Virchows Archiv最新文献

{"title":"Identification of proliferating CD103⁺ CD8⁺ tissue-resident memory-like T-cells in villitis of unknown etiology in human placenta.","authors":"Haruo Ohtani, Yutaka Fujiki, Shiki Takamura, Masaaki Miyazawa","doi":"10.1007/s00428-025-04225-z","DOIUrl":"https://doi.org/10.1007/s00428-025-04225-z","url":null,"abstract":"<p><p>Villitis of unknown etiology (VUE) is a destructive inflammatory lesion of unknown cause in the human placenta. It may be caused by semiallogeneic rejection of fetal tissue by the mother. CD8⁺ tissue-resident memory T (T_RM) cells reside in the peripheral tissues and have an important role in the local defense against reinfection. These cells also contribute to immunopathogenesis under some circumstances and cause local tissue damage and autoimmune disease. In this study, we examine the contribution of CD103⁺ CD8⁺ T_RM-like cells to the development of VUE. The study included 23 cases of human placenta diagnosed as VUE (high-grade). Double-labeling immunohistochemistry was performed in formalin-fixed paraffin-embedded tissues. CD103⁺ CD8⁺ cell accumulation in actively inflamed areas was observed in all cases. The double positivity rate for CD103 and CD8 among the total CD103⁺ and CD8⁺ cells was 95% (71-100%) and 58% (18-90%) [median (range)], respectively. This indicated that the vast majority of CD103⁺ cells in VUE are CD103⁺ CD8⁺ T_RM-like cells. CD103⁺ cells exhibited a significantly high proliferative activity based on a Ki-67 labeling index in CD103⁺ cells of 52% (13-90%). CD103⁺ cells were aligned beneath E-cadherin⁺ syncytiotrophoblast cells (subtrophoblast alignment) in the peripheral areas of the VUE lesions. Syncytiotrophoblast cells in VUE were also characterized by the induction of human leukocyte antigens A, B, and C expression. CD103⁺ cells also expressed granzyme B. Our results suggest that proliferating CD103⁺ CD8⁺ T_RM-like cells work as cytotoxic effector cells and play an important role in VUE pathogenesis.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970824","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":"Survival outcomes after systemic treatment of high-grade triple-negative metaplastic breast cancer versus triple-negative breast cancer of no special type.","authors":"Claudia Grosse, Alexandra Grosse, Heike Kathleen Schwarz, Heike Frauchiger-Heuer, Tamara Rordorf, Alexander Ring, Rupert Langer, Zsuzsanna Varga","doi":"10.1007/s00428-025-04224-0","DOIUrl":"https://doi.org/10.1007/s00428-025-04224-0","url":null,"abstract":"<p><p>This study aimed to evaluate the prognostic impact of adjuvant and neoadjuvant chemotherapy (ACT, NACT) in high-grade triple-negative metaplastic breast cancer (TNMBC) and to compare survival outcomes with those of triple-negative breast cancer of no special type (TNBC NST). A total of 73 patients with high-grade TNMBC and 369 patients with TNBC NST were included in the study. In the non-NACT and ACT subgroups, TNMBC patients exhibited significantly worse overall survival (OS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS), and disease-free survival (DFS) than TNBC NST patients (non-NACT: p < 0.001 for all endpoints; ACT: OS, p < 0.001; DDFS, p < 0.001; BCSS, p = 0.004; DFS, p < 0.001). In the NACT subgroup, TNMBC and TNBC NST patients had similar survival outcomes. Within the TNMBC cohort, patients treated with NACT without achieving a pathological complete response (pCR) demonstrated improved OS (p = 0.045) and a trend toward improved BCSS (p = 0.056) compared to TNMBC patients who did not receive CT. No significant survival difference was observed between TNMBC patients treated with ACT and those without CT, nor between NACT-treated TNMBC patients without a pCR and those treated with ACT. We conclude that survival outcomes of TNMBC vs. TNBC NST patients may be influenced by systemic treatment. NACT-treated TNMBC patients without a pCR demonstrated superior OS compared to TNMBC patients receiving no CT, while no survival difference was observed among TNMBC patients based on treatment sequencing (ACT vs. NACT).</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970940","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":"Definition of parameters and thresholds to detect MYCN amplification in retinoblastomas.","authors":"C Bielefeld, T Hugo, N Sievers, P Ketteler, E Biewald, T Kiefer, K Papaioannou, P Tüller, T Ryl, M Busch, J Rawitzer, H-U Schildhaus, S Ting","doi":"10.1007/s00428-025-04219-x","DOIUrl":"https://doi.org/10.1007/s00428-025-04219-x","url":null,"abstract":"<p><p>Retinoblastoma is a malignant childhood neoplasm where MYCN amplification defines a subset of tumors with worse prognosis. FISH (fluorescence in situ hybridization) represents a fast and reliable method to measure gene copy numbers in various tumors but has not yet been systematically evaluated in retinoblastoma. In this study, we define criteria for FISH detection of MYCN amplification in a systematic unbiased approach by using a well characterized series of 44 clinical retinoblastoma samples. We (i) determined potential measurements and parameters by a comprehensive literature review, (ii) analyzed a retrospective cohort of samples with known MYCN amplification, (iii) determined statistically measurements and cut-offs, which allow reliable detection of amplified tumors, and (iv) applied these criteria to a prospective cohort. We demonstrate that average gene copy number (AVGCN) of MYCN/cell, MYCN/CEN2 ratio, and MYCN-CEN2 difference reveal the lowest statistical variance in amplified samples, if at least 50 cells were counted. The combination of these three parameters and cut-offs, namely AVGCN ≥ 10, MYCN/CEN2 ratio ≥ 3, and MYCN-CEN2 difference ≥ 8, allowed a reliable distinction between amplified and non-amplified cases. The prevalence of MYCN-amplified cases was 4/33 (12.1%) among prospective clinical samples indicating a higher percentage of positive tumors than previously reported. Our data provide the first evidence for well-grounded MYCN FISH criteria in retinoblastoma.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970761","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":"The absence of FOXA2 and HNF1β expression in vasculogenic mesenchymal lesions of germ cell origin suggests an evolutionary pathway similar to that of sarcomatoid yolk sac tumor.","authors":"Costantino Ricci, Luisa Di Sciascio, Francesca Ambrosi, Marco Grillini, Veronica Mollica, Francesco Massari, Michelangelo Fiorentino, Antonio De Leo, Muhammad T Idrees, Thomas M Ulbright, Andres Martin Acosta","doi":"10.1007/s00428-025-04223-1","DOIUrl":"10.1007/s00428-025-04223-1","url":null,"abstract":"<p><p>Vasculogenic mesenchymal lesions (VMLs) are uncommon phenotypes of germ cell tumor (GCT) origin that are mostly found after chemotherapy of mediastinal yolk sac tumor (YST). These lesions typically lack expression of classical YST markers [α-fetoprotein (AFP) and glypican-3 (GPC3)]. FOXA2 and HNF1β are key inducers of the YST phenotype and co-operate to promote transcription of genes involved in YST development (AFP, GPC3, GATA3, among others). Immunohistochemical studies have shown that FOXA2 and HNF1β are more sensitive than AFP, GPC3, and GATA3 for conventional phenotypes of YST, whereas they are typically negative in sarcomatoid YST. In this study, assessment of VMLs showed that they do not express FOXA2 and HNF1β to a significant degree. These results suggest that the combined downregulation of FOXA2 and HNF1β may underlie the transformation of YST to \"mesenchymal\" phenotypes, with additional (still undefined) processes determining the final phenotype (sarcomatoid YST or VMLs).</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875444","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":"Cemento-osseous dysplasia with a NOTCH4 mutation: a case report.","authors":"Gerben E Breimer, Nard G Janssen, Anne M L Jansen, Pieter J Slootweg","doi":"10.1007/s00428-025-04212-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04212-4","url":null,"abstract":"<p><p>Cemento-osseous dysplasia (COD) is a benign fibro-osseous lesion of the jaw that can mimic other entities, particularly cemento-ossifying fibroma (COF), both radiologically and histologically. Although recent research has implicated mutations in the RAS-MAPK pathway in COD, its broader molecular landscape remains insufficiently defined. We report the case of a 32-year-old woman with an incidental lesion in the right mandibular angle. Radiographic assessment revealed a poorly demarcated lesion, and histopathological analysis confirmed features consistent with COD, including fibro-osseous tissue with interconnected bony trabeculae lacking osteoblastic rimming. Next-generation sequencing (TSO500 panel) identified a previously unreported NOTCH4 mutation. This finding expands the spectrum of genetic alterations associated with COD and raises the possibility of Notch signaling involvement in its pathogenesis. Incorporating molecular profiling into the diagnostic workflow may improve discrimination between COD and COF and deepen our understanding of fibro-osseous lesions of the jaw.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856471","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":"GLI1/2-altered mesenchymal tumors: a study of 8 cases expanding the clinicopathological and molecular spectrum including an upstream PTCH1-inactivating mutation.","authors":"L S Hiemcke-Jiwa, R van Ewijk, M M van Noesel, B B J Tops, S A Koppes, S F K Lubeek, G N Jonges, A J Witkamp, A von Deimling, A H G Cleven, L A Kester, U Flucke","doi":"10.1007/s00428-025-04211-5","DOIUrl":"https://doi.org/10.1007/s00428-025-04211-5","url":null,"abstract":"<p><p>GLI1/2 alterations drive mesenchymal tumors harboring rearrangements and amplifications. Affected patients show a broad age range and tumor distribution, and histology varies. We describe the clinicopathologic and molecular characteristics of eight cases (7 females, 1 male, age range 15-82 years). Tumors were located in the ovary (n = 3), endometrium (n = 1), retroperitoneum (n = 1), skin (n = 1), neck (n = 1), and hypopharynx (n = 1). The cases showed epithelioid (n = 2), spindle cell (n = 1), biphasic (n = 1), or round cell (n = 3) morphology. Two of the latter neoplasms had a prominent myxoid stroma. One tumor was polymorphic with brisk mitotic activity. Immunohistochemistry demonstrated variable positivity for S100,  pankeratin AE1/3, EMA, CD56, synaptophysin and chromogranin. MDM2, CDK4, and STAT6 expressions were detected in cases with GLI1 amplification. In three neoplasms, a fusion gene was identified (GLI1::MALAT1, n = 2; PTBP1::GLI2, n = 1). Three cases harbored GLI1-amplification, with co-amplification of MDM2/CDK4 in two of them. GLI2 was amplified in one tumor. Another case had an inactivating PTCH1 mutation. By RNA expression and DNA methylation profiling, the cases formed a cluster. GLI-amplified tumors occurred in older patients (n = 3) who died within 3-27 months. GLI-fusion genes and the PTCH1 mutation were identified in neoplasms of younger patients (n = 3) remaining disease-free (25-31 months). In conclusion, our GLI1/2 altered mesenchymal tumors, clustered at RNA level and epigenetically, confirming that they form one entity, including neoplasms with PTCH1 mutations. Amplified tumors occurred in older patients and behaved more aggressively, in contrast to lesions with a fusion gene originating in younger patients and showing a favorable outcome.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856473","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":"Pediatric Embryonal Rhabdomyosarcoma: An Integrated Study of Clinicopathological Features, Pan-cancer Targeted Next-generation Sequencing, and Chromosomal Microarray Analysis from a Single Institution.","authors":"Bo Yang, Ryan J Schmidt, Gordana Raca, Nick Shillingford, Shengmei Zhou, David M Parham, Bruce Pawel, Larry L Wang","doi":"10.1007/s00428-025-04220-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04220-4","url":null,"abstract":"<p><p>Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents, and embryonal rhabdomyosarcoma (ERMS) is the most common subtype. Previous reports have identified a wide range of genetic aberrations in ERMS. However, the clinicopathological significance of these genetic aberrations is not clear, and further integrated research is needed. To analyze correlations among clinicopathological features, molecular genetic aberrations, and prognosis, we collected 15 cases of pediatric ERMS, including complete data derived from clinicopathological features, pan-cancer targeted next-generation sequencing/OncoKids® panel, and chromosomal microarray. Patient ages ranged from 1 to 15 years (median, 6 years). Eight patients were boys, and 7 were girls. Clinical follow-up information was available for all 15 patients (follow-up duration range, 13-72 months; median, 41 months). Twelve (80.0%) patients were alive without evidence of recurrent or metastatic disease. Two (13.3%) patients were alive with evidence of recurrent or metastatic disease, and one patient (case 9) died with synchronous lung, iliac and sacral bone metastases, 15 months after treatment. We found recurrent mutations of NRAS, FGFR4, and CTNNB1 genes in 3 cases, and mutations of HRAS, MAP2K1, PPM1D, KRAS, PIK3CA, and TP53 genes in 1 case each. Case 1 had heterologous cartilaginous differentiation with germline mutation in CBL but no mutation in DICER1. Case 9 simultaneously showed homozygous loss of CDKN2A/B and TP53 with diffuse anaplastic tumor cells. Nine cases (9/14) exhibited gains of whole chromosome 2. Four cases (4/14) revealed loss of whole chromosome X. Three cases (3/14) contained loss of heterozygosity (LOH) for chromosome 4p16.3q35.2 (2 copies). Our results demonstrate new mutations in MAP2K1 and PPM1D, further expanding the mutation spectrum of ERMS. A germline mutation in CBL may be related to cartilage differentiation in ERMS. Gain of whole chromosome 2 is a frequent copy number alteration (64.3%) in pediatric ERMS. The concurrent homozygous loss of CDKN2A/B and TP53 in ERMS may be associated with diffuse anaplasia and portend a more adverse prognosis.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856474","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":"Diagnostic challenges of faded hematoxylin and eosin slides: limitations of re-staining and re-sectioning and possible reason to go digital.","authors":"Takuma Odate, Kris Lami, Naoko Tsuyama, Ichiro Mori, Yuka Kiriyama, Norihiro Teramoto, Yoko Masuzawa, Odsuren Sukhbaatar, Kenta Masui, Han-Seung Yoon, Junya Fukuoka","doi":"10.1007/s00428-025-04209-z","DOIUrl":"https://doi.org/10.1007/s00428-025-04209-z","url":null,"abstract":"<p><strong>Background: </strong>Archiving hematoxylin and eosin (H&E)-stained slides on glass slides is problematic because the slides fade over time. This study evaluated the diagnostic accuracy of faded slides and their restoration methods to assess the impact and limitations on diagnoses.</p><p><strong>Methods: </strong>The study was conducted in two parts. In the first study, gastric and lung biopsy cases diagnosed between 2011 and 2012 were analyzed. Diagnostic accuracy of the faded slides was compared to the original diagnoses. In the second study, gastric biopsy cases diagnosed in 2011 and 2015 were used to obtain faded slides, create re-stained slides, and re-sectioned slides from the same cases. Diagnostic accuracy was assessed using whole slide images (WSI) and compared to the original diagnoses to evaluate the effectiveness and limitations of the restoration methods.</p><p><strong>Results: </strong>In the first study, diagnostic accuracy for faded slides were 77.5% for gastric biopsies and 73.3% for lung biopsies, both showing significant decreases compared to the original diagnoses. The decrease in accuracy was particularly evident in the diagnosis of malignant lesions. In the second study, diagnostic accuracy was 92.4% for faded slides, slightly improving to 93.9% for re-stained slides. However, challenges such as staining inconsistencies and tissue damage were observed with re-staining. Re-sectioned slides demonstrated higher diagnostic accuracy at 95.5%, but achieving perfect reproducibility was not feasible.</p><p><strong>Conclusion: </strong>Diagnostic accuracy significantly decreased when using faded slides. Our findings suggest the utility of digital archiving rather than glass slide archiving.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856472","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":"Characterizing neurofibromin 1-altered breast cancer through genomic, functional, and clinical analyses.","authors":"Xueyan Mao, Kang Ma, Yunjie Wang, Cheng Long, Xuejing Tan, Xi Chen, Bo Chen","doi":"10.1007/s00428-025-04218-y","DOIUrl":"https://doi.org/10.1007/s00428-025-04218-y","url":null,"abstract":"<p><p>Breast cancer is a leading cause of cancer-related morbidity and mortality among women worldwide, with increasing incidence in China. The neurofibromatosis type 1 (NF1) gene, a critical tumor suppressor regulating the Ras/MAPK pathway, has been implicated in aggressive breast cancer phenotypes, yet its somatic alterations in Asian populations remain poorly characterized. This study integrates genomic, transcriptomic, and clinicopathological data from a Chinese breast cancer cohort (GDPH, n = 680), The Cancer Genome Atlas (TCGA), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) consortium to elucidate the role of NF1 in breast cancer. We identified somatic NF1 alterations in 5.9% of the GDPH cohort, with truncating mutations (41.03%) and co-occurring TP53 (72.5%) and PIK3CA (55.0%) mutations being predominant. Comparative analysis revealed ethnic variations, with higher NF1 mutation frequencies in the GDPH cohort (5.00%) compared to TCGA (2.80%) and METABRIC (3.75%). NF1-altered tumors exhibited elevated tumor mutational burden (TMB) and distinct co-alterations in DNA repair and chromatin remodeling pathways. Survival analysis indicated worse outcomes in NF1-mutated METABRIC patients (HR = 0.747, p = 0.0165). Functional enrichment analysis linked NF1 deficiency to metabolic reprogramming, immune dysregulation, and T-cell dysfunction, supported by murine models showing resistance to anti-PD-1 therapy upon NF1 knockdown. Our findings highlight NF1 as a key modulator of breast cancer progression, immune evasion, and therapeutic response, with implications for precision oncology in diverse populations. This study comprehensively characterizes somatic NF1 alterations and identifies potential therapeutic vulnerabilities in NF1-deficient breast cancers.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849210","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":"Disease patterns and entities in adult liver consult cases highlight challenging areas in diagnostic hepatopathology practice.","authors":"Ioanna Maria Grypari, Iakovos Vlachos, Eleni Stoupi, Despoina Karandrea, Despoina Myoteri, Dina Tiniakos","doi":"10.1007/s00428-025-04215-1","DOIUrl":"https://doi.org/10.1007/s00428-025-04215-1","url":null,"abstract":"<p><p>Difficult liver pathology cases often require expert review for optimal patient care. We reviewed consult cases received in our reference centre aiming to highlight challenging areas in hepatopathology that may benefit from specialist consultation and focused educational activities. We included all primary liver consult cases received between 10/2016 and 12/2022. Data on the sender and aetiology for consultation were collected. Initial and consult reports were screened for adequacy of clinical information, stains performed, final diagnosis and disease grading/staging. We retrieved 219 liver consults, 187 submitted by hepatologists. For medical cases, most common initial diagnoses were non-specific changes, chronic hepatitis and cirrhosis without underlying aetiology. Most common consult diagnoses were vascular disease, primary biliary cholangitis and metabolic dysfunction-associated steatohepatitis (p < 0.001). Major change in initial diagnosis was noted in 72 (49%), minor change in 38 (25.9%) and no change in 23 (15.6%) cases. For focal liver lesions (n = 72), most common initial diagnoses were hepatocellular carcinoma (HCC), non-specific or metastatic. Most common consult diagnoses were HCC, cholangiocarcinoma or non-neoplastic liver (p = 0.033). Major change in initial diagnosis was noted in 30 (41.7%), minor change in 24 (33.3%) and no change in 15 (20.8%) cases. Study of liver consult patterns provides useful information on areas of hepatopathology posing diagnostic difficulty. Most challenging fields are vascular liver disease, interpretation of hepatitic pattern, primary cholangiopathy and classification and subtyping of hepatocellular tumours. These areas can be the subject for future medical educational activities in hepatopathology.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837932","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}