Hisanori Matoba, Mai Iwaya, Chifumi Fujii, Masatomo Kawakubo, Noriyasu Kobayashi, Haruka Kuribayashi, Jun Nakayama
{"title":"Human Intestinal Spirochetosis Shows Higher Positivity in Sessile Serrated Lesions Than in Tubular Adenomas With Preferential Colonization of Absorptive Epithelium.","authors":"Hisanori Matoba, Mai Iwaya, Chifumi Fujii, Masatomo Kawakubo, Noriyasu Kobayashi, Haruka Kuribayashi, Jun Nakayama","doi":"10.1111/pin.70137","DOIUrl":"10.1111/pin.70137","url":null,"abstract":"<p><p>Factors underlying differential colonization by human intestinal spirochetosis (HIS) of various colorectal neoplastic lesions remain unclear. We compared HIS positivity and colonization patterns between sessile serrated lesions (SSLs) and tubular adenomas (TAs) and examined the relationship between spirochetal distribution and epithelial differentiation. HIS positivity was significantly higher in SSLs than TAs at both lesion (26/590 [4.4%] vs. 3/536 [0.6%], p < 0.001) and case (16/421 [3.8%] vs. 1/171 [0.6%], p = 0.03) levels. Because the SSL and TA main cohorts covered different periods, nine HIS-positive SSL cases harboring TAs diagnosed outside the TA cohort period were separately analyzed for within-case comparison, confirming significantly higher HIS positivity in SSLs than TAs (11/12 [91.7%] vs. 6/23 [26.1%], p = 0.003). Among HIS-positive lesions, both SSLs and TAs showed reduced colonization at lesion sites compared to surrounding mucosa, with greater reduction in TAs. GS-II staining demonstrated reduced terminal βGlcNAc on HIS bacterial bodies at SSL lesion sites. HIS preferentially colonized absorptive epithelium, although less evidently in TAs with limited absorptive differentiation. All cases harbored only Brachyspira aalborgi. These results indicate that HIS exhibits universal affinity for absorptive epithelium and that higher HIS positivity in SSLs reflects their greater abundance of absorptive epithelium.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70137"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kirsty Hodgson, Libby Blencoe, Erin Smith, Aswini Sasikumar, Ziqian Peng, Margarita Orozco-Moreno, Richard Beatson, Paula A Videira, Jennifer Munkley
{"title":"Comprehensive Profiling Reveals Sialyl-Tn Upregulation and Prognostic Value in Prostate Cancer.","authors":"Kirsty Hodgson, Libby Blencoe, Erin Smith, Aswini Sasikumar, Ziqian Peng, Margarita Orozco-Moreno, Richard Beatson, Paula A Videira, Jennifer Munkley","doi":"10.1111/pin.70140","DOIUrl":"10.1111/pin.70140","url":null,"abstract":"<p><p>Prostate cancer is a common cancer in males and there is an urgent unmet clinical need to identify new therapies for advanced disease. Aberrant glycosylation is a hallmark of prostate cancer and plays a functional role in disease progression. The sialyl-Tn antigen (sTn) has been widely studied in cancer, yet its involvement in prostate cancer remains relatively unexplored. Here, we utilise a novel anti-sTn antibody (L2A5) to comprehensively monitor sTn expression levels in clinical prostate cancer tissues encompassing normal, benign, primary, metastatic castration-resistant prostate cancer (CRPC), and in patient-derived xenograft (PDX) tissues. We show that while sTn is detected at low or negligible levels in normal prostate tissues, it is expressed in 44% of prostate tumours, and prostate cancer patients with high sTn levels have significantly poorer survival times. Analysis of metastatic therapy-resistant prostate-derived tumours growing in the liver and bone shows sTn is expressed in 37.5% of cases. Furthermore, sTn is expressed in nearly half of the PDX models tested and was found to be broadly androgen-regulated. These findings identify sTn as a potential prognostic biomarker and therapeutic target in prostate cancer and lay the groundwork for the development of sTn-targeted precision therapies for advanced disease.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70140"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of the Mutual Interaction of GPNMB and LPAR1 on Cellular Motility and Tumorigenicity in Mammary Epithelial Cells.","authors":"Minori Kimura, Yukari Okita, Erina Iwabuchi, Xinzhu Hong, Yumu Ichikawa, Manar A Elhinnawi, Hironobu Sasano, Mitsuyasu Kato","doi":"10.1111/pin.70134","DOIUrl":"10.1111/pin.70134","url":null,"abstract":"<p><p>Glycoprotein non-metastatic melanoma protein B (GPNMB) is a poor prognostic factor, which is highly expressed in many types of malignant tumors, including breast cancer. Previously, the overexpression of GPNMB was shown to confer tumorigenic potential like tumor formation and cellular motility to non-tumorigenic mammary gland epithelial cells through the induction of the epithelial-mesenchymal transition (EMT). However, the detailed mechanism by which GPNMB activates cellular motility remains unclear. To address this issue, we focused on the actin reorganization-like elevated stress fiber formation in GPNMB-expressing cells and found that GPNMB enhanced Ras homology family member A (RhoA) activation upon lysophosphatidic acid (LPA) stimulation probably because of the high expression level of LPA receptor (LPAR) 1. We also showed that LPA ligand stimulates cellular motility via the RhoA-ROCK pathway in GPNMB-expressing cells. Moreover, we found that LPAR1 overexpression increases the expression level of GPNMB in NMuMG cells, and that LPA-LPAR1-RhoA signaling could activate GPNMB transcription. In addition, LPAR1-induced sphere-forming ability was impaired by GPNMB knockdown. Collectively, we showed the mutual induction and function of GPNMB and LPAR1 for the activation of cellular motility and the tumorigenic ability of mammary gland epithelial cells.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70134"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jan Hrudka, Jan Hojný, Eva Krkavcová, Jiří Dvořák, Zuzana Prouzová, Michaela Kendall Bártů, Nicolette Zavillová, David Čapka, Radoslav Matěj, Petr Waldauf
{"title":"Immunohistochemistry for p16 and p53 Provides Substantial Agreement With Molecular Tests in Penile Cancer.","authors":"Jan Hrudka, Jan Hojný, Eva Krkavcová, Jiří Dvořák, Zuzana Prouzová, Michaela Kendall Bártů, Nicolette Zavillová, David Čapka, Radoslav Matěj, Petr Waldauf","doi":"10.1111/pin.70138","DOIUrl":"10.1111/pin.70138","url":null,"abstract":"<p><p>Penile squamous cell carcinoma (pSCC) is a rare cancer associated with a relatively poor prognosis. The WHO classifies pSCC into HPV-associated and HPV-independent subtypes, with HPV-positive pSCCs showing slightly better outcomes. A key negative prognostic marker is TP53 mutation. The aim of this study was to evaluate the concordance of (1) p16 immunohistochemistry with HPV status determined by PCR, (2) p53 immunohistochemistry with TP53 mutational status obtained by NGS, and (3) prognostic impact of overexpression and null phenotype p53 immunohistochemistry profiles. Analyzing invasive pSCC from 209 patients, we assessed concordance between p16 immunohistochemistry and HPV status (n = 132) determined by quantitative PCR, obtaining Cohen's kappa Κ = 0.62 (p < 0.0001). For p53 immunohistochemistry versus TP53 status by NGS (n = 145), Cohen's kappa reached Κ = 0.693 (p < 0.0001). We found worse overall survival (Hazard ratio = 3.33, 95% CIs 1.92-5.56, p < 0.0001) in p53 mutated cases (n = 38, both overexpression and null phenotype) compared to wild type (n = 171), but without a significant difference between both mutated profiles. Both HPV status and p53 profile can be reliably assessed by immunohistochemistry with substantial agreement. Patients with a mutated p53 profile showed significantly worse survival, irrespective of the mutated profile variant.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70138"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Low Expression of Cell Adhesion Molecule 1 in Resected Gastroenteropancreatic Neuroendocrine Tumors: Relationship With Lymph Node and Distant Metastasis.","authors":"Ken Miyabe, Michinobu Umakoshi, Yukitsugu Kudo-Asabe, Kei Koyama, Takahiro Ishinari, Ayana Takahashi, Hikaru Tsukita, Yukinobu Ito, Makoto Yoshida, Masato Takahashi, Tatsuo Sugiyama, Masato Sageshima, Hiroshi Nanjo, Yoshinori Murakami, Akiteru Goto","doi":"10.1111/pin.70122","DOIUrl":"10.1111/pin.70122","url":null,"abstract":"<p><p>Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are clinically heterogeneous, making prediction of metastatic behavior challenging. This study examined Cell Adhesion Molecule 1 (CADM1) and the differentially expressed in adenocarcinoma of the lung-1 expression in 75 resected GEP-NETs and evaluated their associations with clinicopathological features, tumor grade, and established adhesion- or prognosis-related markers, including E-cadherin (ECAD), CD56, progesterone receptor (PgR), and cytokeratin 19 (CK19). CADM1 promoter methylation was assessed using methylation-specific PCR, and the miR-214 and miR-375 expressions were analyzed by quantitative real-time PCR. The expression of CADM1 was significantly lower in tumors with lymph node and/or distant metastasis (p = 0.01), and a low CADM1 expression was independently associated with metastatic disease (p = 0.0004; OR = 4.63). Additionally, low PgR (p = 0.014; OR = 4.13) and a high CK19 (p = 0.0002; OR = 4.83) expression, as reported previously, were linked to poor outcomes. In contrast, neither ECAD nor CD56 showed any notable associations with aggressive features in a univariable assessment. No significant relationship was observed between CADM1 promoter methylation and the CADM1 expression. These findings suggest that a reduced CADM1 expression may be associated with lymph node and distant metastasis in GEP-NETs and could be a potential prognostic marker.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70122"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13252909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Morphologic Fault Lines in Distinguishing Gastric Cancer pTis From pT1a in Endoscopic Submucosal Dissection Specimens: An Interobserver Study.","authors":"Rika Omote, Kohei Okura, Eita Kumagai, Ryosuke Ichihara, Takayuki Kodama, Akira Ishikawa, Naoki Sano, Hiroyuki Abe, Minako Fujiwara, Hirokazu Taniguchi","doi":"10.1111/pin.70132","DOIUrl":"10.1111/pin.70132","url":null,"abstract":"<p><p>The 16th edition of the Japanese Classification of Gastric Carcinoma newly distinguishes pTis from pT1a to improve international translatability with the WHO classification and UICC TNM system. However, the histologic boundary between intraepithelial neoplasia and lamina propria invasion remains difficult in routine practice. We retrospectively evaluated interobserver agreement in 50 gastric endoscopic submucosal dissection lesions randomly selected from 238 lesions previously diagnosed as intramucosal carcinoma under the 15th edition criteria. For each lesion, two representative histologic images were independently reviewed by 10 pathologists, who classified each lesion as pTis or pT1a according to predefined architectural criteria. Complete agreement was obtained in 21 lesions, including 10 unanimously diagnosed as pTis and 11 as pT1a, whereas 29 showed disagreement. Overall agreement was moderate, with a Fleiss' kappa value of 0.483. Discordant lesions involved fused or anastomosing glands, cribriform-like structures, crawling or lateral expansion-like patterns, and invasion mimics related to erosion, artifact, or mucosal remodeling. These findings indicate that distinguishing true invasive architecture from morphologic mimics is central to reproducible implementation of the revised classification.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70132"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Homology-Based Application to Diagnose Colorectal Adenoma and Early-Stage Cancer.","authors":"Yuhki Yokoyama, Kazuki Kanayama, Miwa Matsuda, Nobuaki Hatori, Taiki Asano, Eiichi Morii, Hirofumi Yamamoto, Kazuaki Nakane","doi":"10.1111/pin.70143","DOIUrl":"10.1111/pin.70143","url":null,"abstract":"<p><p>Homology is a mathematical concept involving two Betti numbers-b<sub>0</sub>, representing the number of independent objects, and b<sub>1</sub>, representing the number of holes formed by surrounding objects-which can be used to quantify the contact degree. We previously demonstrated the use of a homology-based method to diagnose advanced colorectal cancer. It is clinically important to discriminate adenoma, especially high-grade adenoma, and early-stage cancer from non-cancerous tissue; thus, it was of interest to evaluate whether our homology-based method could also diagnose adenoma and early-stage cancer. In the present study, we developed a homology-based application to calculate b<sub>1</sub> values for a region of interest, and used it to analyze normal tissue, adenoma, and early-stage cancer from the colorectum. Area correction was required for proper comparison of b<sub>1</sub> values. We found that area-corrected b<sub>1</sub> values were significantly higher in high-grade adenoma and early-stage cancer, compared to normal tissue. Although there remains a need for further development of the algorithm to discriminate low-grade adenoma and inflammatory regions, our present findings indicate that our homology-based method using Betti numbers can be useful for distinguishing high-grade adenoma and early-stage cancer from normal tissue, as well as advanced colorectal cancer.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70143"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hoi Wai Chan, Ka Man Cheung, Amy M K Chu, Sharon C L Ho, Chin Pan Kong, Joanna K M Ng, Hei Ming Lai, Peter W T Lee, Joshua J X Li, Chun Yan So, Gabriel C H Wong, Bryan C W Li
{"title":"Significance of Positive Cerebrospinal Fluid Cytology (Leptomeningeal Metastasis) in Central Nervous System Metastasis - A Multicentre Clinicopathological Review.","authors":"Hoi Wai Chan, Ka Man Cheung, Amy M K Chu, Sharon C L Ho, Chin Pan Kong, Joanna K M Ng, Hei Ming Lai, Peter W T Lee, Joshua J X Li, Chun Yan So, Gabriel C H Wong, Bryan C W Li","doi":"10.1111/pin.70142","DOIUrl":"10.1111/pin.70142","url":null,"abstract":"<p><p>Leptomeningeal metastases (LM) is a rare but clinically important subtype in central nervous system (CNS) metastasis. Multicentre data was reviewed to detail the epidemiology, clinicopathological associations among patients with positive cerebrospinal fluid cytology (CSF) cytology. Patients with CNS metastasis and clinical data were identified through the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System (CDARS). In total, through 1st January 2000 to 31st December 2024, 38,893 patients with CNS metastasis were retrieved, 1503 had CSF cytology. The most common primary malignancies were lung (54.16%), breast (11.18%) and gastrointestinal (5.66%; colonic: 3.33%, gastric: 1.86%, esophageal: 0.47%). There were 220 (14.64%) patients with positive CSF, they were younger (57.72 years vs. 60.03, p = 0.005), and likely with breast (20.84%, p = 0.016) and lung primaries (16.47%, p = 0.030). The median overall survival (OS) was 113 days. Positive CSF, age > 60 and gastrointestinal primary were correlated with shorter OS (p < 0.05). The inclusion of brain radiotherapy (260 day vs. 82, p < 0.001) and systemic therapy (496 days vs. 61, p < 0.001) for treatment of leptomeningeal metastases was independently associated with longer OS. Positive CSF cytology is a strong independent indicator of poor outcomes. Radiotherapy and systemic therapy improve overall survival for the medium term (6-12 months).</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70142"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Undifferentiated Carcinoma of the Endometrium: Morphology, Immunophenotype, and Differential Diagnoses to Avoid Diagnostic Pitfalls.","authors":"Atsushi Kihara","doi":"10.1111/pin.70139","DOIUrl":"10.1111/pin.70139","url":null,"abstract":"<p><p>More than 20 years have passed since the distinct definition of undifferentiated endometrial carcinoma (UEC) was proposed in 2005. Based on its distinguishing clinicopathological features, the fourth and fifth editions of the World Health Organization classification of gynecological tumors recognized UEC as a distinct subtype of endometrial carcinoma. An accurate diagnosis of UEC is crucial due to its aggressive clinical behavior and for ensuring appropriate patient management. Many investigators have elucidated clinicopathological and molecular characteristics that are useful for its diagnosis; however, a number of differential diagnoses need to be considered before the final pathological diagnosis. This review summarizes the pathological characteristics of UEC, with a focus on its histological, molecular, and immunophenotypic features, as well as key points for a differential diagnosis. UEC shows diverse immunophenotypes. In addition to the loss of or a marked reduction in epithelial and gynecological markers, UEC frequently expresses ZEB1 and cyclin D1, and occasionally expresses neuroendocrine and germ cell tumor markers. Approximately 60% of UECs show the loss of SMARCA4, SMARCB1, or ARID1A/1B, which may contribute to tumor pathogenesis. These immunophenotypes are not specific because other epithelial and non-epithelial uterine tumors may exhibit overlapping features. Therefore, a comprehensive pathological understanding of UEC is essential for avoiding diagnostic pitfalls and improving diagnostic accuracy.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70139"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glomerular Capillary Microaneurysms in Membranoproliferative Glomerulonephritis: A Clinicopathological Study Highlighting the Involvement of IgG3.","authors":"Akiko Mii, Tomohiro Kaneko, Momoko Arai, Takehisa Yamada, Mayuko Takeuchi, Tetsuya Kashiwagi, Naomi Kuwahara, Arimi Ishikawa, Ryuji Ohashi, Yukinao Sakai, Masato Iwabu, Akira Shimizu","doi":"10.1111/pin.70144","DOIUrl":"10.1111/pin.70144","url":null,"abstract":"<p><p>Glomerular capillary microaneurysm (GCM) is a pathological lesion defined by aneurysmal dilatation of glomerular capillaries resulting from mesangiolysis with severe endothelial damage and is commonly observed in diabetic nephropathy and thrombotic microangiopathy. However, its clinicopathological significance in membranoproliferative glomerulonephritis (MPGN)-pattern glomerular diseases remains unclear. We retrospectively reviewed 50 renal biopsy cases diagnosed as MPGN or MPGN-like glomerulopathy and identified 12 GCM-positive cases for clinicopathological analysis, including Pathologische Anatomie Leiden Endothelium (PAL-E) staining and CD34 immunohistochemistry to assess endothelial injury. Among GCM-positive cases, proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) was significantly enriched; however, exclusive glomerular IgG3 positivity was consistently observed across other diagnostic categories, irrespective of light-chain restriction. Electron microscopy revealed continuous, irregularly shaped, fine granular subendothelial electron-dense materials with endothelial denudation. PAL-E staining was positive in all evaluable cases, with ultrastructurally identified diaphragmed endothelial fenestrae. Furthermore, CD34 staining demonstrated loss of continuous lining in GCM lesions, suggesting severe endothelial injury. Clinically, all patients presented with nephrotic-range proteinuria, and more than half progressed to end-stage kidney disease or died within 3 years. These findings indicate that GCM-positive MPGN-pattern glomerular diseases represent an aggressive subset associated with IgG3-dominant deposition and severe endothelial injury, with important diagnostic implications.</p>","PeriodicalId":19806,"journal":{"name":"Pathology International","volume":"76 6","pages":"e70144"},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13301001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148332140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}