{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T17:53:15Z","timestamp":1774288395083,"version":"3.50.1"},"reference-count":106,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"abstract":"<jats:p>Background: Renal cell carcinoma (RCC) is a heterogeneous disease, with the last World Health Organization (WHO) classification introducing several novel entities, among which the molecularly defined RCCs. This growing complexity highlights the need for integration of morphology, immunohistochemistry (IHC) and molecular techniques, ensuring accurate classification and reducing the \u201cRCC not otherwise specified (NOS) category.\u201d Summary: Molecular assays such as next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) are increasingly necessary for diagnosing molecularly defined RCCs. IHC remains fundamental for diagnosing both \u201cold\u201d and newly defined RCCs, representing a surrogate for molecular alterations such as fumarate-hydratase and succinate-dehydrogenase deficiency, anaplastic lymphoma kinase rearrangements, SMARCB1 loss, and TFE3 rearrangements. However, entities like ELOC-mutated RCC require molecular testing for diagnosis. Liquid biopsy offers a further diagnostic tool. Circulating microRNAs can support diagnosis, classification, and monitoring. Furthermore, circulating tumor DNA (ctDNA) methylation analyses and circulating tumor cells (CTCs) offer promising and minimally invasive tools for stratification, though their clinical use is still evolving. Key Messages: A precise diagnosis integrating histopathology, IHC, and molecular testing is critical for guiding management, identifying hereditary syndromes, and implementing personalized tumor biology-based therapies. With evolving molecular diagnostic and circulating biomarkers, careful clinical integration is needed to optimize outcomes and treatment.<\/jats:p>","DOI":"10.1159\/000550723","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T17:02:13Z","timestamp":1769533333000},"page":"1-20","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Renal Cell Carcinoma Diagnosis: A Review on Biomarkers"],"prefix":"10.1159","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8560-1925","authenticated-orcid":false,"given":"Agnese","family":"Orsatti","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3931-0443","authenticated-orcid":false,"given":"Fernanda","family":"Fernandes-Pontes","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o Ricardo","family":"e Silva","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8426-1838","authenticated-orcid":false,"given":"Nuno Tiago","family":"Tavares","sequence":"additional","affiliation":[]},{"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[]},{"given":"\u00c2ngelo","family":"Rodrigues","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7254-4195","authenticated-orcid":false,"given":"Costantino","family":"Ricci","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-1391","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Lobo","sequence":"additional","affiliation":[]}],"member":"127","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9101418"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.32074\/1591-951X-818"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1097\/MOU.0000000000001000"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030602"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.33679"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1111\/his.14700"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-020-00359-2"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.05.010"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1111\/his.15042"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12346"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2017.09.005"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00737-6"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.21037\/tau-20-1150"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1111\/his.13727"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2012.08.007"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0645-6"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1111\/his.14731"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0420-8"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2021.03.009"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1111\/his.14320"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001288"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0362-1"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2017.01.005"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1177\/1066896917696748"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.4103\/IJPM.IJPM_400_20"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00833-7"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1111\/his.14589"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001150"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16101856"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10020322"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002413"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002435"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1002\/path.5875"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200212000-00003"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-019-02526-8"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31828a69ae"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.99"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001111"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.05.023"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00803-z"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002117"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15164043"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000248"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2020.11.004"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-020-02910-9"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1111\/his.15505"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001422"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2014.105"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1111\/his.13865"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.3389\/pore.2023.1610852"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00896-6"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00967-8"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.05.537"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100194"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001255"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2014.08.004"},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1097\/PAI.0000000000000410"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2025.100777"},{"key":"ref59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0278108"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2022.06.016"},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2023.102558"},{"key":"ref62","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31804375b8"},{"key":"ref63","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22878"},{"key":"ref64","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001372"},{"key":"ref65","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000719"},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0017-7"},{"key":"ref67","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-023-03700-9"},{"key":"ref68","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3788"},{"key":"ref69","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2024.100536"},{"key":"ref70","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2025.155814"},{"key":"ref71","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2024.102266"},{"key":"ref72","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000179"},{"key":"ref73","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2016.07.004"},{"key":"ref74","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-020-02752-5"},{"key":"ref75","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0578-0"},{"key":"ref76","doi-asserted-by":"publisher","DOI":"10.1177\/10668969211003660"},{"key":"ref77","doi-asserted-by":"publisher","DOI":"10.1200\/PO.18.00185"},{"key":"ref78","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2017.07.006"},{"key":"ref79","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2009.255"},{"key":"ref80","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000222"},{"key":"ref81","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2018.09.005"},{"key":"ref82","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3182417d78"},{"key":"ref83","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.04.002"},{"key":"ref84","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0273-1"},{"key":"ref85","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2022.03.002"},{"key":"ref86","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14153645"},{"key":"ref87","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.07.006"},{"key":"ref88","doi-asserted-by":"publisher","DOI":"10.1111\/his.14816"},{"key":"ref89","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.08.020"},{"key":"ref90","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001926"},{"key":"ref91","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvad133"},{"key":"ref92","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16040787"},{"key":"ref93","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-020-00842-y"},{"key":"ref94","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-77774-9"},{"key":"ref95","doi-asserted-by":"publisher","DOI":"10.21037\/tau.2020.03.18"},{"key":"ref96","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14040858"},{"key":"ref97","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27347"},{"key":"ref98","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2016.09.007"},{"key":"ref99","doi-asserted-by":"publisher","DOI":"10.1016\/j.euros.2021.12.006"},{"key":"ref100","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0801-x"},{"key":"ref101","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0933-1"},{"key":"ref102","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.05.520"},{"key":"ref103","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11030801"},{"key":"ref104","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-024-13380-6"},{"key":"ref105","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13842"},{"key":"ref106","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2018.1537576"}],"container-title":["Pathobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000550723","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T17:01:25Z","timestamp":1774285285000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000550723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":106,"URL":"https:\/\/doi.org\/10.1159\/000550723","archive":["Portico"],"relation":{},"ISSN":["1015-2008","1423-0291"],"issn-type":[{"value":"1015-2008","type":"print"},{"value":"1423-0291","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]}}}