed dedifferentiation arising from well differentiated thyroid carcinomas. Only one de novo PDTC showed highly cellular smears composed of discohesive small cells, high nuclear/cytoplasmic (N/C) ratio, prominent micronucleoli, and irregular nuclei. Retrospectively reviewed, these findings are highly suspicious for PDTC. Cytologic findings of nuclear atypia, pleomorphism, and irregularity were frequently found, whereas scattered small cells were seen only in the de novo case.
Conclusions
Heterogeneous cytologic findings of PDTCs are shared with those of WDTCs and contribute to difficult preoperative cytologic diagnoses. Most PDTCs show dedifferentiation from WDTCs. Albeit rare, de novo PDTC should be considered with cytology showing discohesive small cells with high N/C ratio. This will enable precise diagnosis and prompt treatment of this aggressive malignancy

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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 Articles

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.

Citations

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Case report & review: Bilateral NIFTP harboring concomitant HRAS and KRAS mutation: Report of an unusual case and literature review
Marianna Rita Brogna, Francesca Collina, Maria Grazia Chiofalo, Debora De Bartolo, Angela Montone, Maria Rosaria Schiano, Michele Del Sesto, Nubia Pizza, Gerardo Ferrara
Molecular Carcinogenesis.2024; 63(12): 2273. CrossRef
Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): what do we need to know?
Andrés Coca-Pelaz, Juan P. Rodrigo, Abbas Agaimy, Dana M. Hartl, Göran Stenman, Vincent Vander Poorten, Antti A. Mäkitie, Mark Zafereo, Karthik N. Rao, Gregory W. Randolph, Alessandra Rinaldo, Alfio Ferlito
Virchows Archiv.2024; 485(6): 977. CrossRef
Study of non-invasive follicular thyroid neoplasm: A borderline entity
Rupali Bavikar, Ruchi S. Randive, Anubhaw Verma, Madhuri Singh, Vidya Viswanathan, Arpana Dharwadkar
Journal of Cancer Research and Therapeutics.2024; 20(5): 1365. CrossRef
Analysis of a pre-2017 follicular variant papillary thyroid carcinoma cohort reclassified as noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP): an 11-year retrospective single institution experience
Shaham Beg, Sana Irfan Khan, Isabella Cui, Theresa Scognamiglio, Rema Rao
Journal of the American Society of Cytopathology.2023; 12(2): 112. CrossRef
Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: What a Surgeon Should Know
Jabir Alharbi, Thamer Alraddadi, Haneen Sebeih, Mohammad A Alessa, Haddad H Alkaf, Ahmed Bahaj, Sherif K Abdelmonim
Cureus.2023;[Epub] CrossRef
NTRK Fusion in a Cohort of BRAF p. V600E Wild-Type Papillary Thyroid Carcinomas
Seung Eun Lee, Mi-Sook Lee, Heejin Bang, Mi Young Kim, Yoon-La Choi, Young Lyun Oh
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A Comprehensive Study on the Diagnosis and Management of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features
Bayan A. Alzumaili, Lauren N. Krumeich, Reagan Collins, Timothy Kravchenko, Emad I. Ababneh, Adam S. Fisch, William C. Faquin, Vania Nosé, Maria Martinez-Lage, Gregory W. Randolph, Rajshri M. Gartland, Carrie C. Lubitz, Peter M. Sadow
Thyroid.2023; 33(5): 566. CrossRef
Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center
Paola Vignali, Agnese Proietti, Elisabetta Macerola, Anello Marcello Poma, Liborio Torregrossa, Clara Ugolini, Alessio Basolo, Antonio Matrone, Teresa Rago, Ferruccio Santini, Rossella Elisei, Gabriele Materazzi, Fulvio Basolo
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Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy
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Clinicopathological parameters for predicting non-invasive follicular thyroid neoplasm with papillary features (NIFTP)
Eunju Jang, Kwangsoon Kim, Chan Kwon Jung, Ja Seong Bae, Jeong Soo Kim
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The Incidence of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Meta-Analysis Assessing Worldwide Impact of the Reclassification
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Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is rare, benign lesion using modified stringent diagnostic criteria: Reclassification and outcome study
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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; J Pathol Transl Med. 2018;52(6):404-410. Published online October 15, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.20

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Abstract PDF

Background
Fine-needle aspiration cytology serves as a safe, economical tool in evaluating thyroid nodules. However, about 30% of the samples are categorized as indeterminate. Hence, many immunocytochemistry markers have been studied, but there has not been a single outstanding marker. We studied the efficacy of CD56 with human bone marrow endothelial cell marker-1 (HBME-1) in diagnosis in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III.
Methods
We reviewed ThinPrep liquid-based cytology (LBC) samples with Papanicolaou stain from July 1 to December 31, 2016 (2,195 cases) and selected TBSRTC category III cases (n = 363). Twenty-six cases were histologically confirmed as benign (six cases, 23%) or malignant (20 cases, 77%); we stained 26 LBC slides with HBME-1 and CD56 through the cell transfer method. For evaluation of reactivity of immunocytochemistry, we chose atypical follicular cell clusters.
Results
CD56 was not reactive in 18 of 20 cases (90%) of malignant nodules and showed cytoplasmic positivity in five of six cases (83%) of benign nodules. CD56 showed high sensitivity (90.0%) and relatively low specificity (83.3%) in detecting malignancy (p = .004). HBME-1 was reactive in 17 of 20 cases (85%) of malignant nodules and was not reactive in five of six cases (83%) of benign nodules. HBME-1 showed slightly lower sensitivity (85.0%) than CD56. The specificity in detecting malignancy by HBME-1 was similar to that of CD56 (83.3%, p = .008). CD56 and HBME-1 tests combined showed lower sensitivity (75.0% vs 90%) and higher specificity (93.8% vs 83.3%) in detecting malignancy compared to using CD56 alone.
Conclusions
Using CD56 alone showed relatively low specificity despite high sensitivity for detecting malignancy. Combining CD56 with HBME-1 could increase the specificity. Thus, we suggest that CD56 could be a useful preoperative marker for differential diagnosis of TBSRTC category III samples.

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The Effects of Immunocytochemistry on Diagnostic Accuracy in Thyroid Fine Needle Aspiration Cytology: A Retrospective Study
Ali Mızrak, Cansu Benli Işık, Esen Gül Uzuner, Saime Gül Barut
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Preoperative evaluation of thyroid nodules – Diagnosis and management strategies
Tapoi Dana Antonia, Lambrescu Ioana Maria, Gheorghisan-Galateanu Ancuta-Augustina
Pathology - Research and Practice.2023; 246: 154516. CrossRef
Immunocytochemistry in thyroid cytology and its multiple roles: a systematic review
Federica Policardo, Pietro Tralongo, Angela Feraco, Federica Vegni, Angela Carlino, Alfredo Pontecorvi, Celestino Pio Lombardi, Marco Raffaelli, Francesco Pierconti, Luigi Maria Larocca, Esther Diana Rossi
Diagnostic Histopathology.2023; 29(8): 386. CrossRef
Paving the path toward multi-omics approaches in the diagnostic challenges faced in thyroid pathology
Isabella Piga, Vincenzo L’Imperio, Giulia Capitoli, Vanna Denti, Andrew Smith, Fulvio Magni, Fabio Pagni
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CD56 Expression in Papillary Thyroid Carcinoma Is Highly Dependent on the Histologic Subtype: A Potential Diagnostic Pitfall
Uiju Cho, Yourha Kim, Sora Jeon, Chan Kwon Jung
Applied Immunohistochemistry & Molecular Morphology.2022; 30(5): 389. CrossRef

Prognostic Role of Metastatic Lymph Node Ratio in Papillary Thyroid Carcinoma: Jung-Soo Pyo, Jin Hee Sohn, Kyungseek Chang; J Pathol Transl Med. 2018;52(5):331-338. Published online August 30, 2018; DOI: https://doi.org/10.4132/jptm.2018.08.07

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Abstract PDF

Background
The aim of this study is to elucidate the clinicopathological significances, including the prognostic role, of metastatic lymph node ratio (mLNR) and tumor deposit diameter in papillary thyroid carcinoma (PTC) through a retrospective review and meta-analysis.
Methods
We categorized the cases into high (≥ 0.44) and low mLNR (< 0.44) and investigated the correlations with clinicopathological parameters in 64 PTCs with neck level VI lymph node (LN) metastasis. In addition, meta-analysis of seven eligible studies was used to investigate the correlation between mLNR and survival.
Results
Among 64 PTCs with neck level VI LN metastasis, high mLNR was found in 34 PTCs (53.1%). High mLNR was significantly correlated with macrometastasis (tumor deposit diameter ≥ 0.2 cm), extracapsular spread, and number of metastatic LNs. Based on linear regression test, mLNR was significantly increased by the largest LN size but not the largest metastatic LN (mLN) size. High mLNR was not correlated with nuclear factor κB or cyclin D1 immunohistochemical expression, Ki-67 labeling index, or other pathological parameters of primary tumor. Based on meta-analysis, high mLNR significantly correlated with worse disease-free survival at the 5-year and 10-year follow-up (hazard ratio [HR], 4.866; 95% confidence interval [CI], 3.527 to 6.714 and HR, 5.769; 95% CI, 2.951 to 11.275, respectively).
Conclusions
Our data showed that high mLNR significantly correlated with worse survival, macrometastasis, and extracapsular spread of mLNs. Further cumulative studies for more detailed criteria of mLNR are needed before application in daily practice.

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Case Study

Hyalinizing Trabecular Tumor of the Thyroid Gland, a Diagnostic Challenge in Fine-Needle Aspiration Cytology: Case Report: Ye-Young Rhee, Hong Kyu Jung, Se Hoon Kim, Soo Hee Kim; J Pathol Transl Med. 2018;52(4):252-256. Published online June 11, 2018; DOI: https://doi.org/10.4132/jptm.2018.04.28

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Abstract PDF

Hyalinizing trabecular tumor (HTT) is a rare thyroid tumor with low to minimal malignant potential. HTT is often misinterpreted as other thyroid tumors, including papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC), on fine-needle aspiration (FNA) cytology, because of its overlapping cytologic features, such as nuclear grooves and intranulcear pseudoinclusions. Although cytopathologists cannot definitely conclude HTT by FNA cytology, suspicion of HTT is necessary to avoid misdiagnosing HTT as PTC or MTC and to avoid unnecessary aggressive treatment. Here, we report a case of HTT with novel cytologic features in CellPrep liquid based cytology that was diagnosed as suspicious for papillary carcinoma by FNA and finally diagnosed as HTT in the surgical specimen.

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Original Articles

Cytologic Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features and Its Impact on the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience: Milim Kim, Joung Eun Kim, Hyun Jeong Kim, Yul Ri Chung, Yoonjin Kwak, So Yeon Park; J Pathol Transl Med. 2018;52(3):171-178. Published online April 3, 2018; DOI: https://doi.org/10.4132/jptm.2018.04.03

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Abstract PDF

Background
This study was performed to analyze cytologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and its impact on the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).
Methods
Five thousand five hundred and forty-nine cases of thyroid fine-needle aspiration cytology (FNAC) diagnosed between 2012 and 2014 were included in this study. Diagnostic categories based on TBSRTC were compared with final surgical diagnoses, and the ROM in each category was calculated both when NIFTP was included in malignant lesions and when excluded from malignant lesions.
Results
Of the 5,549 thyroid FNAC cases, 1,891 cases underwent surgical resection. In final diagnosis, 1,700 cases were revealed as papillary thyroid carcinoma (PTC), and 25 cases were reclassified as NIFTP. The cytologic diagnoses of NIFTP were non-diagnostic in one, benign in five, atypia of undetermined significance (AUS) in 14, follicular neoplasm in two, and suspicious for malignancy in three cases. Collectively, NIFTP/encapsulated follicular variant of PTC (EFVPTC) were more frequently classified as benign, AUS, or follicular neoplasm and less frequently categorized as malignant compared to conventional PTCs. Exclusion of NIFTP from malignant diagnoses resulted in a slight decrease in malignancy rates in non-diagnostic, benign, AUS, follicular neoplasm, and suspicious for malignancy categories without any statistical significance.
Conclusions
The decrease in the ROM was not significant when NIFTP was excluded from malignant lesions. In thyroid FNACs, NIFTP/EFVPTCs were mostly classified into indeterminate categories. Therefore, it might be feasible to separate NIFTP/EFVPTC from conventional PTC on FNAC to guide clinicians to conservative management for patients with NIFTP/EFVPTC.

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Detailed fine needle aspiration cytopathology findings of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features with nuclear grading correlated to that of biopsy and Bethesda category and systematic review
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Elina Haaga, David Kalfert, Marie Ludvíková, Ivana Kholová
Acta Cytologica.2022; 66(2): 85. CrossRef
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Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma: Jisup Kim, Beom Jin Lim, Soon Won Hong, Ju Yeon Pyo; J Pathol Transl Med. 2018;52(2):105-109. Published online February 12, 2018; DOI: https://doi.org/10.4132/jptm.2017.12.26

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Abstract PDF

Background
Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation.
Methods
Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations.
Results
WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology.
Conclusions
The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.

Citations

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An Algorithmic Approach to Defining Variants of Papillary Thyroid Carcinoma: Accuracy of Fine Needle Aspiration Cytology
Neha Nigam, Neha Kumari, Rishabh Sahai, Nandita Chaudhary, Sabaretnam Mayilvaganan, Pallavi Prasad, Prabhakar Mishra
Journal of Cytology.2025; 42(1): 27. CrossRef
A Case of Warthin-Like Variant of Papillary Thyroid Cancer
Amy Chow, Israa Laklouk
Cureus.2025;[Epub] CrossRef
Warthin-like variant of papillary thyroid carcinoma: a rare case report
Rafif E Mattar, Osama Almubadel, Areej Bokhari
Journal of Surgical Case Reports.2025;[Epub] CrossRef
Warthin-like variant of papillary thyroid carcinoma with lymph node metastases: a case report and review of the literature
Andrii Hryshchyshyn, Andrii Bahrii, Pavlina Botsun, Volodymyr Chuba
Journal of Medical Case Reports.2024;[Epub] CrossRef
Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes
Agnes Stephanie Harahap, Chan Kwon Jung
Journal of Pathology and Translational Medicine.2024; 58(6): 265. CrossRef
Warthin-like papillary thyroid carcinoma: a case report and comprehensive review of the literature
Abdel Mouhaymen Missaoui, Fatma Hamza, Wafa Belabed, Manel Mellouli, Mohamed Maaloul, Slim Charfi, Issam Jardak, Tahya Sellami-Boudawara, Nabila Rekik, Mohamed Abid
Frontiers in Endocrinology.2023;[Epub] CrossRef
The Warthin-like variant of papillary thyroid carcinomas: a clinicopathologic analysis report of two cases
Xing Zhao, Yijia Zhang, Pengyu Hao, Mingzhen Zhao, Xingbin Shen
Oncologie.2023; 25(5): 581. CrossRef
Challenges in Cytology Specimens With Hürthle Cells
Eleni Thodou, Sule Canberk, Fernando Schmitt
Frontiers in Endocrinology.2021;[Epub] CrossRef
Warthin-like variant of Papillary thyroid carcinoma—Case report of an uncommon tumour with review of literature
Pradyumna Kumar Sahoo, Rashmi Patnayak, Perwez Alam Khan, Amitabh Jena
International Journal of Surgery Case Reports.2020; 77(C): 9. CrossRef

The Significance of TROP2 Expression in Predicting BRAF Mutations in Papillary Thyroid Carcinoma: Joon Seog Kong, Hyeon Jin Kim, Min-Jung Kim, Areumnuri Kim, Dalnim Lee, Kanghee Han, Sunhoo Park, Jae Soo Koh, Jae Kyung Myung; J Pathol Transl Med. 2018;52(1):14-20. Published online December 11, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.17

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Abstract PDF

Background
Trophoblast antigen 2 (TROP2) is a human trophoblast cell-surface glycoprotein that is overexpressed in several types of epithelial cancers, and is suggested to be associated with an unfavorable prognosis. BRAF mutations are the most common genetic alteration in papillary thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and BRAF mutation in PTC.
Methods
First, we carried out pyrosequencing for BRAF mutations and immunohistochemistry for TROP2 expression with a tissue microarray consisting of 52 PTC cases. Membranous staining in at least 5% of tumor cells was designated as positive staining and we analyzed the relationship between TROP2 expression and diverse clinicopathological factors, including BRAF mutation. Second, we tested TROP2 mRNA expression in three thyroid cancer cell lines with BRAF mutations (BCPAP, SNU790, and 8505C) and a normal thyroid cell line. Additionally, we checked TROP2 protein levels in a normal thyroid cell line after introduction of the BRAF V600E mutation.
Results
In this study, 21 of 26 cases with BRAF mutation showed TROP2 immunoreactivity, whereas all 26 cases without BRAF mutation showed no immunoreactivity for TROP2 with a statistically significant difference (p<.001). Upregulation of TROP2 mRNA was observed in all three thyroid cancer cell lines, but not in the normal thyroid cell line. Interestingly, however, the TROP2 expression was increased in the normal thyroid cell line after introduction of the BRAF V600E mutation.
Conclusions
Based on these results, we concluded that TROP2 expression is significantly associated with BRAF mutation and that TROP2 immunohistochemistry could be used for predicting BRAF mutations or diagnosing papillary thyroid carcinoma.

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Reviews

Current Status of Thyroid Fine-Needle Aspiration Practice in Thailand: Somboon Keelawat, Samreung Rangdaeng, Supinda Koonmee, Tikamporn Jitpasutham, Andrey Bychkov; J Pathol Transl Med. 2017;51(6):565-570. Published online November 15, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.12

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Abstract PDF

Thyroid carcinoma is one of the leading malignancies in Thailand increasingly prevalent in the female population. Fine-needle aspiration (FNA) cytology is a widely used diagnostic tool for evaluation of thyroid nodules and thyroid cancer. Thyroid FNA is a routine procedure universally performed in Thai hospitals by a variety of clinical specialists. Manual guidance is the first-line choice complemented by ultrasound assistance in selected cases. Despite national guidelines recommendations, the diagnostic criteria and terminology of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was slowly adopted in the local settings. Currently, the Bethesda system is actively promoted by the local professional societies as a uniform reporting system. Experience with thyroid FNA has been rarely reported to date—only a handful of publications are available in local journals. Our review, in addition to presenting various aspects of thyroid FNA in Thailand, established for the first time national references for a certain statistical outputs of TBSRTC based on the original multi-institutional cohort. The risk of malignancy in 2,017 operated thyroid nodules collected from three tertiary thyroid cancer centers was 21.7%, 14.7%, 35.9%, 44.4%, 76.7%, and 92.6% for categories I to VI, respectively. The malignancy risk in several diagnostic categories (II to IV) was higher than the risk estimated by TBSRTC and recent meta-analysis studies. We endorse the use of uniform terminology of the Bethesda system in Thailand, which will help facilitate communication among diverse medical professionals involved in the management of patients with thyroid nodules, to share local experience with the international audience.

Citations

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Journal of Pathology and Translational Medicine.2017; 51(6): 571. 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; 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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191 Download
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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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Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study
Chankyung Kim, Shipra Agarwal, Andrey Bychkov, Jen-Fan Hang, Agnes Stephanie Harahap, Mitsuyoshi Hirokawa, Kennichi Kakudo, Somboon Keelawat, Chih-Yi Liu, Zhiyan Liu, Truong Phan-Xuan Nguyen, Chanchal Rana, Huy Gia Vuong, Yun Zhu, Chan Kwon Jung
Virchows Archiv.2024; 484(4): 645. CrossRef
Fine needle aspiration cytology diagnoses of follicular thyroid carcinoma: results from a multicenter study in Asia
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Chanchal Rana, Neha Nigam, Shipra Agarwal, Prabhakar Mishra, Akanksha Singh, Andrey Bychkov
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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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Farrokh Heidari, Firouzeh Heidari, Mohammad Sadeq Najafi, Reza Ansari, Kayvan Aghazadeh, Saeed Sohrabpour, Ebrahim Karimi
Indian Journal of Otolaryngology and Head & Neck Surgery.2022; 74(S2): 2071. CrossRef
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Mohannad Rajab, Richard J. Payne, Véronique-Isabelle Forest, Marc Pusztaszeri
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Cytologic diagnosis of medullary thyroid carcinoma in the Asia‐Pacific region
Chih‐Yi Liu, Andrey Bychkov, Shipra Agarwal, Yun Zhu, Jen‐Fan Hang, Chiung‐Ru Lai, Hee Young Na, Weiwei Li, Zhiyan Liu, Deepali Jain, Ayana Suzuki, Mitsuyoshi Hirokawa, Noel Chia, Min En Nga, Tikamporn Jitpasutham, Somboon Keelawat, So Yeon Park, Shinya S
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Constitutive Cytomorphologic Features of Medullary Thyroid Carcinoma Using Different Staining Methods
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Molecular Correlates and Nuclear Features of Encapsulated Follicular-Patterned Thyroid Neoplasms
Chan Kwon Jung, Andrey Bychkov, Dong Eun Song, Jang-Hee Kim, Yun Zhu, Zhiyan Liu, Somboon Keelawat, Chiung-Ru Lai, Mitsuyoshi Hirokawa, Kaori Kameyama, Kennichi Kakudo
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Clinical Outcome of Fine Needle Aspiration Cytology and Washout Thyroglobulin in Suspicious Lymph Nodes in Differentiated Thyroid Carcinoma: Discordant Results in Real-World Practice
Jeongmin Lee, Hye Lim Park, Kwanhoon Jo, Min-Hee Kim, Ja Seong Bae, Sohee Lee, Chan Kwon Jung, So-Lyung Jung, Dong-Jun Lim
International Journal of Thyroidology.2021; 14(1): 18. CrossRef
Fine-needle Aspiration Washout Precipitation Specimens: An Acceptable Supplement to Genetic Mutation Detection of Thyroid Nodules
Yongmei Cui, Xiangqi Huang, Jinrui Guo, Nana Zhang, Jing Liang, Yiwang Zhang, Yueting Liao, Dan He
Technology in Cancer Research & Treatment.2021;[Epub] CrossRef
Emerging Biomarkers in Thyroid Practice and Research
Shipra Agarwal, Andrey Bychkov, Chan-Kwon Jung
Cancers.2021; 14(1): 204. CrossRef
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 fine-needle aspiration cytology in Taiwan: a nationwide survey and literature update
Chien-Chin Chen, Jen-Fan Hang, Chih-Yi Liu, Yeh-Han Wang, Chiung-Ru Lai
Journal of Pathology and Translational Medicine.2020; 54(5): 361. CrossRef
Pathological diagnosis of thyroid nodules based on core needle biopsies: comparative study between core needle biopsies and resected specimens in 578 cases
Yan Xiong, Limin Yan, Lin Nong, Yalin Zheng, Ting Li
Diagnostic Pathology.2019;[Epub] CrossRef
Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features in Asian Practice: Perspectives for Surgical Pathology and Cytopathology
Andrey Bychkov, Chan Kwon Jung, Zhiyan Liu, Kennichi Kakudo
Endocrine Pathology.2018; 29(3): 276. CrossRef
The History of Korean Thyroid Pathology
Soon Won Hong, Chan Kwon Jung
International Journal of Thyroidology.2018; 11(1): 15. CrossRef
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
Recent Advances in Core Needle Biopsy for Thyroid Nodules
Chan Kwon Jung, Jung Hwan Baek
Endocrinology and Metabolism.2017; 32(4): 407. CrossRef

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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Differences in surgical resection rate and risk of malignancy in thyroid cytopathology practice between Western and Asian countries: A systematic review and meta‐analysis
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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 Fine-Needle Aspiration in Taiwan: The History and Current Practice: Jen-Fan Hang, Chih-Yi Hsu, Chiung-Ru Lai; J Pathol Transl Med. 2017;51(6):560-564. Published online October 18, 2017; DOI: https://doi.org/10.4132/jptm.2017.09.20

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110 Download
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Abstract PDF

In Taiwan, thyroid cancer is the most common endocrine gland malignancy and the incidence of thyroid cancer has increased four-fold in the past two decades. Fine-needle aspiration is an accurate and cost-effective method of evaluating thyroid nodules and has been the gold-standard diagnostic tool for thyroid tumors in Taiwan since the 1980s. This article reviews the history, current practice, reporting systems, training, and quality assurance for thyroid fine-needle aspiration cytology in Taiwan.

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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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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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Hye Rang Choi, Bo-Yoon Choi, Jae Hoon Cho, Young Chang Lim
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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

Thyroid Cytology in India: Contemporary Review and Meta-analysis: Shipra Agarwal, Deepali Jain; J Pathol Transl Med. 2017;51(6):533-547. Published online October 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.04

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Abstract PDF

Fine-needle aspiration cytology (FNAC) is a screening test for triaging thyroid nodules, aiding in subsequent clinical management. However, the advantages have been overshadowed by the multiplicity of reporting systems and a wide range of nomenclature used. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formulated in 2007, to give the world a uniform thyroid cytology reporting system, facilitating easy interpretation by the clinicians. Here, we review the status of thyroid FNAC in India in terms of various reporting systems used including a meta-analysis of the previously published data. An extensive literature search was performed using internet search engines. The reports with detailed classification system used in thyroid cytology were included. The meta-analysis of published data was compared with the implied risk of malignancy by TBSRTC. More than 50 studies were retrieved and evaluated. TBSRTC is currently the most widely used reporting system with different studies showing good efficacy and interobserver concordance. Ancillary techniques have, as of now, limited applicability and acceptability in thyroid cytology in India. Twenty-eight published articles met the criteria for inclusion in the meta-analysis. When compared with TBSRTC recommendations, the meta-analysis showed a higher risk of malignancy for categories I and III. Thyroid FNAC is practiced all over India. TBSRTC has found widespread acceptance, with most institutions using this system for routine thyroid cytology reporting. However, reasons for a high malignancy risk for categories I and III need to be looked into. Various possible contributing factors are discussed in the review.

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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
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Thyroid Fine-Needle Aspiration Practice in the Philippines: Agustina D. Abelardo; J Pathol Transl Med. 2017;51(6):555-559. Published online October 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.07.14

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Abstract PDF

Fine-needle aspiration (FNA) is a well accepted initial approach in the management of thyroid lesions. It has come a long way since its introduction for nearly a century ago. In the Philippines, FNA of the thyroid was first introduced 30 years ago and has been utilized until now as a mainstay in the diagnosis of thyroid malignancy. The procedure is performed by pathologists, endocrinologists, surgeons, and radiologists. Most pathologists report the cytodiagnosis using a combination of the aspiration biopsy cytology method that closely resembles the histopathologic diagnosis of thyroid disorders and the six-tier nomenclature of The Bethesda System for Reporting Thyroid Cytopathology. Local endocrinologists and surgeons follow the guidelines of the 2015 American Thyroid Association in the management of thyroid disorders. There is still a paucity of local research studies but available data deal with cytohistologic correlations, sensitivity, specificity, and accuracy rates as well as usefulness of ultrasound-guided FNA. Cytohistologic correlations have a wide range of sensitivity from 30.7% to 73% and specificity from 83% to 100%. The low sensitivity can be attributed to poor tissue sampling since a majority of the thyroid FNA is done by palpation only. The reliability can be improved if FNA is guided by ultrasound as attested in both international and local studies. Overall, FNA of the thyroid has enabled the diagnosis of thyroid disorders with an accuracy of 72.8% to 87.2% and it correlates well with histopathology.

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Original Articles

Programmed Death-Ligand 1 Expression and Its Correlation with Lymph Node Metastasis in Papillary Thyroid Carcinoma: Hyo Jung An, Gyung Hyuck Ko, Jeong-Hee Lee, Jong Sil Lee, Dong Chul Kim, Jung Wook Yang, Min Hye Kim, Jin Pyeong Kim, Eun Jung Jung, Dae Hyun Song; J Pathol Transl Med. 2018;52(1):9-13. Published online October 3, 2017; DOI: https://doi.org/10.4132/jptm.2017.07.26

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Abstract PDF

Background
The immunotherapeutic role of programmed death-ligand 1 (PD-L1) in life expectancy in many cancers has been highlighted. However, data regarding PD-L1 expression in papillary thyroid carcinoma (PTC) are limited. In this study, we describe the PD-L1 and programmed cell death protein 1 (PD-1) expressions in PTC and analyze their correlation with lymph node (LN) metastasis.
Methods
Clinicopathological data were obtained from 116 patients with PTC who were treated in Gyeongsang National University Hospital, Jinju, Korea in 2009. Tissue microarray blocks were made using representative paraffin blocks of classical PTCs excluding follicular variants. Two pathologists graded the proportion and intensity of PD-L1 and PD-1 expression in both tumor and inflammatory cells. According to their proportions, positive PTC cells were scored as negative (0%), grade 1 (1%–50%), and grade 2 (51%–100%). Similarly, positive inflammatory cells were graded as negative (0%), grade 1 (1%–10%), and grade 2 (11%–20%). The intensity of each protein expression was simplified as positive or negative.
Results
A statistically significant correlation exists between the proportions of PD-1 and PD-L1 expression both in papillary carcinoma (p=.001) and peritumoral lymphoid cells in the thyroid (p<.001). In addition, the proportion of PD-L1 expression in PTC cells was closely related to metastatic LNs (p=.036).
Conclusions
PD-L1 is a valuable predictive marker for LN metastasis in PTC. Immunomodulating therapies that inhibit PD-L1 might be an option for patients with LN metastasis.

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Summary and Analysis of Molecular Biological Changes, PD-L1 Immune Status and Clinicopathological Features of 78 Cases of Papillary Thyroid Carcinoma (<1 cm in Diameter) Combined With Lateral Cervical Lymph Node Metastasis
Xiaoteng Sun, Zhengyan He, Weijie Yu, Baoyuan Li, Xinmiao Xu, Xiaoqin Zhang, Minglong Yin
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Ilaria Girolami, Liron Pantanowitz, Ozgur Mete, Matteo Brunelli, Stefano Marletta, Chiara Colato, Pierpaolo Trimboli, Anna Crescenzi, Massimo Bongiovanni, Mattia Barbareschi, Albino Eccher
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The Intraoperative Immunohistochemical Staining of CD56 and CK19 Improves Surgical Decision for Thyroid Follicular Lesions: Ju Yeon Pyo, Sung-eun Choi, Eunah Shin, JaSeung Koo, SoonWon Hong; J Pathol Transl Med. 2017;51(5):463-470. Published online August 2, 2017; DOI: https://doi.org/10.4132/jptm.2017.05.25

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Abstract PDF

Background
When differential diagnosis is difficult in thyroid follicular lesions with overlapping histological features, the immunohistochemical staining can help confirm the diagnosis. We aimed to evaluate the effectiveness of rapid immunohistochemical stains of CD56 and cytokeratin 19 on frozen sections of thyroid follicular lesion and explore the possible gains and limitations of the practice. Methods: Eighty-six nodules of 79 patients whose intraoperative frozen sections were selected as the control group, and 53 nodules of 48 patients whose intraoperative frozen sections were subject to rapid immunohistochemistry were selected as the study group. Results: Five nodules (6%) in the control group were diagnosed as follicular neoplasm and six nodules (7%) were deferred. In the study group, six nodules (11%) were follicular neoplasm and none were deferred. Three nodules (4%) in the control group showed diagnostic discrepancy between the frozen and permanent diagnoses, but none in the study group. The average turnaround time for the frozen diagnosis of the control group was 24 minutes, whereas it was 54 minutes for the study group. Conclusions: Intraoperative rapid immunohistochemical stains significantly decreased the diagnostic discrepancy in this study. Considering the adverse effects of indefinite frozen diagnosis or discrepancy with permanent diagnoses, the intraoperative rapid immunohistochemical stain can help to accurately diagnose and hence provide guidance to surgical treatment.

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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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Morphological and Functional Changes in the Thyroid Follicles of the Aged Murine and Humans: Junguee Lee, Shinae Yi, Yea Eun Kang, Hyeon-Woo Kim, Kyong Hye Joung, Hae Joung Sul, Koon Soon Kim, Minho Shong; J Pathol Transl Med. 2016;50(6):426-435. Published online October 14, 2016; DOI: https://doi.org/10.4132/jptm.2016.07.19

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Abstract PDF

Background
Although both thyroid histology and serum concentrations of hormones are known to change with age, only a few reports exist on the relationship between the age-related structural and functional changes of the thyroid follicles in both mice and humans. Our objectives were to investigate age-related histological changes of the thyroid follicles and to determine whether these morphological changes were associated with the functional activity of the follicles.
Methods
The thyroid glands of mice at 18 weeks and at 6, 15, and 30 months of age were histologically examined, and the serum levels of thyroid hormones were measured in 11-week-old and 20-month-old mice. Samples of human thyroid tissue from 10 women over 70 years old and 10 women between 30 and 50 years of age were analyzed in conjunction with serum thyroid hormone level.
Results
The histological and functional changes observed in the thyroid follicles of aged mice and women were as follows: variable sizing and enlargement of the follicles; increased irregularity of follicles; Sanderson’s polsters in the wall of large follicles; a large thyroglobulin (Tg) globule or numerous small fragmented Tg globules in follicular lumens; oncocytic change in follicular cells; and markedly dilated follicles empty of colloid. Serum T3 levels in 20-month-old mice and humans were unremarkable.
Conclusions
Thyroid follicles of aged mice and women show characteristic morphological changes, such as cystic atrophy, empty colloid, and Tg globules.

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Do Helper T Cell Subtypes in Lymphocytic Thyroiditis Play a Role in the Antitumor Effect?: Seok Woo Yang, Seong-Ho Kang, Kyung Rae Kim, In Hong Choi, Hang Seok Chang, Young Lyun Oh, Soon Won Hong; J Pathol Transl Med. 2016;50(5):377-384. Published online September 15, 2016; DOI: https://doi.org/10.4132/jptm.2016.07.25

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Abstract PDF

Background
Papillary thyroid carcinoma (PTC) is frequently accompanied by lymphocytic thyroiditis (LT). Some reports claim that Hashimoto’s thyroiditis (the clinical form of LT) enhances the likelihood of PTC; however, others suggest that LT has antitumor activity. This study was aimed to find out the relationship between the patterns of helper T cell (Th) cytokines in thyroid tissue of PTC with or without LT and the clinicopathological manifestation of PTC.
Methods
Fresh surgical samples of PTC with (13 cases) or without (10 cases) LT were used. The prognostic parameters (tumor size, extra-thyroidal extension of PTC, and lymph node metastasis) were analyzed. The mRNA levels of two subtypes of Th cytokines, Th1 (tumor necrosis factor α [TNF-α], interferon γ [IFN-γ ], and interleukin [IL] 2) and Th2 (IL-4 and IL-10), were analyzed. Because most PTC cases were microcarcinomas and recent cases without clinical follow-up, negative or faint p27 immunoreactivity was used as a surrogate marker for lymph node metastasis.
Results
PTC with LT cases showed significantly higher expression of TNF-α (p = .043), IFN-γ (p < .010), IL-4 (p = .015) than those without LT cases. Although the data were not statistically significant, all analyzed cytokines (except for IL-4) were highly expressed in the cases with higher expression of p27 surrogate marker.
Conclusions
These results indicate that mixed Th1 (TNF-α, IFN-γ , and IL-2) and Th2 (IL-10) immunity might play a role in the antitumor effect in terms of lymph node metastasis.

Citations

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Papillary thyroid carcinoma with Hashimoto’s thyroiditis: impact and correlation
Shengpeng Yao, Hong Zhang
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Fabiana Franchini, Giuseppe Palatucci, Annamaria Colao, Paola Ungaro, Paolo Emidio Macchia, Immacolata Cristina Nettore
International Journal of Environmental Research and Public Health.2022; 19(3): 1116. CrossRef
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Qizhi Tang, Weiyu Pan, Liangyue Peng, Francis Moore
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Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma: Hyekyung Lee, Tae Hwa Baek, Meeja Park, Seung Yun Lee, Hyun Jin Son, Dong Wook Kang, Joo Heon Kim, Soo Young Kim; J Pathol Transl Med. 2016;50(5):355-360. Published online August 22, 2016; DOI: https://doi.org/10.4132/jptm.2016.05.19

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90 Download

Abstract PDF: Background
There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings.
Methods
We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma.
Results
From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings.
Conclusions
Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma.

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