{"title":"Spatial transcriptomics of intraductal carcinoma of the prostate","authors":"Taishi Takahara, Natsuki Taniguchi, Naoto Sassa, Toyonori Tsuzuki","doi":"10.1111/his.15551","DOIUrl":"10.1111/his.15551","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Intraductal carcinoma of the prostate (IDC-P) is a strong indicator of poor prognosis in prostate cancer (PCa). We utilized the Visium Spatial Gene Expression platform to characterize the gene expression profiles and copy number variations (CNVs) of IDC-P.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Manually annotated IDC-P components were relatively enriched in a single transcriptomic cluster identified by principal component analysis, which exhibited elevated expression of <i>FOLH1</i> (PSMA), <i>PSCA</i> and <i>PLA2G2A</i>. Differential gene expression analysis between IDC-P and non-IDC-P cancer tissues revealed up-regulation of pathways related to chemotaxis and leukocyte migration, as well as gene sets associated with small cell lung carcinoma, suggesting a potential link to treatment-related neuroendocrine prostate carcinoma. In contrast, non-IDC-P components showed increased expression of genes associated with extracellular matrix organization.</p>\u0000 \u0000 <p>InferCNV analysis identified distinct CNV patterns differentiating IDC-P from non-IDC-P cancer components in four out of six cases. However, no common CNV alterations were shared across these cases, indicating molecular diversity among IDC-P lesions. In the remaining cases, IDC-P clustered with Gleason pattern 5 carcinoma, and no CNV alterations distinguishing IDC-P from adjacent non-IDC-P components were identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that IDC-P represents a biologically distinct component from conventional acinar adenocarcinoma and may reflect spatial tumour progression through pre-existing ductal structures. Our study also suggests that the molecular mechanisms underlying IDC-P progression may differ between patients, while the limited sample size (<i>n</i> = 6) warrants cautious interpretation and further validation in larger cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"87 5","pages":"745-756"},"PeriodicalIF":4.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-18DOI: 10.1111/his.15554
Phoenix D Bell, Vivek Kaul, Krystle M Bittner, Irene Y Chen, Aaron R Huber, Olivia A Sagan, Wei Chen, ILKe Nalbantoglu, Raul S Gonzalez
{"title":"Margin clearance and post-procedure ablation decrease recurrence risk in endoscopic mucosal resections for Barrett's-related neoplasia.","authors":"Phoenix D Bell, Vivek Kaul, Krystle M Bittner, Irene Y Chen, Aaron R Huber, Olivia A Sagan, Wei Chen, ILKe Nalbantoglu, Raul S Gonzalez","doi":"10.1111/his.15554","DOIUrl":"https://doi.org/10.1111/his.15554","url":null,"abstract":"<p><strong>Aims: </strong>Endoscopic mucosal resection (EMR) is widely used for treating Barrett's-related oesophageal dysplasia and low-stage carcinoma. Disease can recur after this procedure. We analysed a large cohort of EMR specimens to assess clinical and histopathologic factors and their relationship to recurrence.</p><p><strong>Methods and results: </strong>We conducted a retrospective study of 129 patients who had in total 290 oesophageal EMRs for glandular neoplasia. Patient age, patient sex, specimen fragmentation, intestinal metaplasia, highest-grade lesion, margin status and clearance, cancer invasion depth, lymphovascular invasion, tumour budding (using published guidelines for colorectal carcinoma), post-procedure cryoablation/radiofrequency ablation and disease recurrence were recorded. Statistical analyses were performed on 227 eligible cases to determine the significance of these factors in local disease recurrence. Adenocarcinoma was the highest-grade lesion in 42% of the 290 specimens, high-grade dysplasia in 36% and low-grade dysplasia in 22%. Mean age at first EMR was 66 years. Among the 227 statistically analysed cases, post-procedure ablation was performed for 111 (49%) and recurrence of same or worse disease was documented in 104 (46%). Tumour depth and budding did not affect recurrence risk. On multivariate analysis, lack of post-procedure ablation was associated with increased recurrence risk for high-grade dysplasia and carcinoma. Additionally, poor differentiation and margin status were associated with increased recurrence risk for specimens with carcinoma. These relationships mostly held true for recurrence of same/worse neoplasia or recurrence of any neoplasia.</p><p><strong>Conclusions: </strong>Differentiation, margin status and post-EMR ablation influence the risk of local disease recurrence for Barrett's-related adenocarcinoma, while other factors such as tumour budding and lesional depth do not.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-16DOI: 10.1111/his.15558
Wenyi Jing, Dan Ren, Yan Qiu, Sheng Qin, Ting Lan, Xin He, Hongying Zhang
{"title":"EBV-associated smooth muscle tumour: a clinicopathological and genetic study of nine cases revealing heterogeneous immune statuses and novel pathogenic mutations.","authors":"Wenyi Jing, Dan Ren, Yan Qiu, Sheng Qin, Ting Lan, Xin He, Hongying Zhang","doi":"10.1111/his.15558","DOIUrl":"https://doi.org/10.1111/his.15558","url":null,"abstract":"<p><strong>Aims: </strong>EBV-associated smooth muscle tumour (EBV-SMT) is a rare neoplasm, primarily affecting patients with HIV, post-transplantation (PT), and congenital immunodeficiency (CI). Most EBV-SMT cases were reported by case reports, and genetic analyses are limited. Herein, we describe nine patients with EBV-SMTs to further expand the clinicopathological and genetic spectrum of EBV-SMT.</p><p><strong>Methods and results: </strong>Nine patients with EBV-SMTs were identified from 2008 to 2024, and next-generation sequencing (NGS) was performed in six cases with available material. The study comprised four males and five females aged 9-60 years old, including two patients with HIV-SMTs, two with PT-SMTs, three with CI-SMTs, one post-immunosuppressive therapy patient, and one clinically immunocompetent patient. Tumours involved liver (n = 7), adrenal gland (n = 6), retroperitoneum (n = 1) and cervical spinal canal (n = 1). Histologically, eight cases showed characteristic interlacing fascicles of spindled cells with inflammatory cell infiltration. In one CI-SMT case, the tumour cells exhibited epithelioid morphology in a whorled pattern with obvious atypia. All cases showed SMA and EBER positivity. NGS detected recurrent mutations in PIEZO1(3/6), CYP2B6 (2/6), NQO1(2/6), NSMCE3(2/6), and PI4KA (2/6). Novel pathogenic mutations in MAGT1 and CARMIL2 were identified in two CI-SMTs, with the MAGT1 mutation linked to a rare immunodeficiency XMEN disease, reported here for the first time.</p><p><strong>Conclusion: </strong>Our study reported nine EBV-SMT cases from heterogeneous immune statuses, with identification of recurrent mutations and pathogenic mutations in some of these tumours, further expanding its clinicopathological and genetic spectrum. Our findings suggest that EBV-SMT cannot be excluded in clinically immunocompetent patients, and further cytogenetic investigations are warranted.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-12DOI: 10.1111/his.15557
Shorouk Makhlouf, Nabeelah Almalki, Amera Sheha, Nehal M Atallah, Asmaa Ibrahim, Michael Toss, Nigel P Mongan, Emad A Rakha
{"title":"Outcome prediction of oestrogen receptor-positive breast cancer based on a panel of oestrogen receptor-regulated genes.","authors":"Shorouk Makhlouf, Nabeelah Almalki, Amera Sheha, Nehal M Atallah, Asmaa Ibrahim, Michael Toss, Nigel P Mongan, Emad A Rakha","doi":"10.1111/his.15557","DOIUrl":"https://doi.org/10.1111/his.15557","url":null,"abstract":"<p><strong>Background: </strong>The response of oestrogen receptor-positive (ER+) breast cancers (BC) to endocrine therapy (ET) is variable. ER pathway-regulated genes have been proposed to play a role in response to ET. In this study, we investigated the prognostic and predictive impacts of the expression of key ER-regulated genes in BC.</p><p><strong>Methods: </strong>The Cancer Genome Atlas data was used to identify differentially expressed genes (DEG) associated with ER-positivity. Of the DEGs (1329 upregulated and 1188 downregulated genes), 21 top genes showed biological and clinical relevance to ER functions and were further investigated. Publicly available transcriptomic datasets were utilised to evaluate the clinical significance of the expression of these 21 genes. The well-characterised Nottingham operable BC cohort was used to assess their protein expression. Genes that demonstrated prognostic significance on both levels were subsequently tested individually and in combination using multivariate Cox regression analysis.</p><p><strong>Results: </strong>Of the 21 assessed ER-regulated genes, four genes (PR, GREB1, AR and BEX1) maintained their prognostic significance in ER+ BC at both the transcriptomic and proteomic levels. Multivariate Cox regression analyses showed that only PR and GREB1 are predictors of ET response independent of tumour grade, size or lymph node status. The combined PR-GREB1 expression was a strong predictor of ET response.</p><p><strong>Conclusions: </strong>This study showed that when several ER-related biomarkers were evaluated, only PR and GREB1 retained their independent prognostic significance and can be used, individually or in combination, to predict the response to ET in ER+ BC patients.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-09DOI: 10.1111/his.15556
Rajal B Shah, Gladell P Paner, Glen Kristiansen
{"title":"Prostate cancer with favourable histology is not synonymous with prostate cancer indolence","authors":"Rajal B Shah, Gladell P Paner, Glen Kristiansen","doi":"10.1111/his.15556","DOIUrl":"10.1111/his.15556","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"87 5","pages":"777-778"},"PeriodicalIF":4.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-05DOI: 10.1111/his.15550
Felix Elsner, Christiane Kümpers, German Ott, Julia Döring, Katharina Schildknecht, Annette Fisseler-Eckhoff, Maximilian von Laffert, Lea Baier, Luca Giulini, Dietmar Kraus, Jozef Zustin, Florian Weber, Tamas Szöke, Merle Kögel, Annette Arndt, Verena Büchele, Hanibal Bohnenberger, Florian Fuchs, Christian Matek, Konrad Steinestel
{"title":"Current practice of pathologic response assessment following chemoimmunotherapy for non-small cell lung cancer (NSCLC) in Germany: first real-world data from the multicentre Re-GraDE study.","authors":"Felix Elsner, Christiane Kümpers, German Ott, Julia Döring, Katharina Schildknecht, Annette Fisseler-Eckhoff, Maximilian von Laffert, Lea Baier, Luca Giulini, Dietmar Kraus, Jozef Zustin, Florian Weber, Tamas Szöke, Merle Kögel, Annette Arndt, Verena Büchele, Hanibal Bohnenberger, Florian Fuchs, Christian Matek, Konrad Steinestel","doi":"10.1111/his.15550","DOIUrl":"https://doi.org/10.1111/his.15550","url":null,"abstract":"<p><strong>Background: </strong>Given that pathologists now frequently assess pathologic response following neoadjuvant or perioperative chemoimmunotherapy for NSCLC, we set up a multicentre study to evaluate the current practice of regression grading in Germany (Re-GraDE NSCLC).</p><p><strong>Methods: </strong>133 cases of NSCLC resection specimens following chemoimmunotherapy (IO) were collected from 9 high-volume lung cancer centres in Germany. Case characteristics were obtained from pathology reports/electronic medical records. In 107 cases, pretreatment biopsies were available on-site.</p><p><strong>Results: </strong>Residual viable tumour (% RVT) was commonly used to measure therapy response (106/133 resection specimens, 79.7%). The entire tumour bed was submitted for histology in 55.6% of cases; however, in 18%, a tumour bed of ≤3 cm was not completely submitted. Either Junker or IASLC regression grading was applied in 97.7% of primary tumours and 60.2% of lymph nodes with comparable results. Almost half of the tumours (45.9%) showed pathological complete response (pCR and/or regression grade (RG) III) with a very weak correlation between % RVT and pretreatment PD-L1 TPS (r<sup>2</sup> = 0.078, P = 0.007). Pretreatment PD-L1 levels ranged from 0% to 100% (median, 60%) in cases with complete regression, and pCR was observed in 40% of cases with pretreatment PD-L1 TPS <1%.</p><p><strong>Conclusions: </strong>Our multicentre study describes the current practice of histopathological regression grading of NSCLC after IO in Germany, highlighting the widespread use of the Junker system, which is basically comparable to IASLC regression grading. For standardization, we recommend following the IASLC guidelines (submitting of the complete tumour bed if ≤3 cm), while the reporting of % RVT might represent a continuous parameter for therapy response. Our digital nationwide registry, which aims to integrate biopsy results, molecular profiling and % RVT in resection specimens, might develop into a valuable tool to investigate novel predictive biomarkers of IO efficacy.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-05DOI: 10.1111/his.15542
Jiannan Li, Kevin Tanager, Namrata Setia
{"title":"Collagenous gastritis: clinical features, histologic correlates and unanswered questions.","authors":"Jiannan Li, Kevin Tanager, Namrata Setia","doi":"10.1111/his.15542","DOIUrl":"https://doi.org/10.1111/his.15542","url":null,"abstract":"<p><p>Collagenous gastritis (CG) is a rare gastrointestinal disorder characterized by subepithelial collagen deposition and lamina propria inflammation. Despite its first description over four decades ago, the pathogenesis remains unclear, with no standardized pathologic criteria/classification, treatment or established prognosis. A systematic PubMed search identified all English-language case reports, series and observational studies describing CG. Data on demographics, clinical presentation, endoscopic appearance and histologic features were extracted. Of the 133 patients with available demographic data, 101 patients had corresponding histologic information, reflecting the overall rarity and limited characterization of collagenous gastritis in the literature. The most common presenting symptoms were abdominal pain and chronic anaemia. A subset of patients had concurrent collagenous colitis, collagenous sprue, Helicobacter pylori gastritis or celiac disease. The predominant endoscopic finding was gastric mucosal nodularity, typically diffuse or corpus-predominant. Collagen band thickness ranged widely, with a median of 50.5 μm and a maximum of 225 μm. Band distribution was most commonly pan-gastric or corpus-predominant. Among the proposed histologic subtypes of CG, the atrophic pattern was most frequently observed and often correlated with isolated gastric involvement and lack of clinical or histologic remission. This review highlights that histologic classification may help guide differential diagnoses and prognosis. Accordingly, we advocate for explicit reporting of these features in pathology reports. Key gaps in pathogenesis, including the roles of environmental and genetic factors, are also reviewed. This review synthesizes current knowledge of CG and underscores the need for further studies to clarify disease mechanisms. Improved histologic classification and exploration of underlying aetiologies may enhance diagnosis, treatment and research in this underrecognized condition.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HistopathologyPub Date : 2025-09-05DOI: 10.1111/his.15553
Matthias Christgen, Stephan Bartels, Hans Kreipe
{"title":"NMD-insensitive CDH1 mutation as a mechanism for retained E-cadherin protein expression in lobular carcinoma in situ (LCIS).","authors":"Matthias Christgen, Stephan Bartels, Hans Kreipe","doi":"10.1111/his.15553","DOIUrl":"https://doi.org/10.1111/his.15553","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}