Renal epithelial cell tumors are composed of a heterogeneous group of tumors with variable morphologic, immunohistochemical, and molecular features. A "histo-molecular" approach is now an integral part of defining renal tumors, aiming to be clinically and therapeutically pertinent. Most renal epithelial tumors including the new and emerging entities have distinct molecular and genetic features which can be detected using various methods. Most renal epithelial tumors can be diagnosed easily based on pure histologic findings with or without immunohistochemical examination. Furthermore, molecular-genetic testing can be utilized to assist in arriving at an accurate diagnosis. In this review, we presented the most current knowledge concerning molecular-genetic aspects of renal epithelial neoplasms, which potentially can be used in daily diagnostic practice.

Department of Microscopy Institute of Biomedical Sciences Abel Salazar University of Porto 4200 072 Porto Portugal

Department of Pathology Centro Hospitalar de Vila Nova de Gaia Espinho Vila Nova de Gaia Cancer Biology and Epigenetics Group 4200 072 Porto Portugal

Department of Pathology Charles University Prague Faculty of Medicine in Plzen 304 60 Pilsen Czech Republic

Department of Pathology Faculty of Medicine University of British Columbia Royal Columbian Hospital Vancouver BC V3E 0G9 Canada

Department of Pathology Institute Nacional de Cancerologia INCAN Mexico DF 14080 Mexico

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Kovacs G., Akhtar M., Beckwith B.J., Bugert P., Cooper C.S., Delahunt B., Eble J.N., Fleming S., Ljungberg B., Medeiros L.J., et al. The Heidelberg classification of renal cell tumours. J Pathol. 1997;183:131–133. doi: 10.1002/(SICI)1096-9896(199710)183:2<131::AID-PATH931>3.0.CO;2-G. PubMed DOI

Storkel S., Eble J.N., Adlakha K., Amin M., Blute M.L., Bostwick D.G., Darson M., Delahunt B., Iczkowski K. Classification of renal cell carcinoma: Workgroup No. 1. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC) Cancer. 1997;80:987–989. doi: 10.1002/(SICI)1097-0142(19970901)80:5<987::AID-CNCR24>3.0.CO;2-R. PubMed DOI

Eble J.N., Sauter G., Epstein J., Sesterhenn I. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs, WHO Classification of Tumours. 3rd ed. Volume 7 WHO; Geneva, Switzerland: IARC Press; Lyon, Switzerland: 2004.

Delahunt B., Srigley J.R., Montironi R., Egevad L. Advances in renal neoplasia: Recommendations from the 2012 International Society of Urological Pathology Consensus Conference. Urology. 2014;83:969–974. doi: 10.1016/j.urology.2014.02.004. PubMed DOI

Moch H., Humphrey P.A., Ulbright T.M., Reuter V.E. WHO Classification of Tumours of the Urinary System and Male Genital Organs—WHO Classification of Tumours. 4th ed. Volume 8 WHO; Geneva, Switzerland: IARC Press; Lyon, Switzerland: 2016.

Petersson F., Grossmann P., Hora M., Sperga M., Montiel D.P., Martinek P., Gutierrez M.E., Bulimbasic S., Michal M., Branzovsky J., et al. Renal cell carcinoma with areas mimicking renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma. Hum. Pathol. 2013;44:1412–1420. doi: 10.1016/j.humpath.2012.11.019. PubMed DOI

Somoracz A., Kuthi L., Micsik T., Jenei A., Hajdu A., Vrabely B., Raso E., Sapi Z., Bajory Z., Kulka J., et al. Renal Cell Carcinoma with Clear Cell Papillary Features: Perspectives of a Differential Diagnosis. Pathol. Oncol. Res. 2019 doi: 10.1007/s12253-019-00757-3. PubMed DOI PMC

Carroll P.R., Murty V.V., Reuter V., Jhanwar S., Fair W.R., Whitmore W.F., Chaganti R.S. Abnormalities at chromosome region 3p12-14 characterize clear cell renal carcinoma. Cancer Genet. Cytogenet. 1987;26:253–259. doi: 10.1016/0165-4608(87)90059-8. PubMed DOI

Smits K.M., Schouten L.J., van Dijk B.A., Hulsbergen-van de Kaa C.A., Wouters K.A., Oosterwijk E., van Engeland M., van den Brandt P.A. Genetic and epigenetic alterations in the von hippel-lindau gene: The influence on renal cancer prognosis. Clin. Cancer Res. 2008;14:782–787. doi: 10.1158/1078-0432.CCR-07-1753. PubMed DOI

Banks R.E., Tirukonda P., Taylor C., Hornigold N., Astuti D., Cohen D., Maher E.R., Stanley A.J., Harnden P., Joyce A., et al. Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer. Cancer Res. 2006;66:2000–2011. doi: 10.1158/0008-5472.CAN-05-3074. PubMed DOI

Latif F., Tory K., Gnarra J., Yao M., Duh F.M., Orcutt M.L., Stackhouse T., Kuzmin I., Modi W., Geil L., et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993;260:1317–1320. doi: 10.1126/science.8493574. PubMed DOI

Dalgliesh G.L., Furge K., Greenman C., Chen L., Bignell G., Butler A., Davies H., Edkins S., Hardy C., Latimer C., et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature. 2010;463:360–363. doi: 10.1038/nature08672. PubMed DOI PMC

Guo G., Gui Y., Gao S., Tang A., Hu X., Huang Y., Jia W., Li Z., He M., Sun L., et al. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nat. Genet. 2011;44:17–19. doi: 10.1038/ng.1014. PubMed DOI

Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature. 2011;469:539–542. doi: 10.1038/nature09639. PubMed DOI PMC

Suzigan S., Lopez-Beltran A., Montironi R., Drut R., Romero A., Hayashi T., Gentili A.L., Fonseca P.S., deTorres I., Billis A., et al. Multilocular cystic renal cell carcinoma: A report of 45 cases of a kidney tumor of low malignant potential. Am. J. Clin. Pathol. 2006;125:217–222. doi: 10.1309/AH6FC77PYR2V6YAY. PubMed DOI

Williamson S.R., Halat S., Eble J.N., Grignon D.J., Lopez-Beltran A., Montironi R., Tan P.H., Wang M., Zhang S., Maclennan G.T., et al. Multilocular cystic renal cell carcinoma: Similarities and differences in immunoprofile compared with clear cell renal cell carcinoma. Am. J. Surg. Pathol. 2012;36:1425–1433. doi: 10.1097/PAS.0b013e31825b37f0. PubMed DOI

Halat S., Eble J.N., Grignon D.J., Lopez-Beltran A., Montironi R., Tan P.H., Wang M., Zhang S., MacLennan G.T., Cheng L. Multilocular cystic renal cell carcinoma is a subtype of clear cell renal cell carcinoma. Mod. Pathol. 2010;23:931–936. doi: 10.1038/modpathol.2010.78. PubMed DOI

von Teichman A., Comperat E., Behnke S., Storz M., Moch H., Schraml P. VHL mutations and dysregulation of pVHL- and PTEN-controlled pathways in multilocular cystic renal cell carcinoma. Mod. Pathol. 2011;24:571–578. doi: 10.1038/modpathol.2010.222. PubMed DOI

Raspollini M.R., Castiglione F., Martignoni G., Cheng L., Montironi R., Lopez-Beltran A. Unlike in clear cell renal cell carcinoma, KRAS is not mutated in multilocular cystic clear cell renal cell neoplasm of low potential. Virchows Arch. 2015;467:687–693. doi: 10.1007/s00428-015-1859-8. PubMed DOI

Raspollini M.R., Castiglione F., Cheng L., Montironi R., Lopez-Beltran A. Synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential: A clinico-pathologic and molecular study. Pathol. Res. Pr. 2016;212:471–474. doi: 10.1016/j.prp.2016.01.001. PubMed DOI

Szymanska K., Moore L.E., Rothman N., Chow W.H., Waldman F., Jaeger E., Waterboer T., Foretova L., Navratilova M., Janout V., et al. TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe. Cancer Lett. 2010;293:92–98. doi: 10.1016/j.canlet.2009.11.024. PubMed DOI

Gattenlohner S., Etschmann B., Riedmiller H., Muller-Hermelink H.K. Lack of KRAS and BRAF mutation in renal cell carcinoma. Eur. Urol. 2009;55:1490–1491. doi: 10.1016/j.eururo.2009.02.024. PubMed DOI

Bayrak O., Sen H., Bulut E., Cengiz B., Karakok M., Erturhan S., Seckiner I. Evaluation of EGFR, KRAS and BRAF gene mutations in renal cell carcinoma. J. Kidney Cancer VHL. 2014;1:40–45. doi: 10.15586/jkcvhl.2014.10. PubMed DOI PMC

Sato Y., Yoshizato T., Shiraishi Y., Maekawa S., Okuno Y., Kamura T., Shimamura T., Sato-Otsubo A., Nagae G., Suzuki H., et al. Integrated molecular analysis of clear-cell renal cell carcinoma. Nat. Genet. 2013;45:860–867. doi: 10.1038/ng.2699. PubMed DOI

Cancer Genome Atlas Research N. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499:43–49. doi: 10.1038/nature12222. PubMed DOI PMC

Delahunt B., Algaba F., Eble J., Cheville J., Amin M.B., Argani P., Martignoni G., Moch H., Srigley J.R., Tan P.H., et al. Papillary renal cell carcinoma. In: Moch H., Humphrey P.A., Ulbright T.M., Reuter V.E., editors. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th ed. Volume 8. International Agency for Research on Cancer; Lyon, France: 2016. pp. 23–25.

Cancer Genome Atlas Research N., Linehan W.M., Spellman P.T., Ricketts C.J., Creighton C.J., Fei S.S., Davis C., Wheeler D.A., Murray B.A., Schmidt L., et al. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma. N. Engl. J. Med. 2016;374:135–145. doi: 10.1056/NEJMoa1505917. PubMed DOI PMC

Pitra T., Pivovarcikova K., Alaghehbandan R., Hes O. Chromosomal numerical aberration pattern in papillary renal cell carcinoma: Review article. Ann. Diagn. Pathol. 2019;40:189–199. doi: 10.1016/j.anndiagpath.2017.11.004. PubMed DOI

Zbar B., Tory K., Merino M., Schmidt L., Glenn G., Choyke P., Walther M.M., Lerman M., Linehan W.M. Hereditary papillary renal cell carcinoma. J. Urol. 1994;151:561–566. doi: 10.1016/S0022-5347(17)35015-2. PubMed DOI

Schmidt L., Duh F.M., Chen F., Kishida T., Glenn G., Choyke P., Scherer S.W., Zhuang Z., Lubensky I., Dean M., et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat. Genet. 1997;16:68–73. doi: 10.1038/ng0597-68. PubMed DOI

Dharmawardana P.G., Giubellino A., Bottaro D.P. Hereditary papillary renal carcinoma type I. Curr. Mol. Med. 2004;4:855–868. doi: 10.2174/1566524043359674. PubMed DOI

Lefevre M., Couturier J., Sibony M., Bazille C., Boyer K., Callard P., Vieillefond A., Allory Y. Adult papillary renal tumor with oncocytic cells: Clinicopathologic, immunohistochemical, and cytogenetic features of 10 cases. Am. J. Surg. Pathol. 2005;29:1576–1581. doi: 10.1097/01.pas.0000184821.09871.ec. PubMed DOI

Han G., Yu W., Chu J., Liu Y., Jiang Y., Li Y., Zhang W. Oncocytic papillary renal cell carcinoma: A clinicopathological and genetic analysis and indolent clinical course in 14 cases. Pathol. Res. Pr. 2017;213:1–6. doi: 10.1016/j.prp.2016.04.009. PubMed DOI

Kunju L.P., Wojno K., Wolf J.S., Jr., Cheng L., Shah R.B. Papillary renal cell carcinoma with oncocytic cells and nonoverlapping low grade nuclei: Expanding the morphologic spectrum with emphasis on clinicopathologic, immunohistochemical and molecular features. Hum. Pathol. 2008;39:96–101. doi: 10.1016/j.humpath.2007.05.016. PubMed DOI

Hes O., Brunelli M., Michal M., Cossu Rocca P., Hora M., Chilosi M., Mina M., Boudova L., Menestrina F., Martignoni G. Oncocytic papillary renal cell carcinoma: A clinicopathologic, immunohistochemical, ultrastructural, and interphase cytogenetic study of 12 cases. Ann. Diagn. Pathol. 2006;10:133–139. doi: 10.1016/j.anndiagpath.2005.12.002. PubMed DOI

Srigley J.R., Delahunt B., Eble J.N., Egevad L., Epstein J.I., Grignon D., Hes O., Moch H., Montironi R., Tickoo S.K., et al. The International Society of Urological Pathology (ISUP) Vancouver classification of renal neoplasia. Am. J. Surg. Pathol. 2013;37:1469–1489. doi: 10.1097/PAS.0b013e318299f2d1. PubMed DOI

Michalova K., Steiner P., Alaghehbandan R., Trpkov K., Martinek P., Grossmann P., Montiel D.P., Sperga M., Straka L., Prochazkova K., et al. Papillary renal cell carcinoma with cytologic and molecular genetic features overlapping with renal oncocytoma: Analysis of 10 cases. Ann. Diagn. Pathol. 2018;35:1–6. doi: 10.1016/j.anndiagpath.2018.01.010. PubMed DOI

Saleeb R.M., Brimo F., Farag M., Rompre-Brodeur A., Rotondo F., Beharry V., Wala S., Plant P., Downes M.R., Pace K., et al. Toward Biological Subtyping of Papillary Renal Cell Carcinoma With Clinical Implications Through Histologic, Immunohistochemical, and Molecular Analysis. Am. J. Surg. Pathol. 2017;41:1618–1629. doi: 10.1097/PAS.0000000000000962. PubMed DOI

Al-Obaidy K.I., Eble J.N., Cheng L., Williamson S.R., Sakr W.A., Gupta N., Idrees M.T., Grignon D.J. Papillary Renal Neoplasm with Reverse Polarity: A Morphologic, Immunohistochemical, and Molecular Study. Am. J. Surg. Pathol. 2019;43:1099–1111. doi: 10.1097/PAS.0000000000001288. PubMed DOI

Al-Obaidy K.I., Eble J.N., Nassiri M., Cheng L., Eldomery M.K., Williamson S.R., Sakr W.A., Gupta N., Hassan O., Idrees M.T., et al. Recurrent KRAS mutations in papillary renal neoplasm with reverse polarity. Mod. Pathol. 2019 doi: 10.1038/s41379-019-0362-1. PubMed DOI

Marsaud A., Dadone B., Ambrosetti D., Baudoin C., Chamorey E., Rouleau E., Lefol C., Roussel J.F., Fabas T., Cristofari G., et al. Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic profiles suggests several independent diseases. Genes Chromosomes Cancer. 2015;54:369–382. doi: 10.1002/gcc.22248. PubMed DOI

Pivovarcikova K., Peckova K., Martinek P., Montiel D.P., Kalusova K., Pitra T., Hora M., Skenderi F., Ulamec M., Daum O., et al. “Mucin”-secreting papillary renal cell carcinoma: Clinicopathological, immunohistochemical, and molecular genetic analysis of seven cases. Virchows Arch. 2016;469:71–80. doi: 10.1007/s00428-016-1936-7. PubMed DOI

Peckova K., Martinek P., Pivovarcikova K., Vanecek T., Alaghehbandan R., Prochazkova K., Montiel D.P., Hora M., Skenderi F., Ulamec M., et al. Cystic and necrotic papillary renal cell carcinoma: Prognosis, morphology, immunohistochemical, and molecular-genetic profile of 10 cases. Ann. Diagn Pathol. 2017;26:23–30. doi: 10.1016/j.anndiagpath.2016.10.007. PubMed DOI

Ulamec M., Skenderi F., Trpkov K., Kruslin B., Vranic S., Bulimbasic S., Trivunic S., Montiel D.P., Peckova K., Pivovarcikova K., et al. Solid papillary renal cell carcinoma: Clinicopathologic, morphologic, and immunohistochemical analysis of 10 cases and review of the literature. Ann. Diagn. Pathol. 2016;23:51–57. doi: 10.1016/j.anndiagpath.2016.04.008. PubMed DOI

Hes O., Condom Mundo E., Peckova K., Lopez J.I., Martinek P., Vanecek T., Falconieri G., Agaimy A., Davidson W., Petersson F., et al. Biphasic Squamoid Alveolar Renal Cell Carcinoma: A Distinctive Subtype of Papillary Renal Cell Carcinoma? Am. J. Surg. Pathol. 2016;40:664–675. doi: 10.1097/PAS.0000000000000639. PubMed DOI

Trpkov K., Athanazio D., Magi-Galluzzi C., Yilmaz H., Clouston D., Agaimy A., Williamson S.R., Brimo F., Lopez J.I., Ulamec M., et al. Biphasic papillary renal cell carcinoma is a rare morphological variant with frequent multifocality: A study of 28 cases. Histopathology. 2018;72:777–785. doi: 10.1111/his.13432. PubMed DOI

Skenderi F., Ulamec M., Vanecek T., Martinek P., Alaghehbandan R., Foix M.P., Babankova I., Montiel D.P., Alvarado-Cabrero I., Svajdler M., et al. Warthin-like papillary renal cell carcinoma: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 11 cases. Ann. Diagn. Pathol. 2017;27:48–56. doi: 10.1016/j.anndiagpath.2017.01.005. PubMed DOI

Hes O., Vanecek T., Perez-Montiel D.M., Alvarado Cabrero I., Hora M., Suster S., Lamovec J., Curik R., Mandys V., Michal M. Chromophobe renal cell carcinoma with microcystic and adenomatous arrangement and pigmentation--a diagnostic pitfall. Morphological, immunohistochemical, ultrastructural and molecular genetic report of 20 cases. Virchows Arch. 2005;446:383–393. doi: 10.1007/s00428-004-1187-x. PubMed DOI

Michal M., Hes O., Svec A., Ludvikova M. Pigmented microcystic chromophobe cell carcinoma: A unique variant of renal cell carcinoma. Ann. Diagn. Pathol. 1998;2:149–153. doi: 10.1016/S1092-9134(98)80001-4. PubMed DOI

Dundr P., Pesl M., Povysil C., Tvrdik D., Pavlik I., Soukup V., Dvoracek J. Pigmented microcystic chromophobe renal cell carcinoma. Pathol. Res. Pr. 2007;203:593–597. doi: 10.1016/j.prp.2007.05.005. PubMed DOI

Foix M.P., Dunatov A., Martinek P., Mundo E.C., Suster S., Sperga M., Lopez J.I., Ulamec M., Bulimbasic S., Montiel D.P., et al. Morphological, immunohistochemical, and chromosomal analysis of multicystic chromophobe renal cell carcinoma, an architecturally unusual challenging variant. Virchows Arch. 2016;469:669–678. doi: 10.1007/s00428-016-2022-x. PubMed DOI

Peckova K., Martinek P., Ohe C., Kuroda N., Bulimbasic S., Condom Mundo E., Perez Montiel D., Lopez J.I., Daum O., Rotterova P., et al. Chromophobe renal cell carcinoma with neuroendocrine and neuroendocrine-like features. Morphologic, immunohistochemical, ultrastructural, and array comparative genomic hybridization analysis of 18 cases and review of the literature. Ann. Diagn. Pathol. 2015;19:261–268. doi: 10.1016/j.anndiagpath.2015.05.001. PubMed DOI

Parada D.D., Pena K.B. Chromophobe renal cell carcinoma with neuroendocrine differentiation. APMIS. 2008;116:859–865. doi: 10.1111/j.1600-0463.2008.01004.x. PubMed DOI

Kuroda N., Tamura M., Hes O., Michal M., Gatalica Z. Chromophobe renal cell carcinoma with neuroendocrine differentiation and sarcomatoid change. Pathol. Int. 2011;61:552–554. doi: 10.1111/j.1440-1827.2011.02689.x. PubMed DOI

Mokhtar G.A., Al-Zahrani R. Chromophobe renal cell carcinoma of the kidney with neuroendocrine differentiation: A case report with review of literature. Urol. Ann. 2015;7:383–386. doi: 10.4103/0974-7796.158506. PubMed DOI PMC

Ohe C., Kuroda N., Matsuura K., Kai T., Moriyama M., Sugiguchi S., Terahata S., Hosaka N., Hes O., Michal M., et al. Chromophobe renal cell carcinoma with neuroendocrine differentiation/morphology: A clinicopathological and genetic study of three cases. Hum. Pathol. Case Rep. 2014;1:31–39. doi: 10.1016/j.ehpc.2014.08.003. DOI

Kuroda N., Tanaka A., Yamaguchi T., Kasahara K., Naruse K., Yamada Y., Hatanaka K., Shinohara N., Nagashima Y., Mikami S., et al. Chromophobe renal cell carcinoma, oncocytic variant: A proposal of a new variant giving a critical diagnostic pitfall in diagnosing renal oncocytic tumors. Med. Mol. Morphol. 2013;46:49–55. doi: 10.1007/s00795-012-0007-7. PubMed DOI

Speicher M.R., Schoell B., du Manoir S., Schrock E., Ried T., Cremer T., Storkel S., Kovacs A., Kovacs G. Specific loss of chromosomes 1, 2, 6, 10, 13, 17, and 21 in chromophobe renal cell carcinomas revealed by comparative genomic hybridization. Am. J. Pathol. 1994;145:356–364. PubMed PMC

Paner G., Amin M.B., Moch H., Störkel S. Chromophobe renal cell carcinoma. In: Moch H., Humphrey P.A., Ulbright T.M., Reuter V.E., editors. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th ed. Volume 8. International Agency for Research on Cancer; Lyon, France: 2016. pp. 27–28.

Davis C.F., Ricketts C.J., Wang M., Yang L., Cherniack A.D., Shen H., Buhay C., Kang H., Kim S.C., Fahey C.C., et al. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014;26:319–330. doi: 10.1016/j.ccr.2014.07.014. PubMed DOI PMC

Vieira J., Henrique R., Ribeiro F.R., Barros-Silva J.D., Peixoto A., Santos C., Pinheiro M., Costa V.L., Soares M.J., Oliveira J., et al. Feasibility of differential diagnosis of kidney tumors by comparative genomic hybridization of fine needle aspiration biopsies. Genes Chromosomes Cancer. 2010;49:935–947. doi: 10.1002/gcc.20805. PubMed DOI

Sperga M., Martinek P., Vanecek T., Grossmann P., Bauleth K., Perez-Montiel D., Alvarado-Cabrero I., Nevidovska K., Lietuvietis V., Hora M., et al. Chromophobe renal cell carcinoma--chromosomal aberration variability and its relation to Paner grading system: An array CGH and FISH analysis of 37 cases. Virchows Arch. 2013;463:563–573. doi: 10.1007/s00428-013-1457-6. PubMed DOI

Tan M.H., Wong C.F., Tan H.L., Yang X.J., Ditlev J., Matsuda D., Khoo S.K., Sugimura J., Fujioka T., Furge K.A., et al. Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma. BMC Cancer. 2010;10:196. doi: 10.1186/1471-2407-10-196. PubMed DOI PMC

Crotty T.B., Lawrence K.M., Moertel C.A., Bartelt D.H., Jr., Batts K.P., Dewald G.W., Farrow G.M., Jenkins R.B. Cytogenetic analysis of six renal oncocytomas and a chromophobe cell renal carcinoma. Evidence that -Y, -1 may be a characteristic anomaly in renal oncocytomas. Cancer Genet Cytogenet. 1992;61:61–66. doi: 10.1016/0165-4608(92)90372-F. PubMed DOI

Fuzesi L., Gunawan B., Braun S., Boeckmann W. Renal oncocytoma with a translocation t(9;11)(p23;q13) J. Urol. 1994;152:471–472. doi: 10.1016/S0022-5347(17)32766-0. PubMed DOI

Paner G.P., Lindgren V., Jacobson K., Harrison K., Cao Y., Campbell S.C., Flanigan R.C., Picken M.M. High incidence of chromosome 1 abnormalities in a series of 27 renal oncocytomas: Cytogenetic and fluorescence in situ hybridization studies. Arch. Pathol. Lab. Med. 2007;131:81–85. doi: 10.1043/1543-2165(2007)131[81:HIOCAI]2.0.CO;2. PubMed DOI

Lindgren V., Paner G.P., Omeroglu A., Campbell S.C., Waters W.B., Flanigan R.C., Picken M.M. Cytogenetic analysis of a series of 13 renal oncocytomas. J. Urol. 2004;171:602–604. doi: 10.1097/01.ju.0000109172.07081.16. PubMed DOI

Picken M.M., Chyna B., Flanigan R.C., Lee J.M. Analysis of chromosome 1p abnormalities in renal oncocytomas by loss of heterozygosity studies: Correlation with conventional cytogenetics and fluorescence in situ hybridization. Am. J. Clin. Pathol. 2008;129:377–382. doi: 10.1309/KC2465ANDWVAXYDM. PubMed DOI

Anderson C.B., Lipsky M., Nandula S.V., Freeman C.E., Matthews T., Walsh C.E., Li G., Szabolcs M., Mansukhani M.M., McKiernan J.M., et al. Cytogenetic analysis of 130 renal oncocytomas identify three distinct and mutually exclusive diagnostic classes of chromosome aberrations. Genes Chromosomes Cancer. 2019 doi: 10.1002/gcc.22766. PubMed DOI

Joshi S., Tolkunov D., Aviv H., Hakimi A.A., Yao M., Hsieh J.J., Ganesan S., Chan C.S., White E. The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis. Cell Rep. 2015;13:1895–1908. doi: 10.1016/j.celrep.2015.10.059. PubMed DOI PMC

Sukov W.R., Ketterling R.P., Lager D.J., Carlson A.W., Sinnwell J.P., Chow G.K., Jenkins R.B., Cheville J.C. CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas: Frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma. Hum. Pathol. 2009;40:1296–1303. doi: 10.1016/j.humpath.2009.01.016. PubMed DOI

Williamson S.R., Eble J.N., Cheng L., Grignon D.J. Clear cell papillary renal cell carcinoma: Differential diagnosis and extended immunohistochemical profile. Mod. Pathol. 2013;26:697–708. doi: 10.1038/modpathol.2012.204. PubMed DOI

Mantilla J.G., Antic T., Tretiakova M.S. GATA-3 Is a Specific Marker for Clear Cell Papillary Renal Cell Carcinoma. Mod. Pathol. 2017;30:241A. PubMed

Martignoni G., Brunelli M., Segala D., Munari E., Gobbo S., Cima L., Borze I., Wirtanen T., Sarhadi V.K., Atanesyan L., et al. Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker. Pathology. 2017;49:10–18. doi: 10.1016/j.pathol.2016.05.014. PubMed DOI

Hes O., Comperat E.M., Rioux-Leclercq N. Clear cell papillary renal cell carcinoma, renal angiomyoadenomatous tumor, and renal cell carcinoma with leiomyomatous stroma relationship of 3 types of renal tumors: A review. Ann. Diagn. Pathol. 2016;21:59–64. doi: 10.1016/j.anndiagpath.2015.11.003. PubMed DOI

Gandhi J.S., Malik F., Amin M.B., Argani P., Bahrami A. MiT family translocation renal cell carcinomas: A 15th anniversary update. Histol. Histopathol. 2019:18159. doi: 10.14670/HH-18-159. PubMed DOI

Argani P., Antonescu C.R., Illei P.B., Lui M.Y., Timmons C.F., Newbury R., Reuter V.E., Garvin A.J., Perez-Atayde A.R., Fletcher J.A., et al. Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: A distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am. J. Pathol. 2001;159:179–192. doi: 10.1016/S0002-9440(10)61684-7. PubMed DOI PMC

Argani P., Lui M.Y., Couturier J., Bouvier R., Fournet J.C., Ladanyi M. A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23) Oncogene. 2003;22:5374–5378. doi: 10.1038/sj.onc.1206686. PubMed DOI

Argani P., Ladanyi M. Renal carcinomas associated with Xp11.2 translocations / TFE3 gene fusions. In: Eble J.N., Sauter G., Epstein J.I., Sesterhenn I.A., editors. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. 1st ed. IARC Press; Lyon, France: 2004. pp. 37–38.

Argani P., Olgac S., Tickoo S.K., Goldfischer M., Moch H., Chan D.Y., Eble J.N., Bonsib S.M., Jimeno M., Lloreta J., et al. Xp11 translocation renal cell carcinoma in adults: Expanded clinical, pathologic, and genetic spectrum. Am. J. Surg. Pathol. 2007;31:1149–1160. doi: 10.1097/PAS.0b013e318031ffff. PubMed DOI

Argani P., Hicks J., De Marzo A.M., Albadine R., Illei P.B., Ladanyi M., Reuter V.E., Netto G.J. Xp11 translocation renal cell carcinoma (RCC): Extended immunohistochemical profile emphasizing novel RCC markers. Am. J. Surg. Pathol. 2010;34:1295–1303. doi: 10.1097/PAS.0b013e3181e8ce5b. PubMed DOI PMC

Ellis C.L., Eble J.N., Subhawong A.P., Martignoni G., Zhong M., Ladanyi M., Epstein J.I., Netto G.J., Argani P. Clinical heterogeneity of Xp11 translocation renal cell carcinoma: Impact of fusion subtype, age, and stage. Mod. Pathol. 2014;27:875–886. doi: 10.1038/modpathol.2013.208. PubMed DOI

Argani P. MiT family translocation renal cell carcinoma. Semin. Diagn. Pathol. 2015;32:103–113. doi: 10.1053/j.semdp.2015.02.003. PubMed DOI

Argani P., Zhong M., Reuter V.E., Fallon J.T., Epstein J.I., Netto G.J., Antonescu C.R. TFE3-Fusion Variant Analysis Defines Specific Clinicopathologic Associations Among Xp11 Translocation Cancers. Am. J. Surg. Pathol. 2016;40:723–737. doi: 10.1097/PAS.0000000000000631. PubMed DOI PMC

Hayes M., Peckova K., Martinek P., Hora M., Kalusova K., Straka L., Daum O., Kokoskova B., Rotterova P., Pivovarcikova K., et al. Molecular-genetic analysis is essential for accurate classification of renal carcinoma resembling Xp11.2 translocation carcinoma. Virchows Arch. 2015;466:313–322. doi: 10.1007/s00428-014-1702-7. PubMed DOI

Kato I., Furuya M., Baba M., Kameda Y., Yasuda M., Nishimoto K., Oyama M., Yamasaki T., Ogawa O., Niino H., et al. RBM10-TFE3 renal cell carcinoma characterised by paracentric inversion with consistent closely split signals in break-apart fluorescence in-situ hybridisation: Study of 10 cases and a literature review. Histopathology. 2019;75:254–265. doi: 10.1111/his.13866. PubMed DOI

Malouf G.G., Su X., Yao H., Gao J., Xiong L., He Q., Comperat E., Couturier J., Molinie V., Escudier B., et al. Next-generation sequencing of translocation renal cell carcinoma reveals novel RNA splicing partners and frequent mutations of chromatin-remodeling genes. Clin. Cancer Res. 2014;20:4129–4140. doi: 10.1158/1078-0432.CCR-13-3036. PubMed DOI PMC

Thway K., du Parcq J., Larkin J.M., Fisher C., Livni N. Metastatic renal mucinous tubular and spindle cell carcinoma. Atypical behavior of a rare, morphologically bland tumor. Ann. Diagn. Pathol. 2012;16:407–410. doi: 10.1016/j.anndiagpath.2011.04.001. PubMed DOI

Dhillon J., Amin M.B., Selbs E., Turi G.K., Paner G.P., Reuter V.E. Mucinous tubular and spindle cell carcinoma of the kidney with sarcomatoid change. Am. J. Surg. Pathol. 2009;33:44–49. doi: 10.1097/PAS.0b013e3181829ed5. PubMed DOI

Bulimbasic S., Ljubanovic D., Sima R., Michal M., Hes O., Kuroda N., Persec Z. Aggressive high-grade mucinous tubular and spindle cell carcinoma. Hum. Pathol. 2009;40:906–907. doi: 10.1016/j.humpath.2009.03.004. PubMed DOI

Paner G.P., Srigley J.R., Radhakrishnan A., Cohen C., Skinnider B.F., Tickoo S.K., Young A.N., Amin M.B. Immunohistochemical analysis of mucinous tubular and spindle cell carcinoma and papillary renal cell carcinoma of the kidney: Significant immunophenotypic overlap warrants diagnostic caution. Am J Surg. Pathol. 2006;30:13–19. doi: 10.1097/01.pas.0000180443.94645.50. PubMed DOI

Ren Q., Wang L., Al-Ahmadie H.A., Fine S.W., Gopalan A., Sirintrapun S.J., Tickoo S.K., Reuter V.E., Chen Y.B. Distinct Genomic Copy Number Alterations Distinguish Mucinous Tubular and Spindle Cell Carcinoma of the Kidney From Papillary Renal Cell Carcinoma With Overlapping Histologic Features. Am. J. Surg. Pathol. 2018;42:767–777. doi: 10.1097/PAS.0000000000001038. PubMed DOI PMC

Peckova K., Martinek P., Sperga M., Montiel D.P., Daum O., Rotterova P., Kalusova K., Hora M., Pivovarcikova K., Rychly B., et al. Mucinous spindle and tubular renal cell carcinoma: Analysis of chromosomal aberration pattern of low-grade, high-grade, and overlapping morphologic variant with papillary renal cell carcinoma. Ann. Diagn. Pathol. 2015;19:226–231. doi: 10.1016/j.anndiagpath.2015.04.004. PubMed DOI

Sadimin E.T., Chen Y.B., Wang L., Argani P., Epstein J.I. Chromosomal abnormalities of high-grade mucinous tubular and spindle cell carcinoma of the kidney. Histopathology. 2017;71:719–724. doi: 10.1111/his.13298. PubMed DOI

Cossu-Rocca P., Eble J.N., Delahunt B., Zhang S., Martignoni G., Brunelli M., Cheng L. Renal mucinous tubular and spindle carcinoma lacks the gains of chromosomes 7 and 17 and losses of chromosome Y that are prevalent in papillary renal cell carcinoma. Mod. Pathol. 2006;19:488–493. doi: 10.1038/modpathol.3800565. PubMed DOI

Zhou M., Yang X.J., Lopez J.I., Shah R.B., Hes O., Shen S.S., Li R., Yang Y., Lin F., Elson P., et al. Renal tubulocystic carcinoma is closely related to papillary renal cell carcinoma: Implications for pathologic classification. Am. J. Surg. Pathol. 2009;33:1840–1849. doi: 10.1097/PAS.0b013e3181be22d1. PubMed DOI

Tran T., Jones C.L., Williamson S.R., Eble J.N., Grignon D.J., Zhang S., Wang M., Baldridge L.A., Wang L., Montironi R., et al. Tubulocystic renal cell carcinoma is an entity that is immunohistochemically and genetically distinct from papillary renal cell carcinoma. Histopathology. 2016;68:850–857. doi: 10.1111/his.12840. PubMed DOI

Yang X.J., Zhou M., Hes O., Shen S., Li R., Lopez J., Shah R.B., Yang Y., Chuang S.T., Lin F., et al. Tubulocystic carcinoma of the kidney: Clinicopathologic and molecular characterization. Am. J. Surg. Pathol. 2008;32:177–187. doi: 10.1097/PAS.0b013e318150df1d. PubMed DOI

Sarungbam J., Mehra R., Tomlins S.A., Smith S.C., Jayakumaran G., Al-Ahmadie H., Gopalan A., Sirintrapun S.J., Fine S.W., Zhang Y., et al. Tubulocystic renal cell carcinoma: A distinct clinicopathologic entity with a characteristic genomic profile. Mod. Pathol. 2019;32:701–709. doi: 10.1038/s41379-018-0185-5. PubMed DOI PMC

Al-Hussain T.O., Cheng L., Zhang S., Epstein J.I. Tubulocystic carcinoma of the kidney with poorly differentiated foci: A series of 3 cases with fluorescence in situ hybridization analysis. Hum. Pathol. 2013;44:1406–1411. doi: 10.1016/j.humpath.2012.11.015. PubMed DOI

Smith S.C., Trpkov K., Chen Y.B., Mehra R., Sirohi D., Ohe C., Cani A.K., Hovelson D.H., Omata K., McHugh J.B., et al. Tubulocystic Carcinoma of the Kidney With Poorly Differentiated Foci: A Frequent Morphologic Pattern of Fumarate Hydratase-deficient Renal Cell Carcinoma. Am. J. Surg. Pathol. 2016;40:1457–1472. doi: 10.1097/PAS.0000000000000719. PubMed DOI PMC

Kuroda N., Ohe C., Mikami S., Hes O., Michal M., Brunelli M., Martignoni G., Sato Y., Yoshino T., Kakehi Y., et al. Review of acquired cystic disease-associated renal cell carcinoma with focus on pathobiological aspects. Histol. Histopathol. 2011;26:1215–1218. doi: 10.14670/HH-26.1215. PubMed DOI

Kuroda N., Shiotsu T., Hes O., Michal M., Shuin T., Lee G.H. Acquired cystic disease-associated renal cell carcinoma with gain of chromosomes 3, 7, and 16, gain of chromosome X, and loss of chromosome Y. Med. Mol. Morphol. 2010;43:231–234. doi: 10.1007/s00795-009-0465-8. PubMed DOI

Kuroda N., Tamura M., Hamaguchi N., Mikami S., Pan C.C., Brunelli M., Martignoni G., Hes O., Michal M., Lee G.H. Acquired cystic disease-associated renal cell carcinoma with sarcomatoid change and rhabdoid features. Ann. Diagn. Pathol. 2011;15:462–466. doi: 10.1016/j.anndiagpath.2010.07.008. PubMed DOI

Kuroda N., Yamashita M., Kakehi Y., Hes O., Michal M., Lee G.H. Acquired cystic disease-associated renal cell carcinoma: An immunohistochemical and fluorescence in situ hybridization study. Med. Mol. Morphol. 2011;44:228–232. doi: 10.1007/s00795-010-0496-1. PubMed DOI

Cossu-Rocca P., Eble J.N., Zhang S., Martignoni G., Brunelli M., Cheng L. Acquired cystic disease-associated renal tumors: An immunohistochemical and fluorescence in situ hybridization study. Mod. Pathol. 2006;19:780–787. doi: 10.1038/modpathol.3800604. PubMed DOI

Kuntz E., Yusenko M.V., Nagy A., Kovacs G. Oligoarray comparative genomic hybridization of renal cell tumors that developed in patients with acquired cystic renal disease. Hum. Pathol. 2010;41:1345–1349. doi: 10.1016/j.humpath.2009.09.022. PubMed DOI

Ohe C., Smith S.C., Sirohi D., Divatia M., de Peralta-Venturina M., Paner G.P., Agaimy A., Amin M.B., Argani P., Chen Y.B., et al. Reappraisal of Morphologic Differences Between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma. Am. J. Surg. Pathol. 2018;42:279–292. doi: 10.1097/PAS.0000000000001000. PubMed DOI PMC

Jia L., Carlo M.I., Khan H., Nanjangud G.J., Rana S., Cimera R., Zhang Y., Hakimi A.A., Verma A.K., Al-Ahmadie H.A., et al. Distinctive mechanisms underlie the loss of SMARCB1 protein expression in renal medullary carcinoma: Morphologic and molecular analysis of 20 cases. Mod. Pathol. 2019;32:1329–1343. doi: 10.1038/s41379-019-0273-1. PubMed DOI PMC

Calderaro J., Masliah-Planchon J., Richer W., Maillot L., Maille P., Mansuy L., Bastien C., de la Taille A., Boussion H., Charpy C., et al. Balanced Translocations Disrupting SMARCB1 Are Hallmark Recurrent Genetic Alterations in Renal Medullary Carcinomas. Eur. Urol. 2016;69:1055–1061. doi: 10.1016/j.eururo.2015.09.027. PubMed DOI

Carlo M.I., Chaim J., Patil S., Kemel Y., Schram A.M., Woo K., Coskey D., Nanjangud G.J., Voss M.H., Feldman D.R., et al. Genomic Characterization of Renal Medullary Carcinoma and Treatment Outcomes. Clin. Genitourin. Cancer. 2017;15:e987–e994. doi: 10.1016/j.clgc.2017.04.012. PubMed DOI PMC

Calderaro J., Moroch J., Pierron G., Pedeutour F., Grison C., Maille P., Soyeux P., de la Taille A., Couturier J., Vieillefond A., et al. SMARCB1/INI1 inactivation in renal medullary carcinoma. Histopathology. 2012;61:428–435. doi: 10.1111/j.1365-2559.2012.04228.x. PubMed DOI

Liu Q., Galli S., Srinivasan R., Linehan W.M., Tsokos M., Merino M.J. Renal medullary carcinoma: Molecular, immunohistochemistry, and morphologic correlation. Am. J. Surg. Pathol. 2013;37:368–374. doi: 10.1097/PAS.0b013e3182770406. PubMed DOI PMC

Cheng J.X., Tretiakova M., Gong C., Mandal S., Krausz T., Taxy J.B. Renal medullary carcinoma: Rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Mod. Pathol. 2008;21:647–652. doi: 10.1038/modpathol.2008.44. PubMed DOI

Rao P., Tannir N.M., Tamboli P. Expression of OCT3/4 in renal medullary carcinoma represents a potential diagnostic pitfall. Am. J. Surg. Pathol. 2012;36:583–588. doi: 10.1097/PAS.0b013e3182417d78. PubMed DOI

Sirohi D., Smith S.C., Ohe C., Colombo P., Divatia M., Dragoescu E., Rao P., Hirsch M.S., Chen Y.B., Mehra R., et al. Renal cell carcinoma, unclassified with medullary phenotype: Poorly differentiated adenocarcinomas overlapping with renal medullary carcinoma. Hum. Pathol. 2017;67:134–145. doi: 10.1016/j.humpath.2017.07.006. PubMed DOI

Amin M.B., Smith S.C., Agaimy A., Argani P., Comperat E.M., Delahunt B., Epstein J.I., Eble J.N., Grignon D.J., Hartmann A., et al. Collecting duct carcinoma versus renal medullary carcinoma: An appeal for nosologic and biological clarity. Am. J. Surg. Pathol. 2014;38:871–874. doi: 10.1097/PAS.0000000000000222. PubMed DOI

Gill A.J. Succinate dehydrogenase (SDH) and mitochondrial driven neoplasia. Pathology. 2012;44:285–292. doi: 10.1097/PAT.0b013e3283539932. PubMed DOI

Gill A.J. Succinate dehydrogenase (SDH)-deficient neoplasia. Histopathology. 2018;72:106–116. doi: 10.1111/his.13277. PubMed DOI

Gill A.J., Benn D.E., Chou A., Clarkson A., Muljono A., Meyer-Rochow G.Y., Richardson A.L., Sidhu S.B., Robinson B.G., Clifton-Bligh R.J. Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes. Hum. Pathol. 2010;41:805–814. doi: 10.1016/j.humpath.2009.12.005. PubMed DOI

van Nederveen F.H., Gaal J., Favier J., Korpershoek E., Oldenburg R.A., de Bruyn E.M., Sleddens H.F., Derkx P., Riviere J., Dannenberg H., et al. An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: A retrospective and prospective analysis. Lancet Oncol. 2009;10:764–771. doi: 10.1016/S1470-2045(09)70164-0. PubMed DOI PMC

Merino M.J., Linehan W.M. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated renal cell carcinoma. In: Moch H., Humphrey P.A., Ulbright T.M., Reuter V.E., editors. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th ed. Volume 8. International Agency for Research on Cancer; Lyon, France: 2016. pp. 25–26.

Trpkov K., Hes O., Agaimy A., Bonert M., Martinek P., Magi-Galluzzi C., Kristiansen G., Luders C., Nesi G., Comperat E., et al. Fumarate Hydratase-deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome. Am. J. Surg. Pathol. 2016;40:865–875. doi: 10.1097/PAS.0000000000000617. PubMed DOI

Pivovarcikova K., Martinek P., Grossmann P., Trpkov K., Alaghehbandan R., Magi-Galluzzi C., Pane Foix M., Condom Mundo E., Berney D., Gill A., et al. Fumarate hydratase deficient renal cell carcinoma: Chromosomal numerical aberration analysis of 12 cases. Ann. Diagn. Pathol. 2019;39:63–68. doi: 10.1016/j.anndiagpath.2019.02.008. PubMed DOI

Lau H.D., Chan E., Fan A.C., Kunder C.A., Williamson S.R., Zhou M., Idrees M.T., Maclean F.M., Gill A.J., Kao C.S. A Clinicopathologic and Molecular Analysis of Fumarate Hydratase-Deficient Renal Cell Carcinoma in 32 Patients. Am. J. Surg. Pathol. 2019 doi: 10.1097/PAS.0000000000001372. PubMed DOI

Shyu I., Mirsadraei L., Wang X., Robila V., Mehra R., McHugh J.B., Chen Y.B., Udager A.M., Gill A.J., Cheng L., et al. Clues to recognition of fumarate hydratase-deficient renal cell carcinoma: Findings from cytologic and limited biopsy samples. Cancer Cytopathol. 2018 doi: 10.1002/cncy.22071. PubMed DOI PMC

Chen Y.B., Brannon A.R., Toubaji A., Dudas M.E., Won H.H., Al-Ahmadie H.A., Fine S.W., Gopalan A., Frizzell N., Voss M.H., et al. Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: Recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. Am. J. Surg. Pathol. 2014;38:627–637. doi: 10.1097/PAS.0000000000000163. PubMed DOI PMC

Muller M., Guillaud-Bataille M., Salleron J., Genestie C., Deveaux S., Slama A., de Paillerets B.B., Richard S., Benusiglio P.R., Ferlicot S. Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration. Mod. Pathol. 2018;31:974–983. doi: 10.1038/s41379-018-0017-7. PubMed DOI

Harrison W.J., Andrici J., Maclean F., Madadi-Ghahan R., Farzin M., Sioson L., Toon C.W., Clarkson A., Watson N., Pickett J., et al. Fumarate Hydratase-deficient Uterine Leiomyomas Occur in Both the Syndromic and Sporadic Settings. Am. J. Surg. Pathol. 2016;40:599–607. doi: 10.1097/PAS.0000000000000573. PubMed DOI PMC

Guo J., Tretiakova M.S., Troxell M.L., Osunkoya A.O., Fadare O., Sangoi A.R., Shen S.S., Lopez-Beltran A., Mehra R., Heider A., et al. Tuberous sclerosis-associated renal cell carcinoma: A clinicopathologic study of 57 separate carcinomas in 18 patients. Am. J. Surg. Pathol. 2014;38:1457–1467. doi: 10.1097/PAS.0000000000000248. PubMed DOI

Yang P., Cornejo K.M., Sadow P.M., Cheng L., Wang M., Xiao Y., Jiang Z., Oliva E., Jozwiak S., Nussbaum R.L., et al. Renal cell carcinoma in tuberous sclerosis complex. Am. J. Surg. Pathol. 2014;38:895–909. doi: 10.1097/PAS.0000000000000237. PubMed DOI PMC

Trpkov K., Hes O., Bonert M., Lopez J.I., Bonsib S.M., Nesi G., Comperat E., Sibony M., Berney D.M., Martinek P., et al. Eosinophilic, Solid, and Cystic Renal Cell Carcinoma: Clinicopathologic Study of 16 Unique, Sporadic Neoplasms Occurring in Women. Am. J. Surg. Pathol. 2016;40:60–71. doi: 10.1097/PAS.0000000000000508. PubMed DOI

Mehra R., Vats P., Cao X., Su F., Lee N.D., Lonigro R., Premkumar K., Trpkov K., McKenney J.K., Dhanasekaran S.M., et al. Somatic Bi-allelic Loss of TSC Genes in Eosinophilic Solid and Cystic Renal Cell Carcinoma. Eur. Urol. 2018;74:483–486. doi: 10.1016/j.eururo.2018.06.007. PubMed DOI PMC

Palsgrove D.N., Li Y., Pratilas C.A., Lin M.T., Pallavajjalla A., Gocke C., De Marzo A.M., Matoso A., Netto G.J., Epstein J.I., et al. Eosinophilic Solid and Cystic (ESC) Renal Cell Carcinomas Harbor TSC Mutations: Molecular Analysis Supports an Expanding Clinicopathologic Spectrum. Am. J. Surg. Pathol. 2018;42:1166–1181. doi: 10.1097/PAS.0000000000001111. PubMed DOI PMC

Parilla M., Kadri S., Patil S.A., Ritterhouse L., Segal J., Henriksen K.J., Antic T. Are Sporadic Eosinophilic Solid and Cystic Renal Cell Carcinomas Characterized by Somatic Tuberous Sclerosis Gene Mutations? Am. J. Surg. Pathol. 2018;42:911–917. doi: 10.1097/PAS.0000000000001067. PubMed DOI

Tretiakova M.S. Eosinophilic solid and cystic renal cell carcinoma mimicking epithelioid angiomyolipoma: Series of 4 primary tumors and 2 metastases. Hum. Pathol. 2018;80:65–75. doi: 10.1016/j.humpath.2018.05.023. PubMed DOI

Li Y., Reuter V.E., Matoso A., Netto G.J., Epstein J.I., Argani P. Re-evaluation of 33 ‘unclassified’ eosinophilic renal cell carcinomas in young patients. Histopathology. 2018;72:588–600. doi: 10.1111/his.13395. PubMed DOI PMC

Williamson S.R. Renal cell carcinomas with a mesenchymal stromal component: What do we know so far? Pathology. 2019;51:453–462. doi: 10.1016/j.pathol.2019.04.006. PubMed DOI

Williamson S.R., Hornick J.L., Eble J.N., Gupta N.S., Rogers C.G., True L., Grignon D.J., Cheng L. Renal cell carcinoma with angioleiomyoma-like stroma and clear cell papillary renal cell carcinoma: Exploring SDHB protein immunohistochemistry and the relationship to tuberous sclerosis complex. Hum. Pathol. 2018;75:10–15. doi: 10.1016/j.humpath.2017.11.013. PubMed DOI

Parilla M., Alikhan M., Al-Kawaaz M., Patil S., Kadri S., Ritterhouse L.L., Segal J., Fitzpatrick C., Antic T. Genetic Underpinnings of Renal Cell Carcinoma With Leiomyomatous Stroma. Am. J. Surg. Pathol. 2019;43:1135–1144. doi: 10.1097/PAS.0000000000001255. PubMed DOI

Verkarre V., Mensah A., Leroy X., Sibony M., Vasiliu V., Comperat E., Richard S., Mejean A. A Clinico-Pathologic Study of 17 Patients with Renal Cell Carcinoma Associated With Leiomyomatous Stroma Identifies a Strong Association With Tuberous Sclerosis. Lab. Invest. 2015;95:266A.

Jia L., Jayakumaran G., Al-Ahmadie H., Fine S.W., Gopalan A., Sirintrapun S.J., Tickoo S., Reuter V., Cheng Y.B. Expanding the Morphologic Spectrum of Sporadic Renal Cell Carcinoma (RCC) Harboring Somatic TSC or MTOR Alterations: Analysis of 8 Cases with Clear Cytoplasm and Leiomyomatous Stroma. Mod. Pathol. 2019;32:78–79.

Chen Y.B., Mirsadraei L., Jayakumaran G., Al-Ahmadie H.A., Fine S.W., Gopalan A., Sirintrapun S.J., Tickoo S.K., Reuter V.E. Somatic Mutations of TSC2 or MTOR Characterize a Morphologically Distinct Subset of Sporadic Renal Cell Carcinoma with Eosinophilic and Vacuolated Cytoplasm. Am. J. Surg. Pathol. 2019;43:121–131. doi: 10.1097/PAS.0000000000001170. PubMed DOI PMC

He H., Trpkov K., Martinek P., Isikci O.T., Maggi-Galuzzi C., Alaghehbandan R., Gill A.J., Tretiakova M., Lopez J.I., Williamson S.R., et al. “High-grade oncocytic renal tumor”: Morphologic, immunohistochemical, and molecular genetic study of 14 cases. Virchows Arch. 2018;473:725–738. doi: 10.1007/s00428-018-2456-4. PubMed DOI

Trpkov K., Bonert M., Gao Y., Kapoor A., He H., Yilmaz A., Gill A.J., Williamson S.R., Comperat E., Tretiakova M., et al. High-grade oncocytic tumour (HOT) of kidney in a patient with tuberous sclerosis complex. Histopathology. 2019;75:440–442. doi: 10.1111/his.13876. PubMed DOI

Hakimi A.A., Tickoo S.K., Jacobsen A., Sarungbam J., Sfakianos J.P., Sato Y., Morikawa T., Kume H., Fukayama M., Homma Y., et al. TCEB1-mutated renal cell carcinoma: A distinct genomic and morphological subtype. Mod. Pathol. 2015;28:845–853. doi: 10.1038/modpathol.2015.6. PubMed DOI PMC

Favazza L., Chitale D.A., Barod R., Rogers C.G., Kalyana-Sundaram S., Palanisamy N., Gupta N.S., Williamson S.R. Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: A histological review of tumors from the Cancer Genome Atlas database. Mod. Pathol. 2017;30:1603–1612. doi: 10.1038/modpathol.2017.72. PubMed DOI

Hirsch M.S., Barletta J.A., Gorman M., Dal Cin P. Renal Cell Carcinoma With Monosomy 8 and CAIX Expression: A Distinct Entity or Another Member or the Clear Cell Tubulopapillary RCC/RAT Family? Mod. Pathol. 2015;28:229A.

Williamson S.R., Grignon D.J., Cheng L., Favazza L., Gondim D.D., Carskadon S., Gupta N.S., Chitale D.A., Kalyana-Sundaram S., Palanisamy N. Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis? Am. J. Surg. Pathol. 2017;41:287–298. doi: 10.1097/PAS.0000000000000776. PubMed DOI

Argani P., Reuter V.E., Zhang L., Sung Y.S., Ning Y., Epstein J.I., Netto G.J., Antonescu C.R. TFEB-amplified Renal Cell Carcinomas: An Aggressive Molecular Subset Demonstrating Variable Melanocytic Marker Expression and Morphologic Heterogeneity. Am. J. Surg. Pathol. 2016;40:1484–1495. doi: 10.1097/PAS.0000000000000720. PubMed DOI PMC

Gupta S., Johnson S.H., Vasmatzis G., Porath B., Rustin J.G., Rao P., Costello B.A., Leibovich B.C., Thompson R.H., Cheville J.C., et al. TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: A distinct entity with potential implications for clinical management. Mod. Pathol. 2017;30:998–1012. doi: 10.1038/modpathol.2017.24. PubMed DOI

Peckova K., Vanecek T., Martinek P., Spagnolo D., Kuroda N., Brunelli M., Vranic S., Djuricic S., Rotterova P., Daum O., et al. Aggressive and nonaggressive translocation t(6;11) renal cell carcinoma: Comparative study of 6 cases and review of the literature. Ann. Diagn. Pathol. 2014;18:351–357. doi: 10.1016/j.anndiagpath.2014.10.002. PubMed DOI

Skala S.L., Xiao H., Udager A.M., Dhanasekaran S.M., Shukla S., Zhang Y., Landau C., Shao L., Roulston D., Wang L., et al. Detection of 6 TFEB-amplified renal cell carcinomas and 25 renal cell carcinomas with MITF translocations: Systematic morphologic analysis of 85 cases evaluated by clinical TFE3 and TFEB FISH assays. Mod. Pathol. 2018;31:179–197. doi: 10.1038/modpathol.2017.99. PubMed DOI

Durinck S., Stawiski E.W., Pavia-Jimenez A., Modrusan Z., Kapur P., Jaiswal B.S., Zhang N., Toffessi-Tcheuyap V., Nguyen T.T., Pahuja K.B., et al. Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes. Nat. Genet. 2015;47:13–21. doi: 10.1038/ng.3146. PubMed DOI PMC

Gupta S., Argani P., Jungbluth A.A., Chen Y.B., Tickoo S.K., Fine S.W., Gopalan A., Al-Ahmadie H.A., Sirintrapun S.J., Sanchez A., et al. TFEB Expression Profiling in Renal Cell Carcinomas: Clinicopathologic Correlations. Am. J. Surg. Pathol. 2019;43:1445–1461. doi: 10.1097/PAS.0000000000001307. PubMed DOI PMC

Andeen N.K., Qu X., Antic T., Tykodi S.S., Fang M., Tretiakova M.S. Clinical Utility of Chromosome Genomic Array Testing for Unclassified and Advanced-Stage Renal Cell Carcinomas. Arch. Pathol. Lab. Med. 2019;143:494–504. doi: 10.5858/arpa.2018-0104-OA. PubMed DOI

Moch H., Amin M., Argani P., Cheville J., Delahunt B., Martignoni G., Srigley J., Tan P., Tickoo S. Renal cell tumors. In: Moch H., Humphrey P.A., Ulbright T.M., Reuter V.E., editors. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th ed. International Agency for Research on Cancer; Lyon, France: 2016. pp. 14–17.

Debelenko L.V., Raimondi S.C., Daw N., Shivakumar B.R., Huang D., Nelson M., Bridge J.A. Renal cell carcinoma with novel VCL-ALK fusion: New representative of ALK-associated tumor spectrum. Mod. Pathol. 2011;24:430–442. doi: 10.1038/modpathol.2010.213. PubMed DOI

Sugawara E., Togashi Y., Kuroda N., Sakata S., Hatano S., Asaka R., Yuasa T., Yonese J., Kitagawa M., Mano H., et al. Identification of anaplastic lymphoma kinase fusions in renal cancer: Large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method. Cancer. 2012;118:4427–4436. doi: 10.1002/cncr.27391. PubMed DOI

Sukov W.R., Hodge J.C., Lohse C.M., Akre M.K., Leibovich B.C., Thompson R.H., Cheville J.C. ALK alterations in adult renal cell carcinoma: Frequency, clinicopathologic features and outcome in a large series of consecutively treated patients. Mod. Pathol. 2012;25:1516–1525. doi: 10.1038/modpathol.2012.107. PubMed DOI

Bodokh Y., Ambrosetti D., Kubiniek V., Tibi B., Durand M., Amiel J., Pertuit M., Barlier A., Pedeutour F. ALK-TPM3 rearrangement in adult renal cell carcinoma: Report of a new case showing loss of chromosome 3 and literature review. Cancer Genet. 2018;221:31–37. doi: 10.1016/j.cancergen.2017.11.010. PubMed DOI

Cajaiba M.M., Jennings L.J., George D., Perlman E.J. Expanding the spectrum of ALK-rearranged renal cell carcinomas in children: Identification of a novel HOOK1-ALK fusion transcript. Genes Chromosomes Cancer. 2016;55:814–817. doi: 10.1002/gcc.22382. PubMed DOI PMC

Cajaiba M.M., Jennings L.J., Rohan S.M., Perez-Atayde A.R., Marino-Enriquez A., Fletcher J.A., Geller J.I., Leuer K.M., Bridge J.A., Perlman E.J. ALK-rearranged renal cell carcinomas in children. Genes Chromosomes Cancer. 2016;55:442–451. doi: 10.1002/gcc.22346. PubMed DOI

Hodge J.C., Pearce K.E., Sukov W.R. Distinct ALK-rearranged and VCL-negative papillary renal cell carcinoma variant in two adults without sickle cell trait. Mod. Pathol. 2013;26:604–605. doi: 10.1038/modpathol.2012.144. PubMed DOI

Jeanneau M., Gregoire V., Desplechain C., Escande F., Tica D.P., Aubert S., Leroy X. ALK rearrangements-associated renal cell carcinoma (RCC) with unique pathological features in an adult. Pathol. Res. Pr. 2016;212:1064–1066. doi: 10.1016/j.prp.2016.07.015. PubMed DOI

Kuroda N., Liu Y., Tretiakova M., Ulamec M., Takeuchi K., Przybycin C., Magi-Galluzzi C., Agaimy A., Yilmaz A., Trpkov K., et al. Clinicopathological Study of Seven Cases of ALK-positive Renal Tumor Identification of New Fusion Partners including CLIP1 and KIF5B Genes. Mod. Pathol. 2019;32:85.

Kuroda N., Sugawara E., Kusano H., Yuba Y., Yorita K., Takeuchi K. A review of ALK-rearranged renal cell carcinomas with a focus on clinical and pathobiological aspects. Pol. J. Pathol. 2018;69:109–113. doi: 10.5114/pjp.2018.76693. PubMed DOI

Kusano H., Togashi Y., Akiba J., Moriya F., Baba K., Matsuzaki N., Yuba Y., Shiraishi Y., Kanamaru H., Kuroda N., et al. Two Cases of Renal Cell Carcinoma Harboring a Novel STRN-ALK Fusion Gene. Am. J. Surg. Pathol. 2016;40:761–769. doi: 10.1097/PAS.0000000000000610. PubMed DOI

Lee C., Park J.W., Suh J.H., Nam K.H., Moon K.C. ALK-Positive Renal Cell Carcinoma in a Large Series of Consecutively Resected Korean Renal Cell Carcinoma Patients. Korean J. Pathol. 2013;47:452–457. doi: 10.4132/KoreanJPathol.2013.47.5.452. PubMed DOI PMC

Marino-Enriquez A., Ou W.B., Weldon C.B., Fletcher J.A., Perez-Atayde A.R. ALK rearrangement in sickle cell trait-associated renal medullary carcinoma. Genes Chromosomes Cancer. 2011;50:146–153. doi: 10.1002/gcc.20839. PubMed DOI

Pal S.K., Bergerot P., Dizman N., Bergerot C., Adashek J., Madison R., Chung J.H., Ali S.M., Jones J.O., Salgia R. Responses to Alectinib in ALK-rearranged Papillary Renal Cell Carcinoma. Eur. Urol. 2018;74:124–128. doi: 10.1016/j.eururo.2018.03.032. PubMed DOI

Smith N.E., Deyrup A.T., Marino-Enriquez A., Fletcher J.A., Bridge J.A., Illei P.B., Netto G.J., Argani P. VCL-ALK renal cell carcinoma in children with sickle-cell trait: The eighth sickle-cell nephropathy? Am. J. Surg. Pathol. 2014;38:858–863. doi: 10.1097/PAS.0000000000000179. PubMed DOI PMC

Thorner P.S., Shago M., Marrano P., Shaikh F., Somers G.R. TFE3-positive renal cell carcinomas are not always Xp11 translocation carcinomas: Report of a case with a TPM3-ALK translocation. Pathol. Res. Pr. 2016;212:937–942. doi: 10.1016/j.prp.2016.07.004. PubMed DOI

Yu W., Wang Y., Jiang Y., Zhang W., Li Y. Genetic analysis and clinicopathological features of ALK-rearranged renal cell carcinoma in a large series of resected Chinese renal cell carcinoma patients and literature review. Histopathology. 2017;71:53–62. doi: 10.1111/his.13185. PubMed DOI

Cheng J., Zhang J., Han Y., Wang X., Ye X., Meng Y., Parwani A., Han Z., Feng Q., Huang K. Integrative Analysis of Histopathological Images and Genomic Data Predicts Clear Cell Renal Cell Carcinoma Prognosis. Cancer Res. 2017;77:e91–e100. doi: 10.1158/0008-5472.CAN-17-0313. PubMed DOI PMC

Shao W., Han Z., Cheng J., Cheng L., Wang T., Sun L., Lu Z., Zhang J., Zhang D., Huang K. Integrative analysis of pathological images and multi-dimensional genomic data for early-stage cancer prognosis. Ieee Trans. Med. Imaging. 2019 doi: 10.1109/TMI.2019.2920608. PubMed DOI

VENUSS rising for papillary renal cell carcinoma prognostication?