Journal of Pathology and Translational Medicine

Original Articles

Diagnostic value of cytology in detecting human papillomavirus–independent cervical malignancies: a nation-wide study in Korea: Hye-Ra Jung, Junyoung Shin, Chong Woo Yoo, Eun Na Kim, Cheol Lee, Kyeongmin Kim, Ho-chang Lee, Yonghee Lee, Ji Hye Kim, Soo Jin Jung, Yumin Chung, Joo Yeon Kim, Hye Eun Park, Tae Hoen Kim, Wonae Lee, Min-Sun Cho, Ran Hong, Yoon Jung Choi, Younghee Choi, Young Sub Lee, Sang-Ryung Lee, Myunghee Kang, Young Jin Seo, Seung-Sook Lee, Yoon-Jung Hwang, Hyun-Jung Kim; J Pathol Transl Med. 2025;59(6):444-452. Published online November 11, 2025; DOI: https://doi.org/10.4132/jptm.2025.10.21

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Abstract PDF: Background
Human papillomavirus (HPV) independent cervical malignancies (HPV-IDCMs) have recently been classified by the World Health Organization (WHO) 5th edition. These malignancies have historically received limited attention due to their rarity and the potential for evasion of HPV-based screening.
Methods
We retrospectively reviewed 5,854 biopsy-confirmed cervical malignancies from 22 institutions over 3 years (July 2020–June 2023). Histologic classification followed the WHO guidelines. HPV independence was confirmed by dual negativity for p16 and HPV; discordant cases (p16-positive/HPV-negative) underwent additional HPV testing using paraffin-embedded tissue. Cytological results were matched sequentially to histological confirmation.
Results
The prevalence of HPV-IDCM was 4.4% (257/5,854) overall and was 3.6% (208/5,805 cases) among primary cervical malignancy. Patient age of HPV-IDCM was 29 to 89 years (median, 57.79). Its histologic subtypes included primary adenocarcinoma (n = 116), endometrial adenocarcinoma (n = 35), squamous cell carcinoma (n = 72), metastatic carcinoma (n = 14), carcinoma, not otherwise specified (n = 10), neuroendocrine carcinoma (n = 3), and others (n = 7). Among 155 cytology-histological matched cases, the overall and primary Pap test detection rates were 85.2% (132/155) and 83.2% (104/125), respectively. The interval between cytology and histologic confirmation extended up to 38 months.
Conclusions
HPV-IDCMs comprised 3.6% of primary cervical malignancies with a high detection rate via cytology (83.2%). These findings affirm the value of cytological screening, particularly in patients with limited screening history or at risk for HPV-independent lesions, and may guide future screening protocols.

Histologically confirmed distant metastatic urothelial carcinoma from the urinary bladder: a retrospective review of one institution’s 20-year experience: Youngeun Yoo, Junghye Lee, Heae Surng Park, Min-Sun Cho, Sun Hee Sung, Sanghui Park, Euno Choi; J Pathol Transl Med. 2021;55(2):94-101. Published online December 3, 2020; DOI: https://doi.org/10.4132/jptm.2020.10.19

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Background
Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology.
Methods
We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding.
Results
Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis.
Conclusions
Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.

Citations

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Do Histology and Primary Tumor Location Influence Metastatic Patterns in Bladder Cancer?
Hyung Kyu Park
Current Oncology.2023; 30(10): 9078. CrossRef

Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate: Junghye Lee, Youngeun Yoo, Sanghui Park, Min-Sun Cho, Sun Hee Sung, Jae Y. Ro; J Pathol Transl Med. 2020;54(2):146-153. Published online February 10, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.12

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Abstract PDF

Background
Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate.
Methods
Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion.
Results
In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised.
Conclusions
Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.

Citations

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Aberrant expression of GATA3 in metastatic adenocarcinoma of the prostate: an important pitfall
João Lobo, Nazario P Tenace, Sofia Cañete‐Portillo, Isa Carneiro, Rui Henrique, Roberta Lucianò, Lara R Harik, Cristina Magi‐Galluzzi
Histopathology.2024; 84(3): 507. CrossRef
Utility of D2-40, Cytokeratin 5/6, and High–Molecular-weight Cytokeratin (Clone 34βE12) in Distinguishing Intraductal Spread of Urothelial Carcinoma From Prostatic Stromal Invasion
Oleksii A. Iakymenko, Laurence M. Briski, Katiana S. Delma, Merce Jorda, Oleksandr N. Kryvenko
American Journal of Surgical Pathology.2022; 46(4): 454. CrossRef

Brief Case Report

Cytomegalovirus-Associated Intussusception with Florid Vascular Proliferation in an Infant: Heejung Park, Sanghui Park, Young Ju Hong, Sun Wha Lee, Min-Sun Cho; J Pathol Transl Med. 2015;49(3):270-273. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.04.01

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Citations

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Florid vascular proliferation due to focal necrotizing enterocolitis in infancy: A case report
Seyma Ozturk, Selma Erdogan Duzcu, Cetin Boran, Hulya Ozturk
Indian Journal of Medical Sciences.2024; 76: 144. CrossRef
Severe Postnatal Cytomegalovirus Enterocolitis in Immunocompetent Term Infants Requiring Total Parenteral Nutrition
Annaleise R. Howard‐Jones, Giancarlo H. Cristerna‐Tarrasa, Rabia Khan, Michael Stormon, Susan Arbuckle, Philip N. Britton
JPGN Reports.2021;[Epub] CrossRef
Retrospective multicenter matched case–control study on the risk factors for intussusception in infants less than 1 year of age with a special focus on rotavirus vaccines – the German Intussusception Study
Doris Oberle, Marcus Hoffelner, Jutta Pavel, Dirk Mentzer, Immanuel Barth, Ursula Drechsel-Bäuerle, Brigitte Keller-Stanislawski
Human Vaccines & Immunotherapeutics.2020; 16(10): 2481. CrossRef
Ebola Virus Causes Intestinal Tract Architectural Disruption and Bacterial Invasion in Non-Human Primates
Ronald B. Reisler, Xiankun Zeng, Christopher W. Schellhase, Jeremy J. Bearss, Travis K. Warren, John C. Trefry, George W. Christopher, Mark G. Kortepeter, Sina Bavari, Anthony P. Cardile
Viruses.2018; 10(10): 513. CrossRef

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