Virchows Archiv最新文献

{"title":"PAX8 expression in cancerous and non-neoplastic tissue: a tissue microarray study on more than 17,000 tumors from 149 different tumor entities.","authors":"Natalia Gorbokon, Sarah Baltruschat, Maximilian Lennartz, Andreas M Luebke, Doris Höflmayer, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Christoph Fraune, Patrick Lebok, Christian Bernreuther, Guido Sauter, Andreas H Marx, Ronald Simon, Till Krech, Till S Clauditz, Frank Jacobsen, Eike Burandt, Stefan Steurer, Sarah Minner","doi":"10.1007/s00428-024-03872-y","DOIUrl":"10.1007/s00428-024-03872-y","url":null,"abstract":"<p><p>PAX8 plays a role in development of the thyroid, kidney, and the Wolffian and Mullerian tract. In surgical pathology, PAX8 immunohistochemistry is used to determine tumors of renal and ovarian origin, but data on its expression in other tumors are conflicting. To evaluate PAX8 expression in normal and tumor tissues, a tissue microarray containing 17,386 samples from 149 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. PAX8 results were compared with previously collected data on cadherin 16 (CDH16). PAX8 positivity was found in 40 different tumor types. The highest rate of PAX8 positivity was found in thyroidal neoplasms of follicular origin (98.6-100%), gynecological carcinomas (up to 100%), renal tumors (82.6-97.8%), and urothelial neoplasms (2.3-23.7%). Important tumors with near complete absence of PAX8 staining (< 1%) included all subtypes of breast cancers, hepatocellular carcinomas, gastric, prostatic, pancreatic, and pulmonary adenocarcinomas, neuroendocrine neoplasms, small cell carcinomas of various sites, and lymphomas. High PAX8 expression was associated with low tumor grade in 365 non-invasive papillary urothelial carcinomas (p < 0.0001) but unrelated to patient outcome and/or tumor phenotype in clear cell renal cell carcinoma, high-grade serous ovarian cancer, and endometrioid endometrial carcinoma. For determining a renal tumor origin, sensitivity was 88.1% and specificity 87.2% for PAX8, while sensitivity was 85.3% and specificity 95.7% for CDH16. The combination of PAX8 and CDH16 increased specificity to 96.8%. In conclusion, PAX8 immunohistochemistry is a suitable diagnostic tool. The combination of PAX8 and CDH16 positivity has high specificity for renal cell carcinoma.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers.","authors":"Kristýna Němejcová, Adam Šafanda, Michaela Kendall Bártů, Romana Michálková, Marián Švajdler, Tetiana Shatokhina, Jan Laco, Radoslav Matěj, Gábor Méhes, Jana Drozenová, Jitka Hausnerová, Zuzana Špůrková, Monika Náležinská, Pavel Dundr","doi":"10.1007/s00428-024-03854-0","DOIUrl":"10.1007/s00428-024-03854-0","url":null,"abstract":"<p><p>The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the \"traditional\" immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing. The antibodies used included 12 of the \"diagnostic\" antibodies already examined in previous studies, 10 antibodies whose expression has not yet been examined in AGCT, and 7 antibodies with possible predictive significance, including the expression of HER2, PD-L1, CTLA4, and 4 mismatch repair (MMR) proteins. The results of our study showed expression of FOXL2, SF1, CD99, inhibin A, calretinin, ER, PR, AR, CKAE1/3, and CAIX in 98%, 100%, 90%, 78%, 45%, 41%, 94%, 82%, 26%, and 9% of AGCT, respectively. GATA3, SATB2, napsin A, MUC4, TTF1, and CD44 were all negative. PTEN showed a loss of expression in 71% of cases and DPC4 in 4% of cases. The aberrant staining pattern (overexpression) of p53 was found in 1% (3/268) of cases, 2 primary tumors, and 1 recurrent case. Concerning the predictive markers, the results of our study showed that AGCT is microsatellite stable, do not express PD-L1, and are HER2 negative. The CTLA4 expression was found in almost 70% of AGCT tumor cells.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432879","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 clinicopathological and prognostic significance of autonomic nerves in salivary duct carcinoma.","authors":"Manami Kajiwara, Hideaki Takahashi, Masato Nakaguro, Daisuke Kawakita, Hideaki Hirai, Yoshitaka Utsumi, Makoto Urano, Yukiko Sato, Kiyoaki Tsukahara, Satoshi Kano, Kenji Okami, Hiroyuki Ozawa, Keisuke Yamazaki, Takuro Okada, Akira Shimizu, Kenji Hanyu, Akihiro Sakai, Mayu Yamauchi, Mariko Sekimizu, Toyoyuki Hanazawa, Yuki Saito, Yushi Ueki, Yoshitaka Honma, Tomoyuki Arai, Sho Iwaki, Koji Yamamura, Yorihisa Imanishi, Yuichiro Sato, Yuichiro Tada, Toshitaka Nagao","doi":"10.1007/s00428-024-03873-x","DOIUrl":"10.1007/s00428-024-03873-x","url":null,"abstract":"<p><p>Many researchers have focused on the role of the autonomic nervous system in the tumor microenvironment. Autonomic nerves include the sympathetic and parasympathetic nerves, which are known to induce cancer growth and metastasis. However, in salivary duct carcinoma (SDC), a rare and highly malignant tumor, the issue should be investigated from both biological and therapeutic perspectives. We explored the clinicopathological and prognostic implications of the autonomic nerves in 129 SDCs. Immunohistochemistry was performed to determine the nature of each nerve using antibodies against S100, tyrosine hydroxylase (TH) as a sympathetic marker, and vesicular acetylcholine transporter (VAChT) as a parasympathetic marker. The area of each marker-positive nerve was digitized and evaluated quantitatively. Double immunofluorescence for TH and VAChT was performed in selected cases. The expression of the secreted neurotrophins was also examined. S100-positive nerves were present in the cancer tissue in 94 of 129 cases (72.9%). Among them, TH-positive sympathetic nerves and/or VAChT-positive parasympathetic nerves were identified in 92 cases (97.9%), and 59 cases (62.8%) had TH/VAChT-co-expressing nerves. Double immunofluorescence revealed a mosaic pattern of sympathetic and parasympathetic fibers in co-expressing nerve bundles. The presence of autonomic nerves, regardless of their area, was significantly associated with aggressive histological features, advanced T/N classification, and a poor prognosis, with shorter disease-free and overall survival. There was an association between some tumor immune microenvironment-related markers and the autonomic nerve status, but not the latter and the secreted neurotrophin expression. This study suggests that autonomic nerves might play a role in the progression of SDC.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749167","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":"Colorectal adenocarcinoma with clear cell changes: immunohistological and molecular findings in three cases.","authors":"Andreas Gocht, Carsten Heidel, Jutta Kirfel, Rita Vesce, Pamela Lazar-Karsten, Helen Pasternack, Madelaine Melzer, Phillip Hildebrand, Nicole Warkentin, Hendrik Schimmelpenning, Verena-Wilbeth Sailer","doi":"10.1007/s00428-024-03870-0","DOIUrl":"10.1007/s00428-024-03870-0","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Plasma exchange-sensitive syncytial glomerulopathy in a kidney transplant patient.","authors":"Marco Delsante, Elena Martinelli, Chiara Foroni, Serena Maria Bagnasco, Giovanni Maria Rossi, Silvia Giuliodori, Letizia Gnetti, Ilaria Gandolfni, Umberto Maggiore","doi":"10.1007/s00428-024-03910-9","DOIUrl":"https://doi.org/10.1007/s00428-024-03910-9","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112464","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 unclassified high-grade uterine sarcoma: first detailed description of a novel entity.","authors":"Abbas Agaimy, Josephine K Dermawan, Florian Haller, Sabine Semrau, Norbert Meidenbauer, Robert Stoehr, Sigurd Lax, Arndt Hartmann, Ying S Zou, Deyin Xing, Lars Tögel, John M Gross, Michael Michal","doi":"10.1007/s00428-024-03908-3","DOIUrl":"https://doi.org/10.1007/s00428-024-03908-3","url":null,"abstract":"<p><p>With the increasing use of innovative next generation sequencing (NGS) platforms in routine diagnostic and research settings, the genetic landscape of uterine sarcomas has been dynamically evolving during the last two decades. Notably, the majority of recently recognized genotypes in uterine sarcomas represent gene fusions, while recurrent oncogene mutations of diagnostic and/ or therapeutic value have been rare. Recently, a distinctive aggressive uterine sarcoma expressing S100 and SOX10, but otherwise lacking diagnostic morphological, immunophenotypic and molecular features of other uterine malignancies has been presented in a scientific abstract form (USCAP, 2023), but detailed description and delineation of the entity is still missing. We herein describe two high-grade unclassified uterine sarcomas characterized by spindle to round cell morphology and diffuse expression of S100 and SOX10, originating in the uterine body and cervix of 53- and 45-year-old women and carrying an ERBB3 (p.Glu928Gly) and an ERBB2 (p.Val777Leu) mutation, respectively. Both tumors harbored in addition genomic HER2 amplification, ATRX mutation and CDKN2A deletion. Methylation studies revealed a methylome most similar to MPNST-like tumors, but distinct from melanoma, MPNST, clear cell sarcoma, and endometrial stromal sarcoma. Case 1 died of progressive peritoneal metastases after multiple trials of chemotherapy 47 months after diagnosis. Case 2 is a recent case who presented with a cervical mass, which was biopsied. This study defines a novel heretofore unrecognized aggressive uterine sarcoma with unique phenotypic and genotypic features. Given the potential value of targeting HER2, recognizing this tumor type is mandatory for appropriate therapeutic strategies and for better future delineation of the entity.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081802","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":"Identification of a novel RAB6A::TOP2A fusion in acute non-promyelocytic leukemia harboring t(11;17)(q13;q21) translocation.","authors":"Zhan Su, Yahui Du, Chenglu Yuan, Xianzhi Zhao, Xiaoshan Zhang, Hongqing Cui, Ting Yue, Hongguo Zhao, Wei Wang","doi":"10.1007/s00428-024-03853-1","DOIUrl":"https://doi.org/10.1007/s00428-024-03853-1","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056642","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":"Utility of special AT-rich sequence-binding protein 2 (SATB2) immunohistochemistry as a marker for secondary perianal paget disease.","authors":"Krithika Shenoy, Kathleen Byrnes","doi":"10.1007/s00428-024-03906-5","DOIUrl":"https://doi.org/10.1007/s00428-024-03906-5","url":null,"abstract":"<p><p>A panel-based approach using immunohistochemistry (IHC) is currently used for subtyping perianal Paget disease (PPD) in the absence of a synchronous neoplasm. Special AT-rich Sequence Binding Protein 2 (SATB2) has been established as a sensitive and specific marker for lower gastrointestinal tract carcinomas. We evaluated its performance as a marker of secondary PPD. A panel of IHCs including CK7, CK20, GCDFP-15, CDX2, and SATB2 were performed on fifteen cases of PPD (identified between 1991-2001) and seven cases of primary vulvar Paget disease with perianal involvement. Eight cases (53%) were classified as secondary PPD based on the presence of a synchronous (n = 7) or a metachronous neoplasm (n = 1). There was no differential staining for CK7 (positive in 7/7 primary vs. 7/8 secondary PPD; P = 1.00) and CK20 (positive in 4/7 primary vs. 8/8 secondary PPD; P = .08). GCDFP-15 was positive in 5/7 cases of primary PPD while negative in all cases of secondary PPD (P = .01). CDX2 was positive in all cases of secondary PPD (P = .001) while SATB2 was positive in 7/8 cases of secondary PPD (P = .01). Both CDX2 and SATB2 were positive in 1/7 cases of primary PPD. The addition of an IHC panel in conjunction with clinical/imaging findings can help definitively classify PPD as either primary or secondary in most cases. We show that SATB2 has comparable performance to CDX2 and can be a helpful additional tool.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056643","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: Adenotonsillar pathology in mucopolysaccharidoses - lysosomal storage predominates in paracortical CD63 + cells.","authors":"Lenka Murgasova, Helena Hulkova, Veronika Baresova, Michal Jurovcik, Jan Stritesky, Katarina Jurickova, Martin Magner, Jakub Sikora","doi":"10.1007/s00428-024-03902-9","DOIUrl":"https://doi.org/10.1007/s00428-024-03902-9","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037146","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":"Comparative analysis of non-coding and coding DNA mutations in flat urothelial lesions: biological implications and insights.","authors":"Fidele Y Musangile, Ibu Matsuzaki, Ryuta Iwamoto, Kanako Sagan, Mizuki Nishikawa, Yurina Mikasa, Yuichi Takahashi, Ryoma Higashine, Fumiyoshi Kojima, Isao Hara, Shin-Ichi Murata","doi":"10.1007/s00428-024-03901-w","DOIUrl":"10.1007/s00428-024-03901-w","url":null,"abstract":"<p><p>Recent research in urothelial carcinoma (UC) has focused on coding mutations, leaving the significance of non-coding mutations unexplored. This study aims to evaluate non-coding DNA mutation frequencies compared to coding regions in normal urothelium and flat lesions, exploring their implications for tumor biology. Using targeted next-generation sequencing with UC-related gene panel, we analyzed non-coding and coding DNA mutation frequencies across 119 samples of flat urothelium encompassing various lesion types. Mutation patterns were examined based on the presence of associated flat or papillary tumors, and we investigated the correlation between mutation rates in target genes and genetic mutations within genomic regions. Intronic mutations (IMs) displayed variability across lesions, with normal urothelium (NU) exhibiting the highest frequency (43%) and urothelial carcinoma in situ (CIS) the lowest (9%). We observed similar sets of frequently mutated genes in both intronic and exonic regions, distinct from promoter region mutations. Although IMs paralleled exonic mutations in NU, reactive atypia, and atypia of unknown significance (AUS), they were less prevalent in dysplasia (DYS) and CIS. In contrast to CIS-associated AUS and DYS lesions, AUS-DYS lesions associated with papillary tumors exclusively exhibited recurrent intronic mutations involving FGFR3 and ERCC2, aligning with mutation patterns seen in exonic regions. ERCC2 intronic mutations correlated with the mutation rates of the gene panel. Our findings suggest that intronic mutations significantly contribute to tumor heterogeneity in urothelial lesions and may potentially be linked to genomic instability, warranting further investigation.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018788","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}