Journal of Pathology and Translational Medicine

Original Articles

National quality assurance program using digital cytopathology: a 5-year digital transformation experience by the Korean Society for Cytopathology: Yosep Chong, Hyeong Ju Kwon, Soon Auck Hong, Sung Soon Kim, Bo-Sung Kim, Younghee Choi, Yoon Jung Choi, Jung-Soo Pyo, Ji Yun Jeong, Soo Jin Jung, Hoon Kyu Oh, Seung-Sook Lee; J Pathol Transl Med. 2025;59(5):320-333. Published online September 15, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.27

167 View
13 Download

Abstract PDF: Background
Digital cytopathology (DC) is emerging as a transformative approach in quality assurance programs (QAP), though its comprehensive evaluation remains limited. Since 2020, the Korean Society for Cytopathology has progressively incorporated DC into its national QAP, including digital proficiency testing (PT), sample adequacy testing (SAT), a customizable PT module, and a self-assessment module (SAM), aiming for full digital implementation by 2026. Methods: This 5-year study assessed diagnostic concordance between conventional and digital PT formats and analyzed participant feedback on service quality and digital image usability across PT, SAT, and SAM. Parallel testing was conducted during the transitional phase, and satisfaction was measured through structured surveys. Results: Participation in digital PT increased from 48 institutions in 2020 to 93 in 2024, while digital SAT participation rose from 29 to 71 between 2022 and 2024. In 2023, 56 institutions joined SAM. Diagnostic concordance rates were comparable between digital and conventional PTs (78.6%–84.6% vs. 82.0%–85.1%), including similar category C (major discordance) rates. Satisfaction with digital PT services and image quality exceeded 85%, and over 90% of institutions reported positive feedback on SAT and SAM. Over 80% were satisfied with the customizable PT module. Conclusions: DC is a reliable and effective modality for cytopathology QAP. It demonstrates diagnostic equivalence to conventional methods and high user satisfaction, supporting its broader implementation in national quality assurance frameworks.

Frozen section histopathology and preanalytical factors affecting nucleic acid integrity in biobanked fresh-frozen human cancer tissues: Soungeun Kim, Jaewon Kang, Boyeon Kim, Yoonjin Kwak, Hye Seung Lee; Received June 5, 2025 Accepted July 22, 2025 Published online September 12, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.22 [Epub ahead of print]

348 View
14 Download

Abstract PDF Supplementary Material: Background
In this study, we evaluated the effects of storage duration and ischemic time on nucleic acid quality of fresh-frozen tissue (FFT) from colon adenocarcinoma (COAD), hepatocellular carcinoma (HCC), and renal cell carcinoma (RCC) collected at the Cancer Tissue Bank of Seoul National University Hospital. Methods: A total of 102 FFT samples were analyzed to compare DNA integrity number (DIN) and RNA integrity number (RIN) according to storage duration and ischemic time. Additionally, the effects of histopathologic features—such as tumor cell proportion, inflammatory cell infiltration, and stromal fibrosis—on nucleic acid quality were evaluated. Results: DIN and RIN remained stable overall even though the storage duration increased, with no statistically significant differences observed. In particular, there was almost no decrease in RNA quality in HCC and RCC samples, but in COAD samples, RIN tended to decrease slightly as the storage duration increased. No significant difference was confirmed between ischemic time and nucleic acid quality, but in COAD tissue, RNA quality variability tended to increase as the ischemic time increased. Furthermore, RIN increased as the tumor cell proportion increased, whereas inflammatory cell infiltration and extracellular mucin pool were identified as independent negative predictors of RIN. Conclusions: This study confirmed that nucleic acid integrity can be maintained even during long-term storage of FFT and demonstrated that histologic features are closely related to RNA quality. This study would contribute to the establishment of quality assessment and management standards for biobank FFT samples.

Case Study

Cytological characteristics of Müllerian adenosarcoma of the uterine corpus: a case report and literature review: Junko Kuramoto, Chihiro Matsubara, Yasuko Sasamoto, Hitomi Tsukada, Shigemichi Hirose; J Pathol Transl Med. 2025;59(5):340-347. Published online September 11, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.11

318 View
16 Download

Abstract PDF: Müllerian adenosarcoma of the uterus is a rare morphological variant of uterine sarcoma. Müllerian adenosarcoma has been described histologically, though it is rare in the cytological literature. This report describes the cytological findings of a case of adenosarcoma arising from the endometrium. The patient was a Japanese woman in her 40s. Endometrial cytological and histological findings were observed for 5 years, from the appearance of a polypoid lesion until adenosarcoma was suspected, and then hysterectomy was performed. Based on these longitudinal cytological and histological observations, it was possible to identify the cytological characteristics of adenosarcoma: decrease in the glandular-to-stromal ratio; increase in stromal cell density; and progression of stromal cell atypia. This case stresses the importance and usefulness of endometrial cytology in the identification of the sarcomatous component in adenosarcoma.

Original Article

A single-institution demographic study of pathologically proven kidney disease in South Korea over the last 33 years: Hyejin Noh, Jiyeon Kim, Yeong Jin Choi; J Pathol Transl Med. 2025;59(5):306-319. Published online September 10, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.18

345 View
17 Download

Abstract PDF Supplementary Material: Background
To date, epidemiological studies on the entire spectrum of kidney disease based on pathology have been rarely reported. Methods: A retrospective study was conducted on patients diagnosed with kidney disease at Seoul St. Mary's Hospital between 1991 and 2023. Results: Among 7,803 patients with native kidney disease, glomerular disease (70.3%) was the most common, followed by tubulointerstitial (15.1%) and vascular disease (8.8%). In kidney biopsy, glomerular disease (77.8%) showed the highest frequency, particularly in those under 20s (95.6%) (p = .013). Primary glomerulonephritis (GN) (72.8%) was the predominant glomerular disease, with IgA nephropathy (IgAN) (47.3%) being the most common one. Tubulointerstitial and vascular diseases increased with age, showing the highest prevalence in those over 60 years (p = .008 and p = .032, respectively). Glomerular disease was diagnosed at a younger age (39.7 ± 16.7 years) than tubulointerstitial (49.1 ± 16.2) and vascular (48.1 ± 15.3) diseases (p < .001). When glomerular diseases were classified morphologically, proliferative GN (57.9%) was the most common, followed by non-proliferative (39.6%) and sclerosing (1.6%). When classified by etiology, primary GN accounted for the most (72.8%), followed by secondary (19.3%) and hereditary GN (5.7%). In nephrectomy, tubulointerstitial disease (64.6%) was the most common. Those with a tubulointerstitial disease had a higher mean age than those with a glomerular disease (p < .001). In cases where nephrectomy was performed for glomerular diseases, IgAN (34.1%) was the most common diagnosis. Conclusions: Kidney disease has been increasing in South Korea for 33 years. Glomerular disease was the most common across all age groups, tubulointerstitial and vascular diseases increased over 60 years.

Letter to the Editor

Variation in mitotic counting and risk classification practices for gastrointestinal stromal tumors: a survey of pathologists in South Korea: In Hye Song, Soomin Ahn, Jeong-Hyeon Jo, Young Soo Park; J Pathol Transl Med. 2025;59(5):348-352. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.14

529 View
7 Download

PDF

Original Article

Characterization of undifferentiated carcinoma of the salivary gland: clinicopathological and immunohistochemical analyses in comparison with lymphoepithelial carcinoma: Sangjoon Choi, Gyuheon Choi, Hee Jin Lee, Joon Seon Song, Yoon Se Lee, Seung-Ho Choi, Kyung-Ja Cho; Received May 3, 2025 Accepted July 7, 2025 Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.07 [Epub ahead of print]

446 View
17 Download

Abstract PDF: Background
This study aimed to reclassify a subset of poorly differentiated salivary gland carcinoma that do not conform to any entities of the current World Health Organization (WHO) classification into the category of undifferentiated carcinoma (UDC) because they lack specific histologic differentiation or immunophenotype. Methods: Cases of salivary gland carcinomas from Asan Medical Center (2002–2020) that did not fit any existing WHO classification criteria and were diagnosed as poorly differentiated carcinoma, high-grade carcinoma, or UDC, were retrospectively reviewed. Immunohistochemical (IHC) staining for p40, neuroendocrine markers, androgen receptor (AR), and gross cystic disease fluid protein 15 (GCDFP-15) and Epstein-Barr virus (EBV) in situ hybridization (ISH) were performed. Clinical data were collected from the electronic medical records. Results: Six salivary gland carcinomas did not align with any specific entities and lacked distinct differentiation. Two of six cases displayed lymphoepithelial carcinoma (LEC)-like morphology but were negative or showed negligible immunoreactivity for p40 and EBV ISH, distinguishing them from LEC of the salivary gland. Two cases showed strong AR positivity, suggesting a potential overlap with salivary duct carcinoma (SDC) but lacked classic SDC morphologies and GCDFP-15 expression. No cases expressed neuroendocrine markers. Conclusions: This study proposes reclassifying these poorly differentiated or high-grade salivary gland carcinomas as UDC based on their indeterminate differentiation and IHC profiles. This may lead to a clearer diagnostic category and enhance our understanding of these high-grade tumors.

Case Study

Composite chronic lymphocytic leukemia and mantle cell lymphoma involving the bone marrow: a case report and literature review: Roksolana Demianets, Susan O’Brien, Khosrow Mahdavi, Chenchen Niu, Sumayya Aslam, Truc Tran, Ying Zhang, Ashley Gamayo, Xiaohui Zhao, Sherif A. Rezk; J Pathol Transl Med. 2025;59(5):334-339. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.02

552 View
30 Download

Abstract PDF: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a clinically indolent lymphoproliferative disorder characterized by accumulation of mature B-cell lymphocytes. Given the common CD5 co-expression, mantle cell lymphoma (MCL) is one of the most important entities in the differential diagnosis. MCL and CLL/SLL might exhibit overlapping morphologic and immunohistochemical features, making diagnosis particularly difficult in cases of composite lymphomas. Here, we present a unique case of composite lymphoma in an 86-year-old male, along with a literature review on the immunophenotypic variability of both MCL and CLL, which should always be confirmed with additional ancillary cytogenetic and molecular studies.

Original Articles

Evaluation of potential prognostic significance of JUNB in human prostate cancer: a bioinformatic and histopathological study: Noha R. Noufal, Einas M. Yousef, Mohamed Taha; J Pathol Transl Med. 2025;59(5):291-305. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.06

412 View
25 Download

Abstract PDF Supplementary Material: Background
Prostate cancer is one of the most common malignancies in males worldwide. Serum prostate-specific antigen is a frequently employed biomarker in the diagnosis and risk stratification of prostate cancer; however, it is known for its low predictive accuracy for disease progression. New prognostic biomarkers are needed to distinguish aggressive prostate cancer from low-risk disease. This study aimed to identify and validate potential prognostic biomarkers of prostate cancer. Methods: Two prostate cancer datasets from the Gene Expression Omnibus were analyzed to identify differentially expressed genes between benign prostatic hyperplasia (BPH) and prostatic carcinoma. Immunohistochemistry was used to evaluate the JUNB proto-oncogene, a subunit of the AP-1 transcription factor (JUNB), in 70 prostate cancer patients and 10 BPH samples. Results: Our findings showed that JUNB was significantly enriched in prostate cancer-related pathways and biological processes. JUNB expression was considerably higher in prostatic adenocarcinoma patients than in BPH patients. Regarding JUNB expression in prostate cancer cases, lower levels of JUNB expression were associated with higher grades of prostatic adenocarcinoma. Lower JUNB expression was associated with a higher risk of prostatic adenocarcinoma progression and shorter overall survival. Conclusions: These results suggest that JUNB is a promising prognostic biomarker and a potential tumor suppressor in prostate cancer.

Unraveling the crucial role of CCL3 in nasopharyngeal carcinoma: bioinformatics and immunohistochemical insights: Xiaopeng Guo, Zhen Sun, Ya Liang, Aoshuang Chang, Junjun Ling, Houyu Zhao, Xianlu Zhuo; J Pathol Transl Med. 2025;59(5):281-290. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.05.23

373 View
32 Download

Abstract PDF: Background
C-C motif chemokine ligand 3 (CCL3) is a crucial chemokine that plays a fundamental role in the immune microenvironment and is closely linked to the development of various cancers. Despite its importance, there is limited research regarding the expression and function of CCL3 in nasopharyngeal carcinoma (NPC). Therefore, this study seeks to examine the expression of CCL3 and assess its clinical significance in NPC using bioinformatics analysis and experiments. Methods: The bioinformatics approach was employed to assess the expression and function of CCL3 in NPC. Subsequently, protein expression of CCL3 was detected in an NPC cohort using immunohistochemistry based on a tissue microarray. The relationship between CCL3 expression and clinical features was then investigated. Results: A total of 20 CCL3-related genes and 14 possible target genes were identified through bioinformatics analysis, many of which play crucial roles in pathways such as chemokine signaling pathway and transcriptional misregulation in cancer signaling pathways. CCL3 was found to be associated with drug resistance and various immune cell infiltrations. In NPC, CCL3 expression was significantly higher than normal controls, and high expression of CCL3 correlated with cervical lymph node metastasis, tumor recurrence, advanced clinical stage, and poor prognosis. Conclusions: CCL3 may be a key gene in the initiation and progression of NPC. It has the potential to serve as both a diagnostic biomarker and a therapeutic target for NPC.

Review Article

Central nervous system tumors with BCOR internal tandem duplications: a systematic review of clinical, radiological, and pathological features in 69 cases: Ji Young Lee, Sung Sun Kim, Hee Jo Baek, Tae-Young Jung, Kyung-Sub Moon, Jae-Hyuk Lee, Kyung-Hwa Lee; J Pathol Transl Med. 2025;59(5):273-280. Published online September 1, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.23

723 View
43 Download

Abstract PDF Supplementary Material: Central nervous system tumors with BCL6 corepressor (BCOR) internal tandem duplications (ITDs) constitute a rare, recently characterized pediatric neoplasm with distinct molecular and histopathological features. To date, 69 cases have been documented in the literature, including our institutional case. These neoplasms predominantly occur in young children, with the cerebellum representing the most frequent anatomical location. Radiologically, these tumors present as large, well-circumscribed masses frequently demonstrating necrosis, hemorrhage, and heterogeneous enhancement. Histologically, they are characterized by a monomorphic cellular population featuring ependymoma-like perivascular pseudorosettes, myxoid stroma, and elevated mitotic activity. Immunohistochemically, these tumors exhibit sparse glial fibrillary acidic protein expression while consistently demonstrating positive staining for vimentin and CD56. The defining molecular hallmark is a heterozygous ITD within exon 15 of the BCOR gene, with insertions ranging from 9 to 42 amino acids in length. BCOR immunohistochemistry reveals nuclear positivity in 97.9% of examined cases, although this finding is not pathognomonic for BCOR ITDs. This comprehensive review synthesizes data from all published cases of this novel tumor entity, providing a detailed analysis of clinical presentation, neuroimaging findings, histopathological features with differential diagnostic considerations, therapeutic approaches, and prognostic outcomes.

Newsletter

What’s new in medical renal pathology 2025: Updates on podocytopathy and immunofluorescence staining in medical kidney: Astrid Weins, Ibrahim Batal, Paola Romagnani, Geetika Singh, Rahul Raj, Nicole Andeen, Jonathan Zuckerman, Martina Uzzo, Mariam Priya Alexander, Anjali Satoskar; J Pathol Transl Med. 2025;59(4):269-272. Published online July 10, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.19

2,636 View
222 Download

Abstract PDF: Diffuse podocytopathy, including minimal change disease and primary focal segmental glomerulosclerosis, is a common cause of nephrotic syndrome in adults and children. It is increasingly recognized to be autoimmune-mediated associated with anti-nephrin and other emerging anti-slit diaphragm antibodies, and can recur in the kidney allograft. Immunofluorescence is routinely used in evaluation of kidney biopsies, and updates include those on fibrillar diseases, monoclonal staining, lupus-like staining, and use of antibody KM55 in IgA-dominant glomerulonephritis.

Original Articles

Pancreatic cancer in liquid-based cytology: cytological features and cell block utility from 254 fine-needle aspiration samples: Jaeyong Min, Wookjin Oh, Baek-hui Kim; J Pathol Transl Med. 2025;59(4):249-261. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.05.27

1,532 View
156 Download

Abstract PDF Supplementary Material: Background
Despite the increasing use of liquid-based cytology (LBC) for pancreatic cancer diagnosis, relatively few studies have directly examined such research. This study analyzed the cytopathological features of pancreatic cancer in LBC and demonstrated the utility of cell blocks in diagnosing pancreatic lesions. Methods: A retrospective review identified LBC from 254 pancreatic fine-needle aspirations (FNAs) (221 patients). FNAs were categorized into five subgroups based on cytopathological, clinical, and histopathological findings. Two pathologists evaluated cytological features in LBC samples, cell blocks, and tissue slides. Comparative analysis assessed differences between groups. Results: Compared to benign lesions, LBC of pancreatic cancer more frequently showed a necrotic background, intermediate to high cellularity, mixed architecture, nuclear/cytoplasmic ratio >0.8, anisonucleosis >4:1, irregular and thick nuclear membranes, multinucleated tumor cells, hyperchromatic nuclei, coarse to clumped chromatin, and a prominent single nucleolus. In cases of conventional pancreatic ductal adenocarcinoma, the palliative treatment subgroup showed a higher incidence of necrotic background than the resection subgroup. In the cell block analysis, tumor cells not identified in LBC slides were detected in 16 FNAs. Additionally, 13 FNAs contributed to differential diagnosis: ancillary tests aided diagnosis in 12 FNAs, while histopathological evaluation of the cell block slide alone was helpful in one case. Conclusions: The cytological features of pancreatic cancer in LBC are similar to those observed in conventional smears, with a necrotic background suggesting advanced (unresectable) disease. The cell block methodology minimizes tumor cell loss and facilitates differential diagnosis by enabling ancillary testing.

AMACR is a highly sensitive and specific immunohistochemical marker for diagnosing prostate cancer on biopsy: a systematic review and meta-analysis: Johannes Cansius Prihadi, Stevan Kristian Lionardi, Nicolas Daniel Widjanarko, Steven Alvianto, Fransiskus Xaverius Rinaldi, Archie Fontana Iskandar; J Pathol Transl Med. 2025;59(4):235-248. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.16

2,866 View
147 Download

Abstract PDF Supplementary Material: Background
Alpha-methylacyl-CoA racemase (AMACR) is the preferred biomarker for distinguishing malignant from benign glands in prostate biopsies, showing high sensitivity and specificity for prostate cancer. A meta-analysis of immunohistochemistry (IHC) for AMACR is essential to further assess its diagnostic accuracy across diverse sample sources. Methods: A systematic search of databases including MEDLINE, ScienceDirect, ProQuest, Google Scholar, and the Cochrane Library was performed, focusing on studies of AMACR to diagnose prostate cancer, particularly in biopsy samples analyzed through IHC over the last 20 years. Quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, followed by a meta-analysis of regions and subgroups to calculate summary estimates of diagnostic test accuracy. Results: In the final analysis, 37 studies, with a pooled size of 5,898 samples, were included from the examination of 94 full-text papers. Among them, 27 studies with similar sample sources and testing methodologies underwent meta-analysis, yielding a combined sensitivity estimate of 0.90 (95% confidence interval [CI], 0.86 to 0.93) and specificity of 0.91 (95% CI, 0.83 to 0.95), both with significant heterogeneity (p < .01). The region beneath the hierarchical summary receiver operating characteristic curve was 0.95 (95% CI, 0.93 to 0.97), positive likelihood ratio was 9.6 (95% CI, 5.3 to 17.4), negative likelihood ratio was 0.11 (95% CI, 0.08 to 0.15), and diagnostic odds ratio was 88 (95% CI, 42 to 181). Conclusions: Our meta-analysis findings substantiate AMACR as a highly accurate tool for diagnosing prostate cancer, specifically in biopsy samples, via immunohistochemical staining. Further studies involving diverse samples are needed to enhance our understanding of the AMACR diagnostic accuracy in a range of clinical settings.

The Automatable Activity–Based Approach to Complexity Unit Scoring as a task-specific model approach to monetizing outcomes of pathology artificial intelligence solutions: Stavros Pantelakos, Martha Nifora, Georgios Agrogiannis; J Pathol Transl Med. 2025;59(4):225-234. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.15

2,084 View
117 Download

Abstract PDF: Background
Cost-containment policies are increasingly affecting decision-making in healthcare. In this context, the need for monetization of digital health interventions has been recently emphasized. Previous studies have attempted to extrapolate cost containment in conjunction with the implementation of digital pathology solutions mostly on the basis of operational cost savings or diagnostic error reduction. However, no study has attempted to link a wider spectrum of potential diagnostic tasks performed by artificial intelligence algorithms to financial figures.
Methods
Herein, we employ a workload measurement tool for the purpose of monetizing particular outcomes associated with the implementation of a pathology artificial intelligence solution. A hundred and thirty-two prostate core biopsy samples were encoded for workload using the Automatable Activity–Based Approach to Complexity Unit Scoring. Subsequently, avoided workload, full-time equivalent gains, and corresponding cost savings were calculated assuming full clinical deployment of a well-developed prostate cancer screening tool.
Results
For a fixed percentage of negative cores and a steady yearly workload of prostate core biopsies, the estimated total avoided workload amounted to 4,291 complexity units per year, with an average avoidance of 16.25 complexity units per ascension number. The calculated full-time equivalent gains were 0.12, whereas projected cost savings were as high as €2,402.34 per year or €0.55 per complexity unit, which in turn would yield an average of €8.93 per ascension number.
Conclusions
The Automatable Activity–Based Approach to Complexity Unit Scoring appears to be a suitable economic evaluation tool for assessing the possible implementation of task-specific artificial intelligence solutions in a given histopathology laboratory or group of laboratories, considering it is a task-specific workload measurement tool per design.

Review Article

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

1,995 View
208 Download

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

First
Prev
Page of 312
Next
Last

Article category