Histopathology最新文献

{"title":"Direct tumour–adipocyte contact / Stroma AReactive Invasion Front Area (TAC/SARIFA) predicts adverse outcome in colorectal cancer: a focused evidence synthesis and meta-analysis","authors":"Nic G Reitsam,&nbsp;Bruno Märkl,&nbsp;Iris D Nagtegaal,&nbsp;Magali Svrcek","doi":"10.1111/his.70237","DOIUrl":"10.1111/his.70237","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Direct tumour-adipocyte interaction at the invasion front, termed Stroma AReactive Invasion Front Areas (SARIFA), has recently emerged as a novel H&amp;E-based biomarker in colorectal cancer (CRC). SARIFA positivity is defined by a direct tumour–adipocyte contact (TAC) without intervening stroma or inflammatory infiltrate. We performed a focused evidence synthesis of all published studies and a meta-analysis to summarize the evidence on the prognostic value of TAC/SARIFA in CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Eligible studies, identified via PubMed (7 May 2026), were observational cohorts reporting multivariable-adjusted hazard ratios (HRs) for TAC/SARIFA positivity vs negativity, with cancer-specific survival (CSS) and overall survival (OS) as endpoints. All included studies were retrospective in design. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). Adjusted HRs were pooled using random-effects meta-analysis with restricted maximum-likelihood estimation and Hartung–Knapp confidence intervals. Of 17 records identified, 12 CRC-focused original publications were included in the qualitative synthesis. Seven cohorts (5,932 patients) contributed CSS and five cohorts (4,545 patients) OS data, drawn from eight independent cohorts across six studies. All studies were rated good quality (NOS 7–9/9). TAC/SARIFA positivity was associated with inferior CSS (pooled HR 1.77, 95% confidence interval [CI] 1.55–2.01) and OS (pooled HR 1.53, 95% CI 1.39–1.68), with no relevant heterogeneity detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TAC/SARIFA positivity is independently associated with inferior CSS and OS in CRC, warranting prospective validation. We propose TAC as a more descriptive terminology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"835-848"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.70237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondary changes in the peripheral liver due to kaposiform haemangioendothelioma in the hepatic hilum: a report of two transplant cases","authors":"Rishi Agrawal,&nbsp;Owen Lawrence Cain,&nbsp;James Ferguson,&nbsp;Jane Hartley,&nbsp;Rebeca Sanabria Mateos,&nbsp;David C Bartlett,&nbsp;Simon P McGuirk,&nbsp;Rachel Mary Brown","doi":"10.1111/his.70147","DOIUrl":"10.1111/his.70147","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Kaposiform haemangioendothelioma (KHE) is a rare vascular neoplasm of infancy and childhood that typically affects the soft tissues of the extremities; however, a variety of visceral sites have been reported. When KHE is located within the liver hilum, it may involve hilar structures and lead to secondary changes in the hepatic parenchyma. We report the histological changes in the explant livers of two patients transplanted for liver failure secondary to clinically unsuspected KHE at the hepatic hilum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Patient A initially presented with the signs and symptoms of liver failure at the age of 6. Despite extensive clinical work up, no aetiology was identified and she was diagnosed with ‘cryptogenic cirrhosis’. The patient underwent liver transplantation at age 23, and her explanted liver revealed a vasoformative tumour within the hilum surrounding branches of the portal vein. Immunohistochemistry confirmed a diagnosis of KHE. Her peripheral liver showed features of obliterative portal venopathy and nodular regenerative hyperplasia. There was no evidence of cirrhosis. Patient B presented at age 7 with obstructive features of liver failure. Based on imaging studies and initial liver biopsies, a diagnosis of ‘primary sclerosing cholangitis’ (PSC) was rendered. However, liver transplantation at age 11 revealed KHE at the hepatic hilum surrounding the common hepatic duct. The peripheral liver demonstrated biliary-pattern cirrhosis with periductal fibrosis and ductular reaction, supporting a diagnosis of secondary sclerosing cholangitis rather than PSC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In conclusion, changes seen in peripheral liver biopsies can sometimes be a consequence of unsampled lesions at the liver hilum. KHE is a very rare example of this, but this scenario should be considered when liver biopsy findings do not correlate well with the clinical history.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"886-891"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147528557","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}

{"title":"A CRX-positive RB1-deficient bone tumour with a retinoblastoma-like DNA methylation profile","authors":"Akifumi Nozawa,&nbsp;Daichi Hayashi,&nbsp;Shiho Yasue,&nbsp;Saori Endo,&nbsp;Akihito Nagano,&nbsp;Natsuko Suzui,&nbsp;Tatsuhiko Miyazaki,&nbsp;Akihiko Yoshida,&nbsp;Michio Ozeki,&nbsp;Hidenori Ohnishi","doi":"10.1111/his.70232","DOIUrl":"10.1111/his.70232","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"899-901"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345169","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}

{"title":"Immunohistochemical profile of molecularly verified clear cell renal cell carcinomas.","authors":"Kara S Tanaka, Li Zhang, Chien-Kuang Cornelia Ding, Nancy Y Greenland, Jeffry P Simko, Bradley A Stohr, Deepika Sirohi","doi":"10.1111/his.70287","DOIUrl":"https://doi.org/10.1111/his.70287","url":null,"abstract":"<p><strong>Background: </strong>Immunohistochemical (IHC) features of clear cell renal cell carcinomas (CCRCC) have historically been defined by morphologically selected tumours, but aberrant staining patterns that may confound the diagnosis are common. Recent studies have described the prognostic significance of architectural patterns in CCRCC and have proposed grading schemes based on morphology. We investigate a cohort of molecularly verified CCRCC to evaluate their IHC profiles and correlate with architectural patterns and key driver molecular alterations.</p><p><strong>Methods: </strong>Renal cell carcinomas (RCCs) sequenced at our institution between January 2015 and June 2024 by NGS assay were reviewed to identify CCRCCs based on VHL alterations and/or 3p loss. Architectural patterns were classified into low grade (LG) (nested, cystic), intermediate grade (IG) (tubular, tubulopapillary, alveolar), and high grade (HG) (fused nests/solid sheets, rhabdoid, sarcomatoid, low-grade spindled, pleomorphic tumour giant cells), based on findings from recent studies and scored based on highest-grade pattern. IHC staining for CA9, KER7, PAX8, and CD10 were reviewed for percent staining (focal 25% or less, moderate 26%-50%, diffuse greater than 50%). Correlation of aberrant staining with primary/metastatic status, architectural patterns, and molecular alterations was analysed.</p><p><strong>Results: </strong>125 cases of molecularly verified CCRCC were identified and 108 cases with concurrent IHC met inclusion criteria, including 54 primary and 54 metastatic tumours. KER7 positivity was more common in primary vs. metastatic tumours (45% vs. 13%, P = 0.001), in tumours with LG/IG architectural patterns (67% LG and 67% IG vs. 17% HG, P = 0.002) and in PBRM1 wild type (WT) tumours (84% PBRM1 WT vs. 16% PBRM1 mutated, P = 0.021). Negative CA9 staining occurred only in metastatic tumours (15%). PBRM1 mutated tumours were more likely to be KER7-/CA9+/PAX8-, while BAP1 mutated tumours were more likely to have higher-grade architectural patterns and lack CD10 expression.</p><p><strong>Conclusions: </strong>In this cohort of molecularly verified CCRCCS, positive KER7 staining was seen in 30% of tumours with diffuse strong staining in 16%. The IHC profiles correlated with both morphological features and genetic alterations.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109014","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}

{"title":"Mixed neuroendocrine-non-neuroendocrine neoplasms, amphicrine-like carcinoma and related lesions: a review of changes in classification and current concepts.","authors":"Runjan Chetty, Anthony J Gill","doi":"10.1111/his.70291","DOIUrl":"https://doi.org/10.1111/his.70291","url":null,"abstract":"<p><p>To trace the historical evolution of gastrointestinal mixed epithelial-neuroendocrine tumour terminology, clarify current diagnostic criteria, histological features and approach to reporting these lesions in accordance with the latest classification of gastrointestinal tumours, a narrative overview was undertaken on mixed neuroendocrine-non-neuroendocrine neoplasia (MiNEN). The review traces terminology from early descriptions and successive World Health Organization (WHO) classifications culminating in the 2026 WHO classification and recommendations. Definitions, histological grading, immunohistochemistry, molecular evidence and morphological mimics are reviewed. In the 2026 classification, MiNEN remains a mixed tumour composed of two morphologically recognizable components; each component constituting ≥30% of the neoplasm, with clear neuroendocrine marker expression in the neuroendocrine component. It is clarified that neoplasms with a non-neuroendocrine component that is solely a precursor or intramucosal lesion are not MiNEN. For example, appropriate terminology would be a 'neuroendocrine carcinoma arising from an adenoma' rather than a 'MiNEN (mixed adenoma-neuroendocrine carcinoma)' or even a MANET ('mixed adenoma neuroendocrine tumour'). In the WHO 6th edition, to capture another class of tumours with mixed differentiation, the concept of 'amphicrine-like carcinoma' (ALC) is introduced. ALC refers to a tumour where the neuroendocrine and non-neuroendocrine differentiation is intimately intermixed (either in the same cells or morphologically similar cells) rather than forming distinct zones as in MiNEN. Both ALC and MiNEN represent a family of tumours rather than a distinct diagnosis and invariably require confirmation with immunohistochemistry. Molecular data support a clonal origin from a common precursor rather than collision.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109075","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}

{"title":"Distinct Rb expression pattern in HPV-associated neuroendocrine carcinomas of the uterine cervix.","authors":"Nobuko Yasutake, Misato Komamizu, Takeshi Iwasaki, Ryosuke Kuga, Tomomi Manako, Mikiko Hashisako, Rina Jiromaru, Tomoko Sho, Norihito Yuge, Kenzo Sonoda, Hideaki Yahata, Yoshinao Oda, Hidetaka Yamamoto","doi":"10.1111/his.70290","DOIUrl":"https://doi.org/10.1111/his.70290","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to characterize high-risk human papillomavirus (HR-HPV) infection and the expression patterns of p16, Rb, p53 and cyclin D1 in uterine cervical neuroendocrine carcinomas (UCNECs). We also aimed to clarify the similarities and differences between UCNECs and pulmonary neuroendocrine carcinomas (NECs).</p><p><strong>Methods and results: </strong>We examined the expression patterns of p16, Rb, p53, and cyclin D1 by immunohistochemistry (IHC) and HR-HPV infection by mRNA in situ hybridization (ISH) in 29 UCNEC cases, along with histological review. Ten pulmonary small cell neuroendocrine carcinomas (SCNECs) were included for comparison. Histologically, most UCNECs were SCNECs combined with adenocarcinoma or squamous cell carcinoma. HR-HPV ISH was performed in 28 UCNEC cases; 27 (96%) were HPV-positive and 1 (4%) was HPV-negative. All HPV-positive cases (n = 27) showed p16 overexpression, partial Rb loss, a wildtype p53 pattern, and negative cyclin D1 expression. The single HPV-negative case showed focal p16 positivity, retained Rb expression, a wildtype p53 pattern and positive cyclin D1 expression. In contrast, all 10 pulmonary SCNEC cases were negative for HR-HPV and positive for p16, showing complete loss (n = 9) or retained (n = 1) Rb expression, and often aberrant p53 expression (n = 8; 5 diffuse and 3 null).</p><p><strong>Conclusions: </strong>Most UCNECs are associated with HPV infection and characterized by p16 overexpression as well as partial loss of Rb. The Rb expression pattern differs between HPV-positive UCNECs and HPV-negative pulmonary NECs, suggesting the potential diagnostic utility of Rb as well as p16.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109065","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}

{"title":"Tumour deposits are associated with increased metastatic risk in colorectal cancer: a population-based analysis of metastatic patterns and burden.","authors":"Yao Shu, Nelleke P M Brouwer, Marloes A G Elferink, Johannes H W de Wilt, Femke Simmer, Iris D Nagtegaal","doi":"10.1111/his.70297","DOIUrl":"https://doi.org/10.1111/his.70297","url":null,"abstract":"<p><strong>Aims: </strong>Lymph node metastases (LNM) are traditionally regarded as the principal gateway for distant metastases in colorectal cancer (CRC), forming the foundation of TNM staging. Tumour deposits (TD) have emerged as a strong prognostic factor and potential alternative gateway for CRC spread. This study aimed to assess whether TD were associated with the risk of distant metastases and to characterize metastatic patterns and burden.</p><p><strong>Methods and results: </strong>A retrospective, population-based study included 3505 CRC patients without distant metastases at diagnosis, using data from the Netherlands Cancer Registry for the first half of 2015. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for metastatic risk. Metastatic patterns were summarized descriptively using pattern-to-patient ratios. Metastatic burden was categorized by the number of involved sites (1, 2, 3 or ≥4) and evaluated using the linear-by-linear association test. Of the 3505 patients, 2268 were N0, 934 were LNM+ and 303 were LNM + TD+. TD were independently associated with an increased risk of distant metastases (HR = 1.34, 95% CI: 1.03-1.74). Among patients who developed distant metastases, pattern-to-patient ratios were 0.30, 0.34 and 0.39 in the N0, LNM+ and LNM + TD+ groups, respectively, but were not formally compared because of their dependence on sample size. The distribution of metastatic burden differed across the three groups (P for trend = 0.017). The proportion with ≥4 involved sites was descriptively highest in the LNM + TD+ group (18.0% vs. 11.0% in LNM+ and 9.2% in N0).</p><p><strong>Conclusions: </strong>TD are independently associated with an increased risk of distant metastases in CRC. This finding supports consideration of TD in future risk stratification strategies and warrant further investigation into whether TD mark a distinct metastatic phenotype rather than merely reflecting locoregional disease progression.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080819","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}

{"title":"Immunoreactivity of GPNMB (glycoprotein nonmetastatic melanoma protein B) across the spectrum of uterine mesenchymal tumours.","authors":"Josef Skopal, Marián Švajdler, Nikola Ptáková, Tomáš Vaněček, Michael Michal, Polina Gettse, Jiří Presl, Stanislav Kormunda, Jan Novotný, Pavel Dundr, Michal Michal, Květoslava Michalová","doi":"10.1111/his.70288","DOIUrl":"https://doi.org/10.1111/his.70288","url":null,"abstract":"<p><strong>Background: </strong>GPNMB is a lysosomal transmembrane protein that has emerged as a diagnostic marker for tumours driven by the microphthalmia-associated transcription factor family (TFE3 and TFEB) and mTOR pathway activation. Diffuse, moderate-to-strong GPNMB positivity has been proposed as a surrogate marker for both translocation-driven and mTOR pathway-activated neoplasms, including PEComas. This study investigated the diagnostic utility of GPNMB immunohistochemistry in differentiating uterine PEComas from common morphological mimics among uterine mesenchymal tumours.</p><p><strong>Materials and methods: </strong>We analysed a cohort of 115 uterine mesenchymal tumours, which included nine PEComas and a broad panel of differential diagnoses, comprising leiomyosarcoma (LMS, n = 19), STUMP (n = 20), leiomyoma (n = 10), low-grade endometrial stromal sarcoma (LG ESS, n = 18), high-grade ESS (HG ESS, n = 13), adenosarcoma (n = 11), undifferentiated uterine sarcoma (UUS, n = 5), inflammatory myofibroblastic tumour (IMT, n = 3) and a collection of rare entities (1 UTROSCT, 3 KAT6B/A::KANSL1-, 2 PLAG1- and 1 NTRK-rearranged sarcomas). Immunohistochemistry (IHC) for GPNMB was performed, and a case was strictly defined as positive only if it showed diffuse staining (>75% of tumour volume) of moderate to strong intensity.</p><p><strong>Results: </strong>All uterine PEComas (9/9; 100%) showed diffuse moderate to strong GPNMB positivity. However, diagnostically significant expression was also observed in LMS (9/19; 47%), UUS (2/5; 40%), IMT (2/3; 67%) and LG ESS (1/18; 6%). All other entities lacked diagnostic GPNMB expression, showing negative or only focal (1%-75% of tumour cells) or diffuse but weak staining. Low-level GPNMB expression was common, with focal or weak staining present in 65% of non-positive tumours (60/92), supporting the use of strict scoring criteria.</p><p><strong>Conclusions: </strong>Although highly sensitive for uterine PEComa, GPNMB lacks sufficient specificity for distinguishing PEComa from its principal uterine mesenchymal mimics, particularly LMS, IMT and UUS. Although strict scoring criteria (moderate-to-strong positivity in >75% of tumour cells) reduce false-positive interpretation, GPNMB should not be used as a standalone discriminatory marker but interpreted in conjunction with morphology and a broader immunohistochemical panel.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060577","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}

{"title":"Inter-rater reliability of frozen donor liver macrovesicular steatosis assessment applying the Banff consensus method: a real-world, multi-specialty validation study.","authors":"Derek M Loneman, Jarukit Tantipisit, Nicholas J Caldwell, Ting Zhao, Maxwell Roth, Miranda Machacek, Christos Tsokos, Kyle M Devins, Haihui Liao, M Lisa Zhang, Michael G Drage, Stuti Shroff, Ivan Chebib, Anthony Mattia, Jonathan N Glickman, Mari Mino-Kenudson, Angela R Shih","doi":"10.1111/his.70283","DOIUrl":"https://doi.org/10.1111/his.70283","url":null,"abstract":"<p><strong>Introduction: </strong>Reliability of intraoperative assessment of donor liver allografts for steatosis, an important risk factor for future graft dysfunction, is limited by poor inter-observer agreement. To address this issue, consensus guidelines by the Banff working group in 2022 proposed a standardized steatosis algorithm to improve agreement; however, the practical impact of the proposal has not been well-validated across subspecialty practices and experience levels.</p><p><strong>Methods: </strong>This single-institution inter-observer agreement study entailed two rounds of evaluation of 27 frozen donor liver biopsies by 15 pathologists with a range of subspecialty expertise and experience levels. Raters estimated the amount of macrovesicular steatosis (MVS) by individual methods and, subsequently, using the proposed Banff algorithm.</p><p><strong>Results: </strong>Moderate agreement was observed among pooled raters, irrespective of method used (ICC 0.55 vs. 0.47 for individual and Banff methods, respectively) for precise estimation of MVS. Importantly, though, when precise estimates were reduced to clinically relevant grades, the Banff method improved agreement from 'fair' to 'substantial' compared with individual methods, with the most marked improvement among gastrointestinal subspecialists and pathologists with > 10 years of experience. The Banff method also resulted in overall lower grade estimates, with no 'grade 3' estimates provided, including from biopsies with abundant and azonal MVS, which are notoriously challenging.</p><p><strong>Conclusion: </strong>The findings support utilization of the Banff method as a means of improving inter-rater agreement among diverse pathologists, resulting in more reliable estimation of MVS at clinically significant thresholds.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060609","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}

{"title":"Stroma AReactive Invasion Front Areas (SARIFA) is a negative prognostic factor for overall survival in non-intestinal gastric adenocarcinomas.","authors":"Ákos Jakab, Luca Szalai, Bettina Zengő, Ildikó Kocsmár, Tibor Várkonyi, István Kenessey, Attila Szijártó, András Kiss, Tamás Vass, Gábor Lotz, Éva Kocsmár","doi":"10.1111/his.70289","DOIUrl":"https://doi.org/10.1111/his.70289","url":null,"abstract":"<p><strong>Background: </strong>The Stroma AReactive Invasion Front Areas (SARIFA) is a novel histological phenomenon characterized by direct tumour cell-adipocyte interaction without intervening stroma or inflammatory cells and easily identifiable in routine haematoxylin-eosin-stained sections.</p><p><strong>Methods: </strong>This study evaluated the prognostic significance of SARIFA in a cohort consisting of 333 gastric cancer patients, including 171 intestinal and 162 non-intestinal adenocarcinoma cases. Associations between SARIFA and various well-known histopathological tumour parameters, including lymphovascular invasion, perineural invasion, tumour budding and poorly differentiated clusters (PDCs), were investigated and the prognostic value of these features for survival was determined.</p><p><strong>Results: </strong>SARIFA was more frequently observed in non-intestinal carcinomas but was significantly associated with lymphovascular and perineural invasion in both gastric cancer subtypes. Number of SARIFA foci showed a weak positive correlation with the number of tumour buds and PDCs. SARIFA was identified as an independent negative prognostic factor for overall survival in non-intestinal gastric cancers. According to time-dependent ROC curve analysis, quantification of SARIFA foci did not increase the prognostic accuracy beyond detecting their absence or presence in both gastric cancer subtypes. In addition, the lymph node ratio in both subcohorts and perineural invasion in intestinal adenocarcinomas were also found to be independent prognostic factors for overall survival.</p><p><strong>Conclusion: </strong>SARIFA is a robust, easily assessable histological marker with independent prognostic value in non-intestinal gastric adenocarcinomas. Reliable histopathological markers for this group of tumours, characterized by their distinctive morphology and infiltration pattern, remain limited. Integration of SARIFA into routine diagnostics may enhance risk stratification.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060580","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}