Virchows Archiv最新文献

{"title":"Epstein-Barr virus status drives morphological and molecular intra-tumour heterogeneity in gastric cancer: insights from a case report and literature review.","authors":"Irene Gullo, Maria Luísa Sacramento, Rui Morais, Yongsoo Kim, Paul P Eijk, Ana Mafalda Rocha, Diana Baptista, João Santos-Antunes, Bauke Ylstra, Fátima Carneiro","doi":"10.1007/s00428-025-04035-3","DOIUrl":"https://doi.org/10.1007/s00428-025-04035-3","url":null,"abstract":"<p><p>This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion. Immunohistochemical and molecular studies confirmed that, despite the differing morphologies and immunophenotypes, both components were clonally related, with the EBV-negative area showing more complex DNA aberrations, reminiscent of chromosomally instable (CIN) lesions. This case describes clonally related EBV-positive and -negative components within a single gastric cancer, contributing to a better understanding of EBV role in tumour heterogeneity and progression and highlights the impact of EBV loss on tumour behaviour.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053599","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":"MAPK1IP1L::TFE3-rearranged renal cell carcinoma: a novel fusion adding to the differential diagnosis of oncocytic renal neoplasms.","authors":"Anne V Cheng, Douglas J Wu, Lisa Aviva Friedman, Emily Chan, Sean R Williamson, Laurence A Galea, Ankur R Sangoi","doi":"10.1007/s00428-025-04031-7","DOIUrl":"https://doi.org/10.1007/s00428-025-04031-7","url":null,"abstract":"<p><p>Beyond the more common TFE3 fusion partners PRCC, ASPSCR1, and SFPQ, additional less common fusion partners of TFE3-rearranged renal cell carcinoma (RCC) have been described. Herein, we present an example of TFE3-rearranged renal cell carcinoma harboring fusion partner MAPK1IP1L, a rare rearrangement with only one other reported tumor found in the literature. The currently reported TFE3-rearranged RCC demonstrates unique histological features compared to the previously reported tumor including dense eosinophilic cytoplasm and nuclear pseudoinclusions (corroborated by electron microscopic evaluation), with features not typically seen in other TFE3-rearranged RCCs. Recognizing this novel fusion may be important in the identification, classification, and development of potential therapeutic agents of kidney tumors in the future.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042012","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":"Ötzi's perimortem skin changes.","authors":"Jochen Weber, Joachim Wahl, Marco Samadelli, Albert Zink","doi":"10.1007/s00428-025-04036-2","DOIUrl":"https://doi.org/10.1007/s00428-025-04036-2","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042048","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":"Trichogerminoma with malignant transformation.","authors":"Thibault Kervarrec, Maxence Mancini, Anne Tallet, Samia Mourah, Maxime Battistella, Eric Frouin","doi":"10.1007/s00428-025-04032-6","DOIUrl":"https://doi.org/10.1007/s00428-025-04032-6","url":null,"abstract":"<p><p>Trichogerminoma (TG) is a rare adnexal tumor with hair follicle differentiation with less than 50 cases reported in the literature. In 2022, by investigating the genetic profile of 21 cases, our group identified recurrent rearrangements of the GRHL1/2/3 genes in this tumor entity, suggesting such alteration as the main oncogenic driver in TG. Up to now, only one TG case of malignant transformation has been reported. In the present letter, we report a second case of TG with malignant transformation and provide molecular characterization of this tumor.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034195","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":"Correlation between p53 immunoexpression and TP53 mutation status in extrapulmonary small cell neuroendocrine carcinomas and its association with patient survival.","authors":"Klára Pavlíčková, Jan Hojný, Petr Waldauf, Pavel Dundr, Nikola Hájková, Marián Švajdler, Pavel Fabian, Iva Staniczková Zambo, Miroslava Flídrová, Jan Laco, Helena Hornychová, Patricie Delongová, Jozef Škarda, Jan Hrudka, Radoslav Matěj","doi":"10.1007/s00428-025-04024-6","DOIUrl":"https://doi.org/10.1007/s00428-025-04024-6","url":null,"abstract":"<p><p>Extrapulmonary small cell neuroendocrine carcinoma (EP-SCNC) is a rare malignancy with a poor prognosis. Despite its morphological similarity to lung small cell carcinomas, its oncogenesis remains uncertain. One hundred and seventy-one EP-SCNC were enrolled in a multicenter study, and all tissue samples underwent an immunohistochemical p53 analysis. One hundred twenty-five samples were molecularly analyzed using next-generation sequencing (NGS), comprising DNA and RNA analysis. p53 normal/wild type expression was detected in 68 cases (39.8%), whereas aberrant expression was detected in 103 cases (60.2%). Molecular TP53 alteration was detected in 92 out of 125 tumors (73.6%). The TP53 mutation was shown to be prognostic and associated with shorter overall survival (p = 0.041). The multivariate analysis of p53 and TP53 mutational status found that it impacted overall survival relative to distinct sites of tumor locations (p = 0.004 and p = 0.001, respectively). Age did not influenced survival in the multivariate analysis of p53 and TP53 (p = 0.002; p < 0.001 resp.). Among tumors with paired immunohistochemical and molecular results, 108 exhibited concordance between the immunohistochemical and molecular analysis, whereas 17 were discordant. Accordingly, p53 aberrant expression was tightly associated with a TP53 mutation (p < 0.001). In discordant cases, molecular analysis revealed no alteration in three tumors with p53 overexpression. In contrast, in 14 tumors with wild-type p53 expression, TP53 genetic alteration was detected. Possible causes of discordance are discussed in this manuscript. Furthermore, the incidence of aberrant p53 expression / TP53 molecular alteration was noticeably lower in EP-SCNC than in small-cell lung carcinomas. Therefore, in EP-SCNC, other driver mutations should be sought since personalized therapy can improve patient prognosis.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024668","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":"Prognostic impact of fibrosclerotic changes in non-papillary, non-anaplastic, follicular cell-derived thyroid carcinomas.","authors":"Giulia Orlando, Giulia Capella, Giulia Vocino Trucco, Elena Vissio, Jasna Metovic, Francesca Maletta, Marco Volante, Mauro Papotti","doi":"10.1007/s00428-025-04028-2","DOIUrl":"https://doi.org/10.1007/s00428-025-04028-2","url":null,"abstract":"<p><p>In non-papillary follicular cell-derived thyroid carcinomas, prognostic factors are scarce. Intratumoral fibrosis was identified as an adverse factor in papillary and medullary carcinomas, but it has not been investigated in other subtypes. We aimed at exploring the presence of intratumoral fibrosclerosis in a cohort of 132 non-papillary follicular cell-derived thyroid carcinomas (53 follicular and 31 oncocytic carcinomas, including 10 high grade differentiated thyroid carcinomas and 48 poorly differentiated carcinomas) and correlating its presence and extent with clinical and pathological features and survival. For each case, all available hematoxylin and eosin slides were reviewed, and the presence of fibrosclerosis was assessed as the percentage of tumor area and semi-quantitatively scored as absent, mild (≤ 10%) or extensive (> 10%). In addition, digital image analysis was applied in 65 cases. Scoring of intratumoral fibrosis showed a strong agreement between two observers and between observers and digital image quantification. The presence and extent of intratumoral fibrosis were significantly associated with poorly differentiated carcinoma histology, large tumor size, extent of vascular invasion, presence of necrosis, high mitotic index, positive nodal status, and aggressive clinical outcome, and with a shorter disease-free and disease-specific survival, the former also in follicular and oncocytic carcinomas analyzed separately. These data support the potential use of fibrosis in the clinical practice since it is both easily assessable and significantly associated with the presence of parameters of aggressiveness. In addition, fibrosis is correlated with decreased survival rate independently from the tumor histotypes, suggesting its potential role as novel prognostic factor in non-papillary follicular cell-derived thyroid carcinomas.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029385","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":"ACTB::ZMIZ2-rearranged adnexal carcinoma: a second case.","authors":"Carina Dehner, Daniel Pissaloux, Brice Thamphya, Franck Tirode, Andreas Von Deimling, Ruifeng R Guo, Carilyn Wieland, Arnaud de la Fouchardière, Thibault Kervarrec","doi":"10.1007/s00428-025-04030-8","DOIUrl":"https://doi.org/10.1007/s00428-025-04030-8","url":null,"abstract":"<p><p>A case of cutaneous adnexal neoplasm with unusual squamoid morphology and harboring an in frame ACTB::ZMIZ2 fusion transcript was recently described. Herein, we report a second case of adnexal carcinoma harboring similar morphology and an identical in frame ACTB::ZMIZ2 fusion transcript. This 2.2-cm mass was removed from the axilla of a 17-year-old woman. Microscopic examination revealed a large nodular and infiltrative tumor invading the dermis composed of sheets and nests frequently centered by large areas of keratinization. Molecular investigation revealed an in frame ACTB::ZMIZ2 fusion transcript. Clustering analysis revealed close proximity of this case with the ACTB::ZMIZ2-fused adnexal tumor previously reported. Herein, we report a second case of adnexal tumor with ACTB::ZMIZ2 fusion arising in a young adult suggesting that ACTB::ZMIZ2 fusion might be a defining genetic event, specific of a rare and previously undescribed adnexal tumor entity.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024749","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":"Immunohistochemical analysis of 147 cases of low-grade endometrial stromal sarcoma: refining the immunohistochemical profile of LG-ESS on a large, molecularly confirmed series.","authors":"Miroslava Flídrová, Pavel Dundr, Romana Vránková, Kristýna Němejcová, David Cibula, Renata Poncová, Květoslava Michalová, Jiří Bouda, Jan Laco, Munachiso Ndukwe, Janusz Ryś, Mariusz Książek, Alberto Berjon, Ignacio Zapardiel, Ivan Franin, Antonela Njavro, Jitka Hausnerová, Petra Bretová, Vladimír Židlík, Jaroslav Klát, Zoard Tibor Krasznai, Robert Poka, Nataliya Volodko, Iryna Yezhova, Radovan Pilka, Radim Marek, Georgina Kolnikova, Milan Krkoška, Michael Halaška, Jana Drozenová, Dagmar Dolinská, Vladimír Kalist, Marcin Bobiński, Marta Ostrowska-Leśko, Magdalena Bizoń, Włodzimierz Sawicki, Maciej Stukan, Karolina Grabowska, Marcin Jędryka, Tymoteusz Poprawski, Simona Stolnicu, Mihai Emil Căpîlna, Zuzana Špůrková, Michal Zikán, Francesca Ciccarone, Giovanni Scambia, Archil Sharashenidze, Miranda Gudadze, Tetiana Piatnytska, Ihor Varchak, Michaela Kendall Bártů","doi":"10.1007/s00428-025-04026-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04026-4","url":null,"abstract":"<p><p>Low-grade endometrial stromal sarcoma (LG-ESS) can present diagnostic challenges, due to its overlapping morphological features with other uterine mesenchymal tumors. Misdiagnosis rates remain significant, and immunohistochemical data for LG-ESS are limited to small series and inconsistent antibody panels. This study aimed to refine the IHC profile of LG-ESS by analyzing a large, molecularly confirmed series of 147 cases using a panel of 24 antibodies, including newer markers like transgelin and smoothelin. CD10 and IFITM1, key endometrial stromal markers, were expressed in 86% (92% of those extensively) and 69% (60% of those extensively) of cases, with fusion-positive tumors showing significantly higher expression. Smooth muscle markers (α-SMA, desmin, h-caldesmon, calponin, transgelin) were variably expressed, predominantly in focal or low-intensity patterns, with α-SMA reaching the highest frequency of expression (44%). However, the intensity of smooth muscle marker expression was usually very low. Smoothelin was rarely expressed. Hormone receptors were frequently positive, with PR showing a higher frequency (92% vs. 83%) and intensity than ER. Markers like S-100, HMB45, and CD117 were largely negative; all tumors were p53 wild-type, with preserved SMARCB1/SMARCA4 expression and ALK and ROS1 negativity. This work represents the largest molecularly validated IHC study on LG-ESS, providing a robust diagnostic profile for routine pathology. By addressing key diagnostic limitations and examining newer markers, our study supports a more standardized approach to diagnosing LG-ESS and underscores the value of immunohistochemical panels, particularly in fusion-negative tumors where diagnosis relies on morphological and immunohistochemical interpretation. These findings contribute critical data for improving diagnostic accuracy.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012588","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":"Misdiagnosing Bayesian statistics.","authors":"Vincenzo Guastafierro, Devin Nicole Corbitt, Alessandra Bressan, Bethania Fernandes, Ömer Mintemur, Francesca Magnoli, Susanna Ronchi, Stefano La Rosa, Silvia Uccella, Salvatore Lorenzo Renne","doi":"10.1007/s00428-025-04027-3","DOIUrl":"https://doi.org/10.1007/s00428-025-04027-3","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012602","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":"Atypical and worrisome histological features in pleomorphic adenoma: challenging and potentially significant diagnostic pitfall.","authors":"Reydson Alcides de Lima-Souza, Klára Bělohlávková, Michal Michal, Albina Altemani, Fernanda Viviane Mariano, Alena Skálová","doi":"10.1007/s00428-024-04015-z","DOIUrl":"https://doi.org/10.1007/s00428-024-04015-z","url":null,"abstract":"<p><p>Pleomorphic adenoma (PA), the most prevalent salivary gland tumor, exhibits a diverse histological spectrum characterized by epithelial, myoepithelial, and mesenchymal patterns, and secretory products. However, a subset of PAs presents microscopic features suggestive of malignancy, leading to challenging and potentially significant diagnostic pitfalls. A comprehensive retrospective analysis was conducted on the Salivary Gland Tumor Registry, compiled by the authors. A total of 104 cases diagnosed between 1960 and 2023 were retrieved. Clinical findings, pathological features, and molecular genetic results were analyzed. In the study of 104 PA cases, 23 (22.1%) presented features suggestive of pseudoinvasion, with satellite nodules being the most common (43.5%) along with capsular penetration, irregular growth, pseudopodia, lipomatous changes, and vascular permeation. Features of pseudomalignant cytomorphology were found in 97 cases (93.3%), characterized by increased cellularity, cellular atypia, heightened proliferative activity, oncocytic metaplasia, and necrosis. Additionally, 30 cases (28.8%) displayed features resembling other defined malignant salivary gland tumors, particularly myoepithelial carcinoma, adenoid cystic carcinoma, and polymorphous adenocarcinoma. Despite PA's generally straightforward diagnosis, cases with these features may be mistakenly interpreted as malignant tumors. The shared morphocytological features underscore the complexity of an accurate diagnosis, emphasizing the need for meticulous examination and a comprehensive assessment, incorporating morphological, molecular, and immunohistochemical analyses to differentiate between benign and malignant salivary gland tumors, in selected cases.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012585","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}