Virchows Archiv最新文献

{"title":"The Amsterdam Criteria and beyond: development of a Standardized Structured Reporting (SSR) tool for diagnosis of placental pathology.","authors":"Ekaterina Bazyleva, Lotte E van der Meeren, Mirthe H Schoots, Linda M Ernst, T Yee Khong, Neil J Sebire, Paul Seegers, Sanne J Gordijn","doi":"10.1007/s00428-025-04143-0","DOIUrl":"https://doi.org/10.1007/s00428-025-04143-0","url":null,"abstract":"<p><p>The lack of standardized reporting in placental pathology limits research scalability and clinical application despite consensus-based criteria like the Amsterdam Criteria. This study presents the development and implementation of a comprehensive Standardized Structured Reporting (SSR) tool for placental pathology. Utilizing the LogicNets© platform, the tool incorporates the Amsterdam Criteria, Freedman placental phenotype classification system, and consensus recommendations on placental examination. Development involved collaboration with placental pathology experts, literature review, and iterative feedback from pathologists to address reporting inconsistencies and ensure practicality. The SSR tool integrates evidence-based standards for examining and phenotyping the placenta, including structured gross and microscopic analyses. It introduces control mechanisms for severity grading and phenotype assignment, enabling precise assessment of placental lesions, even in multiple births. Organized into sections-Demographics, Macroscopy, Microscopy, and Group and Phenotype-it efficiently records and analyzes data. Additional functionalities include automated calculations of gross placental features, built-in controls, and versatile documentation of microscopic observations. The tool is designed for seamless integration into clinical workflows. Implementing the SSR tool could enhance placental pathology reporting quality, completeness, and consistency, facilitating large-scale analyses. Discrete data capture enables robust research, potentially improving the clinical utility and understanding of placenta-mediated diseases. However, further validation is required before widespread adoption. Embracing SSR could standardize placental examination, improve clinical interpretation, and advance research in placental pathology for enhanced utility in both research and clinical care.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression of dysplasia in sessile serrated lesions with proliferative zone redistribution: 'Top-down growth' as a marker of malignant potential.","authors":"Kaori Takamura, Yoichi Ajioka, Tatsuya Abé, Tatiana Gritcun, Saori Takashima, Shuhei Kondo, Yusuke Tani, Riuko Ohashi","doi":"10.1007/s00428-025-04144-z","DOIUrl":"https://doi.org/10.1007/s00428-025-04144-z","url":null,"abstract":"<p><p>This study aimed to elucidate the morphological and proliferative progression of dysplasia in sessile serrated lesions (SSLs) to submucosal invasive carcinoma (SIC). Seventy-six SSLs with dysplasia, including 20 with SIC, were analysed. Each lesion was systematically partitioned into morphological units (MUs) based on cytological atypia (low/high) and gland pattern (serrated/tubular), resulting in 200 MUs: serrated-low (n = 76), serrated-high (n = 34), tubular-low (n = 26), and tubular-high (n = 64). These MUs were further categorised as SIC-related (n = 21) or -unrelated (n = 179). Ki67 immunostaining defined proliferative zones within each MU: lower (Ki67-L, n = 70), upper (Ki67-U, n = 40), diffuse (Ki67-D, n = 58), and other (n = 32, excluded from statistical analyses). Fisher's exact test was used in the following specific analyses. Significant associations between serrated-low MUs and SIC-unrelated MUs, and between tubular-high MUs and SIC-related MUs (p < 0.001, respectively) were observed. Moreover, Ki67-L patterns were absent in SIC-related MUs (0/70, 0%, p < 0.001), predominantly in serrated-low MUs (45/70, 64%, p < 0.001). Conversely, Ki67-D patterns were enriched in SIC-related (20/58, 34%, p < 0.001) and tubular-high MUs (39/58, 67%, p < 0.001). Furthermore, Ki67-U patterns exhibited intermediate frequencies between Ki67-L and Ki67-D patterns, with one (2.5%) in SIC-related MUs, six (15%) in serrated-low MUs, and 16 (40%) in tubular-high MUs. This study revealed a significant correlation between Ki67 expression patterns and morphological progression of dysplasia in SSLs. Additionally, the observed Ki67 redistribution, from lower to upper mucosa, followed by diffuse downward spread, mirrors the top-down growth pattern observed in conventional adenomas. Further molecular studies focusing on these proliferative zones are crucial for elucidating the underlying mechanisms of dysplasia progression in SSLs.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphodiesterase 3 A expression in gastrointestinal stromal tumors.","authors":"Harri Sihto, Olivier Giger, Kirsi Toivanen, Sami Salmikangas, Tiina Vesterinen, Mika Sampo, Tom Böhling","doi":"10.1007/s00428-025-04150-1","DOIUrl":"https://doi.org/10.1007/s00428-025-04150-1","url":null,"abstract":"<p><p>Phosphodiesterase 3A (PDE3A) is an emerging therapy target in various cancers with high expression, as in the majority of gastrointestinal stromal tumors (GISTs). However, its association with clinicopathological factors and patient survival in GISTs remains unexplored. We investigated PDE3A expression using a novel mouse monoclonal antibody and immunohistochemistry in two GIST patient series consisting of 173 formalin-fixed, paraffin-embedded tissue samples on tissue microarrays. In addition, we analyzed the association between PDE3A staining intensity and clinicopathological variables and patient survival. We also assessed PDE3A mRNA expression using qPCR in a subset of the samples. We found that all GISTs expressed PDE3A. The staining pattern was weak in 6.3%, intermediate in 35.8%, and strong in 57.8% of tumors. Weak PDE3A expression was associated with a lower median mitotic count (1/50 HPF vs. 4/50 HPF vs. 5/50 HPF; p = 0.007) and higher incidence of metastases at diagnosis (28% vs. 8% vs. 3.3%; p = 0.040) than in tumors with intermediate or strong expression, respectively. PDE3A and CD117 staining intensities correlated positively (p < 0.001), but PDE3A expression showed no association with sex, age, tumor size, location, risk stratification, mutation profile, Schlafen 12 expression, or metastasis-free or overall survival. We conclude that PDE3A expression can be reliably assessed in archived tumor material using immunohistochemistry. GISTs, with their consistently high PDE3A expression, are a promising target for PDE3A-targeted therapies. This method may also aid in stratifying patients in cancers where PDE3A expression is less common.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basal cell adenoma with S100 protein-positive \"stroma\": a distinct triphasic salivary gland neoplasm characterized by CTNNB1 mutation.","authors":"Alena Skálová, Martina Bradová, Jan Laco, Tomáš Vaněček, Veronika Hájková, Petr Martínek, Marián Grendár, Giulia Querzoli, Ilmo Leivo, Michal Michal","doi":"10.1007/s00428-025-04141-2","DOIUrl":"https://doi.org/10.1007/s00428-025-04141-2","url":null,"abstract":"<p><p>Basal cell adenoma (BCA) is a benign salivary neoplasm that exhibits a divergent spectrum of growth patterns, including cribriform, tubular, trabecular, membranous, and solid. A subset of BCAs is characterized by the presence of abundant S100 protein-positive stroma, which makes this variant unique and potentially represents a hybrid lesion or an entity intermediate between BCA and pleomorphic adenoma (PA). From the authors' registry, we selected 17 cases of BCA with abundant S100 protein-positive stromal components and compared them with 7 cases of BCA without S100 protein-positive stroma, and 6 cases of myoepithelial cell-rich PAs. All cases were analyzed by immunohistochemistry (IHC) using antibodies to S100 protein, SOX10, PLAG1, HMGA2, p63/p40, cytokeratins, EMA, LEF1, and/or β-catenin. Next-generation sequencing (NGS), fluorescence in situ hybridization (FISH) for the rearrangement of PLAG1, and methylation analysis were performed. The BCA S100 protein stromal cell-rich group consisted of 7 males and 10 females with an average age of 62 years. Their tumors showed typical S100 protein-positive stroma, which was also positive for SOX10 in all cases. The stromal and/or epithelial components showed expression of LEF1 and β-catenin in 17 and 15 cases, respectively. HMGA2 IHC showed nuclear expression in one case while PLAG1 was negative in all cases. In 11 cases, one or more mutations were present, including CTNNB1 mutation (n = 11). The first control cohort of BCA without S100 protein-positive stroma consisted of 1 male and 6 females with an average age of 50 years. This group showed LEF1 and nuclear β-catenin expression in 1 and 2 cases, respectively. The second control group of PA (including 4 spindle-shaped cellular and 2 oncocytic PAs) was devoid of CTNNB1 mutations. Two cases presented with gene fusions, including MEG3::PLAG1 and ACTA2::PLAG1, and an additional two cases showed PLAG1 break. It has been proposed earlier that BCA is related to PA based on a shared biphasic nature and a divergent spectrum of growth patterns. Our findings suggest that BCAs with abundant S100 protein-positive stroma are tumors that morphologically display tricellular differentiation into inner (luminal) ductal epithelial cells, outer (abluminal) basaloid myoepithelial cells, and spindle-shaped stromal S100-positive cells (stromal abluminal). According to our investigation, BCAs with S100 protein-positive stroma represent a distinctive triphasic subset of BCA, which is substantially different from PA, both in immunoprofile and molecular underpinnings.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on the clinicopathological analysis of thyroid carcinomas with the RET and NTRK fusion genes: characterization for genetic analysis in thyroidology.","authors":"Ilker Sengul, Demet Sengul","doi":"10.1007/s00428-025-04145-y","DOIUrl":"https://doi.org/10.1007/s00428-025-04145-y","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the spectrum of AFF2 carcinoma: clinical, morphological, immunohistochemical, and molecular characteristics of five cases harboring alternate fusions.","authors":"Gerben E Breimer, Martin D Hyrcza, Elan Hahn, Sophie C Prendergast, Stephen M Smith, Anne Chambers, Emma Todorovic, Doreen Palsgrove, Daniel L Miller, Robert J Heinhuis, Johannes A Rijken, Lennart A Kester, Cuihong Wei, Ilan Weinreb, Justin A Bishop","doi":"10.1007/s00428-025-04140-3","DOIUrl":"https://doi.org/10.1007/s00428-025-04140-3","url":null,"abstract":"<p><p>In recent years, multiple molecularly defined entities have emerged in head and neck pathology, especially among sinonasal squamous and basaloid carcinomas, including NUT carcinoma, SWI/SNF-deficient carcinoma, and DEK::AFF2 carcinoma. These tumors show significant morphological and immunophenotypic diversity. We present five novel head and neck carcinomas harboring AFF2 rearrangements involving previously unreported fusion partners. Five cases (3 males, 2 females; ages 35-72 years) presented with tumors in the sinonasal region (n = 4) and parotid gland (n = 1), measuring between 3.3 and 6.3 cm. RNA sequencing identified fusions involving AFF2 with H3-3A, EWSR1, CHD4 (two cases: neck lymph node metastasis, which turned out to be sinonasal primary and parotid mass), and NUCKS1. Tumors harboring H3-3A::AFF2 and NUCKS1::AFF2 fusions exhibited bland transitional cell-like morphology with acantholytic changes similar to classic DEK::AFF2 carcinoma; the NUCKS1 fusion also demonstrated clear cell features. In contrast, the EWSR1::AFF2 fusion tumor showed high-grade adenocarcinoma morphology with focal neuroendocrine marker expression, lacking p63 and CK5/6. The two CHD4::AFF2 fusion cases demonstrated neuroendocrine differentiation; one was a cytokeratin-negative small blue round cell carcinoma, and the other showed mixed squamoid-neuroendocrine features with strong cytokeratin and p63 expression. All tumors demonstrated consistent AFF2 immunoreactivity. These findings suggest that AFF2-rearranged tumors form a spectrum of carcinomas with diverse morphologies, immunophenotypes, and differentiation patterns. Given the consistent involvement of the AFF2 gene and uniform AFF2 immunohistochemical positivity despite morphological heterogeneity, we propose naming this entity AFF2 carcinoma.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hiding in the kidney: a series of 13 lymphoid proliferations clinically mimicking renal carcinoma.","authors":"Jihoon William Lee, Marie E Perrone, Daniel E Sabath, Daniel W Lin, George R Schade, Funda Vakar-Lopez, Maria Tretiakova","doi":"10.1007/s00428-025-04137-y","DOIUrl":"https://doi.org/10.1007/s00428-025-04137-y","url":null,"abstract":"<p><p>Masses are commonly detected in the kidneys either as incidental findings or upon workup of urinary symptoms on an initial presentation. We describe a large series of rare cases in which individuals presented with symptoms or imaging findings of kidney masses concerning for primary carcinoma of renal cell or urothelial origin but were found on pathological analysis to be lymphomas or atypical lymphoid proliferations, with or without an accompanying renal malignancy. These mass lesions, including some unique mimics of renal carcinomas such as reactive follicular hyperplasia and IgG4-related disease primary to the kidney, are all lymphoid kidney proliferations from a single institution. Herein, we demonstrate the need for consideration of lymphoid abnormalities in the diagnosis of renal masses, which can affect further workup and management. We also review the differential diagnosis of primary renal masses originating from neoplastic and non-neoplastic lymphoid disorders.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of PD-L1, TERT promoter mutations, and BRAFV600E mutation in poorly differentiated, differentiated high grade thyroid carcinoma and anaplastic carcinoma of the thyroid: our institutional experience.","authors":"Alessia Piermattei, Giuseppe Migliara, Angela Feraco, Carmine Bruno, Luisa Cioni, Qianqian Zhang, Belen Padial-Urtueta, Elisabetta Merenda, Guido Fadda, Marco Raffaelli, Luigi Maria Larocca, Antonino Mule, Alfredo Pontecorvi, Esther Diana Rossi","doi":"10.1007/s00428-025-04134-1","DOIUrl":"https://doi.org/10.1007/s00428-025-04134-1","url":null,"abstract":"<p><p>Although many thyroid cancers are well-differentiated carcinomas with an indolent behavior, poorly differentiated (PDTC) and anaplastic thyroid carcinomas (ATC) represent a minority of thyroid malignancies with an aggressive and/or lethal course, followed by limited effective treatment options. Recently, the WHO 2022 introduced the concept of high-grade follicular cell-derived malignancy, including both the traditional PDTC as well as the new definition of high-grade differentiated thyroid carcinomas (DHGTC). Both are characterized by increased mitotic activity and tumor necrosis without anaplastic features and similar clinical behavior. In the last years, immune checkpoint inhibitors (ICIs) have shown to be an effective treatment for a variety of carcinomas, especially aggressive types such as PDTC and ATC, with less data available about DHGTC. The current study analyzes a cohort of patients with PDTC, DHGTC and ATC focusing on the expression of programmed cell death-ligand 1 (PD-L1) and BRAFV600E correlated with aggressive features. From January 2010 to December 2023, 73 patients including a diagnosis of PDTC, DHGTC, and ATC were diagnosed. All these cases were analyzed for the PD-L1 expression and BRAFV600E and correlated with the clinic-pathological features. Among the 73 cases, 42 (57.5%) were women. The median age was 64.2 years. Histological diagnoses included 35 (38.4%) PDTC, 8 DHGTC, and 30 (46.1%) ATC. Lymph-nodal involvement was seen in 27 cases (including 12 N1a, and 15 N1b), while vascular invasion in 34 cases. A differentiated component was seen in all DHGTC, 5PDTC, 11 ATC. Evaluating the stage, 60 cases were from pT3a to pT4b. PD-L1 was expressed in 24/73 (5DHGTC, 0 PDTC, 19 ATC); BRAFV600E and TERT were positive in 19 cases and 16 cases respectively. PD-L1 was confirmed to be a potential biomarker for the management of patients with DHGTC and ATC. Although it did not yield a prognostic role in PDTC and ATC, it is likely to define a subset of patients directed to the checkpoint inhibitor therapy. Furthermore, TERT mutations showed a strong correlation with overall survival rate.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive morphological, immunohistochemical, and molecular characterization of congenital pulmonary airway malformation (CPAM).","authors":"S Schweitzer, M Stiller, M Lacher, O Aubert, S Krämer, F W Hirsch, D Gräfe, K Hauptmann, A Arnold, D Horst, M Chirica, F Klauschen, U Obeck, M Boeschen, H Bläker, M von Laffert","doi":"10.1007/s00428-025-04131-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04131-4","url":null,"abstract":"<p><p>Congenital pulmonary airway malformation (CPAM) is among the most common congenital lung disorders. Possible findings are foci of mucinous cell clusters (MCCs), harboring KRAS mutations. Studies combining morphology, immunohistochemistry (IHC), and molecular data are scarce. A total of. 46 CPAM lesions were assessed by conventional histomorphology. IHC was performed to analyze lung-specific markers, transcription factors, and epithelial markers reflecting the structural composition of the bronchial tree and alveolar system. Next-generation sequencing (NGS) was conducted to identify mutations and fusions. CPAM type 1 was found in 50%, type 2 in 22%, and type 3 in 6%. A mixed pattern of types 1 and 2 was observed in 22%. The epithelial lining was strongly positive for CK7 and TTF-1 in all samples. Expression for Napsin A, Surfactant A, p40, CK5/6, and CK20 varied within and between subtypes. P40 and CK5/6 were more enriched in type 1 compared to type 2. MCCs occurred in 17%. Mutations were found in 24% (9 × KRAS; 2 × FGFR2). Besides classical KRAS mutations (G12D, G12V), two cases showed a double-mutation pattern (G12D/G12V; G12D/TP53). In all MCC cases, the same mutation with comparable allele frequencies was found in mucinous and non-mucinous areas. No fusions were detected. The presence of mixed-type patterns supports the hypothesis that CPAM represents a continuum of developmental disturbances occurring at various stages of lung branching morphogenesis. This is further corroborated by the divergent protein expression patterns. Our study confirms recent findings that the same KRAS mutations occur in mucinous and non-mucinous areas. The identification of additional mutations, including potential co-mutations, underscores the need for further investigation into molecularly defined CPAM subtypes.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of highest and overall percentage Gleason pattern 4 in prostate cancer biopsies.","authors":"L J Kroon, K P Leeuwenburgh, S Remmers, C F Kweldam, R C N van den Bergh, C H Bangma, G J L H van Leenders","doi":"10.1007/s00428-025-04117-2","DOIUrl":"https://doi.org/10.1007/s00428-025-04117-2","url":null,"abstract":"<p><p>Current guidelines recommend pathologists to report percentage Gleason pattern 4 (GP4%) in Gleason score (GS) 7 prostate cancer (PCa) biopsies. However, it is unspecified whether the highest or overall GP4% should be reported. This study aims to clarify which quantification method correlates best with radical prostatectomy (RP) pathology. This study included 308 men with the highest GS 3 + 4 = 7, 4 + 3 = 7, or 4 + 4 = 8 on centrally revised systematic and/or targeted biopsies who underwent RP between 2018 and 2022. The highest and overall biopsy GP4% were compared with RP GP4% using Spearman's rank correlation coefficient and adverse pathology (AP) (pT-stage ≥ T3, GS ≥ 4 + 3 = 7 and/or pN1) using multivariable logistic regression models adjusted for clinical tumor stage, prostate specific antigen (PSA), percentage of tumor positive biopsies, biopsy modality (systematic/targeted/both), and cribriform pattern. Both quantification methods correlated with RP GP4% (both rho = 0.59), and no significant difference was found between them (p = 0.78). On multivariable analyses, both GP4% quantification methods were significantly associated with AP (per 10% increase, highest GP4% odds ratio [OR] 1.26 [95% CI 1.14-1.39], overall GP4% OR 1.38 [95% CI 1.22-1.58], both p < 0.001). The area under the curve (AUC) was slightly better for overall (0.78 [95% CI 0.73-0.83]) than the highest GP4% (0.76 [95% CI 0.71-0.81], p = 0.041). This study found that the highest and overall biopsy GP4% both correlated with RP GP4%. Although the discriminative performance of the highest and overall GP4% was comparable with respect to AP at RP, the overall GP4% statistically slightly outperformed the highest GP4%. Including the overall GP4% may have added value in risk stratification and clinical decision-making in a subset of PCa patients.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}