Abstract
Accurate subtyping of renal cell carcinomas (RCCs) has become clinically important for therapy and prognostication. RCC subtypes are defined by distinct morphologic and immunohistochemical profiles, and in some instances recurrent cytogenetic and molecular properties. However, some tumors exhibit overlapping morphologic and immunophenotypic features, frequent enough to pose diagnostic dilemmas. This report concerns six histologically unusual RCCs that showed tubulopapillary architecture, clear cell phenotype, and non-diagnostic immunohistochemical profiles. Further investigation of these tumors utilized a single nucleotide polymorphism (SNP) microarray platform (OncoScan®, Affymetrix) that employed molecular inversion probe (MIP) technology to investigate genome-wide chromosomal copy number changes and loss of heterozygosity in formalin-fixed paraffin-embedded sections. The six tumors were assayed in parallel with and in comparison to RCC with typical morphologic or immunohistochemical features for a specific subtype (clear cell, clear cell papillary, and microphthalmia transcription factor (MiT) family translocation RCC). Three of the unusual RCCs showed a molecular signature of clear cell RCC and one of papillary RCC. The remaining two showed monosomy of chromosome 8. Those two cases were tested via next-generation sequencing, and no pathogenic variants were detected, including those in the genes VHL, PBRM1, SETD2, KDM5C, or BAP1. The addition of molecular investigations such as reported here as applied to histologically and immunohistochemically unusual RCC may help to define additional subtypes and contribute to the development of targeted therapy for renal cancer.
Similar content being viewed by others
References
Eble JN, Sauter G, Epstein JI, et al. (2004) Tumors of the kidney. In WHO classification of tumours: tumours of the urinary system and male genital organs. IARC Press, Lyon, France
Srigley JR, Delahunt B, Eble JN, et al. (2013) The International Society of Urological Pathology (ISUP) Vancouver classification of renal neoplasia. Am J Surg Pathol 37(10):1469–1489
Zbar B, Brauch H, Talmadge C, et al. (1987) Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. Nature 327:721–724
Marsaud A, Dadone B, Ambrosetti D, et al. (2015) Dismantling papillary renal cell carcinoma classification: the heterogeneity of genetic profiles suggests several independent diseases. Genes Chromosomes Cancer 54(6):369–382
Renshaw AA, Fletcher JA (1997) Trisomy 3 in renal cell carcinoma. Mod Pathol 10(5):481–484
Argani P, Olgac S, Tickoo S, et al. (2007) Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic and genetic spectrum. Am J Surg Pathol 31(8):1149–1160
Argani P, Marick L, Hutchinson B, et al. (2005) Renal cell carcinomas with the t(6;11)(p21;q12): clinicopathologic features and demonstration of the specific alpha TFEB gene fusion by immunohistochemistry, RT-PCR, and DNA PCR. Am J Surg Pathol 29(2):230–240
Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25(14):1754–1760
Mose LE, Wilkerson MD, Hayes DN, et al. (2014) ABRA: improved coding indel detection via assembly-based realignment. Bioinformatics 30(19):2813–2815
Li H, Handsaker B, Wysoker A, 1000 Genome Project Data Processing Subgroup, et al. (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25(16):2078–2079
Aron M, Chang E, Herrera L, et al. (2015) Clear cell-papillary renal cell carcinoma of the kidney not associated with end-stage renal disease: clinicopathologic correlation with expanded immunophenotypic and molecular characterization of a large cohort with emphasis on relationship with renal angiomyoadenomatous tumor. Am J Surg Pathol 39(7):873–888
Diolombi ML, Cheng L, Argani P et al. (2015) Do clear cell papillary renal cell carcinomas have malignant potential? Am J Surg Pathol 39(12):1621-1634
Chandler MW, Rowe LR, Florell SR, et al. (2012) Differentiation of malignant melanoma from benign nevus using a novel genomic microarray with low specimen requirements. Arch Pathol Lab Med 136(8):947–955
Hansen TV, Vikesaa J, Buhl SS, et al. (2015) High-density SNP array improve detection of Her2 amplification and polyploidy in breast tumors. BMC Cancer 15:35
Hirsch M, Barletta J, Gorman M, et al. (2015) Renal cell carcinoma with monosomy 8 and CAIX expression; a distinct entity or another member or the clear cell tubulopapillary RCC/RAT family? Modern Pathol 28(2):229A
Kaymak-Cihan M, Tükün A, Kuşkonmaz B, et al. (2014) Chronic eosinophilic leukemia with monosomy 8 in five-year-old girl: a rare case. Turk J Pediatr 56(4):444–451
Alcaraz A, Corral JM, Ribal MJ (2004) Fluorescence in situ hybridization analysis of matched primary tumour and lymph-node metastasis of D1 (pT2-3pN1M0) prostate cancer. BJU Int 94(3):407–411
Xu PX, Adams J, Peters H, et al. (1999) Eya1-deficient mice lacks ears and kidneys and show abnormal apoptosis of organ primordial. Nat Genet 23:113–117
Varon R, Vissinga C, Platzer M, et al. (1998) Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93(3):467–476
Carney JP, Maser RS, Olivares H, et al. (1998) The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93(3):477–486
Kim HG, Kurth I, Lan F, et al. (2008) Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet 83(4):511–519
Schurman SH, Hedayati M, Wang Z, et al. (2009) Direct and indirect roles of RECQL4 in modulating base excision repair capacity. Hum Mol Genet 18(18):3470–3483
Baird DM, Davis T, Rowson J, et al. (2004) Normal telomere erosion rates at the single cell level in Werner syndrome fibroblast cells. Hum Mol Genet 13(14):1515–1524
Hakimi AA, Tickoo SK, Jacobsen A, et al. (2015) TCEB1-mutated renal cell carcinoma: a distinct genomic and morphologic subtype. Mod Pathol 28:845–853
Acknowledgments
The authors would like to thank Bradley C. Long for the help with this project.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study was approved by the Institutional Review Board at the University of Chicago and was carried out in accordance with the guidelines for archived specimens and patient chart review. The authors do not have any conflict of interest or disclosures and are in compliance with ethical standards. No funding was used in this study.
Rights and permissions
About this article
Cite this article
Lan, T.T.H., Keller-Ramey, J., Fitzpatrick, C. et al. Unclassified renal cell carcinoma with tubulopapillary architecture, clear cell phenotype, and chromosome 8 monosomy: a new kid on the block. Virchows Arch 469, 81–91 (2016). https://doi.org/10.1007/s00428-016-1952-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-016-1952-7