{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:12:49Z","timestamp":1785420769764,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy"},{"id":[{"id":"https:\/\/ror.org\/00afdp487","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Renal cell carcinoma (RCC) exhibits heterogeneous and sometimes unpredictable metastatic behavior, involving both common and uncommon anatomic sites. Institutional analyses of histopathologically confirmed metastatic RCC may improve diagnostic recognition and clinical awareness. This study aimed to characterize the metastatic distribution and histopathologic features of RCC diagnosed in a single tertiary center over a five-year period. Materials and Methods: A retrospective review of the pathology database of the Department of Pathology, \u201cPius Br\u00eenzeu\u201d Emergency County Hospital, Timi\u0219oara, was performed to identify all histologically confirmed cases of metastatic RCC diagnosed between January 2020 and December 2024. Case identification was based on pathology reports of metastatic lesions. In a subset of cases, corresponding pathology reports of the primary renal tumor were available and reviewed. Histopathological data collected included WHO\/ISUP grade, tumor necrosis, sarcomatoid and\/or rhabdoid differentiation, vascular invasion, surgical margin status, tumor size, and pathological T stage (pT). Exploratory analyses were performed to assess associations between metastatic site and selected histopathological features. Results: Thirty-two cases of metastatic RCC were identified, all demonstrating clear cell morphology. The mean patient age was 62.9 years, with a marked male predominance. Among cases with available primary tumor data, high WHO\/ISUP grade and adverse histopathologic features were frequently observed. The most common metastatic sites in our institution were the brain and bone, followed by the adrenal gland, lymph nodes, and liver. Less frequent metastatic involvement included the pancreas, testis, vagina, skin, and peritoneum. Exploratory analyses did not demonstrate statistically significant associations between metastatic site and tumor grade, necrosis, or sarcomatoid\/rhabdoid differentiation; however, descriptive trends were observed, including the association of brain metastases with high-grade tumors and the high prevalence of tumor necrosis across metastatic sites. Conclusions: This pathology-based retrospective series highlights the broad metastatic spectrum of RCC, including both typical and rare anatomic sites. The predominance of clear cell morphology and the frequent association with adverse histopathologic features support the link between aggressive tumor biology and metastatic disease. Although no statistically significant associations were identified, the observed patterns suggest potential relationships between metastatic distribution and tumor characteristics, warranting further investigation in larger studies.<\/jats:p>","DOI":"10.3390\/medicina62050905","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T14:05:46Z","timestamp":1778162746000},"page":"905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metastatic Patterns and Adverse Histopathologic Features in Advanced Renal Cell Carcinoma: A Five-Year Single-Center Retrospective Pathology Study"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7072-6083","authenticated-orcid":false,"given":"Adelina","family":"Vidac","sequence":"first","affiliation":[{"name":"ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alis","family":"Dema","sequence":"additional","affiliation":[{"name":"ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"},{"name":"Department of Pathology, \u201cPius Br\u00eenzeu\u201d Emergency County Hospital, 300723 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4634-969X","authenticated-orcid":false,"given":"Robert","family":"Barna","sequence":"additional","affiliation":[{"name":"ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0898-795X","authenticated-orcid":false,"given":"Aura","family":"Jurescu","sequence":"additional","affiliation":[{"name":"ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Natar\u00e2\u0219","sequence":"additional","affiliation":[{"name":"ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Hurmuz","sequence":"additional","affiliation":[{"name":"ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8560-9493","authenticated-orcid":false,"given":"Diana","family":"Nicolcea","sequence":"additional","affiliation":[{"name":"ANAPATMOL Research Center, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0140-701X","authenticated-orcid":false,"given":"Vlad","family":"Dema","sequence":"additional","affiliation":[{"name":"Department of Urology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.14740\/wjon1279","article-title":"Epidemiology of Renal Cell Carcinoma","volume":"11","author":"Padala","year":"2020","journal-title":"World J. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.eururo.2018.08.036","article-title":"Epidemiology of Renal Cell Carcinoma","volume":"75","author":"Capitanio","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1177\/10668969241256111","article-title":"Clear Cell Renal Cell Carcinoma: A Comprehensive Review of its Histopathology, Genetics, and Differential Diagnosis","volume":"33","author":"Nezami","year":"2025","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Baston, C., Parosanu, A.I., Stanciu, I.M., and Nitipir, C. (2024). Metastatic Kidney Cancer: Does the Location of the Metastases Matter? Moving towards Personalized Therapy for Metastatic Renal Cell Carcinoma. Biomedicines, 12.","DOI":"10.3390\/biomedicines12051111"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1093\/annonc\/mdr362","article-title":"Distribution of metastatic sites in renal cell carcinoma: A population-based analysis","volume":"23","author":"Bianchi","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S587","DOI":"10.4103\/jcrt.jcrt_972_22","article-title":"Outcomes and prognostic factors in metastatic renal cell carcinoma patients with brain metastases","volume":"19","author":"Dogan","year":"2023","journal-title":"J. Cancer Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1186\/1752-1947-5-429","article-title":"Atypical presentations and rare metastatic sites of renal cell carcinoma: A review of case reports","volume":"5","author":"Sountoulides","year":"2011","journal-title":"J. Med. Case Rep."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Boiangiu, A., Cioca, A.M., Gorecki, G.P., Sima, R.M., Ple\u0219, L., Novac, M.B., Coman, I.S., Grigorean, V.T., Lungu, V., and Georgescu, M.T. (2024). Vulvar Metastasis in Renal Cell Carcinoma: A Case Report Highlighting the Aggressive Nature of Clear Cell Renal Cell Carcinoma. Curr. Oncol., 32.","DOI":"10.3390\/curroncol32010004"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1159\/000473698","article-title":"Testicular Metastasis from Renal Cell Carcinoma: A Case Report and Review of the Literature","volume":"10","author":"Rouvinov","year":"2017","journal-title":"Case Rep. Oncol."},{"key":"ref_11","first-page":"661.e7","article-title":"Metastatic renal cell carcinoma: Patterns and predictors of metastases\u2014A contemporary population-based series","volume":"35","author":"Chandrasekar","year":"2017","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e293","DOI":"10.3346\/jkms.2024.39.e293","article-title":"Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma: Results from the Korean Renal Cancer Study Group Database","volume":"39","author":"Lee","year":"2024","journal-title":"J. Korean Med. Sci."},{"key":"ref_13","first-page":"149","article-title":"Unusual Metastases in Renal Cell Carcinoma: A Single Institution Experience and Review of Literature","volume":"1","year":"2010","journal-title":"World J. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s13244-025-02164-6","article-title":"From Radiomics to Radiogenomics: Decoding Renal Cell Carcinoma Biology for Precision Medicine\u2014A narrative review","volume":"16","author":"He","year":"2025","journal-title":"Insights Imaging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101335","DOI":"10.1016\/j.mam.2024.101335","article-title":"The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy","volume":"101","author":"Xie","year":"2025","journal-title":"Mol. Asp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1002\/cncr.11234","article-title":"Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: A stratification tool for prospective clinical trials","volume":"97","author":"Leibovich","year":"2003","journal-title":"Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3892\/mco.2023.2662","article-title":"Prognostic factors in renal cell carcinoma: A single-center study","volume":"19","author":"Ali","year":"2023","journal-title":"Mol. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e178915","DOI":"10.1172\/JCI178915","article-title":"Renal cell carcinoma histologic subtypes exhibit distinct transcriptional profiles","volume":"134","author":"Barata","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Makino, T., Kadomoto, S., Izumi, K., and Mizokami, A. (2022). Epidemiology and Prevention of Renal Cell Carcinoma. Cancers, 14.","DOI":"10.3390\/cancers14164059"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Peired, A.J., Campi, R., Angelotti, M.L., Antonelli, G., Conte, C., Lazzeri, E., Becherucci, F., Calistri, L., Serni, S., and Romagnani, P. (2021). Sex and Gender Differences in Kidney Cancer: Clinical and Experimental Evidence. Cancers, 13.","DOI":"10.3390\/cancers13184588"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1056\/NEJM199609193351207","article-title":"Renal-Cell Carcinoma","volume":"335","author":"Motzer","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.amsu.2018.01.002","article-title":"Skeletal metastasis in renal cell carcinoma: A review","volume":"27","author":"Umer","year":"2018","journal-title":"Ann. Med. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/iju5.12179","article-title":"Rapid progression of recurrent disease in a patient with renal cell carcinoma with vaginal metastasis","volume":"3","author":"Hisano","year":"2020","journal-title":"IJU Case Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"847.e1","DOI":"10.1016\/j.urology.2005.10.047","article-title":"Renal cell carcinoma presenting as a perineal mass: Case report and review of the literature","volume":"67","author":"Mendese","year":"2006","journal-title":"Urology"},{"key":"ref_25","first-page":"469","article-title":"Secondary Tumors of Testis: Two Rare Cases and Review of the Literature","volume":"48","author":"Blefari","year":"1992","journal-title":"Urol. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2165\/00128071-200607040-00010","article-title":"Cutaneous Metastasis of Renal Cell Carcinoma","volume":"7","author":"Opper","year":"2006","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1001\/archderm.1957.01550190100018","article-title":"Involvement of the Skin in Renal Carcinoma: Report of Two Cases with Review of the Literature","volume":"76","author":"Rosenthal","year":"1957","journal-title":"AMA Arch. Derm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ijscr.2016.02.008","article-title":"Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy: A case report","volume":"21","author":"Acar","year":"2016","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/00004728-199105000-00019","article-title":"Renal Cell Carcinoma Presenting with Diffuse Peritoneal Metastases: CT Findings","volume":"15","author":"Tartar","year":"1991","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_30","first-page":"169","article-title":"Renal Cell Carcinoma Presenting as a Large Abdominal Mass with an Extensive Peritoneal Metastasis","volume":"54","author":"Stavropoulos","year":"1995","journal-title":"Urol. Int."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Balaban, D.V., Coman, L., Marin, F.S., Balaban, M., Tabacelia, D., Vasilescu, F., Costache, R.S., and Jinga, M. (2023). Metastatic Renal Cell Carcinoma to Pancreas: Case Series and Review of the Literature. Diagnostics, 13.","DOI":"10.3390\/diagnostics13081368"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1245\/ASO.2006.03.064","article-title":"Solitary and Multiple Isolated Metastases of Clear Cell Renal Carcinoma to the Pancreas: An Indication for Pancreatic Surgery","volume":"13","author":"Sellner","year":"2006","journal-title":"Ann. Surg. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.juro.2008.04.034","article-title":"Prognostic Significance of Perinephric Fat Infiltration and Tumor Size in Renal Cell Carcinoma","volume":"180","author":"Yoo","year":"2008","journal-title":"J. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.urology.2003.09.081","article-title":"Tumor-size breakpoint for prognostic stratification of localized renal cell carcinoma","volume":"63","author":"Ficarra","year":"2004","journal-title":"Urology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1200\/JCO.2008.21.4809","article-title":"Prognostic Factors for Overall Survival in Patients with Metastatic Renal Cell Carcinoma Treated with Vascular Endothelial Growth Factor\u2013Targeted Agents: Results from a Large, Multicenter Study","volume":"27","author":"Heng","year":"2009","journal-title":"J. Clin. Oncol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:02:58Z","timestamp":1778166178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["medicina62050905"],"URL":"https:\/\/doi.org\/10.3390\/medicina62050905","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]}}}