Journal of Pathology and Translational Medicine

Original Articles

Current status of cytopathology practice in Korea: impact of the coronavirus pandemic on cytopathology practice: Soon Auck Hong, Haeyoen Jung, Sung Sun Kim, Min-Sun Jin, Jung-Soo Pyo, Ji Yun Jeong, Younghee Choi, Gyungyub Gong, Yosep Chong; J Pathol Transl Med. 2022;56(6):361-369. Published online October 27, 2022; DOI: https://doi.org/10.4132/jptm.2022.09.21

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Background
The Continuous Quality Improvement program for cytopathology in 2020 was completed during the coronavirus pandemic. In this study, we report the result of the quality improvement program.
Methods
Data related to cytopathology practice from each institute were collected and processed at the web-based portal. The proficiency test was conducted using glass slides and whole-slide images (WSIs). Evaluation of the adequacy of gynecology (GYN) slides from each institution and submission of case glass slides and WSIs for the next quality improvement program were performed.
Results
A total of 214 institutions participated in the annual cytopathology survey in 2020. The number of entire cytopathology specimens was 8,220,650, a reduction of 19.0% from the 10,111,755 specimens evaluated in 2019. Notably, the number of respiratory cytopathology specimens, including sputum and bronchial washing/ brushing significantly decreased by 86.9% from 2019, which could be attributed to the global pandemic of coronavirus disease. The ratio of cases with atypical squamous cells to squamous intraepithelial lesions was 4.10. All participating institutions passed the proficiency test and the evaluation of adequacy of GYN slides.
Conclusions
Through the Continuous Quality Improvement program, the effect of coronavirus disease 2019 pandemic, manifesting with a reduction in the number of cytologic examinations, especially in respiratory-related specimen has been identified. The Continuous Quality Improvement Program of the Korean Society for Cytopathology can serve as the gold standard to evaluate the current status of cytopathology practice in Korea.

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A stepwise approach to fine needle aspiration cytology of lymph nodes
Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee
Journal of Pathology and Translational Medicine.2023; 57(4): 196. CrossRef
Diagnostic proficiency test using digital cytopathology and comparative assessment of whole slide images of cytologic samples for quality assurance program in Korea
Yosep Chong, Soon Auck Hong, Hoon Kyu Oh, Soo Jin Jung, Bo-Sung Kim, Ji Yun Jeong, Ho-Chang Lee, Gyungyub Gong
Journal of Pathology and Translational Medicine.2023; 57(5): 251. CrossRef

Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma: Myung-Giun Noh, Sung Sun Kim, Eu Chang Hwang, Dong Deuk Kwon, Chan Choi; J Pathol Transl Med. 2017;51(4):365-373. Published online June 9, 2017; DOI: https://doi.org/10.4132/jptm.2017.05.04

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Abstract PDF

Background
Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma.
Methods
The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data.
Results
YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10) than in carcinomas with a low Gleason grades (6–7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)–free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model.
Conclusions
The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

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Deep learning uncovers histological patterns of YAP1/TEAD activity related to disease aggressiveness in cancer patients
Benoit Schmauch, Vincent Cabeli, Omar Darwiche Domingues, Jean-Eudes Le Douget, Alexandra Hardy, Reda Belbahri, Charles Maussion, Alberto Romagnoni, Markus Eckstein, Florian Fuchs, Aurélie Swalduz, Sylvie Lantuejoul, Hugo Crochet, François Ghiringhelli, V
iScience.2025; 28(1): 111638. CrossRef
Connecting Hippo Pathway and Cytoophidia in Drosophila Posterior Follicle Cells
Rui-Yu Weng, Lei Zhang, Ji-Long Liu
International Journal of Molecular Sciences.2024; 25(3): 1453. CrossRef
TLK1>Nek1 Axis Promotes Nuclear Retention and Activation of YAP with Implications for Castration-Resistant Prostate Cancer
Damilola Olatunde, Arrigo De Benedetti
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NEK1-Mediated Phosphorylation of YAP1 Is Key to Prostate Cancer Progression
Ishita Ghosh, Md Imtiaz Khalil, Rusella Mirza, Judy King, Damilola Olatunde, Arrigo De Benedetti
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Epigenetic Inheritance From Normal Origin Cells Can Determine the Aggressive Biology of Tumor-Initiating Cells and Tumor Heterogeneity
Jiliang Feng, Dawei Zhao, Fudong Lv, Zhongyu Yuan
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A Yes-Associated Protein (YAP) and Insulin-Like Growth Factor 1 Receptor (IGF-1R) Signaling Loop Is Involved in Sorafenib Resistance in Hepatocellular Carcinoma
Mai-Huong T. Ngo, Sue-Wei Peng, Yung-Che Kuo, Chun-Yen Lin, Ming-Heng Wu, Chia-Hsien Chuang, Cheng-Xiang Kao, Han-Yin Jeng, Gee-Way Lin, Thai-Yen Ling, Te-Sheng Chang, Yen-Hua Huang
Cancers.2021; 13(15): 3812. CrossRef
Evidence for discrete modes of YAP1 signaling via mRNA splice isoforms in development and diseases
Jan Vrbský, Vladimir Vinarský, Ana Rubina Perestrelo, Jorge Oliver De La Cruz, Fabiana Martino, Antonio Pompeiano, Valerio Izzi, Ota Hlinomaz, Vladimir Rotrekl, Marius Sudol, Stefania Pagliari, Giancarlo Forte
Genomics.2021; 113(3): 1349. CrossRef
Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers
Andreas Marx, Aljoscha Schumann, Doris Höflmayer, Elena Bady, Claudia Hube-Magg, Katharina Möller, Maria Christina Tsourlakis, Stefan Steurer, Franziska Büscheck, Till Eichenauer, Till S. Clauditz, Markus Graefen, Ronald Simon, Guido Sauter, Jakob R. Izbi
Scientific Reports.2020;[Epub] CrossRef
NEK1 Phosphorylation of YAP Promotes Its Stabilization and Transcriptional Output
Md Imtiaz Khalil, Ishita Ghosh, Vibha Singh, Jing Chen, Haining Zhu, Arrigo De Benedetti
Cancers.2020; 12(12): 3666. CrossRef

Brief Case Reports

Hybrid Granular Cell Tumor/Perineurioma: Sung Sun Kim, Yoo Duk Choi, Jae Hyuk Lee, Chan Choi, Chang Soo Park; Korean J Pathol. 2014;48(6):409-412. Published online December 31, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.409

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Rare Hybrid Perineurioma and Granular Cell Tumor: A Pediatric Case
Kennedy H. Sun, Sonia P. Goyal, Evelyn M. Kim, Esperanza Mantilla-Rivas, Gary F. Rogers, Sam P. Gulino
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Ani Toklu, Gauri Panse, George Jour, Konstantinos Linos, Jeffrey M. Cloutier, Carina A. Dehner
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What’s new in nerve sheath tumors
Anders Meyer, Steven D. Billings
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A Rare Perineurioma/Granular Cell Tumor Hybrid Peripheral Nerve Sheath Tumor
Koorosh Haghayeghi, Gladys Telang, Sonja Chen, Jack Bevivino, Shamlal Mangray, Yiang Hui, Leslie Robinson-Bostom
The American Journal of Dermatopathology.2020; 42(10): 762. CrossRef

Cytokeratin-Positive Gastrointestinal Stromal Tumor of Biphasic Morphology: A Case Report: Sung Sun Kim, Yoo Duk Choi, Jae Hyuk Lee, Chan Choi; Korean J Pathol. 2014;48(5):375-378. Published online October 27, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.375

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CYTOKERATINS: NOT AN EPITHELIAL ENTITY ANYMORE?
Geetpriya Kaur, Devicharan Shetty, Seema Sikka, Aparna Pathak
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Gastrointestinal stromal tumors of the stomach in a 10-year-old child
Saeed Nasher, Fayed Al-Yousofy, Faisal Ahmed
Journal of Pediatric Surgery Case Reports.2021; 74: 102044. CrossRef

Original Articles

HPV Genotyping in Squamous Cell Carcinoma of Upper Aerodigestive Tract.: Young Kim, Eun Hui Jeong, Byung Woo Min, Sung Sun Kim, Yoo Duk Choi, Woon Jae Jung, Jong Hee Nam, Chang Soo Park; Korean J Pathol. 2010;44(5):483-487.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.483

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Abstract PDF

BACKGROUND
Smoking and alcohol consumption are the main risk factors for squamous cell carcinoma of the upper aerodigestive tract (SCCUAT). However, human papillomavirus (HPV) has been etiologically linked with tonsillar squamous cell carcinoma (TSCC). Therefore, we investigated the etiologic role of HPV in the context of SCCUAT in Korea.
METHODS
Archival paraffin block samples from 136 cases previously diagnosed as SCCUAT were randomly selected. A commercial HPV DNA chip was used for HPV genotyping.
RESULTS
One hundred and seventeen cases were available after checking beta-globin (47 cases of tonsil and 70 of non-tonsil). A HPV-positive result (HPV 16 and 18) occurred in 13 cases of SCCUAT, and 12 cases were tonsil (25.5%, 12/47). Among the 12 HPV-positive patients with TSCC, nine were non-smokers and non-drinkers. Most HPV-negative patients with TSCC had a history of alcohol drinking and smoking (32/35, 91.4%). HPV infection status was not significantly associated with histological grade, clinical stage, or survival in patients with TSCC.
CONCLUSIONS
HPV infection was significantly higher in patients with TSCC among those with SCCUAT. HPV may be independent risk factor in development of TSCC, such as smoking and alcohol drinking.

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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
Journal of Pathology and Translational Medicine.2020; 54(5): 411. CrossRef

DNA Methylation Profiles of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 in B-Cell Lymphomas.: Sung Sun Kim, Young Hyo Choi, Chang Woo Han, Yoo Duk Choi, Youngkyu Park, Je Jung Lee, Hyeoung Joon Kim, Il Kwon Lee, Ji Shin Lee, Sang Woo Juhng, Chan Choi; Korean J Pathol. 2009;43(5):420-427.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.420

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Abstract PDF

BACKGROUND
This study was designed to examine the prevalence of aberrant promoter methylation in a selected panel of genes potentially involved in lymphoid tumors.
METHODS
The promoter hypermethylation status of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 was measured by methylation-specific PCR for 82 cases of B-cell lymphoma. Immunohistochemical staining using MGMT and SHP1 antibodies was conducted on 43 out of 82 cases.
RESULTS
The number of MGMT aberrant methylations was lower in diffuse large B-cell lymphoma (DLBCL) than in other malignant lymphomas. The methylation of DAPK1 was frequently detected in follicular lymphoma (FL), marginal zone B-cell lymphoma (MZL) and DLBCL. With one exception, methylation of hMLH1 was not observed in B-cell lymphomas. The methylation frequency of CDH1, and HIC1 was similar in B-cell lymphomas. However, the methylation of SHP1 gene was more frequently observed in cases of FL, DLBCL, and MZL than in chronic lymphocytic lymphoma. MGMT and SHP1 promoter methylation were inversely correlated with the protein expression observed upon immunohistochemical staining.
CONCLUSIONS
Aberrant promoter methylation of multiple genes occurs with variable frequency throughout the B-cell lymphomas, and methylation of hMLH1 is rarely observed in B-cell lymphomas.

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Plasma DNA methylation of p16 and shp1 in patients with B cell non-Hodgkin lymphoma
Kai Ding, Xiaoshuang Chen, Yihao Wang, Hui Liu, Wenjing Song, Lijuan Li, Guojin Wang, Jia Song, Zonghong Shao, Rong Fu
International Journal of Clinical Oncology.2017; 22(3): 585. CrossRef
Hypermethylation of p15 Gene in Diffuse – Large B‐Cell Lymphoma: Association with Less Aggressiveness of the Disease
Milena Krajnović, Maja Peruničić Jovanović, Biljana Mihaljević, Boško Anđelić, Olivera Tarabar, Slavica Knežević‐Ušaj, Koviljka Krtolica
Clinical and Translational Science.2014; 7(5): 384. CrossRef

Case Report

Cytologic Diagnosis of Malignant Pleural Effusion in Multiple Myeloma: Two Case Reports.: Yoo Duk Choi, Sung Sun Kim, Chang Woo Han, Ji Shin Lee, Jong Hee Nam, Sang Woo Juhng, Chan Choi; Korean J Pathol. 2009;43(4):382-385.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.382

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Abstract PDF

Malignant pleural effusion in multiple myeloma (MM) is extremely rare and is associated with poor prognosis. We experienced two cases of MM IgA type with malignant pleural effusion. The diagnoses were based on characteristic cytology and CD138 immunocytochemistry. The patients received several cycles of combination chemotherapy, since symptoms were more aggressive with an uncontrolled pleural effusion. We review the clinical features of these cases and literature concerning myelomatous pleural effusion.

Citations

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Características de los pacientes con derrame pleural mielomatoso. Revisión sistemática
V. Riveiro, L. Ferreiro, M.E. Toubes, A. Lama, J.M. Álvarez-Dobaño, L. Valdés
Revista Clínica Española.2018; 218(2): 89. CrossRef
Characteristics of patients with myelomatous pleural effusion. A systematic review
V. Riveiro, L. Ferreiro, M.E. Toubes, A. Lama, J.M. Álvarez-Dobaño, L. Valdés
Revista Clínica Española (English Edition).2018; 218(2): 89. CrossRef
A 76-Year-Old Man With Anemia, Bone Pain, and Progressive Dyspnea
Thitiporn Suwatanapongched, Prapaporn Pornsuriyasak, Wasana Kanoksil, Thotsaporn Morasert, Warapat Virayavanich
Chest.2014; 145(4): 913. CrossRef

Original Articles

An Immunohistochemical Study of Angiogenesis in Tumor Emboli.: Jo Heon Kim, Chan Choi, Jae Hyuk Lee, Ji Shin Lee, Sung Sun Kim, Chang Woo Han, Sang Woo Juhng; Korean J Pathol. 2007;41(4):252-257.

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Abstract PDF: BACKGROUND
Angiogenesis, which is essential for tumor growth, is known to occur in the extravascular stroma. However, vascular structures were noted in intravascular tumor emboli in surgical specimens. This prompted our investigation of the frequency and morphology of angiogenesis in tumor emboli.
METHODS
Hematoxylin-eosin stained specimens were reviewed for tumor emboli, in 21 cases of stomach adenocarcinoma and 22 cases of colon adenocarcinoma. The cases were examined with immunohistochemistry using antibodies against epithelial antigen (cytokeratin), endothelial antigens (CD31, CD34), lymphatic endothelial antigen (D2-40), and proliferation-associated antigen (MIB1).
RESULTS
Endothelial cells were observed in 16 tumor emboli among four (19.1%) of the 21 cases of stomach adenocarcinoma and in 32 tumor emboli among four (18.2%) of the 22 cases of colon adenocarcinoma. The endothelial cells in the tumor emboli showed papillary ingrowth from the vessel wall, formation of vascular lumens, scattered distribution, or surface coating of the emboli. Some of the endothelial cells in the tumor emboli were D2-40-positive, and some were MIB1- positive.
CONCLUSIONS
These findings demonstrated that angiogenesis occurs in intravascular tumor emboli as well as in the extravascular stroma. Angiogenesis in the tumor emboli may reflect an active process and may facilitate tumor growth.

Expression of VEGF, MMP-9 and Neovascularization in Relationship to the Clinical Behavior of Giant Cell Tumors of Bone.: Kyung Hwa Lee, Jo Heon Kim, Min Keun Shim, Chang Woo Han, Sung Sun Kim, Sang Woo Juhng, Sung Taek Jung, Jae Hyuk Lee; Korean J Pathol. 2006;40(6):420-426.

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Abstract PDF: BACKGROUND
Giant cell tumors (GCT(s)) of bone are benign but can be locally aggressive neoplasms. Their clinical behavior has been difficult to predict on the basis of histology alone. This study investigated the neovascularization and expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-9 (MMP-9) in GCT(s) of bone; in addition we evaluated their relationship to clinical behavior.
METHODS
We evaluated the microvessel number and density in 33 samples of giant cell tumor using CD34 immunohistochemistry. In addition, we examined the immunohistochemical expression of VEGF and MMP-9.
RESULTS
The microvessel number alone, not the microvessel density, had statistical association with the clinical stage of GCT(s) (p=0.045). The proportion of cases with strong expression of VEGF increased with advancing clinical stage, however, these results were not statistically significant (p=0.257). The percentage of the cases with strong expression of MMP-9 also increased with advancing clinical stage and this was statistically significant (p=0.022).
CONCLUSIONS
These results suggest that intratumor microvessel count and the expression of MMP-9 correlate with GCT stage. Evaluation of their expression may therefore provide prognostic information on the aggressive behavior of GCT(s) of bone.

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