Virchows Archiv最新文献

{"title":"GLI1::FOXO4-rearranged kidney tumors: a potentially distinct renal subtype within the spectrum of GLI1-altered tumors?","authors":"Tamás Pancsa, Natálie Klubíčková, Nooshin K Dashti, Isidro Machado, Antonio Llombart-Bosch, Konstantinos Linos, Elaheh Mosaieby, Tomáš Vaněček, Lenka Maňáková, Michal Michal, Michael Michal","doi":"10.1007/s00428-024-03998-z","DOIUrl":"https://doi.org/10.1007/s00428-024-03998-z","url":null,"abstract":"<p><p>Pathogenic alterations, namely, fusions and amplifications, of the GLI1 gene have been identified in various mesenchymal tumors, including pericytoma with t(7;12), plexiform fibromyxoma, gastroblastoma, and other malignant mesenchymal neoplasms arising in the soft tissues, as well as in various visceral organs. However, only three cases of GLI1-rearranged renal tumors have been reported to date, comprising two low-grade spindle cell tumors with GLI1::FOXO4 fusion along with one GLI1-rearranged case with an unknown fusion partner. In this study, we analyzed three cases with GLI1::FOXO4 fusion and overlapping morphology. One of the cases was reported previously, but an extended clinical and immunohistochemical information is provided. The studied cases occurred in 2 female and 1 male patients aged 35, 55, and 62 years (mean 51 years). All three tumors affected the renal parenchyma and grew as unencapsulated but well-circumscribed solid masses containing occasional entrapped and dilated renal tubules. The tumor cells were organized in cords, nests, or fascicles, had a round to spindled shape, and exhibited only mild nuclear atypia and minimal mitotic activity. They had a sparse eosinophilic to clear cytoplasm and were embedded in myxocollagenous stroma. Immunohistochemically, all cases expressed GLI1 (albeit with variable intensity) and harbored GLI1::FOXO4 fusion. All three patients were treated solely by complete surgical excision. Case 1 was alive with unknown disease status, case 2 was alive without evidence of disease, and case 3 died of unrelated causes. Our study doubles the number of reported cases with GLI1::FOXO4 fusion. The so far absolute predilection of this fusion for renal tumors, coupled with the absence of reports of other GLI1 fusions in tumors of the kidney, might indicate the potential existence of a distinct renal subtype with morphological features similar to other GLI1-altered tumors. All four reported cases had an uneventful follow-up which, together with their low-grade morphological features, suggests that these tumors might have a favorable prognosis.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839791","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":"Next-generation sequencing in the molecular classification of endometrial carcinomas: Experience with 270 cases suggesting a potentially more aggressive clinical behavior of multiple classifier endometrial carcinomas.","authors":"Kvetoslava Michalova, Andrea Strakova-Peterikova, Ondrej Ondic, Tomas Vanecek, Michael Michal, Nikola Hejhalova, Petr Holub, Petr Slavik, Adam Hluchy, Polina Gettse, Ondrej Daum, Marian Svajdler, Michal Michal, Jiri Presl","doi":"10.1007/s00428-024-03996-1","DOIUrl":"https://doi.org/10.1007/s00428-024-03996-1","url":null,"abstract":"<p><p>Molecular classification of endometrial carcinomas (EC) divides these neoplasms into four distinct subgroups based on their molecular background. Given its clinical significance, genetic examination is becoming integral to the diagnostic process. This study aims to share our experience with the molecular classification of EC using immunohistochemistry (IHC) and next-generation sequencing (NGS). We included all ECs diagnosed at two institutions from 2020 to the present. All cases were prospectively examined by IHC for MMR proteins and p53, followed by NGS using a customized panel covering 18 genes, based on which ECs were classified into four molecular subgroups: POLE mutated, hypermutated (MMR deficient), no specific molecular profile (NSMP), and TP53 mutated. The cohort comprised 270 molecularly classified ECs: 18 (6.6%) POLE mutated, 85 (31.5%) hypermutated, 137 (50.7%) NSMP, and 30 (11.1%) TP53 mutated. Twelve cases (4.4%) were classified as 'multiple classifier' EC. Notably, most of these cases with available follow-up (6/9) behaved aggressively. Within the POLEmut EC group, 3/4 cases had advanced tumors, including one patient who died of the disease. Similarly, in the MMRd/TP53mut group, 3/5 patients with available follow-up had metastatic disease, leading to death of the patient in 1 case. ECs of NSMP showed multiple genetic alterations, with the most common mutations being PTEN (44% within the group of NSMP), followed by PIK3CA (30%), ARID1A (21%), and KRAS (9%). Our findings suggest that combining immunohistochemistry with NGS offers a more reliable classification of ECs, including 'multiple classifier' cases, which, based on our observations, tend to exhibit aggressive behavior. Additionally, our data highlight the complex genetic background of NSMP ECs, which can facilitate further stratification of tumors within this group and potentially help select patients for dedicated clinical trials.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830066","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":"Aggressive renal cell carcinoma with somatic BRCA2 mutation-an emerging entity? A case report with literature review.","authors":"Jung Woo Kwon, Priscilla Louise Natcher, Tatjana Antic","doi":"10.1007/s00428-024-04008-y","DOIUrl":"https://doi.org/10.1007/s00428-024-04008-y","url":null,"abstract":"<p><p>Role of BRCA2 gene mutation in renal tumorigenesis remains largely unclear. There are only two case reports of renal cell carcinoma (RCC) with BRCA2 mutation, both of which showed a high-grade RCC with various architectural patterns including tubulopapillary and solid. The tumor cells were described as having eosinophilic cytoplasm and prominent nucleoli. The current study describes another case of high-grade RCC with somatic BRCA2 mutation with various architectural patterns and cells with eosinophilic cytoplasm and prominent nucleoli. Immunohistochemical staining showed co-expression of PAX8, CAIX, CD10, CK7, CK20, and P504S. This unusual co-expression of the commonly used IHC stains during the workup of RCC could serve as a potential diagnostic pitfall. Although very rare, it is important for pathologists to be aware of this form of RCC due to its aggressive clinical behavior, possibility of a germline mutation, and current therapeutic options for tumors with BRCA2 mutation.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824517","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: Localized cystic disease of the kidney: study of 14 cases and review of the literature.","authors":"Elie Tannous, Shreya Patel, Burak Muratoglu, Andrea R Lightle, Richard R Pacheco, Reza Hosseini, Robert R Pacheco, Peter Kim, Gamze T Cetinkaya, Dilek Ertoy Baydar, Kemal Kosemehmetoglu, Yasemin Yuyucu Karabulut, Sree Appu, Laurence A Galea, Adrien N Bernstein, Mahmut Akgul","doi":"10.1007/s00428-024-04004-2","DOIUrl":"10.1007/s00428-024-04004-2","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819289","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 relevance of p53 and Rb status in neuroendocrine tumors G3 from different organs: an immunohistochemical study of 465 high-grade neuroendocrine neoplasms.","authors":"Christina Kanaan, Mohamed-Amine Bani, Michel Ducreux, David Planchard, Livia Lamartina, Sophie Moog, Thomas Pudlarz, Eric Baudin, Julien Hadoux, Abir Al-Ghuzlan, Jean-Yves Scoazec","doi":"10.1007/s00428-024-04006-0","DOIUrl":"https://doi.org/10.1007/s00428-024-04006-0","url":null,"abstract":"<p><p>The double inactivation of TP53 and RB1 is considered typical of neuroendocrine carcinomas (NECs) but is assumed to be rare in high-grade neuroendocrine tumors (NETs). The immunohistochemical determination of the p53 and Rb status has therefore been proposed as a diagnostic tool. We studied this status in a large series of high-grade neuroendocrine neoplasms, from multiple origins, in order to (a) assess the patterns observed in the different histopathological categories, (b) compare them between the various anatomic sites, and (c) evaluate their possible diagnostic relevance. Four hundred sixty-five cases from 9 organ systems (142 high-grade NETs -NET-G3-, 162 large-cell NECs -LCNEC-, 144 small-cell NECs -SCNEC-) and 60 cases of NET G1/G2 were included. The expression of both proteins was normal in 96.7% of NET G1/G2, 76.7% of NET-G3, and 5.8% of all NECs. p53 expression was abnormal in 12.7% of NET-G3 and 91.5% of NECs. Rb expression was lost in 10.6% of NET-G3 and 68.3% of NECs. Rb loss was significantly less frequent in LCNEC than in SCNEC (57.3% versus 80.6%); abnormal p53 expression was comparable in the two categories. Patterns were comparable between primary sites, except for head and neck NECs. For diagnostic purposes, taking into account, Rb status improved, but only marginally, the performances of p53 status. In conclusion, our study underlines the molecular heterogeneity of NET-G3 and LCNEC, irrespectively of the primary, and provides further insight on the diagnostic relevance of p53/Rb immunodetection in high-grade neuroendocrine neoplasms.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819298","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":"ERBB2/ERBB3-mutated S100/SOX10-positive uterine sarcoma: something new.","authors":"Wangpan J Shi, Oluwole Fadare","doi":"10.1007/s00428-024-04003-3","DOIUrl":"https://doi.org/10.1007/s00428-024-04003-3","url":null,"abstract":"<p><p>A distinctive subset of uterine mesenchymal tumors display recurrent genetic fusions involving receptor tyrosine kinases, including NTRK, PDGFB, FGFR1, and RET, presumably leading to aberrant pathway activation. A pair of recent studies have highlighted the existence of a genetic fusion-negative uterine sarcoma that is characterized by activating mutations in ERBB2/ERBB3, CDKN2A deletion, inactivating ATRX mutation, and a S100 + /SOX10 + immunohistochemical profile. This report describes another case of this emerging entity that was diagnosed in a 57-year-old woman. The 8-cm tumor was centered in the uterine cervix and was comprised mostly of spindle cells configured in fascicles. The tumor was diffusely immunoreactive for SOX10 and S100, with more localized staining for CD68, CD56, MITF, and PRAME. HMB-45, ER, PR, HER2, Melan-A/MART1, STAT6, pan-TRK, ALK, CD34, desmin, CD10, myogenin, and pancytokeratins were all negative, and there was retained expression of H3K27me3. The following molecular alterations were found: ERBB2 p.Val777Leu, ATRX p.F2113Sfs*, CDKN2A deep deletion, NF1 p.W2317*, SMARCA4 p691Sfs*. The authors review the sparse literature on molecular-genetic aberrations involving the epidermal growth factor receptor family of receptor tyrosine kinases (ERBB1/EGFR, ERBB2, ERBB3, and ERBB4) in uterine mesenchymal tumors, a review that suggests that such tumors may be pathologically heterogeneous. The potential clinical significance of demonstrating a targetable ERBB2/ERBB3 tyrosine kinase mutation or other EGFR family aberrations, as well as its distinctive pathologic profile, supports the segregation of the tumor reported herein as a distinct and emerging entity.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814285","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":"Unveiling the risks of ChatGPT in diagnostic surgical pathology: correspondence.","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1007/s00428-024-04002-4","DOIUrl":"https://doi.org/10.1007/s00428-024-04002-4","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807164","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: Sclerosing epithelioid fibrosarcoma: a new mesenchymal non-meningothelial tumor involving the central nervous system?","authors":"Thibaut Wolf, Victor Sinnes, Damien Reita, Agathe Chammas, Justine Gantzer, Noelle Weingertner, Marie-Pierre Chenard, Julien Todeschi, Chinar Salmanli, Marlène Deschuyter, Georges Noel, Natacha Entz-Werle, Benoît Lhermitte","doi":"10.1007/s00428-024-03990-7","DOIUrl":"10.1007/s00428-024-03990-7","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802379","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":"Polarised light scanner for digital pathology.","authors":"Dunia Al Sheikhyaqoob, André Oliveira, Manuel Fella, Don Laferty, Gerald Niedobitek","doi":"10.1007/s00428-024-03967-6","DOIUrl":"https://doi.org/10.1007/s00428-024-03967-6","url":null,"abstract":"<p><p>Digital pathology is rapidly transforming diagnostic pathology by allowing remote work and integration of artificial intelligence solutions. Nevertheless, certain technical issues remain to be resolved. Notably, digital images captured by conventional scanners cannot be subjected to polarised light analysis [1]. We have therefore studied if images obtained using the Glissando POL Brightfield and Polarised Light Scanner are comparable to those obtained using conventional polarised light microscopy. Hematoxylin and eosin stained sections from 75 cases, including cases of amyloidosis, periprosthetic membranes, foreign body granulomas, gout, pseudogout, and breast tissues with calcium oxalate crystals were examined using both, a polarised light microscope and the Glissando POL scanner. Representative digital images were acquired for comparison. We here show that in all settings, the images obtained by conventional polarised light microscopy and using the Glissando POL scanner were comparable. We conclude that the Glissando POL scanner can be safely integrated into a digital pathology workflow.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795132","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":"High interobserver variability of PTEN immunohistochemistry defining PTEN status in low- to intermediate-risk prostate cancer: results of the first German ring trial.","authors":"Oliver Hommerding, Marit Bernhardt, Tobias Kreft, Anna Scherping, Mahmoud Abbas, Gustavo Baretton, Jan Hinrich Bräsen, Johannes Breyer, Christopher Darr, Franz Friedrich Dressler, Jörg Ellinger, Ramona Erber, Irene Esposito, Arndt Hartmann, Wolfgang Hartmann, Barbara Heitplatz, Hans Kreipe, Marcel Lafos, Johannes Linxweiler, Cristina Lopez-Cotarelo, Verena Sailer, Henning Reis, Matthias Saar, Hans-Ulrich Schildhaus, Katrin Schlack, Matthias Schmid, Maximilian Seidl, Axel Semjonow, Ulrich Sommer, Phillip Rolf Stahl, Verena Tischler, Florian Weber, Anna-Lena Wulf, Bernd Wullich, Glen Kristiansen","doi":"10.1007/s00428-024-03999-y","DOIUrl":"https://doi.org/10.1007/s00428-024-03999-y","url":null,"abstract":"<p><p>The prognostication of individual disease trajectory and selection of optimal therapy in patients with localized, low-grade prostate cancer often presents significant difficulty. The phosphatase and tensin homolog on chromosome 10 (PTEN) has emerged as a potential novel biomarker in this clinical context, based on its demonstrated prognostic significance in multiple retrospective studies. Incorporation into standard clinical practice necessitates exceptional diagnostic accuracy, and PTEN's binary readout-retention or loss-suggests its suitability as a biomarker. This multi-institutional ring trial aimed to validate the diagnostic precision of PTEN immunohistochemistry in localized, low- to intermediate-risk prostate cancer, across ten university pathology institutes in Germany. The trial incorporated 90 cases of patients diagnosed with acinar adenocarcinoma of the prostate of grade groups 1 (n = 8, 8.9%) and 2 (n = 82, 91.1%) post-radical prostatectomy. Remarkably, the interpretation of PTEN immunohistochemistry displayed substantial variation (12.5-51.2% PTEN loss rates) within an identical cohort of prostate cancer. Fluorescence in situ hybridization analysis demonstrated PTEN hemizygous deletions in 5.5% (5/90) of cases. All cases with hemizygous deletions presented a distinct loss of PTEN expression by immunohistochemistry and were unanimously identified as PTEN loss by all participants (sensitivity 100%). However, negative (loss) immunohistochemistry was relatively non-specific for an underlying genomic deletion. Improved inter-observer agreement was observed in a subsequent ring trial. Finally, we identify S473-pAKT immunohistochemistry as a useful marker in equivocal cases. In summary, this multi-institutional ring trial illustrates surprisingly heterogeneous outcomes in defining PTEN status by immunohistochemistry.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802380","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}