Journal of Pathology and Translational Medicine

Original Article

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea: Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho; J Pathol Transl Med. 2023;57(3):166-177. Published online May 10, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.12

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Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Citations

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Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy
Sangjoon Choi, Mofazzal Hossain, Hyun Lee, Jina Baek, Hye Seon Park, Chae-Lyul Lim, DoYeon Han, Taehyun Park, Jong Hyeok Kim, Gyungyub Gong, Mi-Na Kweon, Hee Jin Lee
Cancer Immunology, Immunotherapy.2024;[Epub] CrossRef

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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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
Cancer Cytopathology.2024; 132(6): 348. CrossRef
ThyroSeq overview on indeterminate thyroid nodules: An institutional experience
Sam Sirotnikov, Christopher C. Griffith, Daniel Lubin, Chao Zhang, Nabil F. Saba, Dehong Li, Amanda Kornfield, Amy Chen, Qiuying Shi
Diagnostic Cytopathology.2024; 52(7): 353. CrossRef
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
Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy
Chan Kwon Jung
Journal of Pathology and Translational Medicine.2023; 57(4): 208. CrossRef
Strategies for Treatment of Thyroid Cancer
Deepika Yadav, Pramod Kumar Sharma, Rishabha Malviya, Prem Shankar Mishra
Current Drug Targets.2023; 24(5): 406. CrossRef
Identification of NIFTP-Specific mRNA Markers for Reliable Molecular Diagnosis of Thyroid Tumors
So-Yeon Lee, Jong-Lyul Park, Kwangsoon Kim, Ja Seong Bae, Jae-Yoon Kim, Seon-Young Kim, Chan Kwon Jung
Endocrine Pathology.2023; 34(3): 311. CrossRef

Original Article

Diagnostic distribution and pitfalls of glandular abnormalities in cervical cytology: a 25-year single-center study: Jung-A Sung, Ilias P. Nikas, Haeryoung Kim, Han Suk Ryu, Cheol Lee; J Pathol Transl Med. 2022;56(6):354-360. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.09.05

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Abstract PDF

Background
Detection of glandular abnormalities in Papanicolaou (Pap) tests is challenging. This study aimed to review our institute’s experience interpreting such abnormalities, assess cytohistologic concordance, and identify cytomorphologic features associated with malignancy in follow-up histology.
Methods
Patients with cytologically-detected glandular lesions identified in our pathology records from 1995 to 2020 were included in this study.
Results
Of the 683,197 Pap tests performed, 985 (0.144%) exhibited glandular abnormalities, 657 of which had tissue follow-up available. One hundred eighty-eight cases were cytologically interpreted as adenocarcinoma and histologically diagnosed as malignant tumors of various origins. There were 213 cases reported as atypical glandular cells (AGC) and nine cases as adenocarcinoma in cytology, yet they were found to be benign in follow-up histology. In addition, 48 cases diagnosed with AGC and six with adenocarcinoma cytology were found to have cervical squamous lesions in follow-up histology, including four squamous cell carcinomas. Among the cytomorphological features examined, nuclear membrane irregularity, three-dimensional clusters, single-cell pattern, and presence of mitoses were associated with malignant histology in follow-up.
Conclusions
This study showed our institute’s experience detecting glandular abnormalities in cervical cytology over a 25-year period, revealing the difficulty of this task. Nonetheless, the present study indicates that several cytological findings such as membrane irregularity, three-dimensional clusters, single-cell pattern, and evidence of proliferation could help distinguishing malignancy from a benign lesion.

Citations

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Analysis of atypical glandular cells in ThinPrep Pap smear and follow-up histopathology
Tengfei Wang, Yinan Hua, Lina Liu, Bing Leng
Baylor University Medical Center Proceedings.2024; 37(3): 403. CrossRef

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.

Citations

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Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review
Suyeon Kim, Hyunsik Bae, Hyun-Soo Kim
Diagnostics.2024; 14(2): 160. CrossRef

Original Articles

Evaluation of the characteristics of multiple human papillomavirus (HPV) infections identified using the BD Onclarity HPV assay and comparison with those of single HPV infection: Jinhee Kim, Moonsik Kim, Ji Young Park; J Pathol Transl Med. 2022;56(5):289-293. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.02

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Abstract PDF Supplementary Material

Background
Human papillomavirus (HPV) infection is a major cause of cervical cancer and associated precursor lesions. Multiple HPV genotype infections have been reported. However, their clinicopathological characteristics still remain elusive.
Methods
For this study, 814 consecutive patients who had undergone colposcopy and HPV genotyping test using BD Onclarity HPV assay were retrospectively selected. Clinicopathological parameters of multiple HPV infections were compared with those of single HPV infection.
Results
Multiple HPV infections were found in 110 out of 814 cases (13.5%). Multiple HPV infections were associated with a significantly higher incidence of high-grade intraepithelial lesions (HSILs) compared with single HPV infection. Other high-risk HPV genotypes, in addition to HPV 16, were found more frequently in the multiple HPV infections group; these included HPV 51, 52, 33/58, 56/59/66, and 35/39/68. No specific coinfection pattern was not identified. Additionally, the number of HPV genotypes in multiple HPV infections was not associated with the progression to HSIL or squamous cell carcinoma.
Conclusions
Multiple HPV infections have distinct clinicopathological characteristics (compared with single HPV infection). As their biological behavior is uncertain, close and frequent follow-up is warranted.

Citations

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Relative distribution of HPV genotypes in histological cervical samples and associated grade lesion in a women population over the last 16 years in Burgundy, France
Christelle Auvray, Serge Douvier, Odile Caritey, Jean-Baptiste Bour, Catherine Manoha
Frontiers in Medicine.2023;[Epub] CrossRef
Epidemiologic characteristics of high-risk HPV and the correlation between multiple infections and cervical lesions
Qinli Luo, Xianghua Zeng, Hanyi Luo, Ling Pan, Ying Huang, Haiyan Zhang, Na Han
BMC Infectious Diseases.2023;[Epub] CrossRef

Cytopathologic features of human papillomavirus–independent, gastric-type endocervical adenocarcinoma: Min-Kyung Yeo, Go Eun Bae, Dong-Hyun Kim, In-Ock Seong, Kwang-Sun Suh; J Pathol Transl Med. 2022;56(5):260-269. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.07.05

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Abstract PDF

Background
Gastric-type endocervical adenocarcinoma (GEA) is unrelated to human papillomavirus (HPV) infection and is clinically aggressive compared with HPV-associated usual-type endocervical adenocarcinoma (UEA). The cytological diagnosis falls short of a definitive diagnosis of GEA and is often categorized as atypical glandular cells (AGCs). To improve cytologic recognition, cytological findings of HPV-independent GEA were analyzed and the results compared with HPV-associated UEA.
Methods
Cervical Papanicolaou (Pap) smears from eight patients with a histopathologic diagnosis of GEA and 12 control cases of UEA were reviewed. All slides were conventionally prepared and/or liquid-based prepared (ThinPrep) and stained following the Pap method. A mucinous background, architectural, nuclear, and cytoplasmic features were analyzed and compared with UEA.
Results
Preoperative cytologic diagnoses of the eight GEA cases were AGCs, favor neoplastic in three cases, adenocarcinoma in situ in one case, and adenocarcinoma in four cases. Cytologically, monolayered honeycomb-like sheets (p = .002) of atypical endocervical cells with vacuolar granular cytoplasm (p = .001) were extensive in GEA, and three-dimensional clusters (p = .010) were extensive in UEA. Although the differences were not statistically significant, background mucin (p = .058), vesicular nuclei (p = .057), and golden-brown intracytoplasmic mucin (p = .089) were also discriminatory findings for GEA versus UEA.
Conclusions
Although GEA is difficult to diagnose on cytologic screening, GEA can be recognized based on cytologic features of monolayered honeycomb sheets of atypical endocervical cells with abundant vacuolar cytoplasm and some golden-brown intracytoplasmic mucin. UEA cases are characterized by three-dimensional clusters.

Citations

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Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus–Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern
Bong Kyung Bae, Hyunsik Bae, Won Kyung Cho, Byoung-Gie Kim, Chel Hun Choi, Tae-Joong Kim, Yoo-Young Lee, Jeong-Won Lee, Hyun-Soo Kim, Won Park
International Journal of Gynecological Pathology.2024;[Epub] CrossRef
Tall‐columnar glandular cells in SurePath™ liquid‐based cytology Pap sample: Learning from mimics/pitfalls
Nalini Gupta, Vanita Jain, Radhika Srinivasan, Tulika Singh
Cytopathology.2024; 35(4): 510. CrossRef

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.

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification: Hye Ju Kang, Sun Young Kwon, Ahrong Kim, Woo Gyeong Kim, Eun Kyung Kim, Ae Ree Kim, Chungyeul Kim, Soo Kee Min, So Young Park, Sun Hee Sung, Hye Kyoung Yoon, Ahwon Lee, Ji Shin Lee, Hyang Im Lee, Ho Chang Lee, Sung Chul Lim, Sun Young Jun, Min Jung Jung, Chang Won Jung, Soo Youn Cho, Eun Yoon Cho, Hye Jeong Choi, So Yeon Park, Jee Yeon Kim, In Ae Park, Youngmee Kwon; J Pathol Transl Med. 2021;55(6):380-387. Published online October 6, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.29

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Abstract PDF Supplementary Material

Background
Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification.
Methods
Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier).
Results
On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems.
Conclusions
Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Citations

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Invasive papillary carcinoma of the breast
Shijing Wang, Qingfu Zhang, Xiaoyun Mao
Frontiers in Oncology.2024;[Epub] CrossRef
Encapsulated papillary carcinoma of the breast: A single institution experience
Liang Xu, Qixin Mao, Qiuming Liu, Yufeng Gao, Lihua Luo, Chungen Guo, Wei Qu, Ningning Yan, Yali Cao
Oncology Letters.2023;[Epub] CrossRef
High-risk and selected benign breast lesions diagnosed on core needle biopsy: Evidence for and against immediate surgical excision
Aparna Harbhajanka, Hannah L. Gilmore, Benjamin C. Calhoun
Modern Pathology.2022; 35(11): 1500. CrossRef

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.

Citations

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Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α
Juan Liu, Chao Yang, Xiao-Mei Huang, Pan-Pan Lv, Ya-Kun Yang, Jin-Na Zhao, Si-Yuan Zhao, Wan-Jun Sun
Frontiers in Oncology.2021;[Epub] CrossRef

Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization: Hezhen Ren, Jennifer Pors, Christine Chow, Monica Ta, Simona Stolnicu, Robert Soslow, David Huntsman, Lynn Hoang; J Pathol Transl Med. 2020;54(6):480-488. Published online August 31, 2020; DOI: https://doi.org/10.4132/jptm.2020.07.18

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Abstract PDF

Background
The International Endocervical Adenocarcinoma Criteria and Classification (IECC) separated endocervical adenocarcinomas into human papillomavirus (HPV) associated (HPVA) and non–HPV-associated (NHPVA) categories by morphology alone. Our primary objective was to assess the accuracy of HPV prediction by the IECC system compared to p16 immunohistochemistry and HPV RNA in-situ hybridization (RISH). Our secondary goal was to directly compare p16 and HPV RISH concordance.
Methods
Cases were classified by IECC and stained for p16 and HPV RISH on tissue microarray, with discordant p16/HPV RISH cases re-stained on whole tissue sections. Remaining discordant cases (p16/HPV, IECC/p16, IECC/HPV discordances) were re-reviewed by the original pathologists (n = 3) and external expert pathologists (n = 2) blinded to the p16 and HPV RISH results. Final IECC diagnosis was assigned upon independent agreement between all reviewers.
Results
One hundred and eleven endocervical adenocarcinomas were classified originally into 94 HPVA and 17 NHPVA cases. p16 and HPV RISH was concordant in 108/111 cases (97%) independent of the IECC. HPV RISH and p16 was concordant with IECC in 103/111 (93%) and 106/111 (95%), respectively. After expert review, concordance improved to 107/111 (96%) for HPV RISH. After review of the eight discordant cases, one remained as HPVA, four were reclassified to NHPVA from HPVA, two were unclassifiable, and one possibly represented a mixed usual and gastric-type adenocarcinoma.
Conclusions
p16 and HPV RISH have excellent concordance in endocervical adenocarcinomas, and IECC can predict HPV status in most cases. Focal apical mitoses and apoptotic debris on original review led to the misclassification of several NHPVA as HPVA.

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Joint detection of multiple HPV-testing technologies and evaluation of clinicopathological characteristics discriminate between HPV-independent and low-copy HPV-associated cervical squamous cell carcinoma (CSCC) -an analysis of 3869 cases
Linghui Lu, Tianqi Liu, Shunni Wang, Jing Li, Feiran Zhang, Yan Ning, Yiqin Wang
Gynecologic Oncology.2023; 170: 59. CrossRef
Incidence and Clinicopathologic Characteristics of Human Papillomavirus–independent Invasive Squamous Cell Carcinomas of the Cervix
Simona Stolnicu, Douglas Allison, Aaron M. Praiss, Basile Tessier-Cloutier, Amir Momeni Boroujeni, Jessica Flynn, Alexia Iasonos, Rene Serrette, Lien Hoang, Andrei Patrichi, Cristina Terinte, Anna Pesci, Claudia Mateoiu, Ricardo R. Lastra, Takako Kiyokawa
American Journal of Surgical Pathology.2023; 47(12): 1376. CrossRef
Testing Algorithms for the Diagnosis of Malignant Glandular Tumors of the Uterine Cervix Histotyped per the International Endocervical Adenocarcinoma Criteria and Classification (IECC) System
Máire A. Duggan, Qiuli Duan, Ruth M. Pfeiffer, Mary Anne Brett, Sandra Lee, Mustapha Abubakar, Martin Köbel, Monica Rodriguez, Aylin Sar
Applied Immunohistochemistry & Molecular Morphology.2022; 30(2): 91. CrossRef
Local and Metastatic Relapses in a Young Woman with Papillary Squamous Cell Carcinoma of the Uterine Cervix
Ha Young Woo, Hyun-Soo Kim
Diagnostics.2022; 12(3): 599. CrossRef
Clinical correlation of lymphovascular invasion and Silva pattern of invasion in early-stage endocervical adenocarcinoma: proposed binary Silva classification system
Simona Stolnicu, Lien Hoang, Noorah Almadani, Louise De Brot, Glauco Baiocchi, Graziele Bovolim, Maria Jose Brito, Georgia Karpathiou, Antonio Ieni, Esther Guerra, Takako Kiyokawa, Pavel Dundr, Carlos Parra-Herran, Sofia Lérias, Ana Felix, Andres Roma, An
Pathology.2022; 54(5): 548. CrossRef
Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study
Pinar Bulutay, Nihan Haberal, Özlem Özen, Özlem Erdem, Emine H. Zeren, İbrahim Kulac, Çagatay Taskiran, Dogan Vatansever, Ali Ayhan, Nilgün Kapucuoğlu
International Journal of Gynecological Pathology.2022; 41(5): 447. CrossRef
HPV-Negative Cervical Cancer: A Narrative Review
Francesca Arezzo, Gennaro Cormio, Vera Loizzi, Gerardo Cazzato, Viviana Cataldo, Claudio Lombardi, Giuseppe Ingravallo, Leonardo Resta, Ettore Cicinelli
Diagnostics.2021; 11(6): 952. CrossRef
International Endocervical Adenocarcinoma Criteria and Classification (IECC): An Independent Cohort With Clinical and Molecular Findings
Hezhen Ren, Noorah Almadani, Jennifer Pors, Samuel Leung, Julie Ho, Christine Chow, Monica Ta, Kay J. Park, Simona Stolnicu, Robert Soslow, David Huntsman, Blake C. Gilks, Lynn Hoang
International Journal of Gynecological Pathology.2021; 40(6): 533. CrossRef

Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas: Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee; J Pathol Transl Med. 2020;54(5):411-418. Published online July 21, 2020; DOI: https://doi.org/10.4132/jptm.2020.06.22

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Abstract PDF

Background
High-risk (HR) human papillomavirus (HPV) is found in a subset of head and neck (HN) squamous cell carcinomas (SCCs). For oropharyngeal SCCs, HR HPV positivity is known to be associated with good prognosis, and a separate staging system for HPV-associated carcinomas using p16 immunohistochemistry (IHC) as a surrogate test has been adopted in the 8th American Joint Committee on Cancer staging system. We examined the HR HPV status and the genotype distribution in five HN subsites.
Methods
Formalin-fixed paraffin-embedded tissue sections were used for p16 IHC and DNA extraction. HPV DNA detection and genotyping were done employing either a DNA chip-based or real-time polymerase chain reaction–based method.
Results
During 2011–2019, a total of 466 SCCs were tested for HPV DNA with 34.1% positivity for HR HPV. Among HN subsites, the oropharynx showed the highest HR HPV prevalence (149/205, 75.1%), followed by the sinonasal tract (3/14, 21.4%), larynx (5/43, 11.6%), hypopharynx (1/38, 2.6%), and oral cavity (1/166, 0.6%). The most common HPV genotype was HPV16 (84.3%) followed by HPV35 (6.9%) and HPV33 (4.4%). Compared with HR HPV status, the sensitivity and specificity of p16 IHC were 98.6% and 94.3% for the oropharynx, and 99.2% and 93.8% for the tonsil, respectively.
Conclusions
Using a Korean dataset, we confirmed that HR HPV is most frequently detected in oropharyngeal SCCs. p16 positivity showed a good concordance with HR HPV DNA for oropharyngeal and especially tonsillar carcinomas. The use of p16 IHC may further be extended to predict HR HPV positivity in sinonasal tract SCCs.

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Characteristics of human papillomavirus infection among oropharyngeal cancer patients: A systematic review and meta-analysis
Meimei Cui, Jinling Cheng, Huijuan Cheng, Ming Zhao, Dan Zhou, Min Zhang, Jingjing Jia, Limei Luo
Archives of Oral Biology.2024; 157: 105830. CrossRef
Impact of histopathological parameters in prognosis of oral squamous cell carcinoma
R. P. Ekanayaka, W. M. Tilakaratne
Oral Diseases.2024;[Epub] CrossRef
High-risk HPV Does not Appear to be an Important Risk Factor for Sinonasal Carcinomas in Turkish Population: A Tertiary Center Experience
Evsen Apaydin Arikan, Levent Aydemir, Murat Ulusan, Dilek Yilmazbayhan, Yasemin Ozluk
International Journal of Surgical Pathology.2023; 31(2): 124. CrossRef
Practical Application of Circulating Tumor-Related DNA of Human Papillomavirus in Liquid Biopsy to Evaluate the Molecular Response in Patients with Oropharyngeal Cancer
Agnieszka M. Mazurek, Tomasz W. Rutkowski
Cancers.2023; 15(4): 1047. CrossRef
The Prevalence of HPV in Oral Cavity Squamous Cell Carcinoma
Seyed Keybud Katirachi, Mathias Peter Grønlund, Kathrine Kronberg Jakobsen, Christian Grønhøj, Christian von Buchwald
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The Protective Role of Cranberries and Blueberries in Oral Cancer
César Esquivel-Chirino, Mario Augusto Bolaños-Carrillo, Daniela Carmona-Ruiz, Ambar Lopéz-Macay, Fernando Hernández-Sánchez, Delina Montés-Sánchez, Montserrat Escuadra-Landeros, Luis Alberto Gaitán-Cepeda, Silvia Maldonado-Frías, Beatriz Raquel Yáñez-Ocam
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Unusual cases of sinonasal malignancies: a letter to the editor on HPV-positive sinonasal squamous cell carcinomas
Benedicte Bitsch Lauritzen, Sannia Sjöstedt, Jakob Myllerup Jensen, Katalin Kiss, Christian von Buchwald
Acta Oncologica.2023; 62(6): 608. CrossRef
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Yy Jean Tan, Ken Wong Siong Hou, Galvin Sim Siang Lin, Jasmine Lim Suk Wun, Wan Nor Amira Wan Ahmad Abdul Nasir, Lynn Wei Linn Ko
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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; 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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Review

Clinical management of abnormal Pap tests: differences between US and Korean guidelines: Seyeon Won, Mi Kyoung Kim, Seok Ju Seong; J Pathol Transl Med. 2020;54(3):213-219. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.11

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Abstract PDF

Cervical cancer has been the most common gynecological cancer in Korea but has become a preventable disease with regular screening and proper vaccination. If regular screening is provided, cervical cancer does not progress to more than carcinoma in situ, due to its comparatively long precancerous duration (years to decades). In 2012, the American Society for Colposcopy and Cervical Pathology published guidelines to aid clinicians in managing women with abnormal Papanicolaou (Pap) tests, and they soon became the standard in the United States. Not long thereafter, the Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology published practical guidelines to reflect the specific situation in Korea. The detailed screening guidelines and management options in the case of abnormal Pap test results are sometimes the same and sometimes different in the United States and Korean guidelines. In this article, we summarize the differences between the United States and Korean guidelines in order to facilitate physicians’ proper management of abnormal Pap test results.

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Analysis of HR-HPV Infection Concordance Rates in Cervical and Urine Specimens; Proposal of Additional Cervical Screening Process for Women Who Refuse Invasive Cervical Sampling
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Original Articles

Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution: Myunghee Kang, Seung Yeon Ha, Hyun Yee Cho, Dong Hae Chung, Na Rae Kim, Jungsuk An, Sangho Lee, Jae Yeon Seok, Juhyeon Jeong; J Pathol Transl Med. 2020;54(1):112-118. Published online January 15, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.29

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Abstract PDF

Background
The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution.
Methods
Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations.
Results
Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively).
Conclusions
Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

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Challenges in the diagmosis of cervical pathologies
D. Y. Chernov, O. A. Tikhonovskaya, S. V. Logvinov, I. A. Petrov, Y. S. Yuriev, A. A. Zhdankina, A. V. Gerasimov, I. V. Zingalyuk, G. A. Mikheenko
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“Barriers and Advantages of Self-Sampling Tests, for HPV Diagnosis: A Qualitative Field Experience Before Implementation in a Rural Community in Ecuador”
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T. Stverakova, I. Baranova, P. Mikyskova, B. Gajdosova, H. Vosmikova, J. Laco, V. Palicka, H. Parova
Frontiers in Oncology.2023;[Epub] CrossRef
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Bernardo Vega Crespo, Vivian Alejandra Neira, José Ortíz Segarra, Ruth Maldonado Rengel, Diana López, María Paz Orellana, Andrea Gómez, María José Vicuña, Jorge Mejía, Ina Benoy, Tesifón Parrón Carreño, Veronique Verhoeven
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A Multi-institutional Study of Prevalence and Clinicopathologic Features of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) in Korea: Ja Yeong Seo, Ji Hyun Park, Ju Yeon Pyo, Yoon Jin Cha, Chan Kwon Jung, Dong Eun Song, Jeong Ja Kwak, So Yeon Park, Hee Young Na, Jang-Hee Kim, Jae Yeon Seok, Hee Sung Kim, Soon Won Hong; J Pathol Transl Med. 2019;53(6):378-385. Published online October 21, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.18

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Abstract PDF

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

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