Virchows Archiv最新文献

{"title":"In this issue: exploring the boundaries between neoplastic and reactive lymphoproliferations.","authors":"Stefan Dirnhofer","doi":"10.1007/s00428-025-04206-2","DOIUrl":"https://doi.org/10.1007/s00428-025-04206-2","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822732","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":"Proportion of histologic component predicts lymph node metastasis risk in undifferentiated-type mucosal and submucosal gastric cancers.","authors":"Yoonjin Kwak, In Hye Song, Sangjeong Ahn, An Na Seo, Joon Mee Kim, Hyunki Kim, Hee Kyung Kim, Hee Sung Kim, Ji Hae Nahm, Ok Ran Shin, Sung Hak Lee, Hye Seung Lee, Hee Kyung Chang, Mee-Yon Cho, Hye Seung Han, Han Ik Bae, Jin Hee Sohn, Su-Jin Shin, Hyeon Jeong Oh, Jie-Hyun Kim, Keun Won Ryu, Young-Il Kim, Il Ju Choi, Boram Park, Do Youn Park, Myeong-Cherl Kook","doi":"10.1007/s00428-025-04201-7","DOIUrl":"https://doi.org/10.1007/s00428-025-04201-7","url":null,"abstract":"<p><p>Undifferentiated-type (UD-type) gastric cancer is associated with a high frequency of lymph node metastasis (LNM); however, recent reports indicate that LNM frequency varies according to specific histologic components. We conducted a multicenter study to define criteria for distinguishing low- and high-risk histology groups for LNM in UD-type gastric cancers. Histologic components were classified into four types: poorly cohesive signet ring cells (SRC), poorly cohesive non-signet ring cells (non-SRCs), poorly differentiated tubular (PD), and differentiated-type (D-type). Their proportions were measured semi-quantitatively. The proportion of extracellular mucin (EMC) and the predominant histologic components within EMC were also recorded. LNM risk was analyzed based on pathological findings. Overall, 2256 mucosal and 688 submucosal UD-type cancers were analyzed. A higher SRC amount was linked to lower LNM frequency. Non-SRCs showed no association with LNM. Increased PD and D-type were linked to more frequent LNM; however, PD-predominant cases (PD ≥ 90%) showed paradoxically lower LNM frequency. SRC proportion > 10% was essential for low LNM probability. PD or D-type proportion > 10% is important for high LNM probability. Most compositions with low LNM probability (< 5%) showed a SRC majority (SRC > 50%) and ≤ 10% of PD or D-type. Pure poorly cohesive carcinomas with > 10% SRC and no PD or D-type were classified as low-risk histology (LNM probability 2.6%-3.4%). We developed a risk assessment method for tumor histology based on the composition of all histologic components and defined criteria to identify low-risk histology for LNM among UD-type cancers.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812476","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":"Localization of parvovirus B19 in the renal allografts of healthy donors.","authors":"Dan Inoue, Takashi Oda, Tadaki Suzuki, Michiyo Kataoka, Sachiko Iwama, Yuko Dohi, Osamu Konno, Muneharu Yamada, Hironori Takeuchi, Hitoshi Iwamoto","doi":"10.1007/s00428-025-04214-2","DOIUrl":"https://doi.org/10.1007/s00428-025-04214-2","url":null,"abstract":"<p><p>Parvovirus B19 (PVB19) is usually not a subject of pre-transplant evaluation. Little is known regarding the localization of PVB19 in normal kidneys, particularly in relation to its cellular receptor, the P antigen. Tissue specimens obtained from 0-h renal allograft biopsies were investigated for the presence of PVB19 DNA by polymerase chain reaction (PCR) and the relative localization of P antigen and PVB19-related protein by double immunofluorescence staining. Double staining of in situ hybridization for PVB19 DNA and immunofluorescence staining for PVB19-related proteins was also performed. The presence of the virus was further evaluated by electron microscopy in selected biopsy specimens. PCR analysis detected PVB19 DNA in 39 out of 112 (35%) tissue samples. Immunohistochemical analysis of these 39 PVB19 DNA-positive samples revealed that 28 (72%) exhibited positive staining for PVB19-related proteins within some tubular epithelial cells. Electron microscopy demonstrated regular polygonal virus-like particles within tubular epithelial cells. Furthermore, most PVB19-positive tubular epithelial cells expressed the P antigen on their apical surfaces. PVB19 DNA and PVB19-related proteins co-localized in some tubular epithelial cells. Thus, approximately 1/3 of healthy adult kidneys contain PVB19, which is localized mainly in distal tubules expressing P antigens on their apical surface. The concurrent detection of PVB19 DNA and proteins, along with the visualization of virus-like particles by electron microscopy, suggests that PVB19 could live with protein-producing capacity. Given the relatively high frequency of detection, the possibility of PVB19 infection should be carefully considered in the context of kidney transplantation.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812475","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":"Small bowel metastatic SWI/SNF-deficient undifferentiated carcinoma may be predictive of lung primary-a rare presentation with novel SMARCA2 mutation findings in a study of three cases.","authors":"Chi Sing Ng, Jilong Qin, Chi Hang Kan, Kristopher T Cheng","doi":"10.1007/s00428-025-04208-0","DOIUrl":"https://doi.org/10.1007/s00428-025-04208-0","url":null,"abstract":"<p><p>The gastrointestinal tract (GIT) is an uncommon destination for metastasis, and the small bowel (SB) is among the more common sites. The SB metastatic carcinoma is often undifferentiated, usually with variable components of rhabdoid tumor cells. Primary lung non-small cell carcinoma (NSCLC) is a commonly implicated source and is often undifferentiated, though other differentiated histotypes may be responsible. Both primary lung and metastatic GIT poorly or undifferentiated carcinomas often show SWI/SNF deficiency especially of SMARCA4 and SMARCA2, singly or co-deficient. We report three such rare cases, in complementation of an earlier larger series, of SB metastatic SMARCA4/A2-deficient undifferentiated carcinoma from lung primary, with full immunophenotypic and genetic workup. We made the novel discovery of the same SMARCA2 mutations in the lung tumors of two of our cases which could have contributed to SMARCA2 deficiency. This contrasts with the conventional belief that SMARCA2 deficiency is mostly related to epigenetic events. It is important to differentiate these metastatic tumors from primary GIT SWI/SNF-deficient undifferentiated carcinomas and possible secondary SB undifferentiated carcinoma from female genital tract (FGT) primary, which are often morphologically difficult to distinguish. The primary GI and secondary FGT carcinomas usually show broader deficiency of SWI/SNF subunits, microsatellite instability-high or mismatch repair protein deficiency. Correlation with clinical and imaging findings is important in making the distinction. As primary NSCLC is a commonly implicated tumor causing SB metastatic undifferentiated carcinoma, discovery of the latter should instigate investigation for possible lung primary which may be helpful for timely introduction of possibly effective therapies such as cisplatin chemotherapy, immunotherapy, and epigenetics or synthetic lethality-based treatment.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795652","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":"Correction to: ZC3H7A/B:BCOR fusion fbromyxoid sarcoma of soft tissue: an emerging aggressive sarcoma overlapping with malignant ossifying fbromyxoid tumors.","authors":"Bharat Rekhi, Altan Kavuncuoglu, Nasir Ud Din, Sameer Rastogi, Ali Abdelsatir, Robert Stoehr, Abbas Agaimy, Kemal Kosemehmetoglu","doi":"10.1007/s00428-025-04217-z","DOIUrl":"https://doi.org/10.1007/s00428-025-04217-z","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790159","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":"Diagnosing the silent: the molecular landscape of non-functional parathyroid carcinoma.","authors":"Maaia Margo Jentus, Willem E Corver, Marieke Snel, Femke M van Haalen, Tom van Wezel, Dina Ruano, Ellen Kapiteijn, Stijn Crobach, Natasha M Appelman-Dijkstra, Abbey Schepers, Hans Morreau","doi":"10.1007/s00428-025-04193-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04193-4","url":null,"abstract":"<p><p>Non-functional parathyroid carcinoma (NFPC) is an exceptionally rare malignancy, with approximately 50 cases reported since the parathyroid glands were first described in the late nineteenth century. Unlike functional parathyroid carcinomas (PC), which typically present with severe hyperparathyroidism (HPT) and are monitored via serum calcium and parathyroid hormone (PTH) levels, NFPC lacks biochemical markers and is monitored solely through imaging. In this study, we present two new cases of primary NFPC and provide a comprehensive review of the literature, including a detailed analysis of immunohistochemical and molecular testing. We also explore potential mechanisms underlying the non-functional state in PC. In one case, the tumor lacked PTH expression by immunohistochemistry, yet low levels of PTH mRNA expression were consistently detected. Differential diagnoses-including medullary and non-medullary thyroid carcinoma, paraganglioma, and other head and neck tumors-were excluded. The second case demonstrated patchy residual PTH immunostaining. Both tumors exhibited extensive whole chromosome losses resulting in a near-haploid genome, with (NFPC 2) or without (NFPC 1) subsequent endoreduplication/genome doubling. The mutational landscape differed between the two, with neither showing CDC73 mutations or loss of parafibromin expression. Diagnosing primary non-functional parathyroid carcinoma can be especially challenging in cases with negative PTH immunohistochemistry.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785402","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":"HER2/CEP17 ratio predicts residual cancer burden after neoadjuvant dual HER2 blockade: real-world data in patients with primary HER2-amplified breast cancer.","authors":"Myriam Stolz, Alex Farr, Kristina A Tendl-Schulz, Florian Frommlet, Helga Reckendorfer, Oskar Koperek, Barbara Neudert, Maximilian Marhold, Ulrike Heber, Ruth Exner, Christian F Singer, Rupert Bartsch, Zsuzsanna Bago-Horvath","doi":"10.1007/s00428-025-04203-5","DOIUrl":"https://doi.org/10.1007/s00428-025-04203-5","url":null,"abstract":"<p><p>Novel human epidermal growth factor receptor 2 (HER2)-directed therapies have significantly improved outcomes for patients with HER2-positive early-stage breast cancer. Our study assessed the impact of HER2/chromosome enumeration probe 17 (CEP17) ratio on residual cancer burden (RCB) and long-term prognosis following neoadjuvant chemotherapy with dual HER2-targeted therapy using trastuzumab and pertuzumab to identify candidates for chemotherapy de-escalation. Our study included 169 patients with primary invasive HER2-positive breast cancer who received neoadjuvant chemotherapy with trastuzumab and pertuzumab at the Medical University of Vienna from 2014 to 2020. HER2 (ERBB2) gene copy number and HER2/CEP17 ratio were assessed by in situ hybridization. RCB and pathologic complete remission (pCR) served as primary and secondary endpoints, respectively. Univariate and multivariate logistic regression models were applied to analyze associations between outcomes and predictor variables, focusing on the predictive role of HER2/CEP17 ratio, with cutoff values estimated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. HER2/CEP17 ratio was significantly associated with response to dual-targeted neoadjuvant chemotherapy in primary HER2-positive breast cancer. Optimal HER2/CEP17 cutoff for predicting RCB 0/I was identified at 5.19. HER2/CEP17 ratio was also significantly associated with PFS as a continuous predictor. Multivariate analysis showed that hormone receptor status and the presence of an in situ tumor component significantly influenced therapy response. HER2/CEP17 ratio predicts therapy response and therefore might aid patient stratification for therapy de-escalation with respect to dual neoadjuvant HER2 blockade. Further investigations are warranted to confirm its relevance with other HER2-targeted agents.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785403","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":"Report of a national external quality assessment program for HER2-low expression in breast cancer-options for increased accuracy with standardized methodology.","authors":"Carsten Denkert, Florian Sperling, Anika Pehl, Ramona Erber, Paul Jank, Hans-Ulrich Schildhaus, Korinna Jöhrens, Maja Grassow-Narlik, Celina Lindner, Almuth Forberger, Reinhard von Wasielewski, Annette Lebeau","doi":"10.1007/s00428-025-04139-w","DOIUrl":"https://doi.org/10.1007/s00428-025-04139-w","url":null,"abstract":"<p><p>HER2-low breast cancer is an important new diagnostic tumor category with promising therapeutic options. The aim of this study was to evaluate the quality of HER2-low determination in a national prospective external quality assessment (EQA) and to identify pitfalls and options for improvement. Slides were distributed to 66 pathology institutions for diagnostic assessment according to pre-defined HER2-low categories. After local staining and evaluation, slides were collected for central re-evaluation for quality parameters. Endpoints included the percentage of correct HER2-assessments and subgroup analyses for selected technical parameters. Within this prospective proficiency test, a total of 659 individual HER2 evaluations were performed by 66 participating institutions with 86% correct results. Of the incorrect results, 82% (73 of 89) reported a HER2 category that was too high, and only 18% reported a category that was too low. A successful participation was achieved by 71% of 66 pathology institutions. In central re-evaluation, technical limitations were identified as the most important parameters for suboptimal results. In defined institutional subgroups with optimal technical parameters (antibodies, automation platforms and detection systems) a success rate of up to 86-91% was achieved. In this prospective EQA assessment, the concordance rate of pathology institutions is now much higher compared to previous retrospective studies. However, the quality assurance results are still lower compared to classical HER2 proficiency tests focusing on HER2 3 + tumors, and further optimization is necessary. The results will contribute to further improve the reliability of HER2 testing, which could also be applied to HER2-ultralow in the future.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785414","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":"Characterization of autopsy findings including multivisceral glomeruloid vascular bodies in hereditary thrombotic thrombocytopenic purpura with two new variants in ADAMTS13 gene.","authors":"Roberta Maragliano, Adélie Perrot, Philippe Loget, Claire Combescure, Nicolas Belhomme, Marie Faoucher, Christele Dubourg, Mélanie Fradin, Sophie Collardeau-Frachon","doi":"10.1007/s00428-025-04200-8","DOIUrl":"https://doi.org/10.1007/s00428-025-04200-8","url":null,"abstract":"<p><p>Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare genetic disorder caused by a severe deficiency in ADAMTS13 enzyme activity, leading to potentially fatal perinatal outcomes and requiring urgent management. While the clinical and biological aspects of the disease are well-documented, pathological findings are less commonly described. We report two cases of cTTP within the same family, both resulting in perinatal death. Autopsies of the neonate and the subsequent fetal recurrence revealed a distinctive and prominent multivisceral glomeruloid vascular proliferation, an unreported feature in this syndrome. However, the presence of multiple thrombi along with ischemic and hemorrhagic changes suggested an underlying thrombotic microangiopathy.Whole genome sequencing confirmed cTTP, identifying two novel pathogenic variants in the ADAMTS13 gene. Beyond expanding the phenotypic and genotypic spectrum of this disorder, the unusual vascular proliferation contributes to a deeper understanding of the underlying physiopathological mechanisms.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785400","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 between a Luminex-based multiplex kit with a sequence-specific oligonucleotide probe and next-generation sequencing for the detection of POLE oncogenic mutations in endometrial cancer.","authors":"Mayumi Kobayashi Kato, Takayuki Kawai, Hideki Okada, Takuya Kondo, Tetsuro Shiraishi, Maiko Yamaguchi, Daiki Higuchi, Masaaki Komatsu, Ryuji Hamamoto, Koji Matumoto, Yasuhisa Terao, Tomoyasu Kato, Takashi Kohno, Mitsuya Ishikawa, Kouya Shiraishi, Hiroshi Yoshida","doi":"10.1007/s00428-025-04204-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04204-4","url":null,"abstract":"<p><p>In endometrial cancer, detection of oncogenic mutations in the polymerase epsilon (POLE) gene is crucial for accurate staging according to the 2023 International Federation of Gynecology and Obstetrics classification and for minimizing overtreatment. However, POLE sequencing is expensive, time-consuming, and often inaccessible in settings without specialized equipment. We developed a novel multiplex kit for the detection of POLE mutations using a Luminex (xMAP) assay in a single reaction. The aim of this study was to evaluate the accuracy of the multiplex kit for routine clinical samples and compare it with that of conventional next-generation sequencing (NGS). Hysterectomy specimens and endometrial biopsies were collected at the National Cancer Center Hospital between 1999 and 2023. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissues. Both the Luminex (xMAP)-based multiplex kit and NGS targeting all POLE exons were used. Concordance was assessed using Cohen's kappa. Of the 502 samples, 432 were hysterectomy specimens and 70 were biopsies. In the surgical samples, both the Luminex (xMAP)-based kit and NGS detected 52 POLE mutations (12.0%) with perfect concordance (κ = 1.000). In the biopsies, 33 POLE mutations were identified using both methods, with complete concordance. Notably, the Luminex (xMAP)-based kit successfully analyzed all 28 samples that failed NGS quality control and detected four cases with POLE mutations. The Luminex (xMAP)-based kit demonstrates high concordance with NGS for the detection of POLE mutations. With further external validation, this kit could become a reliable and accessible alternative to NGS.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785401","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}