Journal of Pathology and Translational Medicine

Original Article

Digital image analysis–based quantification of p53 immunohistochemistry in gastric cancer: a systematic comparison of three-tier cutoff-derivation strategies in tissue microarrays: Jaeyoung Ahn, Kyungeun Kim, Hee-Jung Yang, Boram Song, Dong Hoon Kim, Yumin Chung, Seoung Wan Chae; J Pathol Transl Med. 2026;60(6):593-610. Published online October 19, 2026; DOI: https://doi.org/10.4132/jptm.2026.08.13; Funded: Korea Health Industry Development Institute, Ministry of Health and Welfare

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Abstract PDF Supplementary Material: Background
p53 immunohistochemistry (IHC) is a common surrogate for TP53 alteration, but in gastric cancer, its concordance is imperfect and depends on a non-standardized cutoff. Digital pathology enables H-score quantification, yet neither its reproducibility nor the choice of cutoff- derivation strategy has been systematically compared. Methods: A semi-automated digital workflow quantified p53 IHC in tissue microarrays from 528 gastric cancer patients. Tumor cells were detected with a deep-learning model (InstanSeg), and nuclear staining was expressed as a continuous H-score (0–300). Reproducibility was assessed at each observer-dependent step. Five thresholding strategies were compared: manual cutoffs, tertiles, log-rank optimization, the extended Youden index, and volume under the receiver operating characteristic surface (VUS). The latter two strategies used the manual three-tier IHC interpretation as the reference standard. Results: Quantification was reproducible: two independent manual interpretations agreed in 91.7% of cores (κ = 0.845). The H-score was robust to the detection algorithm (intraclass correlation coefficient, 0.990) and to repeated threshold determination (0.954). H-scores were right-skewed (median, 45.5), and the strategies yielded distinct cutoffs (8.0–27.6 and 78.6–106.0). Log-rank optimization provided the widest separation but lost significance after multiplicity adjustment (p = .168). The extended Youden and VUS cutoffs were statistically indistinguishable. As a supporting check, all classifications showed nominal overall-survival separation, with low and overexpression faring similarly worse than wild-type. Conclusions: Digital p53 IHC quantification was reproducible at each observer-dependent step. The extended Youden and VUS criteria performed equivalently; therefore, we propose Youden as a reasonable default, pending validation and TP53 correlation.

Case Study

Colorectal intramucosal carcinoma with lymphatic invasion and lymph node metastasis: a case report: Joon Mee Kim, Lucia Kim, Jee Young Han, Suk Jin Choi, Jongbeom Shin, Sun Keun Choi; J Pathol Transl Med. 2026;60(6):698-703. Published online October 19, 2026; DOI: https://doi.org/10.4132/jptm.2026.08.14; Funded: Inha University

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Abstract PDF: Colorectal intramucosal carcinoma (IMC) is considered to carry negligible risk of lymph node metastasis, reflecting the presumed absence of lymphatics within the lamina propria, and current guidelines endorse endoscopic resection alone as curative. We report a 64-year-old man in whom endoscopic submucosal dissection of a lower rectal tumor revealed a well-differentiated IMC with extensive lymphatic invasion confirmed by D2-40 immunostaining. Subsequent laparoscopic ultralow anterior resection showed no residual tumor at the primary site but confirmed metastasis in one of 12 regional lymph nodes. The tumor was microsatellite-stable, epidermal growth factor receptor–positive, and harbored a KRAS codon 13 mutation (G13X). The patient received adjuvant chemoradiotherapy and remained disease-free at 2 years. This case demonstrates that regional lymph node metastasis can occur in colorectal IMC even without conventional adverse histologic features such as poor differentiation or tumor budding, challenging current risk-stratification frameworks and supporting a more cautious approach when lymphatic invasion is identified.

Original Articles

Diagnostic pitfalls leading to delayed diagnosis of human papillomavirus (HPV)–independent cervical malignancies in the era of HPV-based screening: clinicopathologic analysis of diagnostic pathways: Hye Eun Park, Hye-Ra Jung, Hyun-Jung Kim; J Pathol Transl Med. 2026;60(6):670-679. Published online November 13, 2026; DOI: https://doi.org/10.4132/jptm.2026.08.26; Funded: Korean Society for Cytopathology

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Abstract PDF: Background
Human papillomavirus (HPV)–independent cervical malignancies (HPV-IDCM) are a rare but clinically important subset that may escape detection by HPV-based screening. This study investigated diagnostic pitfalls contributing to delayed HPV-IDCM diagnosis and assessed the role of cervical cytology in the diagnostic pathway. Methods: This multicenter retrospective case series was conducted as a policy research project of the Korean Society for Cytopathology. Patients with HPV-IDCM and repeated abnormal cytologic findings before definitive histologic diagnosis were identified. Clinical, cytologic, histologic, and HPV test results were reviewed to identify factors associated with diagnostic delay. Results: Four patients were included, with a median age of 74 years (range, 62 to 79 years). Histologic diagnoses comprised three HPV-independent gastric-type adenocarcinomas and one HPV-independent squamous cell carcinoma. The median interval from the first abnormal cytologic finding to definitive diagnosis was 18.5 months (range, 11 to 30 months). Before diagnosis, all patients underwent a median of 3.5 cytologic examinations (range, 3 to 5). Associated factors included repeatedly negative HPV test results (3/4), nondiagnostic biopsy or conization (2/4), delayed tissue evaluation despite persistent cytologic abnormalities (1/4), deeply located endocervical lesions (3/4), and a concurrent HPV-associated squamous lesion (1/4). Re-review identified atypical or malignant cells in all cases, indicating that the delay did not result from failure of cytologic detection. Conclusions: HPV-IDCM remain vulnerable to delayed diagnosis in the era of HPV-based screening. Persistent abnormal cytologic findings should not be dismissed solely because HPV test results are negative. Careful correlation of cytologic, clinical, and histologic findings remains essential for timely HPV-IDCM detection.

Targeted next-generation sequencing–based mutational signature analysis in endometrial cancer: utility and limitations across molecular subtypes: Uijin Kim, Ahwon Lee, Keun Ho Lee, Sung Jong Lee, Sook Hee Hong, Donghyuk Lee, Jun Kang, Miseon Lee; J Pathol Transl Med. 2026;60(6):625-634. Published online November 10, 2026; DOI: https://doi.org/10.4132/jptm.2026.09.07; Funded: Uijeongbu St. Mary’s Hospital

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Abstract PDF Supplementary Material: Background
Molecular subtype classification is essential for staging endometrial cancer, planning adjuvant treatments, and stratifying prognosis. However, the correlation between mutational signature analysis using tumor-only targeted next-generation sequencing (NGS) data and molecular subtypes, as well as the interpretive value at the individual case level, remains inadequately characterized. Methods: We performed mutational signature analysis on tumor-only targeted NGS data from 72 endometrial cancer cases using the SATS R package. Molecular classification into four subtypes (POLE-mutated, mismatch repair deficient [MMRd], TP53-mutant, and no specific molecular profile [NSMP]) was established through a standard stepwise algorithm that integrated NGS and immunohistochemistry. Results: Out of the 72 endometrial cancers, 12 were classified as POLE-mutated, 10 as MMRd, six as TP53-mutant, and 44 as NSMP. All POLE-mutated tumors exhibited POLE-associated signatures (SBS10a/SBS10b), including cases with non-hotspot POLE exonuclease variants and tumor mutation burdens below the conventional ultramutation threshold. MMRd-associated signatures showed a broader distribution across molecular subtypes; while the summed MMRd-associated signatures were typically higher in MMRd tumors, low-level contributions were also noted in subsets of NSMP and TP53-mutant tumors. Within the POLE-mutated group, MMRd-associated signatures were more pronounced in cases displaying subclonal MMR protein loss as determined by immunohistochemistry. Conclusions: In this small, clinically selected cohort, targeted NGS-based mutational signatures provided exploratory, complementary information regarding POLE-associated mutagenesis and mixed MMR-related patterns. Overlapping signature distributions, dependence on the analytical pipeline, and the use of tumor-only targeted sequencing limit case-level interpretation. Mutational signature analysis should be interpreted in conjunction with established molecular tests and should not be used as a stand-alone classifier.

Concordance of flow cytometric E6/E7 mRNA detection with human papillomavirus DNA testing and cervical cytology in a cervical cancer screening cohort: Dat Quoc Ngo, Trang Kieu Ha, Mi Ngoc Thi Tran, Anh Mai Thi Nguyen, Truong Nhat Trinh, Thien Thanh Ly, Linh Ngoc Khanh Nguyen, Thu Dang Anh Phan; J Pathol Transl Med. 2026;60(6):680-686. Published online November 10, 2026; DOI: https://doi.org/10.4132/jptm.2026.09.09; Funded: University of Medicine and Pharmacy at Ho Chi Minh City

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Abstract PDF: Background
Overexpression of viral oncogenes E6 and E7 of high-risk (HR)–human papillomavirus (HPV) plays a key role in the progression to cervical intraepithelial neoplasia (CIN) and cancer. Detection of E6/E7 mRNA may help distinguish between transient and transforming infections, thus improving cervical cancer screening accuracy. This study aimed to evaluate the association of E6/E7 mRNA expression with HR-HPV infection, cervical cytology, and histologically confirmed cervical lesions and to compare its agreement with HPV DNA testing and cytology. Methods: A total of 526 women undergoing cervical cancer screening between January 2023 and May 2025 were enrolled. E6/E7 mRNA expression was assessed using flow cytometry with the HPV OncoTect 3Dx E6/E7 mRNA assay and compared with HR-HPV DNA testing, cervical cytology, and available histopathologic findings from biopsy specimens. Results: Among 526 samples, eight (1.5%) tested positive for E6/E7 mRNA, compared to 30 (5.7%) HR-HPV DNA–positive and 17 (3.2%) abnormal cytology results. Median E6/E7 mRNA expression was higher in HR-HPV– positive cases and in cytologically abnormal cases. Almost perfect agreement was observed between E6/E7 mRNA results, HR-HPV DNA testing, and cytology. Histopathologic follow-up was available for nine women with cytological abnormalities ≥low-grade squamous intraepithelial lesion, including four CIN2 and five CIN1 cases. E6/E7 mRNA expression was markedly elevated in one CIN2 case associated with HPV16 infection (37.51%), while two CIN1 cases demonstrated high mRNA expression despite negative HPV DNA results. Conclusions: Flow-cytometric E6/E7 mRNA detection showed high overall agreement with HPV DNA testing and cytology in this screening cohort. Larger prospective studies with comprehensive histologic follow-up are needed to determine its clinical utility.

Case Study

Intracranial malignant peripheral nerve sheath tumor with myxoid morphology evolving across recurrences: a case report: Frantisek Vana, Petra Pokorna, Petr Pospisil, Zdenek Mackerle, Marketa Hermanova, Iva Staniczkova Zambo, Martin Barak, Robin Jugas, Radim Jancalek, Ondrej Slaby, Michal Hendrych; J Pathol Transl Med. 2026;60(6):718-725. Published online November 11, 2026; DOI: https://doi.org/10.4132/jptm.2026.09.17; Funded: Masaryk University, Ministry of Health, St. Anne’s University Hospital Brno, National Institute for Cancer Research, Next Generation EU

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Abstract PDF: A malignant peripheral nerve sheath tumor (MPNST) is a rare, aggressive spindle-cell sarcoma that exceptionally occurs intracranially. Herein, we report a case of intracranial spindle-cell neoplasm with abundant myxoid stroma. The immunophenotype of the primary tumor did not align with any known peripheral nerve sheath tumor and the lesion did not correspond to any methylation category defined by the Heidelberg classifier with a sufficiently high classification score, although MPNST was the highest-scoring category. Over the course of repeated recurrences, the tumor acquired increased cellularity, mitotic activity and loss of H3K27me3 expression. Subsequent methylation profiling supported a diagnosis of MPNST. The tumor harbored a gain-of-function variant in NRAS p.Gly13Arg and TP53 p.Arg273Cys from the initial tumor onwards, consistent with previous reports describing activation of Ras/mitogen-activated protein kinase as an early event in MPNST tumorigenesis. These findings illustrate the diagnostic complexity of rare intracranial sarcomas with myxoid morphology and suggest that some may represent early MPNST.

Original Articles

Clinicopathological associations and prognostic significance of EZH2, H3K27me3, pRB, p53, and p16 expression in diffuse large B-cell lymphoma: Ishan Gupta, Surabhi Jain, Moien Rasheed Lone, Ajay Gogia, Chandan Krushna Das, Mehar Chand Sharma, Ashish Datt Upadhyay, Saumyaranjan Mallick; J Pathol Transl Med. 2026;60(6):635-645. Published online November 13, 2026; DOI: https://doi.org/10.4132/jptm.2026.09.14; Funded: All India Institute of Medical Sciences

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Abstract PDF Supplementary Material: Background
Diffuse large B-cell lymphoma (DLBCL) is characterized by pronounced heterogeneity in its morphological and biological attributes, with emerging evidence highlighting the pivotal role of epigenomic alterations in its pathogenesis. This study aimed to investigate the relationship between EZH2 expression and cell-cycle regulatory proteins, focusing on their prognostic implications. Methods: This retrospective study included 131 patients with nodal primary DLBCL, who were categorized according to the Hans algorithm and additional immunohistochemistry was performed for selected epigenetic (EZH2 and H3K27me3) and cell-cycle regulatory markers (phosphorylated retinoblastoma [pRB], p16 and p53). Receiver operating characteristic (ROC) curve analysis and Cox regression models were applied to assess prognostic utility. Appropriate statistical analysis was performed. Results: EZH2 was expressed in 59.5% of cases and significantly associated with p53 (p = .003), germinal center B-cell-like (GCB) subtype (p = .031), and CD10 positivity (p = .030). pRB positivity was more frequent in the activated B-cell-like subtype (82.5% vs. 64.3%, p = .024) and was associated with MUM1 (p = .028), while p16 expression was linked to BCL6 (p = .004). ROC analyses demonstrated poor discriminatory ability for overall survival (area under the curve, 0.39 to 0.54), with no clinically actionable cutoffs identified. Stepwise Cox regression identified age >60 years (hazard ratio [HR], 2.04; p = .042) and Eastern Cooperative Oncology Group ≥ 2 (HR, 3.46; p = .001) as independent predictors of overall survival. For progression-free survival, no biomarker reached statistical significance. Conclusions: EZH2 and related cell-cycle proteins demonstrate biological associations in DLBCL but lack robust prognostic utility when assessed by immunohistochemistry. Clinical variables showed stronger predictive value for survival, while no biomarker reached statistical significance for survival, underscoring the need for integrated molecular approaches to improve risk stratification and therapeutic targeting in DLBCL.

A demographic study of pathology-proven kidney tumors at a single institution in South Korea over the past 33 years: 1991–2023: Seon Ung Kim, Hyejin Noh, Jiyeon Kim, Yeong Jin Choi; J Pathol Transl Med. 2026;60(6):657-669. Published online November 13, 2026; DOI: https://doi.org/10.4132/jptm.2026.10.19; Funded: Korea Medical Device Development Fund, Ministry of Science and ICT, Ministry of Trade, Industry and Energy, Ministry of Health and Welfare, Ministry of Food and Drug Safety

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Abstract PDF: Background
While the incidence of kidney tumors is increasing, long-term demographic analyses based on pathological diagnoses remain insufficient. This study aimed to investigate demographic changes regarding pathology-proven kidney tumors over the past 33 years. Methods: We retrospectively analyzed 4,555 cases from 4,350 patients who underwent renal biopsy or nephrectomy for suspected kidney tumors at Seoul St. Mary’s Hospital from 1991 to 2023. Results: The average age was 58 years, and the male-to-female ratio was 1.7:1. Among 4,555 cases, 7.0% were biopsies and 93.0% were nephrectomies. Tumors were classified into four diagnostic categories: malignant (79.3%), benign (18.5%), undefined (1.5%), and other lesions (0.7%). Over 33 years, biopsies increased 14.3-fold and nephrectomies 11.5-fold, while malignant tumors increased 12.6-fold and benign tumors 9.4-fold. Over time, the proportion of malignant tumors increased (p < .001), while benign tumors decreased (p < .001). As age increased, the proportion of malignant tumors increased (p = .013), while benign tumors showed a decreasing trend (p = .070). Malignant tumors showed a male predominance, while benign tumors showed a female predominance. The frequency of malignant tumors was similar at approximately 80% in biopsy and nephrectomy. However, benign tumors were more common in nephrectomy (19.1%) than in biopsy (10.9%) (p < .001), and unclassified tumors (4.1%) were more common in biopsies (p < .001). Renal cell carcinoma was most common (61.5% of total cases, 77.6% of malignant tumors). Lymphoproliferative tumors were diagnosed more frequently by biopsy (12.5%) than nephrectomy (0.1%) (p < .001). Conclusions: This study demonstrates a long-term increase in the incidence of renal tumors in South Korea. These findings can serve as foundational data for patients with kidney tumors.

Case Study

Clinicopathological characteristics of primary malignant cutaneous perivascular epithelioid cell tumor: case report and literature review: Huaming Li, Dan Zhang, Shiwu Zhang; J Pathol Transl Med. 2026;60(5):572-577. Published online July 20, 2026; DOI: https://doi.org/10.4132/jptm.2026.05.10; Funded: Foundation of Tianjin Science and Technology Bureau, Foundation of Tianjin Key Medical Discipline Construction Project, Foundation sponsored by Tianjin Health Research Project

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Abstract PDF: Primary cutaneous malignant perivascular epithelioid cell tumors (PEComas) are extremely rare. Accurate diagnosis is critical for prognostic evaluation and guiding clinical management. Here, we report a case of a 19-year-old woman with a 1.1 cm exophytic red mass on her left upper limb. Histological examination revealed a dermal tumor composed of clear cells with prominent nucleoli. The tumor cells displayed cytologic atypia, nuclear pleomorphism, multinucleated giant cells, mitoses and invasive growth, with a multinodular distribution within the dermis and vascular invasion. Immunohistochemically, the tumor cells expressed cathepsin K, HMB45, and CD10. Based on morphological and immunohistochemical findings, we classified it as a primary malignant cutaneous PEComa. To date, only eight reported cases have been described as primary malignant cutaneous PEComas. The present case appears to be the youngest patient reported among all malignant PEComas.

Original Article

Development of a prognostic prediction model for tumor recurrence or progression in gastrointestinal stromal tumors: integrating inflammatory blood indices with 5 mm² versus 50 high-power field mitotic counts: Waratchaya Tirasarnvong, Thammasin Ingviya, Paramee Thongsuksai; J Pathol Transl Med. 2026;60(5):527-538. Published online July 31, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.15; Funded: Faculty of Medicine, Prince of Songkla University

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Abstract PDF Supplementary Material: Background
The behavior of gastrointestinal stromal tumors varies according to tumor size, location, mitotic rate, and rupture. Traditional mitotic counting in 50 high-power fields (HPF; 5.3 mm2) may overestimate progression risk, as 5 mm2 corresponds to 20–25 HPF under modern microscopy. However, the 50-HPF method remains widely used. This study evaluated the impact of two mitotic counting methods on risk classification and developed a prognostic model combining inflammatory biomarkers with clinicopathological factors. Methods: We retrospectively analyzed 150 patients who underwent resection at Songklanagarind Hospital between 2009 and 2021. Patients who had received neoadjuvant therapy or had a second primary cancer were excluded. Mitosis was evaluated using both methods. Clinicopathological and serum biomarker data were collected. The primary outcome was 5-year disease-free or progression-free survival. The model was developed using forward stepwise variable selection based on the time-dependent area under the curve and internally validated by bootstrapping. Results: The 50-HPF method overestimated the Armed Forces Institute of Pathology classification in 14.2% of cases. A model incorporating tumor size, location, rupture, mitotic count within 5 mm2, and systemic immune-inflammation index achieved the highest area under the curve of 0.939 in both training and validation sets, outperforming previous models. The 5-mm2 method demonstrated superior performance to the 50-HPF method across all models (0.939 vs. 0.919 for the proposed model). Conclusions: Mitotic counting in 50 HPF overestimated risk classification in certain cases. Incorporating systemic immune-inflammation index and using a 5 mm2 mitotic count enhanced prognostic model performance.

Review Article

Spread through air spaces as a marker of nonlinear evolutionary trajectories in lung cancer: implications for the 9th edition TNM classification: Jin-Haeng Chung; J Pathol Transl Med. 2026;60(5):463-475. Published online September 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.16; Funded: National Research Foundation of Korea

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Abstract PDF: Recent advancements in the diagnosis and therapeutic management of lung cancer have contributed to an evolution in pathological reporting standards. The 8th edition of the TNM classification of lung tumors has introduced the invasive size of adenocarcinoma—rather than total tumor size—as the primary determinant for staging. Concurrently, histological grading criteria proposed by the International Association for the Study of Lung Cancer (IASLC), based on predominant and highest-grade architectural patterns, appear to offer improved clinical utility over legacy systems. In addition, tumor spread through air spaces (STAS) has emerged as an actively investigated pattern of invasion, characterized by the presence of neoplastic cells beyond the main tumor mass within the adjacent pulmonary parenchyma. STAS is frequently observed in advanced-stage and node-positive non–small cell lung cancer and often correlates with distant metastasis. Recognizing its clinical relevance, the IASLC Staging Project recently recommended incorporating STAS as a histologic T descriptor in the 9th edition of the TNM classification. Expanding upon this framework, this review explores STAS not merely as a prognostic indicator, but as a potential reflection of divergent evolutionary trajectories influenced by underlying driver mutations. Accordingly, this review aims to comprehensively synthesize the prevailing controversies and recent academic milestones regarding STAS, the current limitations in preoperative STAS risk prediction, the logistical hurdles of intraoperative diagnosis, and critically evaluates the need for prospective clinical trials to validate STAS as a predictive biomarker for adjuvant systemic therapy.

Original Articles

Bronchial lesions in a high serum IgA mouse model: pulmonary venular IgA deposition and spatially distinct lymphoid cell aggregation: Areum Kim, Minhyeok Lee, Yohan Park, Wan Jin Hwang, Hyeseung Lee, Joo Heon Kim, Jin Man Kim, Yong Min Kim, Jin Sun Park, Junguee Lee; J Pathol Transl Med. 2026;60(5):516-526. Published online July 16, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.01; Funded: Konyang University Hospital

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Abstract PDF: Background
Immunoglobulin A (IgA) nephropathy is a systemic immune complex–mediated disease primarily affecting the kidneys, yet pulmonary involvement remains poorly characterized. This study investigated pulmonary structural alterations, IgA deposition, immune cell distribution, and the impact of chronic environmental immune stimulation. Methods: High-IgA (HIGA) mice and BALB/c controls were examined under baseline conditions and following chronic particulate matter (PM) exposure. Histopathology, immunofluorescence, immunohistochemistry, and lectin-based assays were used to assess pulmonary IgA deposition, lymphoid cell aggregation, and immune activation. Results: Compared with BALB/c controls, HIGA mice exhibited pulmonary venular remodeling characterized by thickening of the venular tunica media and IgA deposition within the smooth muscle layer. Under baseline conditions, lymphoid cell aggregation in HIGA mice was predominantly localized to peribronchial regions, whereas IgA deposition and C3a deposition were confined to pulmonary venules with minimal spatial overlap. Following PM exposure, HIGA mice developed additional perivenular lymphoid cell aggregation that spatially corresponded with IgA deposition, whereas BALB/c mice showed predominantly peribronchial aggregation. PM exposure was associated with increased pulmonary Toll-like receptor 9 (TLR9) expression in both strains. In HIGA mice, TLR9-positive immune cells and interleukin-6 (IL6) expression were enriched in perivenular lymphoid cell aggregates. Conclusions: Pulmonary IgA deposition in HIGA mice is associated with vascular remodeling and compartment-specific immune cell distribution, particularly under environmental stimulation. These findings support an association between IgA deposition and localized immune activation in the lung. However, the causal roles of TLR9 and IL6 in this process remain to be determined.

BRCA1/2-stratified immune profiling of treatment-naive high-grade serous ovarian cancer ascites identifies a Treg-enriched ascitic immune phenotype: Megha Sharma, Bhavneet Kaur, Bhavana Rai, Man Updesh Singh Sachdeva, Amit Raj Sharma, Parikshaa Gupta, Upasana Gautam, Rashmi Bagga, Radhika Srinivasan; J Pathol Transl Med. 2026;60(5):558-571. Published online September 11, 2026; DOI: https://doi.org/10.4132/jptm.2026.07.27; Funded: Indian Council of Medical Research, Council of Scientific and Industrial Research

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Abstract PDF Supplementary Material: Background
Malignant ascites is a common presentation in advanced high-grade serous ovarian carcinoma (HGSOC), yet its immune composition and genetic correlates remain poorly defined. This study explored the immune microenvironment of ascitic fluid in ovarian carcinoma and its association with BRCA mutation status, chemotherapy response, and survival. Methods: Ascitic fluid from 133 patients (33 non-malignant controls, 31 non-ovarian carcinoma, and 69 HGSOC cases) was analyzed using multiparameter flow cytometry to quantify lymphocyte and macrophage subsets, and programmed cell death 1/programmed cell death ligand 1 immune-checkpoint marker expression. Targeted sequencing of TP53 and BRCA1/2 was performed in HGSOC, and findings were correlated to immune parameters, chemotherapy response, progression-free and overall survival. Results: Ovarian carcinoma ascites, compared with non-malignant effusions, showed increased CD3+ and CD8+ T-cell frequencies, higher regulatory T cell (Treg)–associated populations, and reduced CD19+CD20+ B-cell levels. Targeted sequencing identified TP53 mutations in 97.4% and BRCA1/2 mutations in 35.9% of sequenced HGSOC cases. BRCA-wild-type cases showed significantly lower CD4+ T-cell and B-cell levels, higher Treg levels, and shorter progression-free and overall survival than BRCA1/2-mutated cases. Higher CD3+ and CD8+ T-cell levels were associated with poor chemotherapy response. In exploratory multivariable Cox models, BRCA-wild-type status remained significantly associated with poorer overall survival, whereas immune-cell groups were not independently significant. Conclusions: HGSOC ascites showed a Treg-enriched immune profile, with relatively higher Treg levels in BRCA-wild-type cases. BRCA-wild-type status was associated with poorer outcomes, while the evaluated immune-cell subsets were not independently prognostic in exploratory analysis. Ascitic fluid-based immune and molecular profiling may provide prognostic information worthy of validation in larger independent cohorts.

A single-institution demographic study of pathologically proven renal disease in kidney transplant recipients over the last 33 years: Hyejin Noh, Jiyeon Kim, Yeong Jin Choi; J Pathol Transl Med. 2026;60(4):398-412. Published online May 26, 2026; DOI: https://doi.org/10.4132/jptm.2026.03.28; Funded: Korea Medical Device Development Fund, Ministry of Science and ICT, Ministry of Trade, Industry and Energy, Ministry of Health and Welfare, Ministry of Food and Drug Safety

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Abstract PDF Supplementary Material: Background
While the number of kidney transplants for end-stage renal disease (ESRD) is increasing, studies examining the long-term demographic analyses based on pathological diagnosis of transplant kidney remain limited. Methods: We conducted a retrospective analysis of 4,188 transplant recipients who underwent either biopsy or nephrectomy from 1991 to 2023 at Seoul St. Mary’s Hospital. Results: Among 7,229 pathologically confirmed cases, rejection was the most prevalent (37.7%), followed by tubulointerstitial (25.4%), glomerular, drug toxicity, and vascular diseases. In 7,053 transplant biopsies, rejection was predominant across all age groups, with T-cell mediated (TCM) category being the most common (60.1%), followed by antibody-mediated and mixed. Drug toxicity increased with age (p = .047), while glomerular and tubulointerstitial diseases were highest in recipients under 20 (p < .001). Among glomerular diseases, IgA-related glomerulonephritis (45.2%) was the most common. In 176 transplant nephrectomies, the most common diagnosis was rejection (33.5%), followed by renal infarction (19.9%), tubulointerstitial, vascular, glomerular disease, and drug toxicity. “Others” included infarction, ESRD, and lymphangiectasia, which increased with age (p = .011). In nephrectomy cases, rejection decreased over time, with chronic TCM rejection (40.7%) being the most frequent. Conclusions: This study provides valuable insights into transplant kidney disease in South Korea. The number of transplant biopsies has increased over the past 33 years, while the number of nephrectomies has remained unchanged. Rejection was the most common finding in all age groups in biopsies, but decreased with age in nephrectomies, with TCM being the most common and observed more often in younger recipients.

Increased Toll-like receptor 9 expression associated with cellular proliferation and poor prognosis in pleural mesothelioma: Ali Omar Abdelaziz, Dina Moustafa Thabit, Rehab Mohamed Kamal, Hend Moness, Rasha Fouad Ahmed, Mariana Fathy Gayyed, Fatma El Zahraa Ammar Mohamed; J Pathol Transl Med. 2026;60(4):413-421. Published online May 26, 2026; DOI: https://doi.org/10.4132/jptm.2026.04.01; Funded: Alexander von Humboldt Foundation

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Abstract PDF Supplementary Material

Background
Pleural mesothelioma is an aggressive malignancy with a poor prognosis. The epithelioid subtype is the most common and can be challenging to distinguish from metastatic lung adenocarcinoma (MLAC). The role of Toll-like receptor 9 (TLR9) in the progression of pleural mesothelioma remains unclear. Methods: A total of 30 pleural biopsy specimens were collected, comprising 10 cases of pleural epithelioid mesothelioma and 20 cases of MLAC. The mRNA expression levels of TLR9 and proliferating cell nuclear antigen (PCNA) were quantified. In addition, sixty archived formalin-fixed, paraffin-embedded tissue blocks (40 epithelioid mesothelioma and 20 MLAC) were analyzed via immunohistochemistry using an anti-TLR9 antibody in relation to various clinicopathological parameters. Results: TLR9 expression was significantly higher in epithelioid mesothelioma cases than in MLAC cases (p < .001), with mean values of 1.54 ± 0.09 and 1.02 ± 0.08, respectively. A significant positive correlation was observed between TLR9 and PCNA expression levels specifically in the epithelioid mesothelioma cohort (p < .001, r = 0.8). Furthermore, immunohistochemical analysis confirmed that high TLR9 immunoexpression was significantly more prevalent in epithelioid mesothelioma (36/40 cases; 90%) than in MLAC (3/20 cases; 15%) (p < .001). Notably, elevated TLR9 expression was associated with a significantly shorter overall survival (p = .001). Conclusions: In conclusion, TLR9 expression is significantly elevated in epithelioid mesothelioma compared to MLAC at both the molecular and cellular levels, and its expression correlates with increased tumor proliferation and poorer prognosis. Our data suggest that TLR9 could represent a promising diagnostic and prognostic biomarker, warranting further investigation into its potential therapeutic applicability.

Citations

Citations to this article as recorded by

Damage-Associated Molecular Patterns in Mesothelioma: Drivers of Inflammation and Therapeutic Targets
Annamaria Molinario, Francesca Caprioglio, Angela A. Rilievo, Marco E. Bianchi, Rosanna Mezzapelle
International Journal of Molecular Sciences.2026; 27(17): 7859. CrossRef

The impairment of CD3⁺ T lymphocytes in sentinel lymph node of high-risk cutaneous melanoma patients in stage IIB and IIC: Emilija Filipović, Katarina Mirjačić Martinović, Ognjen Živković, Nataša Medić Milijić, Ana Lazarević, Zoran Bukumirić, Marko Jevrić, Milan Žegarac; J Pathol Transl Med. 2026;60(4):422-435. Published online July 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.04.02; Funded: Ministry of Science, Technological Development and Innovation

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Abstract PDF: Background
The sentinel lymph node (SLN) in melanoma is almost always the first site of metastasis and its histopathological assessment is essential for the determination of staging and clinical outcome. Furthermore, this procedure offers the investigation of the early immune response in SLN as melanoma-derived factors suppress the immunity in an early stage that may facilitate metastasis. A better understanding of the immunological changes in SLN may help in the therapeutic stimulation of melanoma immunity to prevent tumor metastasis. Methods: SLN tissues without malignant cells from 74 cutaneous melanoma patients (stage I and II) were analyzed. By flow cytometry, we measured the percentage of natural killer cells, CD3+ T lymphocytes, and their expression of interferon-γ (IFN-γ) and inhibitory immune checkpoint molecules (ICMs), and the percentage of CD4+Foxp3+ regulatory T cells (Tregs). Results: Melanoma patients with worse prognosis, in stage IIB–C, had decreased percentage of total CD3+ and CD3+CD8+ T lymphocytes, trend of IFN-γ decrease, increased inhibitory programmed cell death 1 and T cell immunoglobulin and mucin-domain containing 3 ICMs, and higher percentage of Tregs in their SLNs compared with stage I-IIA patients. Furthermore, patients with nodular melanoma had decreased CD3+CD8+ cells compared with patients with superficial spreading melanoma and together with patients with localization of primary tumor on extremities had an increase in the expression of analyzed ICMs. Conclusions: This study provides new results of the impairment of immune response in SLN of cutaneous melanoma patients with high risk for metastasis and could help in the introduction of new immunotherapies that could restore immunity and prevent metastasis in SLN.

Case Study

Multidimensional analysis of concurrent proximal bronchiolar adenoma and lung carcinoma: Lu-Yao Li, Gong-Ming Dong, Yun-Peng Zhang, Ting-Ting Wang, Fu-Quan Jia, Guan-Jun Zhang; J Pathol Transl Med. 2026;60(3):356-363. Published online March 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.31; Funded: Xi’an Jiaotong University

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Abstract PDF Supplementary Material: Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

Original Articles

Expression of PD-1/PD-L1 pathway molecules in human cardiac allograft according to acute cellular rejection status: insights from a Korean Heart Transplant Cohort: Jeemin Yim, Yoon Kyung Jeon, Doo Hyun Chung, Jaemoon Koh; J Pathol Transl Med. 2026;60(3):319-330. Published online March 27, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.02; Funded: Korea Health Industry Development Institute, Ministry of Health and Welfare

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Abstract PDF

Background
Acute cellular rejection (ACR) following heart transplantation (TPL) compromises graft function and survival. The programmed cell death-1 (PD-1)/PD-1 ligand-1 (PD-L1) pathway represents an immune checkpoint that maintains peripheral immune tolerance, but its expression and significance in human cardiac allografts with ACR remain unclear. Thus, we investigated PD-1/ PD-L1 expression in endomyocardial biopsies from heart TPL recipients to clarify the role of this pathway in the ACR of human cardiac allografts and explore the potential of therapeutic modulation of PD-1/PD-L1 in this setting. Methods: Endomyocardial biopsies of 78 patients with heart TPL were subjected to immunohistochemistry for PD-L1, PD-1, CD4, and CD8. PD-L1 expression and quantities of PD-1+, CD4+, and CD8+ infiltrating lymphocytes were evaluated according to clinicopathological features, ACR presence, and clinical outcomes. Results: Allografts with high-grade ACR (International Society for Heart and Lung Transplantation grades 2R and 3R) demonstrated markedly higher PD-L1 expression than did those without ACR (62.5% vs. 16.1%, p < .001). PD-L1 expression was positively associated with CD4+ lymphocyte infiltration (p = .025), whereas CD8 and PD-1+ lymphocyte counts were higher in PD-L1-positive allografts without reaching statistical significance (p = .059 and p = .390, respectively). Serial biopsies revealed that PD-L1 expression was upregulated in patients with high-grade ACR compared with that in previous non-ACR tissues, and follow-up biopsies were performed after ACR resolution. Conclusions: The PD-1/PD-L1 pathway is involved in ACR regulation in human cardiac allografts. Increased PD-L1 expression during ACR may represent a counteractive mechanism to limit alloimmune-mediated tissue injury, supporting PD-1/PD-L1 as a potential therapeutic target in heart TPL recipients.

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Immune Responses in Checkpoint Inhibitor–Associated Cardiovascular Immune–Related Adverse Events
Kerry L. Reynolds, Alexandra-Chloé Villani, Zsófia Dora Drobni, Tomas G. Neilan, Han Zhu, Noah S. Wagner, Justin M. Balko, Reilly Fankhauser, Javid J. Moslehi, Nicolas L. Palaskas, Kristen E. Pauken, Bilal A. Siddiqui, Steven M. Blum, Daniel A. Zlotoff
JACC: CardioOncology.2026; 8(5): 463. CrossRef

Aquaporin 1 promotes proliferation and migration of tumor by up-regulating claudin-1 expression in colon cancer: Wei Wei Xie, Lin Xu, Qian Li, Dao Quan Zhang, Yu Bao Zhou; J Pathol Transl Med. 2026;60(3):307-318. Published online March 20, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.01; Funded: Anhui Medical University, Higher Education Institutions in Anhui Province

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Abstract PDF: Background
With the rising incidence of colon cancer, several studies have indicated that aquaporin 1 (AQP1) expression is associated with the development of colon cancer. This study aims to elucidate the potential molecular mechanisms between them. Methods: We screened data from The Cancer Genome Atlas (TCGA) database and retrospectively examined AQP1 protein expression in 127 colon cancer patients to analyze the relationship between AQP1 expression and pathological stages, prognosis. We created stable colon cancer cell lines with differential AQP1 expression, the effect of AQP1 expression on the proliferation and migration of colon cancer cells was assessed by in vitro and in vivo studies, and explored potential molecular mechanisms through Western blotting. Results: High AQP1 expression was associated with poorer survival (overall survival [OS], p = .028) in colon cancer patients from the TCGA database. Similarly, retrospective clinical data indicated that high AQP1 expression was associated with reduced disease-free survival and OS (p = .036 and p = .017, respectively). The low-expressing AQP1 colon cancer cells exhibited a decrease in proliferation and migration ability of colon cancer cells compared to the overexpressing AQP1 group (p < .05) in vitro and in vivo. Immunohistochemistry and western blotting experiments validated heightened expression of N-cadherin, vimentin, and claudin- 1 in the tumor tissues of the overexpressing AQP1 group. Conversely, reduced AQP1 expression resulted in decreased expression of claudin- 1. Conclusions: AQP1 correlates with unfavorable prognosis in colon cancer and potentially enhances the proliferation and migration of colon cancer by up-regulating claudin-1 expression.

Prevalence of HER2-ultralow breast cancer in South Korea: a multicenter study by reassessment of HER2-zero cases: Min Chong Kim, Eun Yoon Cho, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Wan Seop Kim, Chungyeul Kim, Sun-Young Jun, Hye Jeong Choi, So Mang Lee, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae; J Pathol Transl Med. 2026;60(2):184-192. Published online February 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.22; Funded: Korean Society of Pathologists

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Abstract PDF Supplementary Material

Background
This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

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HER2-Low Breast Cancer: A Review of Epidemiology, Diagnostic Challenges, Targeted Therapies, and Clinical Outcomes
Maedeh Mirasheh, Zahra Shahabinia, Mai Abdel Haleem A. Abusalah, Afrooz Mazidimoradi, Leila Allahqoli, Hamid Salehiniya, Do-Youn Lee
Journal of Clinical Medicine.2026; 15(19): 7559. CrossRef
Interobserver Reproducibility of Treatment-Defining HER2-Low and HER2-Ultralow Immunohistochemical Scoring in Breast Carcinoma: A Systematic Review
Vishal Tayade, Gyanendra Singh
Applied Immunohistochemistry & Molecular Morphology.2026;[Epub] CrossRef

Multicenter evaluation of the PASS score as a negative predictive tool and the impact of inter-observer variability in pheochromocytoma and paraganglioma risk stratification: Sungyeon Jung, Hye-Ri Shin, Su-Jin Shin, Hee Young Na, Soon-Won Hong, So Yeon Park, Chan Kwon Jung, Kyeong Cheon Jung, Young Lyun Oh, Jae-Kyung Won; J Pathol Transl Med. 2026;60(2):202-213. Published online February 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.11.05; Funded: Korean Society of Pathologists

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Abstract PDF

Background
The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.

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Pheochromocytomas with Aggressive Histopathological Features Have Reduced Apelin and Increased VEGF Expression: Diagnostic and Prognostic Implications
Hatice Çalışkan Burgucu, Tuğba Günler, Ethem Ömeroğlu, Yaşar Ünlü, Oğuzhan Aksu
Pathophysiology.2026; 33(4): 72. CrossRef

Mutational status of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): molecular analysis should be performed for NIFTPs with nuclear score 3: Ayaka Sako, Mitsuyoshi Hirokawa, Michiko Matsuse, Miyoko Higuchi, Akira Miyauchi, Takashi Akamizu, Atsushi Kawakami, Norisato Mitsutake; J Pathol Transl Med. 2026;60(2):214-219. Published online February 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.06; Funded: JSPS KAKENHI, Network-Type Joint Usage/Research Center, Nagasaki University

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Abstract PDF: Background
The classification of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced to prevent the overtreatment of indolent tumors that were formerly diagnosed as non-invasive encapsulated follicular variant papillary thyroid carcinomas (NIEFV-PTCs). Although NIFTP was initially estimated to account for 10%–20% of papillary thyroid carcinomas in Western populations, its incidence is substantially lower in Asian cohorts. However, a multi-institutional Japanese study revealed that 31.0% of tumors previously diagnosed as follicular adenomas (FAs) were reclassified as NIFTPs. NIFTP diagnosis requires a nuclear score (NS) of 2–3, and according to the recent World Health Organization criteria, molecular analysis is recommended, but not mandatory, to exclude high-risk subtypes, namely cases with the BRAFV600E mutation, particularly for NS3 tumors. Methods: We performed genetic analysis on 92 archival thyroid tumor samples, including 69 previously diagnosed as FA, of which 34 remained as FA upon re-evaluation (group A) and 35 were reclassified as NIFTP with NS2 (group B). Additional 23 tumors previously diagnosed as NIEFV-PTC were reclassified as NIFTP with NS3 (group C). Results: RAS mutations were detected in 8.8%, 34.3%, and 21.7% of the tumor samples in groups A, B, and C, respectively, whereas BRAF mutations were present in 43.5% of the tumor samples in group C only. Conclusions: These findings suggest the presence of two distinct tumor subsets within NIFTP-NS3, underscoring the need for routine molecular diagnostics in NIFTP-NS3 to facilitate appropriate clinical management.

Review Article

The evolving role of TRPS1 in dermatopathology: insights from the past 4 years: Mokhtar H. Abdelhammed, Woo Cheal Cho; J Pathol Transl Med. 2026;60(2):129-143. Published online January 29, 2026; DOI: https://doi.org/10.4132/jptm.2025.11.25; Funded: University of Texas MD Anderson Cancer Center

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Abstract PDF: Over the past 4 years, trichorhinophalangeal syndrome type 1 (TRPS1) has rapidly gained attention among practicing pathologists, with numerous studies emerging that both support and question its diagnostic utility. Initially regarded as a highly specific marker for tumors of mammary origin, TRPS1 is now recognized to have broader expression patterns, including in a variety of cutaneous neoplasms. This is likely due to embryologic parallels between breast tissue and skin adnexal structures, an overlap that was underappreciated in early investigations. Although TRPS1 lacks absolute specificity—even among cutaneous neoplasms—it can still offer meaningful diagnostic value when interpreted alongside conventional immunohistochemical markers and within the appropriate morphologic context. Noteworthy diagnostic applications include mammary Paget disease, primary extramammary Paget disease, rare adnexal neoplasms such as endocrine mucin-producing sweat gland carcinoma and primary cutaneous NUT adnexal carcinoma, and cutaneous metastases from breast carcinoma. In this review, we present the most comprehensive and up-to-date evaluation of the utility and limitations of TRPS1 immunohistochemistry in dermatopathology. Our aim is to deepen understanding of this emerging marker and provide practical guidance on its optimal integration with established immunohistochemical panels to enhance diagnostic accuracy in routine practice.

Original Articles

Can micro-CT distinguish between solid lung tumors? A comparative evaluation including solid adenocarcinoma, non-keratinizing squamous cell carcinoma, and carcinoid tumor: Selim Sevim, Serpil Dizbay Sak, Kaan Orhan, Arda Buyuksungur, Duru Karasoy, Hilal Ozakinci, Ayten Kayi Cangir; J Pathol Transl Med. 2026;60(2):231-245. Published online March 10, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.16; Funded: Ankara University

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Abstract PDF Supplementary Material: Background
Some pulmonary carcinomas display a solid pattern, and immunohistochemistry is commonly used for tumor differentiation. Micro–computed tomography (micro-CT), with its ability to produce detailed three-dimensional images using small voxel sizes, may offer additional insights. This study investigates whether three solid tumor types, solid adenocarcinoma (sAC), non-keratinizing squamous cell carcinoma, and carcinoid tumor (CaT), can be differentiated using micro-CT. Methods: Fifteen paraffin blocks, five for each type, were scanned with micro-CT (Skyscan 1275, Bruker). These images were compared to whole slide images (WSIs) of the same tumors. Consequently, tumoral (n = 74) and non-tumoral (n = 49) regions of interest (tumor ROIs [tROIs] and non-tumor ROIs [ntROIs]) were selected on the micro-CT images and evaluated in terms of certain structural variables (percent object volume, structure model index, structure thickness, structure linear density, connectivity, connectivity density, open porosity, closed porosity) to investigate whether tumors can be differentiated from normal parenchyma and from each other. Results: Although detailed images comparable to WSIs could not be obtained, it was considered an important advantage to be able to examine the entire depth of the paraffin blocks. tROIs and ntROIs could be distinguished based on all variables (p < .001). Additionally, sAC showed a notable difference from CaT in “percent object volume” (p = .011). Conclusions: With ongoing technological advancements, improving image quality without compromising tissue integrity will likely accelerate the adoption of micro-CT in pathology labs. Moreover, structural variables derived from micro-CT images may support differentiation among tumor types.

3-Dimensional reconstruction reveals frequent intraluminal growth of submucosal veins in surgically resected pT1 colorectal cancers: Jihyun Park, Mi-Ju Kim, Yeon Wook Kim, Byong-Wook Lee, Junyoung Shin, Jinho Shin, Chan-Gi Pack, Dong-Hoon Yang, Jihun Kim, In Ja Park, Ralph H. Hruban, Seung-Mo Hong; J Pathol Transl Med. 2026;60(2):246-262. Published online March 10, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.19; Funded: National Research Foundation of Korea, Ministry of Science and ICT

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Abstract PDF: Background
Although venous invasion (VI) is associated with distant metastasis and observed in >50% of pT2–4 colorectal cancers (CRCs), the role of VI in pT1 CRCs is not well-defined. Methods: Thirty-four surgically resected pT1 CRCs were reevaluated for 2-dimensional (2D) VI using hematoxylin and eosin (H&E)–stained slides with additional elastic and desmin immunohistochemical staining (cohort A). Additionally, 27 pT1 CRCs without knowing VI status were selected for 3-dimensional (3D) VI evaluation only (cohort B). All 61 cases (cohorts A and B) were studied in 3D using tissue clearing. Results: VI was detected more commonly in 3D (17/34, 50.0%) than in 2D H&E slide evaluation (9/34, 26.5%, p = .047). When VI was identified in 3D (27/61, 44.3%), the most common phase was that of intraluminal growth (22/27, 81.5%), followed by intravasation (7/27, 25.9%) and extravasation (5/27, 18.5%). E-cadherin expression was characterized in 3D in foci of VI and varied in each phase of invasion. Conclusions: All three phases were observed in VI of pT1 CRCs. The extravasation of neoplastic cells from foci of VI in pT1 CRC suggests that VI could be a route of intratumoral spreading in a subset of pT1 CRCs.

Deep learning–driven immunohistochemical analysis of renal lymphatics for chronic kidney disease: bioinformatic and histopathological study: Xin Xu, YanPing Lin, Guangchang Pei, Rui Zeng, Gang Xu; J Pathol Transl Med. 2026;60(2):220-230. Published online March 13, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.15; Funded: National Nature Science Foundation of China, National Natural Science Foundation of China

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Abstract PDF Supplementary Material: Background
Renal lymphatic vessel density is clinically relevant in kidney disease but is still assessed by slow, subjective visual estimation. We evaluated a weakly supervised, attention-based multiple-instance learning framework for automated detection and quantification of renal lymphatic vessel density on D2-40-stained whole-slide images (WSIs). Methods: Two independent internal datasets from Tongji Hospital were collected, including 198 cases of chronic kidney disease (CKD) and 50 cases of hypertensive nephropathy (HTN). All biopsies were immunohistochemically stained for D2-40 and digitized as WSIs. Pathologists provided only slide-level labels (D2-40 high vs. D2-40 low). Tissue regions were automatically segmented, tiled into patches, and encoded using a pretrained convolutional neural network. Patch embeddings were then analyzed with a clustering-constrained attention multiple-instance learning (CLAM) model. Unlike conventional multiple-instance learning (MIL) methods that only weight instances, CLAM jointly performs attention-based instance selection and instance-level clustering to distinguish positive from negative evidence within each slide, yielding more discriminative slide-level features and interpretable attention maps. Performance was compared with a classic MIL model trained on the same features. Results: CLAM achieved area under the receiver operating characteristic curves of 0.942 and 0.858 on the CKD and HTN datasets, respectively, outperforming classic MIL (0.866 and 0.801). Attention maps highlighted lymphatic-rich regions consistent with renal pathologists’ assessments. Conclusions: This clustering-constrained, attention-based weakly supervised framework enables fully automated, reproducible quantification of renal lymphatic vessel density from WSIs, providing renal pathologists with rapid visual and numerical support for diagnosis and risk stratification in CKD and HTN.

Clinicopathological and molecular mechanisms of CLDN18.2 in gastric cancer aggressiveness: a high-risk population study with multi-omics profiling: Hengquan Wu, Mei Li, Gang Wang, Peiqing Liao, Peng Zhang, Luxi Yang, Yumin Li, Tao Liu, Wenting He; J Pathol Transl Med. 2026;60(1):47-57. Published online January 5, 2026; DOI: https://doi.org/10.4132/jptm.2025.09.11; Funded: The Fundamental Research Funds for The Science and Technology Program of Gansu Province, International science and technology cooperation project of Gansu Provincial Science and Technology Department

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Abstract PDF Supplementary Material

Background
The tight junction protein claudin18.2 (CLDN18.2) has been implicated in poor prognosis and suboptimal immunotherapy response in gastric cancer (GC). This study investigates the clinicopathological relevance of CLDN18.2 expression and its association with molecular subtypes in GC patients from a high-incidence region, combining transcriptomic and proteomic approaches to explore how CLDN18.2 contributes to progression and metastasis.
Methods
A retrospective cohort of 494 GC patients (2019–2024) underwent immunohistochemical analysis for CLDN18.2, Epstein-Barr virus (Epstein–Barr virus–encoded RNA), p53, human epidermal growth factor receptor 2 (HER2), and mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6). CLDN18.2 positivity was defined as moderate to strong (2+/3+) membranous staining in ≥75% of tumor cells. Clinicopathological correlations, biomarker associations, and survival outcomes were evaluated. Transcriptomic and proteomic sequencing was performed to explore molecular mechanisms.
Results
CLDN18.2 positivity was observed in 26.9% (133/494) of gastric adenocarcinomas. CLDN18.2-positive tumors correlated with TNM stage (p = .003) and shorter overall survival (p = .018). No associations were identified with age, sex, HER2 status, microsatellite instability, or Epstein-Barr virus infection. Transcriptomic profiling revealed CLDN18.2-high tumors enriched in pathways involving cell junction disruption, signaling regulation, and immune modulation. Proteomic profiling showed that tumors with high CLDN18.2 were enriched in multiple mechanism-related pathways such as integrated metabolic reprogramming, cytoskeletal recombination, immune microenvironment dysregulation, and pro-survival signaling. These mechanisms may collectively contribute to tumor progression and metastasis.
Conclusions
CLDN18.2 overexpression is associated with poor prognosis in GC patients. Transcriptomic and proteomic analyses demonstrate that CLDN18.2 promotes tumor progression and metastasis, underscoring its potential as an independent prognostic factor in regions with a high incidence of GC.

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The evolving role of OMICS in gastrointestinal tumor biology and clinical practice
Qing Li, Junfeng Zhang, Junli Chen, Qiang Zhang, Ruihan Liu, Jialin Zhu, Yi Qing, Xi Wei, Jianpeng Sheng
Molecular Cancer.2026;[Epub] CrossRef
Pretreatment Claudin-18.2 Expression Predicts Poorer Survival Outcomes in Locally Advanced Gastric Cancer Treated with Perioperative Chemotherapy
Gürkan Gül, Özlem Kutlu, Asuman Argon, Halil Taşkaynatan, Özlem Özdemir
Diagnostics.2026; 16(9): 1277. CrossRef
Prevalence of Claudin 18.2 Expression in Gastric and Gastroesophageal Junction Adenocarcinoma: A Systematic Review and Meta-Analysis
Fazal Elahi Khan, Rajendranandini Majumdar, Mohan Dodeja, Gabriel Amorim Moreira Alves, Amr Harby, Rida Siddiqui, Shahbaz Madappattuparambil
Journal of Gastrointestinal Cancer.2026;[Epub] CrossRef
Comparative efficacy of CLDN18.2-directed regimens in advanced gastric/gastroesophageal junction adenocarcinoma: a meta-analysis of single-arm trials
Yue Yuan, Hongkai Yan, Qinhang Wu
Investigational New Drugs.2026;[Epub] CrossRef

Review Article

A comprehensive review of ossifying fibromyxoid tumor: insights into its clinical, pathological, and molecular landscape: Kyriakos Chatzopoulos, Antonia Syrnioti, Mohamed Yakoub, Konstantinos Linos; J Pathol Transl Med. 2026;60(1):6-19. Published online January 14, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.02; Funded: MSK NIH

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Abstract PDF: Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm first described in 1989. It typically arises in the superficial soft tissues of the extremities as a slow-growing, painless mass. Histologically, it is commonly characterized by a multilobular architecture composed of uniform epithelioid cells embedded in a fibromyxoid matrix, often surrounded by a rim of metaplastic bone. While classic cases are readily identifiable, the tumor's histopathological heterogeneity can mimic a range of benign and malignant neoplasms, posing significant diagnostic challenges. Molecularly, most OFMTs harbor PHF1 rearrangements, commonly involving fusion partners such as EP400, MEAF6, or TFE3. This review underscores the importance of an integrated diagnostic approach- incorporating histopathological, immunohistochemical, and molecular data- to accurately classify OFMT and distinguish it from its mimics. Expanding awareness of its morphologic and molecular spectrum is essential for precise diagnosis, optimal patient management, and a deeper understanding of this enigmatic neoplasm.

Original Articles

Significance of KM55 immunohistochemical staining in the diagnosis and prognosis of IgA nephropathy: Hoe In Jeong, Beom Jin Lim, Minsun Jung; J Pathol Transl Med. 2026;60(1):69-82. Published online January 14, 2026; DOI: https://doi.org/10.4132/jptm.2025.09.17; Funded: The Korean Society of Pathologist

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Abstract PDF

Background
Galactose-deficient IgA1 (Gd-IgA1) plays a crucial role in IgA nephropathy (IgAN). The monoclonal antibody KM55 has emerged as a simplified method for detecting Gd-IgA1; however, the clinicopathological significance of immunohistochemistry for Gd-IgA1 remains underexplored. This study evaluated the prognostic and clinicopathological significance of KM55 immunohistochemistry in IgAN. Methods: A total of 114 native kidney biopsies showing at least mild mesangial IgA positivity on immunofluorescence were retrospectively analyzed. Patients were categorized as having IgAN or non-IgAN diseases. The KM55 immunohistochemical staining was graded as 0, 1+, 2+, 3, or 4+. Data on Oxford classification, laboratory parameters, and renal outcomes were collected. Results: The IgAN group showed significantly higher KM55 scores than the non-IgAN group (median: 3 vs. 1; p < .001). IgAN cases were further stratified into KM55-high (≥3+, n = 38) and -low groups (≤2+, n = 37). The KM55-high group had significantly higher diastolic blood pressure, blood urea nitrogen, creatinine, urine protein/creatinine ratio, and Oxford mesangial hypercellularity scores, along with lower estimated glomerular filtration rate (eGFR) and serum albumin. Cox analysis revealed significantly poorer outcomes in the KM55-high group for chronic kidney disease stage 4 (p = .015), end-stage renal disease (p = .024), and 75% eGFR decline (p = .016). Conclusions: Mesangial Gd-IgA1 deposition graded by KM55 immunohistochemistry may be a useful adjunct for IgAN diagnosis and a potential prognostic biomarker.

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IgA Nephropathy: Mechanisms, Risk Stratification, and Precision Therapy
Sami Alobaidi
Diagnostics.2026; 16(9): 1259. CrossRef
Development and validation of a predictive model for rapid renal function decline in early IgA nephropathy: a multicenter retrospective study
Junan Zhou, Yang Liu, Lixia Huo, Xu Wu, Zhelun Zhou, Haodong Liu, Rong Wu, Jiaai Zhang, Yiqing Yu, Deyong Fan, Xiaoyi Wang
Frontiers in Medicine.2026;[Epub] CrossRef

Correlations and prognostic impacts of tumor spread through airspaces in surgically resected non–small cell lung cancer: a retrospective study from Jordan: Ola Abu Al Karsaneh, Amani Al-Rousan, Sofian Al Shboul, Mohammed El-Sadoni, Anas Hayajneh, Moath Alrjoub, Sura Al-Rawabdeh, Tareq Saleh; J Pathol Transl Med. 2026;60(1):92-106. Published online January 9, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.15; Funded: Hashemite University

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Abstract PDF Supplementary Material: Background
Spread through air spaces (STAS) has been identified as an invasion pattern in non–small cell lung cancer (NSCLC). This study evaluated the association between tumor STAS and various clinicopathological parameters of NSCLC, with emphasis on the prognostic role of STAS. Methods: We evaluated 96 cases of NSCLC for STAS. STAS-positive cases were graded according to the distance between the edge of the primary tumor and the furthest STAS, in millimeters, or the number of alveoli separating STAS from the tumor. Results: STAS was observed in 33 patients (34.4%). In 28 cases, STAS was located in airspaces >3 alveoli away from the primary tumor. In 18 cases, STAS was found in airspaces > 2.5 mm away from the edge of the primary tumor. Morphologically, 18 cases of STAS demonstrated a solid nest pattern, eight showed a micropapillary cluster pattern, and seven exhibited a single-cell pattern. In multivariate analysis, only high tumor grade (p = .001) was independently associated with STAS in NSCLC. The presence of STAS (p = .047), lymphovascular invasion (p = .001), positive surgical margin (p = .021), adenocarcinoma histology (p = .020), and postoperative therapy (p = .049) showed a statistically significant lower overall survival (OS). However, multivariate analyses showed that STAS is not an independent predictor of OS in NSCLC. In addition, STAS-positive cases with an extension of >2.5 mm had significantly lower disease-free survival (DFS) (p = .018). Conclusions: The findings demonstrated that STAS is independently associated with a higher tumor grade and appears to have an adverse impact on OS and DFS in the examined subpopulation.

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; J Pathol Transl Med. 2025;59(6):398-407. Published online September 12, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.22; Funded: National Research Foundation of Korea, Ministry of Science and ICT

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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.

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Day surgery mode of multi-modal image AI fusion targeted transperineal biopsy technique using electromagnetic navigation tracking system under local anesthesia
Zhiyong Liu, Jianhe Wu, Yuanwei Li, Qiang Lu, Yongjun Yang
BMC Urology.2026;[Epub] CrossRef
Research progress on the impact of pre-analytical variables on RNA quality in biobank tissue samples
Yang-Si ZHENG, Xuan-Hao LIN, Yuan-Yuan WANG
Chinese Bulletin of Life Sciences.2026; 38(5): 932. CrossRef

Modified plasma-thrombin method using patient-derived plasma for cell block preparation in endobronchial ultrasound–guided transbronchial fine-needle aspiration: Xizhe Zhang, Chunli Tang, Yingying Gu, Zeyun Lin, Shiqi Tang, Anzi Tan, Mengshi Li, Zhucheng Chen, Yuying Chen, Shi-yue Li, Juhong Jiang; J Pathol Transl Med. 2025;59(6):434-443. Published online November 11, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.20; Funded: National Natural Science Foundation of China, Open Project of the State Key Laboratory of Respiratory Disease

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Background
The plasma-thrombin method, which uses expired blood bank plasma as an ancillary component, has been widely used in cell block (CB) preparation. However, the application of expired blood bank plasma raises concerns about nucleic acid contamination. This study investigated the feasibility of using patient-derived plasma as a substitute for blood bank plasma in the modified plasma-thrombin (MPT) method for CB preparation in endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) samples. Methods: A prospective study was conducted to compare the adequacy of CB preparation between a previously used self-clotting (SC) method and the MPT method. The EBUS-TBNA specimens from each targeted lesion were divided into paired samples: one processed using the SC method and the other using the MPT method, substituting the blood bank plasma with patient-derived plasma. Results: A total of 82 paired EBUS-TBNA samples from 59 patients were analyzed. The diagnostic yield of the SC method and the MPT method was 86.6% and 97.6%, respectively. Among patients diagnosed with non–small cell lung cancer, the adequacy rate for molecular testing was 79.2% with the SC method and 91.7% with the MPT method. Conclusions: The MPT method significantly improved the cellular yield of EBUS-TBNA–derived CBs. Using patient-derived fresh plasma rather than expired blood bank plasma avoids a known contamination risk. The additional step modestly prolongs the procedure and introduces minimal risks by vein puncture. This approach is generally considered cost-effective.

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Validation of a modified plasma-based cell block technique using activated partial thromboplastin time–ellagic acid reagent in body fluid and fine needle aspiration samples in cytology
Sandhyarani Mahadev Kanna, Hima Sree Edupuganti, Archana Shetty, Nirupama Murali, Varshitha Muniraju
American Journal of Clinical Pathology.2026;[Epub] CrossRef

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; Funded: The Korean Society for Cytopathology

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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.

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Machine learning-assisted SERS for rapid and accurate early screening of cervical cancer
Dawei Cao, Fanfeng Shi, Yuting Huang, Li Zhang, Meng Ge, Hongmei Lu
Analytical and Bioanalytical Chemistry.2026; 418(17): 5475. CrossRef

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; Funded: Guizhou Science and Technology Project, Cultivation project of Affiliated Hospital of Guizhou Medical University

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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.

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Prognostic Significance and Immune Correlation of CCL3 Expression in Colon Adenocarcinoma: Insights From Multidatabase Analysis
Vikrant Kumar, Nawaid Hussain Khan, Shashi Nandar Kumar, Neeraj Mahajan, Wafa Aziz, Vinay Kumar, Chaitenya Verma, Harleen Khatra
Biochemistry Research International.2026;[Epub] CrossRef

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; Funded: Dar Al Uloom University

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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.

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; Funded: Korea Medical Device Development Fund, Ministry of Science and ICT, Ministry of Trade, Industry and Energy, Ministry of Health and Welfare, Ministry of Food and Drug Safety

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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.

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A single-institution demographic study of pathologically proven renal disease in kidney transplant recipients over the last 33 years
Hyejin Noh, Jiyeon Kim, Yeong Jin Choi
Journal of Pathology and Translational Medicine.2026; 60(4): 398. CrossRef

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; Funded: The Korean Society for Cytopathology, National Research Foundation of Korea, Ministry of Science and ICT

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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.

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Practice of Cytopathology in Korea: A 40‐Year Evolution Through Standardization, Digital Transformation, and Global Partnership
Yosep Chong, Ran Hong, Hyeong Ju Kwon, Haeryoung Kim, Lucia Kim, Soon Jae Kim, Yoon Jung Choi
Diagnostic Cytopathology.2026; 54(2): 146. CrossRef
Validation of Digital Cytology for Primary Diagnosis Across a Range of Specimen Types
Talisa Mistry, Harriet Hunter, Dahmane Oukrif, Sabine Pomplun, Reena Khiroya, Mary Falzon, Tanya Alan, Manuel Rodriguez‐Justo, Adam P. Levine
Cytopathology.2026; 37(3): 222. CrossRef
Review of the Changing Roles of Clinical Laboratory Scientists and Strategies for Curricular Innovation in the Era of Artificial Intelligence
Hee Sung KIM
Korean Journal of Clinical Laboratory Science.2026; 58(1): 1. CrossRef
Telecytology in head and neck cytopathology: current applications and practical considerations
Yeongjoon Kim
Kosin Medical Journal.2026; 41(2): 126. CrossRef
Diagnostic concordance of remote WSI-based thyroid cytology compared to conventional cytological diagnosis: a pilot study
Abdullah Fahri Şahi̇n, Özben Yalçin, Seyma Büyücek, Merve Dogan Ayan, Hatice Elmas
Diagnostic Pathology.2026;[Epub] CrossRef

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; Funded: Chonnam National University Hospital Biomedical Research Institute

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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.

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Guidance for the Diagnosis and Treatment of Rare Embryonal and Sarcomatous Brain Tumors—a Report from the Central Nervous System-International Registry for Rare Embryonal and Sarcomatous Tumors German Society of Ped
Pascal Johann, Dominik Sturm, Rolf Kortmann, Brigitte Bison, David Capper, Ahmed El Damaty, Lars Behrens, Selma Manea, Johannes Gojo, Michael Frühwald, Ulrich-Wilhelm Thomale, Martin U. Schuhmann, Rudolf Schwarz, Anna Tietze, Matthias Wagner, Beate Timmer
Klinische Pädiatrie.2026;[Epub] CrossRef
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Shane Eaton, Ahmad Almotairi, Adrian Levine, Cynthia Hawkins
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Original Articles

Lessons learned from the first 2 years of experience with thyroid core needle biopsy at an Indonesian national referral hospital: Agnes Stephanie Harahap, Maria Francisca Ham, Retno Asti Werdhani, Erwin Danil Julian, Rafi Ilmansyah, Chloe Indira Arfelita Mangunkusumso, Tri Juli Edi Tarigan; J Pathol Transl Med. 2025;59(3):149-160. Published online April 25, 2025; DOI: https://doi.org/10.4132/jptm.2025.02.19; Funded: Dr. Cipto Mangunkusumo Hospital

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Abstract PDF

Background
Core needle biopsy (CNB) improves diagnostic accuracy by providing precise tissue sampling for histopathological evaluation, overcoming the limitation of inconclusive fine-needle aspiration results. This study evaluated the diagnostic performance of CNB in assessing thyroid nodules, with additional analysis of the benefits of BRAF V600E and RAS Q61R immunohistochemical (IHC) markers.
Methods
This retrospective study enrolled patients with thyroid nodules who underwent CNB at Dr. Cipto Mangunkusumo Hospital, Jakarta, from July 2022 to July 2024. CNB diagnoses were classified using the Korean Thyroid Association Criteria. Diagnostic efficacy was evaluated for neoplastic and malignant lesions, both independently and with BRAF V600E and RAS Q61R IHC. The correlation between nodule size and postoperative diagnosis was also analyzed.
Results
A total of 338 thyroid nodule samples was included, and 52.7% were classified as CNB category II. In the 104 samples with postoperative diagnoses, category IV was the most prevalent (39.4%). CNB demonstrated a sensitivity of 74% and a specificity of 100% for neoplastic lesions and 23.8% sensitivity and 100% specificity for malignant lesions. Combining CNB with BRAF V600E and RAS Q1R IHC increased the sensitivity to 77% for neoplastic lesions and 28.8% for malignant lesions. Larger nodules (>3 cm) were significantly associated with neoplastic (p = .005) and malignant lesions (p = .004).
Conclusions
CNB performs well in identifying neoplastic lesions, with or without BRAF V600E and RAS Q61R IHC, but its low sensitivity for malignant lesions warrants caution. While CNB categories V–VI indicate malignancy, the possibility of malignancy in categories I–IV should not be overlooked.

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Clinicopathological profile of high-grade differentiated thyroid carcinoma in an Indonesian tertiary hospital
Novita, Agnes Stephanie Harahap, Maria Francisca Ham, Alfianto Widiono, Chan Kwon Jung
Journal of Pathology and Translational Medicine.2026; 60(3): 338. CrossRef
Integrating Digital Ki-67 Labeling Index and K-TIRADS for Malignancy Risk Stratification in Thyroid Core Needle Biopsies
Yujin Cha, Sue Youn Kim, Chankyung Kim, Ja Seong Bae, Dong-Jun Lim, So-Lyung Jung, Chan Kwon Jung
Cancers.2026; 18(14): 2260. CrossRef
Clinicopathological Correlation of Core-Needle Biopsy in Thyroid Nodule Assessment: Insights from a Tertiary Care Center
Neha Nigam, Rishabh Sahai, Anil Singh, Anjali Mishra, Sabaretnam Mayilvaganan, Ojas Gupta, Prabhakar Mishra, Nirbhay Kumar, Amit Rastogi
Journal of Cytology.2026; 43(4): 235. CrossRef

Diagnostic yield of fine needle aspiration with simultaneous core needle biopsy for thyroid nodules: Mohammad Ali Hasannia, Ramin Pourghorban, Hoda Asefi, Amir Aria, Elham Nazar, Hojat Ebrahiminik, Alireza Mohamadian; J Pathol Transl Med. 2025;59(3):180-187. Published online April 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.03.04; Funded: Tehran University of Medical Sciences

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Abstract PDF

Background
Fine needle aspiration (FNA) is a widely utilized technique for assessing thyroid nodules; however, its inherent non-diagnostic rate poses diagnostic challenges. The present study aimed to evaluate and compare the diagnostic efficacy of FNA, core needle biopsy (CNB), and their combined application in the assessment of thyroid nodules.
Methods
A total of 56 nodules from 50 patients was analyzed using both FNA and simultaneous CNB. The ultrasound characteristics were categorized according to the American College of Radiology Thyroid Imaging Reporting and Data Systems classification system. The study compared the sensitivity, specificity, and accuracy of FNA, CNB, and the combination of the two techniques.
Results
The concordance between FNA and CNB was notably high, with a kappa coefficient of 0.837. The sensitivity for detecting thyroid malignancy was found to be 25.0% for FNA, 66.7% for CNB, and 83.3% for the combined FNA/CNB approach, with corresponding specificities of 84.6%, 97.4%, and 97.4%. The accuracy of the FNA/CNB combination was the highest at 94.1%.
Conclusions
The findings of this study indicate that both CNB and the FNA/CNB combination offer greater diagnostic accuracy for thyroid malignancy compared to FNA alone, with no significant complications reported. Integrating CNB with FNA findings may enhance management strategies and treatment outcomes for patients with thyroid nodules.

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Clinicopathological Correlation of Core-Needle Biopsy in Thyroid Nodule Assessment: Insights from a Tertiary Care Center
Neha Nigam, Rishabh Sahai, Anil Singh, Anjali Mishra, Sabaretnam Mayilvaganan, Ojas Gupta, Prabhakar Mishra, Nirbhay Kumar, Amit Rastogi
Journal of Cytology.2026; 43(4): 235. CrossRef

Categorizing high-grade serous ovarian carcinoma into clinically relevant subgroups using deep learning–based histomic clusters: Byungsoo Ahn, Eunhyang Park; J Pathol Transl Med. 2025;59(2):91-104. Published online February 18, 2025; DOI: https://doi.org/10.4132/jptm.2024.10.23; Funded: Korea Health Industry Development Institute, Ministry of Health and Welfare, Yonsei University College of Medicine

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Background
High-grade serous ovarian carcinoma (HGSC) exhibits significant heterogeneity, posing challenges for effective clinical categorization. Understanding the histomorphological diversity within HGSC could lead to improved prognostic stratification and personalized treatment approaches. Methods: We applied the Histomic Atlases of Variation Of Cancers model to whole slide images from The Cancer Genome Atlas dataset for ovarian cancer. Histologically distinct tumor clones were grouped into common histomic clusters. Principal component analysis and K-means clustering classified HGSC samples into three groups: highly differentiated (HD), intermediately differentiated (ID), and lowly differentiated (LD). Results: HD tumors showed diverse patterns, lower densities, and stronger eosin staining. ID tumors had intermediate densities and balanced staining, while LD tumors were dense, patternless, and strongly hematoxylin-stained. RNA sequencing revealed distinct patterns in mitochondrial oxidative phosphorylation and energy metabolism, with upregulation in the HD, downregulation in the LD, and the ID positioned in between. Survival analysis showed significantly lower overall survival for the LD compared to the HD and ID, underscoring the critical role of mitochondrial dynamics and energy metabolism in HGSC progression. Conclusions: Deep learning-based histologic analysis effectively stratifies HGSC into clinically relevant prognostic groups, highlighting the role of mitochondrial dynamics and energy metabolism in disease progression. This method offers a novel approach to HGSC categorization.

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Ovarian Cancer: Epidemiology, Disease Mechanisms, New Diagnosis and Treatment Strategies, and Research Directions
Zunera Khalid, Weirong Fan, Farah Nazir, Yixiang Xing, Tengchuan Jin
iNew Medicine.2026;[Epub] CrossRef
Learning Disabilities in the 21st Century: Integrating Neuroscience, Education, and Technology for Better Outcomes
Syed Mohammed Basheeruddin Asdaq, Ahmad H. Alhowail, Syed Imam Rabbani, Naira Nayeem, Syed Mohammed Emaduddin Asdaq, Faiqa Nausheen
SAGE Open.2025;[Epub] CrossRef

Characteristics of RET gene mutations in Vietnamese medullary thyroid carcinoma patients: a single-center analysis: Van Hung Pham, Quoc Thang Pham, Minh Nguyen, Hoa Nhat Ngo, Thao Thi Thu Luu, Nha Dao Thi Minh, Trâm Đặng, Anh Tu Thai, Hoang Anh Vu, Dat Quoc Ngo; J Pathol Transl Med. 2025;59(2):125-132. Published online March 14, 2025; DOI: https://doi.org/10.4132/jptm.2025.01.18; Funded: University of Medicine and Pharmacy

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Abstract PDF Supplementary Material

Background
The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

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Mechanism of and research progress on alterations in the RET gene in thyroid cancer (Review)
Meng Wei, Rui Wang, Jincan Qian, Qiang Fang, Jun Tao
Molecular Medicine Reports.2026; 33(6): 1. CrossRef
Targeted therapy in thyroid cancer: molecular alterations and clinical management
YiHeng Yang, YeSheng Zhang, YongCan Xu, XiaoXin Gu, Neng Lou, GuoChao Ye
Frontiers in Endocrinology.2026;[Epub] CrossRef

The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers: Ji-Ae Lee, Hye Eun Park, Hye-Yeong Jin, Lingyan Jin, Seung Yeon Yoo, Nam-Yun Cho, Jeong Mo Bae, Jung Ho Kim, Gyeong Hoon Kang; J Pathol Transl Med. 2025;59(1):50-59. Published online October 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.26; Funded: National Research Foundation of Korea, Ministry of Science and ICT

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Background
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

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Comparative study of the tumor-infiltrating lymphocytes before and after neoadjuvant chemoimmunotherapy in esophageal squamous cell carcinoma
Yanzhao Xu, Hao Wang, Na Wang, Saijin Cui, Jinyang Guo, Chao Huang, Mingbo Wang, Peng Su, Junhao Qi, Ziqiang Tian
Journal of Cardiothoracic Surgery.2026;[Epub] CrossRef

Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning: Truong Phan-Xuan Nguyen, Minh-Khang Le, Sittiruk Roytrakul, Shanop Shuangshoti, Nakarin Kitkumthorn, Somboon Keelawat; J Pathol Transl Med. 2025;59(1):39-49. Published online October 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.14; Funded: Chulalongkorn University

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Abstract PDF Supplementary Material

Background
Although the criteria for follicular-pattern thyroid tumors are well-established, diagnosing these lesions remains challenging in some cases. In the recent World Health Organization Classification of Endocrine and Neuroendocrine Tumors (5th edition), the invasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as its own entity. It is crucial to differentiate this variant of papillary thyroid carcinoma from low-risk follicular pattern tumors due to their shared morphological characteristics. Proteomics holds significant promise for detecting and quantifying protein biomarkers. We investigated the potential value of a protein biomarker panel defined by machine learning for identifying the invasive encapsulated follicular variant of papillary thyroid carcinoma, initially using formalin- fixed paraffin-embedded samples.
Methods
We developed a supervised machine-learning model and tested its performance using proteomics data from 46 thyroid tissue samples.
Results
We applied a random forest classifier utilizing five protein biomarkers (ZEB1, NUP98, C2C2L, NPAP1, and KCNJ3). This classifier achieved areas under the curve (AUCs) of 1.00 and accuracy rates of 1.00 in training samples for distinguishing the invasive encapsulated follicular variant of papillary thyroid carcinoma from non-malignant samples. Additionally, we analyzed the performance of single-protein/gene receiver operating characteristic in differentiating the invasive encapsulated follicular variant of papillary thyroid carcinoma from others within The Cancer Genome Atlas projects, which yielded an AUC >0.5.
Conclusions
We demonstrated that integration of high-throughput proteomics with machine learning can effectively differentiate the invasive encapsulated follicular variant of papillary thyroid carcinoma from other follicular pattern thyroid tumors.

Citations

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Advances in immunotherapy for thyroid malignancies: from molecular targets to clinical outcomes
Shuo Lv, Jinbao Wang, Guohao Chen, Yongshun Wang, Naiqing Liu
Frontiers in Medicine.2026;[Epub] CrossRef
Misdiagnosed follicular adenoma with 11 year postoperative liver and lung metastases a case report and literature review
Kai-Li Yang, Heng-Tong Han, Shou-Hua Li, Xiao-Xiao Li, Ze Yang, Li-Bin Ma, Yong-Xun Zhao
Discover Oncology.2025;[Epub] CrossRef

Comparison of tissue-based and plasma-based testing for EGFR mutation in non–small cell lung cancer patients: Yoon Kyung Kang, Dong Hoon Shin, Joon Young Park, Chung Su Hwang, Hyun Jung Lee, Jung Hee Lee, Jee Yeon Kim, JooYoung Na; J Pathol Transl Med. 2025;59(1):60-67. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.10.01; Funded: Pusan National University

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Abstract PDF: Background
Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods.
Methods
A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2.
Results
All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%).
Conclusions
Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.

Review

Professional biobanking education in Korea based on ISO 20387: Jong Ok Kim, Chungyeul Kim, Sangyong Song, Eunah Shin, Ji-Sun Song, Mee Sook Roh, Dong-chul Kim, Han-Kyeom Kim, Joon Mee Kim, Yeong Jin Choi; J Pathol Transl Med. 2025;59(1):11-25. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.04; Funded: The Korean Society for Pathologists

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Abstract PDF

To ensure high-quality bioresources and standardize biobanks, there is an urgent need to develop and disseminate educational training programs in accordance with ISO 20387, which was developed in 2018. The standardization of biobank education programs is also required to train biobank experts. The subdivision of categories and levels of education is necessary for jobs such as operations manager (bank president), quality manager, practitioner, and administrator. Essential training includes programs tailored for beginner, intermediate, and advanced practitioners, along with customized training for operations managers. We reviewed and studied ways to develop an appropriate range of education and training opportunities for standard biobanking education and the training of experts based on KS J ISO 20387. We propose more systematic and professional biobanking training programs in accordance with ISO 20387, in addition to the certification programs of the National Biobank and the Korean Laboratory Accreditation System. We suggest various training programs appropriate to a student’s affiliation or work, such as university biobanking specialized education, short-term job training at unit biobanks, biobank research institute symposiums by the Korean Society of Pathologists, and education programs for biobankers and researchers. Through these various education programs, we expect that Korean biobanks will satisfy global standards, meet the needs of users and researchers, and contribute to the advancement of science.

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Establishing and Managing a Biobank at an Academic Institution in a Resource-Limited Setting: A Case Study from Ecuador
Alexander Maldonado, Andrés Herrera-Yela, Evaluna Chicango, Micaela Gómez, Gabriela Naranjo, Camila Maldonado, Paula Echeverría
Biopreservation and Biobanking.2026;[Epub] CrossRef
Biobanking for intelligent medicine: assessment and evaluation with the SHARE principle
Yin Yang, Amin Ullah, Yingbo Zhang, Hui Zong, Xingyun Liu, Chi Zhang, Shanshan Hu, Jiakun Li, Bairong Shen
Journal of the American Medical Informatics Association.2026; 33(7): 1333. CrossRef
From Donor to Discovery and Diagnosis: A Comprehensive 2026 Review of International Biobanking Guidelines Underpinning Molecular Pathology-Driven Cancer Diagnostics, with a Practical Roadmap for Establishing a New Biobank
Andreea-Adriana Neamțu, Robert Barna, Alon Vigdorovits, Iulian-Andrei Hotinceanu, Mihaela-Mirela Muresan, Andrei-Vasile Pascalau, Ovidiu-Laurean Pop
Cancers.2026; 18(18): 2974. CrossRef
Experience and Operation of Establishing the Korea Biobank Network for Inflammatory Bowel Disease and Colorectal Cancer
Yu-Jin Ko, Mihyang Jeon, Ji-Hyeon Lee, Daeun Kwak, Eun Ju Kim, Hye-Ra Jung, Ji-Hyun Seo, Eun-Young Kim, Eun Soo Kim, Ben Kang, Soo Yeun Park, Man-Hoon Han, An Na Seo
Journal of Clinical Medicine.2026; 15(21): 8485. CrossRef
Development of a big data platform for collecting and utilizing clinical information from the Korea Biobank Network
Yun Seon Im, Seol Whan Oh, Ki Hoon Kim, Wona Choi, In Young Choi
BMC Medical Informatics and Decision Making.2025;[Epub] CrossRef
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
Journal of Pathology and Translational Medicine.2025; 59(6): 398. CrossRef

Original Article

PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma: Ranran Feng, Yilin Guo, Meilin Chen, Ziying Tian, Yijun Liu, Su Jiang, Jieyu Zhou, Qingluan Liu, Xiayu Li, Wei Xiong, Lei Shi, Songqing Fan, Guiyuan Li, Wenling Zhang; J Pathol Transl Med. 2025;59(1):68-83. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.27; Funded: National Natural Science Foundation of China, Hunan Province Natural Science Foundation

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Background
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

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Breaking the shackles of morphology: a novel perspective on immunotherapy evaluation for nasopharyngeal carcinoma using multimodal imaging and radiomics – a review
Shaoxi Yang
Nuclear Medicine Communications.2026; 47(6): 621. CrossRef
Core regulatory mechanisms of the PD-L1 axis and clinical strategies for immune escape and immunotherapy response in nasopharyngeal carcinoma
Hanxiong Li, Mengyun Yang, Dingbo Li, Chong Wang
Translational Oncology.2026; 68: 102764. CrossRef
Sinonasal biphasic seromucinous adenocarcinomas: a report of two morphologically distinct cases with multimodal omics characterization
Diana Bell, Randal S. Weber, Miao Zhang, Michelle Afkhami, Raja R. Seethala
Virchows Archiv.2026;[Epub] CrossRef
The Potential Role of SP-G and PLUNC in Tumor Pathogenesis and Wound Healing in the Human Larynx
Aurelius Scheer, Lars Bräuer, Markus Eckstein, Heinrich Iro, Friedrich Paulsen, Fabian Garreis, Martin Schicht, Antoniu-Oreste Gostian
Biomedicines.2025; 13(5): 1240. CrossRef
Role of DEAD/DEAH-box helicases in immunity, infection and cancers
Rex Devasahayam Arokia Balaya, Saptami Kanekar, Shreya Kumar, Richard K. Kandasamy
Cell Communication and Signaling.2025;[Epub] CrossRef
CHIP modulates Wnt/β-catenin signalling in colorectal cancer through proteasomal degradation of DDX17
Sunny Kumar, Sayani Ghosh, Malini Basu, Mrinal K. Ghosh
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2025; 1872(8): 120049. CrossRef

Case Study

Colorectal cancer with a germline BRCA1 variant inherited paternally: a case report: Kyoung Min Kim, Min Ro Lee, Ae Ri Ahn, Myoung Ja Chung; J Pathol Transl Med. 2024;58(6):341-345. Published online September 5, 2024; DOI: https://doi.org/10.4132/jptm.2024.08.14; Funded: Biomedical Research Institute, Jeonbuk National University Hospital

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Abstract PDF

BRCA genes have well-known associations with breast and ovarian cancers. However, variations in the BRCA gene, especially germline variations, have also been reported in colorectal cancer (CRC). We present the case of a rectal cancer with a germline BRCA1 variation inherited from the paternal side. A 39-year-old male was admitted with rectal cancer. The patient underwent surgical resection and the pathologic diagnosis was adenocarcinoma. Next-generation sequencing was performed and a BRCA1 variant was detected. Reviewing the public database and considering the young age of the patient, the variant was suggested to be germline. The patient’s father had had prostate cancer and next-generation sequencing testing revealed an identical BRCA1 variant. In the BRCA cancer group, there is relatively little attention paid to male cancers. The accumulation of male CRC cases linked to BRCA variations may help clarify the potential pathological relationship between the two.

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Aggressive Right-Sided Colon Cancer in a Young Adult: Triple-Whammy Mutations (POLE, KRAS, BRCA1/2) Highlight Emerging Genetic Associations
Ravi Patel, Ganesh Kumar, Yash Shah, Dushyant Singh Dahiya, Sumant Inamdar
ACG Case Reports Journal.2026;[Epub] CrossRef

Original Articles

Histopathologic classification and immunohistochemical features of papillary renal neoplasm with potential therapeutic targets: Jeong Hwan Park, Su-Jin Shin, Hyun-Jung Kim, Sohee Oh, Yong Mee Cho; J Pathol Transl Med. 2024;58(6):321-330. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.31; Funded: Korean Society of Pathologists

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Abstract PDF

Background
Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms
Methods
We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets.
Results
We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063).
Conclusions
Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.

Citations

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Tissue-Based Biomarkers Important for Prognostication and Management of Genitourinary Tumors, Including Surrogate Markers of Genomic Alterations
Leonie Beauchamp, Shreeya Indulkar, Eric Erak, Mohammad Salimian, Andres Matoso
Surgical Pathology Clinics.2025; 18(1): 175. CrossRef
Papillary renal neoplasm with reverse polarity: a case report and literature review
Diego Gonzalez, Kris Kokoneshi, Sam Kwon, Ryan Thomas Mathews, Ryan Michael Antar, Maher Ali, Abiye Kassa, Michael Whalen
Frontiers in Oncology.2025;[Epub] CrossRef

Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study: Agnes Stephanie Harahap, Mutiah Mutmainnah, Maria Francisca Ham, Dina Khoirunnisa, Abdillah Hasbi Assadyk, Husni Cangara, Aswiyanti Asri, Diah Prabawati Retnani, Fairuz Quzwain, Hasrayati Agustina, Hermawan Istiadi, Indri Windarti, Krisna Murti, Muhammad Takbir, Ni Made Mahastuti, Nila Kurniasari, Nungki Anggorowati, Pamela Abineno, Yulita Pundewi Setyorini, Kennichi Kakudo; J Pathol Transl Med. 2024;58(6):299-309. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.25; Correction in: J Pathol Transl Med 2025;59(3):201; Funded: Universitas Indonesia

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Abstract PDF Supplementary Material

Background
The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms.
Methods
This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test.
Results
Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = –0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001).
Conclusions
The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.

Citations

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Risk of recurrence in differentiated thyroid cancer: beyond baseline stratification
Fabián Pitoia, Erika Abelleira, Anabella Smulever, Luis Agustín Ramírez Stieben, Inés Califano, Fernando Jerkovich
Endocrine.2026;[Epub] CrossRef
Nuclear pseudoinclusion is associated with BRAFV600E mutation: Analysis of nuclear features in papillary thyroid carcinoma
Agnes Stephanie Harahap, Dina Khoirunnisa, Salinah, Maria Francisca Ham
Annals of Diagnostic Pathology.2025; 75: 152434. CrossRef

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