{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:02:40Z","timestamp":1770742960390,"version":"3.49.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Urol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Renal medullary carcinoma (RMC) is an aggressive tumor representing less than 0.5% of renal cell carcinomas (RCC), and it is considered rare. When it occurs, patients typically have sickle cell trait, sickle cell disease, or an associated hemoglobinopathy, which is a necessary characteristic for diagnosis. Additionally, RMC is characterized by the inactivation of alterations in the SMARCB1 (INI1) tumor suppressor gene, resulting in the loss of INI1 immunohistochemical expression. However, there are tumors reported in the literature with the same morphological and phenotypic characteristics as RMC but without hemoglobinopathy, referred to as \u201cunclassified RCC with medullary phenotype.\u201d<\/jats:p><\/jats:sec><jats:sec><jats:title>Case report<\/jats:title><jats:p>We present the 13th case of unclassified renal cell carcinoma with a medullary phenotype in a 20-year-old woman. The patient was admitted with complaints of macroscopic hematuria, with no significant findings on physical examination. Diagnostic investigation included a computed tomography urogram, which revealed a hypovascular oval image with central cystic\/necrotic areas in the middle third of the right kidney, measuring 32 mm, suggesting a possible diagnosis of an infected renal cyst. Subsequent magnetic resonance imaging showed findings consistent with an atypical presentation of primary neoplasia in the differential diagnosis, prompting a renal biopsy for case definition. Histopathological analysis revealed a high-grade infiltrative epithelioid neoplasm. Immunohistochemistry showed positivity for PAX8 and loss of INI-1 expression. No hemoglobinopathies were identified in the patient, in this context, the neoplasm is appropriately classified as unclassified renal cell carcinoma (RCC) with medullary phenotype and SMARCB1 deficiency. The instituted therapy consisted of right radical nephrectomy with retroperitoneal lymphadenectomy, with nodal metastases detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Given the rarity of unclassified RCC with a medullary phenotype, continuous documentation and analysis of individual cases not associated with sickle cell trait are crucial to understanding its behavior, prognosis, and potential therapeutic approaches, considering its aggressiveness and high metastatic potential.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fruro.2025.1582675","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T04:10:49Z","timestamp":1749183049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Unclassifiable renal carcinoma with medullary phenotype and SMARCB1 deficiency: case report"],"prefix":"10.3389","volume":"5","author":[{"given":"Samya H.","family":"Mehanna","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago Gabriel","family":"Ronkoski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassiano","family":"Machado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas S.","family":"Wolff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre C.","family":"Cavalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago","family":"Hota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando C.","family":"Koleski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0090-4295(02)02154-4","article-title":"Renal medullary carcinoma: clinical, pathologic, immunohistochemical, and genetic analysis with pathogenetic implications","volume":"60","author":"Swartz","year":"2002","journal-title":"Urology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2020-0464-RA","article-title":"The differential diagnosis of medullary-based renal masses","volume":"145","author":"Baniak","year":"2021","journal-title":"Arch Pathol Lab Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3182770406","article-title":"Renal Medullary Carcinoma: molecular, immunohistochemistry, and morphologic correlation","volume":"37","author":"Liu","year":"2013","journal-title":"Am J Surg Pathol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2017.07.006","article-title":"Renal cell carcinoma, unclassified with medullary phenotype: poorly differentiated adenocarcinomas overlapping with renal medullary carcinoma","volume":"67","author":"Sirohi","year":"2017","journal-title":"Hum Pathol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.2017.020909","article-title":"Renal medullary carcinoma: establishing standards in practice","volume":"13","author":"Beckermann","year":"2017","journal-title":"J Oncol Pract"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2017-0492-RS","article-title":"Renal medullary carcinoma","volume":"143","author":"Elliott","year":"2019","journal-title":"Arch Pathol Lab Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s11934-019-0865-9","article-title":"Renal medullary carcinoma: a report of the current literature","volume":"20","author":"Blas","year":"2019","journal-title":"Curr Urol Rep"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/00000478-199501000-00001","article-title":"Renal medullary carcinoma the seventh sickle cell nephropathy","volume":"19","author":"Davis","year":"1995","journal-title":"Am J Surg Pathol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2022.06.016","article-title":"The 2022 world health organization classification of tumours of the urinary system and male genital organs\u2014Part A: renal, penile, and testicular tumours","volume":"82","author":"Moch","year":"2022","journal-title":"Eur Urol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.835599","article-title":"Case report: unclassified renal cell carcinoma with medullary phenotype and SMARCB1\/INI1 deficiency, broadening the spectrum of medullary carcinoma","volume":"9","author":"Valeri","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.12657","article-title":"Renal cell carcinoma, unclassified with medullary phenotype and synchronous renal clear cell carcinoma present in a patient with no sickle cell trait\/disease: diagnostic and therapeutic challenges","volume":"38","author":"Lai","year":"2018","journal-title":"Anticancer Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30030255","article-title":"Renal cell carcinoma unclassified with medullary phenotype in a patient with neurofibromatosis type 2","volume":"30","author":"Sarkar","year":"2023","journal-title":"Curr Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.934991","article-title":"Case report: A case of renal cell carcinoma unclassified with medullary phenotype exhibiting a favorable response to combined immune checkpoint blockade","volume":"13","author":"Takeda","year":"2022","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"360","DOI":"10.3760\/cma.j.cn112151-20190731-00423","article-title":"Renal carcinoma unclassified with medullary phenotype: report of a case","volume":"49","author":"Ma","year":"2020","journal-title":"Zhonghua Bing Li Xue Za Zhi."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/PAT.0000000000000175","article-title":"Renal cell carcinoma with rhabdoid features and loss of INI1 expression in an individual without sickle cell trait","volume":"46","author":"Scarpelli","year":"2014","journal-title":"Pathology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2009.255","article-title":"Renal medullary-like carcinoma in an adult without sickle cell hemoglobinopathy","volume":"7","author":"O\u2019Donnell","year":"2010","journal-title":"Nat Rev Urol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1001\/jama.1974.03230350051035","article-title":"Sickle cell nephropathy","volume":"228","author":"Berman","year":"1974","journal-title":"JAMA"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3182417d78","article-title":"Expression of OCT3\/4 in renal medullary carcinoma represents a potential diagnostic pitfall","volume":"36","author":"Rao","year":"2012","journal-title":"Am J Surg Pathol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2015.02.004","article-title":"Distal nephron neoplasms","volume":"32","author":"Fleming","year":"2015","journal-title":"Semin Diagn Pathol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2016-203650","article-title":"Gene of the month: SMARCB1","volume":"69","author":"Kalimuthu","year":"2016","journal-title":"J Clin Pathol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-3296","article-title":"A model linking sickle cell hemoglobinopathies and SMARCB1 loss in renal medullary carcinoma","volume":"24","author":"Msaouel","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.5858\/2003-127-e135-RMCARO","article-title":"Renal medullary carcinoma: A report of 2 cases and review of the literature","volume":"127","author":"Dimashkieh","year":"2003","journal-title":"Arch Pathol Lab Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3747\/co.27.5043","article-title":"Renal medullary carcinoma and its association with sickle cell trait: a case report and literature review","volume":"27","author":"Holland","year":"2020","journal-title":"Curr Oncol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1177\/1093526617749671","article-title":"SMARCB1 -deficient tumors of childhood: A practical guide","volume":"21","author":"Pawel","year":"2018","journal-title":"Pediatr Dev Pathol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1097\/PAP.0000000000000138","article-title":"Clinicopathologic and molecular pathology of collecting duct carcinoma and related renal cell carcinomas","volume":"24","author":"Seo","year":"2017","journal-title":"Adv Anat Pathol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.44","article-title":"Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior","volume":"21","author":"Cheng","year":"2008","journal-title":"Modern Pathol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0273-1","article-title":"Distinctive mechanisms underlie the loss of SMARCB1 protein expression in renal medullary carcinoma: morphologic and molecular analysis of 20 cases","volume":"32","author":"Jia","year":"2019","journal-title":"Mod Pathol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001000","article-title":"Reappraisal of morphologic differences between renal medullary carcinoma, collecting duct carcinoma, and fumarate hydratase\u2013deficient renal cell carcinoma","volume":"42","author":"Ohe","year":"2018","journal-title":"Am J Surg Pathol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2012-0196-CR","article-title":"High-grade carcinomas involving the renal sinus: report of a case and review of the differential diagnosis and immunohistochemical expression","volume":"136","author":"Young","year":"2012","journal-title":"Arch Pathol Lab Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2012.04228.x","article-title":"SMARCB1\/INI1 inactivation in renal medullary carcinoma","volume":"61","author":"Calderaro","year":"2012","journal-title":"Histopathology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31822b325b","article-title":"INI1-deficient tumors: diagnostic features and molecular genetics","volume":"35","author":"Hollmann","year":"2011","journal-title":"Am J Surg Pathol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2017.04.012","article-title":"Genomic characterization of renal medullary carcinoma and treatment outcomes","volume":"15","author":"Carlo","year":"2017","journal-title":"Clin Genitourin Cancer"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-016-0206-1","article-title":"Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma","volume":"5","author":"Beckermann","year":"2017","journal-title":"J Immunother Cancer"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.5489\/cuaj.2373","article-title":"Clinical outcome and prognostic factors in renal medullary carcinoma: A pooled analysis from 18 years of medical literature","volume":"9","author":"Iacovelli","year":"2015","journal-title":"Can Urol Assoc J"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25832","article-title":"Is there a role for antiangiogenic therapy in renal medullary carcinoma","volume":"63","author":"Batra","year":"2016","journal-title":"Pediatr Blood Cancer"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137097","article-title":"Recent advances in renal medullary carcinoma","volume":"23","author":"Su","year":"2022","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in Urology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fruro.2025.1582675\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T04:10:50Z","timestamp":1749183050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fruro.2025.1582675\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":36,"alternative-id":["10.3389\/fruro.2025.1582675"],"URL":"https:\/\/doi.org\/10.3389\/fruro.2025.1582675","relation":{},"ISSN":["2673-9828"],"issn-type":[{"value":"2673-9828","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,6]]},"article-number":"1582675"}}