Journal of Pathology and Translational Medicine

Original Article

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.

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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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.

Citations

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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

Original Articles

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.

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: https://doi.org/

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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.

Citations

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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

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
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: 9. CrossRef

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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Obesity and Thyroid Cancer Risk: An Update
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
Association between Hashimoto thyroiditis and clinical outcomes of papillary thyroid carcinoma: A meta-analysis
Qizhi Tang, Weiyu Pan, Liangyue Peng, Francis Moore
PLOS ONE.2022; 17(6): e0269995. CrossRef
The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines
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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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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.

Case Studies

Recurrent Thyroid Papillary Carcinoma in Children Under Ten Years Old: Report of Two Cases and Literature Review: Byeong-Joo Noh, Ji-Youn Sung, Youn-Wha Kim, Yong-Koo Park; Korean J Pathol. 2014;48(4):297-301. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.297

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Abstract PDF

Papillary thyroid carcinoma (PTC) in children under ten years old is very rare. To date, 18 cases of PTC in children under ten years old (including our two cases) have been reported in Korea. Here, we describe two cases of recurrent PTC with follicular variant and conventional type in an 8-year-old boy and a 7-year-old boy, respectively, and discuss clinicopathologic and molecular characteristics that differ in pediatric patients from adults.

Citations

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Extremely Well-Differentiated Papillary Thyroid Carcinoma Resembling Adenomatous Hyperplasia Can Metastasize to the Skull: A Case Report
Ju Yeon Pyo, Jisup Kim, Sung-eun Choi, Eunah Shin, Seok-Woo Yang, Cheong Soo Park, Seok-Mo Kim, SoonWon Hong
Yonsei Medical Journal.2017; 58(1): 255. CrossRef

Anaplastic Transformation of Papillary Thyroid Carcinoma in a Young Man: A Case Study with Immunohistochemical and BRAF Analysis: Ji Hye Park, Hyeong Ju Kwon, Cheong Soo Park, SoonWon Hong; Korean J Pathol. 2014;48(3):234-240. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.234

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Abstract PDF

This study reports a case of anaplastic transformation from a well-differentiated thyroid carcinoma in a young patient. The first recurrent tissue contained poorly differentiated foci that revealed lower thyroglobulin, thyroid transcription factor 1 (TTF-1), and galectin-3 expression than the well-differentiated area. However there was no increased p53 or Ki-67 expression in the poorly differentiated foci, nor in the well-differentiated area. The tissue subsequently relapsed and revealed only anaplastic features, complete loss of thyroglobulin, TTF-1, and galectin-3 expression and revealed an increase in p53 and Ki-67 expression. The BRAF V600E and BRAF V600V mutation were found in the initially diagnosed papillary thyroid carcinoma and the poorly differentiated foci of the recurring papillary thyroid carcinoma; however, only the BRAF V600V mutation was found in the anaplastic carcinoma. These results suggest that overexpression of p53 and Ki-67 contributed to the anaplastic transformation. We also found that the BRAF type changed during the tumor relapse.

Citations

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Bozidar Kovacevic, Bojana Rancic, Sasa Jovic, Snezana Cerovic, Vesna Skuletic, Jelena Karajovic, Milka Gardasevic, Gordana Supic, Kennichi Kakudo
Diagnostics.2025; 15(5): 523. CrossRef
Rare but Complex: Outcomes and Challenges in Managing Composite Follicular-Anaplastic Thyroid Cancer
Dilay Aykan, Hala al Asadi, Anjani Turaga, Lutske Lodewijk, Brendan M. Finnerty, Thomas J. Fahey, Inne H. M. Borel Rinkes, Menno R. Vriens, Rasa Zarnegar
Annals of Surgical Oncology.2025;[Epub] CrossRef
Immunomodulation exerted by galectins: a land of opportunity in rare cancers
Laura Díaz-Alvarez, Georgina I. López-Cortés, Erandi Pérez-Figueroa
Frontiers in Immunology.2023;[Epub] CrossRef
Coexisting well-differentiated and anaplastic thyroid carcinoma in the same primary resection specimen: immunophenotypic and genetic comparison of the two components in a consecutive series of 13 cases and a review of the literature
Moira Ragazzi, Federica Torricelli, Benedetta Donati, Alessia Ciarrocchi, Dario de Biase, Giovanni Tallini, Eleonora Zanetti, Alessandra Bisagni, Elisabetta Kuhn, Davide Giordano, Andrea Frasoldati, Simonetta Piana
Virchows Archiv.2021; 478(2): 265. CrossRef
HDAC Inhibition Induces PD-L1 Expression in a Novel Anaplastic Thyroid Cancer Cell Line
Luca Hegedűs, Dominika Rittler, Tamás Garay, Paul Stockhammer, Ildikó Kovács, Balázs Döme, Sarah Theurer, Thomas Hager, Thomas Herold, Stavros Kalbourtzis, Agnes Bankfalvi, Kurt W. Schmid, Dagmar Führer, Clemens Aigner, Balázs Hegedűs
Pathology & Oncology Research.2020; 26(4): 2523. CrossRef
EWSR1 rearrangement is a frequent event in papillary thyroid carcinoma and in carcinoma of the thyroid with Ewing family tumor elements (CEFTE)
G. Oliveira, A. Polónia, J. M. Cameselle-Teijeiro, D. Leitão, S. Sapia, M. Sobrinho-Simões, C. Eloy
Virchows Archiv.2017; 470(5): 517. CrossRef
Anaplastic carcinoma of the thyroid in a 12-year old girl
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Original Articles

Tumor Sprouting in Papillary Thyroid Carcinoma Is Correlated with Lymph Node Metastasis and Recurrence: Eunjung Lee, Wonkyung Jung, Jeong-Soo Woo, Jae Bok Lee, Bong Kyung Shin, Han Kyeom Kim, Aeree Kim, Baek-hui Kim; Korean J Pathol. 2014;48(2):117-125. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.117

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Abstract PDF

Background

Identification of poor prognostic factors in papillary thyroid carcinoma (PTC) patients is important for the patients' care and follow-up. We can sometimes see small tumor clusters without desmoplasia and no evidence of lymphatic emboli around the main tumor mass of PTC. We termed this form of tumor clustering, 'tumor sprouting,' and determined whether these tumors correlate with lymphovascular invasion, lymph node metastasis, and recurrence.

Methods

We analyzed a total of 204 cases of papillary thyroid macrocarcinoma. Number, size and distance from the main tumor of the tumor sprouting were observed and analyzed with clinicopathologic characteristics.

Results

Tumor sprouting was observed in 101 patients. Presence of tumor sprouting was significantly associated with positive resection margin (p=.002), lymphovascular invasion (p=.001), lymph node metastasis (p<.001), and recurrence (p=.004). Univariate analysis of recurrence-free survival revealed that tumor multiplicity (p=.037), positive resection margin (p=.007), lymphovascular invasion (p=.004), lymph node metastasis (p<.001), and tumor sprouting (p=.004) were poor prognostic factors. In multivariate analysis, positive resection margin was an independent poor prognostic factor of recurrence.

Conclusions

In conclusion, tumor sprouting is significantly correlated with lymph node metastasis and recurrence. Evaluation of tumor sprouting in PTC patients could be helpful in predicting tumor recurrence or lymph node metastasis.

Citations

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Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 5. Evaluation of Recurrence Risk Postoperatively and Initial Risk Stratification in Different
Eun Kyung Lee, Young Shin Song, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Shin Je Moon, Dong-Jun Lim, Kyong Yeun Jung, Yun Jae Chung, Chan Kwon Jung, Young Joo Park
International Journal of Thyroidology.2024; 17(1): 68. CrossRef
Significance of Lymphovascular Invasion as a Prognostic Factor in Patients with Papillary Thyroid Cancer: a Systematic Review and Meta-Analysis
Ho-Ryun Won, Bon Seok Koo
International Journal of Thyroidology.2023; 16(2): 157. CrossRef
Peripheral Versus Intraparenchymal Papillary Thyroid Microcarcinoma: Different Morphologies and PD-L1 Expression
Bozidar Kovacevic, Dragana Vucevic, Snezana Cerovic, Catarina Eloy
Head and Neck Pathology.2022; 16(1): 200. CrossRef
Lymphovascular invasion and risk of recurrence in papillary thyroid carcinoma
Katy Wagner, Earl Abraham, Bryan Tran, David Roshan, James Wykes, Peter Campbell, Ardalan Ebrahimi
ANZ Journal of Surgery.2020; 90(9): 1727. CrossRef
The Predictors of Multicentricity in Well-Differentiated Thyroid Cancer
Mohamed Hegazi, Waleed El Nahas, Mohamed Elmetwally, Amr Hassan, Waleed Gado , Islam Abdou, Ahmed Senbel, Mohamed Samir Abou-Sheishaa
Journal of Analytical Oncology.2018; 7(4): 65. CrossRef
Prognostic impact of vascular invasion in differentiated thyroid carcinoma: a systematic review and meta-analysis
Huy Gia Vuong, Tetsuo Kondo, Uyen N P Duong, Thong Quang Pham, Naoki Oishi, Kunio Mochizuki, Tadao Nakazawa, Lewis Hassell, Ryohei Katoh
European Journal of Endocrinology.2017; 177(2): 207. CrossRef
Detection of Tumor Multifocality Is Important for Prediction of Tumor Recurrence in Papillary Thyroid Microcarcinoma: A Retrospective Study and Meta-Analysis
Jung-Soo Pyo, Jin Hee Sohn, Guhyun Kang
Journal of Pathology and Translational Medicine.2016; 50(4): 278. CrossRef

P2X₇ Receptor Expression in Coexistence of Papillary Thyroid Carcinoma with Hashimoto's Thyroiditis: Ji Hyun Kwon, Eun Sook Nam, Hyung Sik Shin, Seong Jin Cho, Hye Rim Park, Mi Jung Kwon; Korean J Pathol. 2014;48(1):30-35. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.30

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Abstract PDF

Background

This study was aimed at investigating the relation of P2X₇ receptor (P2X₇R) expression with the clinicopathological features of papillary thyroid carcinoma (PTC) coexisting with Hashimoto's thyroiditis (HT).

Methods

We examined 170 patients (84, PTC with HT; 86, PTC without HT). P2X₇R expression was examined by immunohistochemical methods. The staining intensity and patterns were evaluated and scored using a semi-quantitative method.

Results

The PTC with HT group was more likely to contain women and had less extrathyroid extension, lymph node (LN) metastasis, lymphovascular invasion, and recurrence than the PTC without HT group. Patients positive for P2X₇R had significantly higher frequencies of lymphovascular invasion, extrathyroid extension, LN metastasis, and absence of HT. As shown by multivariate analysis, the expression of P2X₇R was significantly higher if HT was absent and extrathyroid extension was present. In the PTC with HT group, the expression of P2X₇R was significantly higher in patients with tumor multifocality, lymphovascular invasion, and extrathyroid extension. In the PTC without HT group, the expression of P2X₇R was significantly higher in women and those having tumor multifocality.

Conclusions

Coexistence of PTC with HT is associated with good prognostic factors, and P2X₇R expression in PTC was correlated with poor prognostic factors and the absence of HT.

Citations

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Yiqing Tang, Cuicui Qiao, Qianqian Li, Xiaodi Zhu, Ronglan Zhao, Xiaoxiang Peng
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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
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Mapping the path towards novel treatment strategies: a bibliometric analysis of Hashimoto’s thyroiditis research from 1990 to 2023
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Association between Hashimoto thyroiditis and clinical outcomes of papillary thyroid carcinoma: A meta-analysis
Qizhi Tang, Weiyu Pan, Liangyue Peng, Francis Moore
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Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas
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Patients with Oncocytic Variant Papillary Thyroid Carcinoma Have a Similar Prognosis to Matched Classical Papillary Thyroid Carcinoma Controls
Azadeh A. Carr, Tina W.F. Yen, Diana I. Ortiz, Bryan C. Hunt, Gilbert Fareau, Becky L. Massey, Bruce H. Campbell, Kara L. Doffek, Douglas B. Evans, Tracy S. Wang
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Extracellular purines, purinergic receptors and tumor growth
F Di Virgilio, E Adinolfi
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Head & Neck.2016;[Epub] CrossRef
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Case Study

Papillary Carcinoma of the Thyroid Gland with Nodular Fasciitis-like Stroma: Ki Yong Na, Hyun-Soo Kim, Ji-Youn Sung, Won Seo Park, Youn Wha Kim; Korean J Pathol. 2013;47(2):167-171. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.167

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Abstract PDF

Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is a rare variant of PTC. The term 'PTC with fibromatosis-like stroma' has been used as a synonym to describe this variant. It is characterized by extensive proliferation of fibroblasts and myofibroblasts in the tumor stroma, which occurs in up to 80% of the tumors. We herein describe a case of PTC-NFS which developed in a 49-year-old woman with the demonstration of findings of ultrasonography, fine needle aspiration cytology and histological examination of the lesion. To characterize the stromal components, we investigated the expression of several immunohistochemical markers which have been shown to be expressed differently in nodular fasciitis (NF) and fibromatosis (FM). The immunostaining results demonstrated nuclear and cytoplasmic accumulation of β-catenin, cytoplasmic transforming growth factor-β expression and nuclear Smad expression in the stromal cells, suggesting that the stromal cells in this case have similar molecular profiles to those of FM rather than NF.

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Papillary thyroid carcinoma with desmoid-type fibromatosis: the clinicopathological features with characteristic imaging and molecular correlation requiring comprehensive treatment
Haining Huang, Lei Li, Xiaolong Liu, Lihua Zhao, Zhihong Cui, Renya Zhang, Shuai Chen
Human Pathology.2023; 136: 84. CrossRef
Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis: Review of Published Cases
Abdallah Roukain, Stefano La Rosa, Massimo Bongiovanni, Marie Nicod Lalonde, Valérie Cristina, Michael Montemurro, Stephane Cochet, Alexandra Luquain, Peter A. Kopp, Gerasimos P. Sykiotis
Cancers.2021; 13(17): 4482. CrossRef
Case of medullary thyroid carcinoma with desmoid‐type fibromatosis
Yoon Ah Cho, Young Lyun Oh
Pathology International.2020; 70(6): 364. CrossRef
SOX11 expression in a case of papillary thyroid carcinoma with fibromatosis/fasciitis-like stroma containing BRAF c.1799_1801delTGA and CTNNB1 c.133T>C mutations
Soon Boon Justin Wong, Min En Nga, Michal Michal, Tomas Vanecek, Ju Ee Seet, Fredrik Petersson
Virchows Archiv.2019; 475(4): 519. CrossRef
Papillary thyroid cancer with extrathyroidal extension of desmoid-type fibromatosis. A case report of an aggressive presentation of an uncommon pathologic entity
Eve M. Roth, Courtney E. Barrows, Michiya Nishino, Barry Sacks, Per-Olof Hasselgren, Benjamin C. James
International Journal of Surgery Case Reports.2019; 63: 5. CrossRef
Papillary thyroid carcinoma with nodular fasciitis-like stroma and β-catenin mutations should be renamed papillary thyroid carcinoma with desmoid-type fibromatosis
Caterina Rebecchini, Antoine Nobile, Simonetta Piana, Rossella Sarro, Bettina Bisig, Sykiotis P Gerasimos, Chiara Saglietti, Maurice Matter, Laura Marino, Massimo Bongiovanni
Modern Pathology.2017; 30(2): 236. CrossRef
Papillary thyroid carcinoma with desmoid-type fibromatosis: A clinical, pathological, and immunohistochemical study of 14 cases
Nami Takada, Mitsuyoshi Hirokawa, Masahiro Ito, Aki Ito, Ayana Suzuki, Miyoko Higuchi, Seiji Kuma, Toshitetsu Hayashi, Masao Kishikawa, Shuichi Horikawa, Akira Miyauchi
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A Case of Papillary Thyroid Carcinoma with Fasciitis-like Stroma
Toshihiko WAKU, Hiroshi SONOBE
Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association).2016; 77(12): 2892. CrossRef
Stromal Modulation and its Role in the Diagnosis of Papillary Patterned Thyroid Lesions
Sahar Aly Daoud, Reham Shehab El Nemr Esmail, Amal Ahmed Hareedy, Abdullah Khalil
Asian Pacific Journal of Cancer Prevention.2015; 16(8): 3307. CrossRef
Papillary Thyroid Carcinoma With Nodular Fasciitis–Like Stroma
Paula S. Ginter, Theresa Scognamiglio
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Notch and TGF-β/Smad3 pathways are involved in the interaction between cancer cells and cancer-associated fibroblasts in papillary thyroid carcinoma
Jie Zhang, Yuan Wang, Dan Li, Shanghua Jing
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Case Report

Papillary Carcinoma of Thyroid Metastatic to Adenocarcinoma In Situ of Lung: Report of an Unusual Case: Kyoung Min Kim, Yo Na Kim, Hyun Hee Chu, Heung Yong Jin, Min Ho Kim, Myoung Ja Chung; Korean J Pathol. 2012;46(3):282-286. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.282

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Abstract PDF

The tumor-to-tumor metastasis is a rare event. The lung tumors are the most common donor tumors in tumor-to-tumor metastasis, but are exceedingly rare as a recipient. Here, we report a case of papillary thyroid carcinoma (PTC) metastasizing to adenocarcinoma in situ (AIS, formerly bronchioloalveolar carcinoma) of the lung in a 44-year-old woman who underwent total thyroidectomy for PTC 8 years ago. To the best of our knowledge, the present case is the first case reporting on PTC metastasized to AIS. A review of the relevant literature is presented.

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A case of colorectal cancer with intratumoral metastasis to primary lung cancer
Yasushi Cho, Mitsuhito Kaji, Shunsuke Nomura, Yusuke Motohashi, Masaaki Sato, Motoya Takeuchi
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Tumor-to-tumor metastasis: metastatic invasive lobular carcinoma of the breast within adenocarcinoma of the lung
Myoung Jae Kang, Ae Ri An, Myoung Ja Chung, Kyoung Min Kim
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Metastatic Renal Cell Neoplasm Within a Papillary Thyroid Carcinoma as Incidental Finding in an Asymptomatic Patient: a Case Report
Maria-Rosa Bella-Cueto, Mireia Pascua-Solé, Albert Cano-Palomares, M. Àngels Cabezuelo-Hernandez, Maria-Rosa Escoda-Giralt, Santiago Barcons-Vilaplana, Paula Serret-Miralles, Carmen Caral-Vanaclocha, Xavier Guirao-Garriga, Joan Prats-Lopez, Meritxell Meda
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A Rare Case of Tumor-to-Tumor Metastasis of Thyroid Papillary Carcinoma within a Pulmonary Adenocarcinoma
Taebum Lee, Yoon Jin Cha, Sangjeong Ahn, Joungho Han, Young Mog Shim
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Tumour-to-tumour metastasis from papillary thyroid carcinoma withBRAFmutation to lung adenocarcinoma withEGFRmutation: the utility of mutation-specific antibodies
Yuki Katsuya, Akihiko Yoshida, Shun-ichi Watanabe, Koji Tsuta
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Pulmonary metastasis of a papillary thyroid carcinoma and primary lung adenocarcinoma: two coincident carcinomas at the same location
Liyan Xue, Zhonghua Luan, Ying Liu, Shuangmei Zou, Jun Jiang, Ning Wu, Ning Lu, Dongmei Lin
Diagnostic Pathology.2013;[Epub] CrossRef

Original Articles

Detection of BRAF^V600E Mutations in Papillary Thyroid Carcinomas by Peptide Nucleic Acid Clamp Real-Time PCR: A Comparison with Direct Sequencing: Dongjun Jeong, Yujun Jeong, Sungche Lee, Hyeran Lee, Wanju Lee, Hyungjoo Kim, Doosan Park, Soyoung Park, Wenxia Mu, Hyun-Deuk Cho, Mee-Hye Oh, Sung Soo Lee, Seung-Ha Yang, Chang-Jin Kim; Korean J Pathol. 2012;46(1):61-67. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.61

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Abstract PDF

Background

Papillary thyroid carcinoma (PTC) of the thyroid is the most common endocrine malignancy. High prevalence of an activating point mutation of BRAF gene, BRAF^V600E, has been reported in PTC. We assessed the efficiency of peptide nucleic acid clamp real-time polymerase chain reaction (PNAcqPCR) for the detection of BRAF^V600E mutation in PTC in comparison with direct sequencing (DS).

Methods

A total of 265 thyroid lesions including 200 PTCs, 5 follicular carcinomas, 60 benign lesions and 10 normal thyroid tissues were tested for BRAF^V600E mutation by PNAcqPCR and DS.

Results

The sensitivity and accuracy of the PNAcqPCR method were both higher than those of DS for the detection of the BRAF^V600E mutation. In clinical samples, 89% of PTCs harbored the BRAF^V600E mutation, whereas 5 follicular carcinomas, 50 benign lesions and 10 normal thyroid tissues lacked the mutation. The mutation was associated with aggressive clinical behaviors as extrathyroid invasion (p=0.015), lymph node metastasis (p=0.002) and multiple tumor numbers (p=0.016) with statistical significance.

Conclusions

The PNAcqPCR method is efficiently applicable for the detection of the BRAF^V600E mutation in PTCs in a clinical setting.

Citations

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Diagnostic utilities of washout CYFRA 21-1 combined with washout thyroglobulin for metastatic lymph nodes in thyroid cancer: a prospective study
Joonseon Park, Solji An, Kwangsoon Kim, Jeong Soo Kim, Chan Kwon Jung, Ja Seong Bae
Scientific Reports.2024;[Epub] CrossRef
BRAFV600E Positivity-Dependent Effect of Age on Papillary Thyroid Cancer Recurrence Risk
Joonseon Park, Solji An, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim
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TROP-2 and 5hmC expression in follicular-patterned thyroid neoplasm emphasizing tiny well-formed papillae
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Null Association between BRAF V600E Mutation and Tumor Recurrence in Patients with Papillary Thyroid Microcarcinoma in South Korea
Ji Yoon Kim, Kyoung Jin Kim, Jae Hyun Bae, Joo Hyung Kim, Nam Hoon Kim, Hee Young Kim, Hoon Yub Kim, Seung-Kuk Baek, Sin Gon Kim, Kwang Yoon Jung, Kyeong Jin Kim
International Journal of Thyroidology.2021; 14(2): 135. CrossRef
Evaluation of the expression levels of BRAFV600E mRNA in primary tumors of thyroid cancer using an ultrasensitive mutation assay
Tien Viet Tran, Kien Xuan Dang, Quynh Huong Pham, Ung Dinh Nguyen, Nhung Thi Trang Trinh, Luong Van Hoang, Son Anh Ho, Ba Van Nguyen, Duc Trong Nguyen, Dung Tuan Trinh, Dung Ngoc Tran, Arto Orpana, Ulf-Håkan Stenman, Jakob Stenman, Tho Huu Ho
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Irene Vanni, Enrica Teresa Tanda, Francesco Spagnolo, Virginia Andreotti, William Bruno, Paola Ghiorzo
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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
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Development of ultra-short PCR assay to reveal BRAF V600 mutation status in Thai colorectal cancer tissues
Nunthawut Chat-Uthai, Pichpisith Vejvisithsakul, Sutthirat Udommethaporn, Puttarakun Meesiri, Chetiya Danthanawanit, Yannawan Wongchai, Chinachote Teerapakpinyo, Shanop Shuangshoti, Naravat Poungvarin, John Souglakos
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T-blocker: a Simple and Robust Probe-Free Quantitative PCR Assay to Detect Somatic Mutations Down to 0.1% Frequency
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The usefulness of a novel fully automated PCR-based Idylla test for detection of the BRAF V600E mutation in thyroid tissue: comparison with PNA-clamping PCR, real-time PCR and pyrosequencing
Min-Kyung Yeo, Min-Kyu Jung, Su-Yel Lee, Yong-Moon Lee, Gang Min Hur, Jin-Man Kim
Journal of Clinical Pathology.2017; 70(3): 260. CrossRef
KRAS mutation analysis of washing fluid from endoscopic ultrasound-guided fine needle aspiration improves cytologic diagnosis of pancreatic ductal adenocarcinoma
Joo Kyung Park, Yoon Jung Lee, Jong Kyun Lee, Kyu Taek Lee, Yoon-La Choi, Kwang Hyuck Lee
Oncotarget.2017; 8(2): 3519. CrossRef
Application of Peptide Nucleic Acid-based Assays Toward Detection of Somatic Mosaicism
Christopher S Hong, Chunzhang Yang, Zhengping Zhuang
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Prediction Table and Nomogram as Tools for Diagnosis of Papillary Thyroid Carcinoma
Seo Ki Kim, Jun Ho Lee, Jung-Woo Woo, Inhye Park, Jun-Ho Choe, Jung-Han Kim, Jee Soo Kim
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The association between BRAF V600E mutation and pathological features in PTC
Xin Liu, Kangkang Yan, Xuejun Lin, Longyu Zhao, Wenxiu An, Chunpeng Wang, Xiaodong Liu
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Recurrent Thyroid Papillary Carcinoma in Children Under Ten Years Old: Report of Two Cases and Literature Review
Byeong-Joo Noh, Ji-Youn Sung, Youn-Wha Kim, Yong-Koo Park
Korean Journal of Pathology.2014; 48(4): 297. CrossRef
KRASMutation Detection in Non-small Cell Lung Cancer Using a Peptide Nucleic Acid-Mediated Polymerase Chain Reaction Clamping Method and Comparative Validation with Next-Generation Sequencing
Boram Lee, Boin Lee, Gangmin Han, Mi Jung Kwon, Joungho Han, Yoon-La Choi
Korean Journal of Pathology.2014; 48(2): 100. CrossRef
VE1 immunohistochemistry in pituitary adenomas is not associated with BRAF V600E mutation
Jan Sperveslage, Midea Gierke, David Capper, Jürgen Honegger, Bence Sipos, Rudi Beschorner, Jens Schittenhelm
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BRAF Mutations in Iranian Patients with Papillary Thyroid Carcinoma
Nastran Ranjbari, Sara Almasi, Javad Mohammadi-asl, Fakher Rahim
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Detection of Survivin and COX-2 in Thyroid Carcinoma: Anaplastic Carcinoma Shows Overexpression of Nuclear Survivin and Low COX-2 Expression: Young A Kim, Meesoo Chang, Young Joo Park, Ji Eun Kim; Korean J Pathol. 2012;46(1):55-60. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.55

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Abstract PDF

Background

Overexpression of survivin, a member of the inhibitors of apoptosis protein, has been reported in various carcinomas, and its interaction with cyclooxygenase 2 (COX-2) results in accelerated tumor progression. The purpose of this study is to investigate the immunohistochemical expression of survivin and COX-2 in benign and malignant thyroid tissues and to define its association with pathologic and clinical features.

Methods

We examined expression of survivin and COX-2 by immunohistochemistry in 334 benign and malignant thyroid tissues and evaluated their clinical significance.

Results

Expression of survivin showed an increase along the spectrum of thyroid carcinoma progression; rarely positive in adenomatous goiter, moderately positive in papillary carcinoma, and strongly positive in anaplastic carcinoma (AC). Papillary microcarcinoma revealed the highest COX-2 positivity and AC demonstrated the lowest positivity among thyroid cancers. Node negative carcinomas showed higher COX-2 expression than node positive tumors. Survivin expression did not correlate with COX-2.

Conclusions

Our findings suggest that survivin overexpression may be related to the pathogenesis of AC and can be a predictor of disease progression. COX-2 may be involved in the early phase of thyroid carcinoma.

Citations

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Survivin as a diagnostic and therapeutic marker for thyroid cancer
Mohammad-Reza Mahmoudian-Sani, Arash Alghasi, Ali Saeedi-Boroujeni, Akram Jalali, Mohammad Jamshidi, Ali Khodadadi
Pathology - Research and Practice.2019; 215(4): 619. CrossRef
TFAP2B overexpression contributes to tumor growth and progression of thyroid cancer through the COX-2 signaling pathway
Xiaoyan Fu, Huayong Zhang, Zhipeng Chen, Zhongyuan Yang, Dingbo Shi, Tianrun Liu, Weichao Chen, Fan Yao, Xuan Su, Wuguo Deng, Miao Chen, Ankui Yang
Cell Death & Disease.2019;[Epub] CrossRef
Expression of nm23-H1 and COX-2 in thyroid papillary carcinoma and microcarcinoma
Marija Milkovic Perisa, Bozena Sarcevic, Koraljka Gall Troselj, Kresimir Grsic, Sanda Sitic, Sven Seiwerth
Oncology Letters.2017; 13(5): 3547. CrossRef
The Diagnostic Usefulness of HMGA2, Survivin, CEACAM6, and SFN/14-3-3 δ in Follicular Thyroid Carcinoma
Min Hye Jang, Kyeong Cheon Jung, Hye Sook Min
Journal of Pathology and Translational Medicine.2015; 49(2): 112. CrossRef
Evaluation of survivin expression and its prognostic value in papillary thyroid carcinoma
Sonja Selemetjev, Tijana Isic Dencic, Ilona Marecko, Jelena Jankovic, Ivan Paunovic, Svetlana Savin, Dubravka Cvejic
Pathology - Research and Practice.2014; 210(1): 30. CrossRef

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