title: Unclassified renal cell carcinoma with tubulopapillary architecture, clear cell phenotype, and chromosome 8 monosomy: a new kid on the block.
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.
authors.affiliation: Department of Pathology, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
authors.forename: Thanh T H
authors.initials: TT
authors.lastname: Lan
authors.affiliation: Department of Pathology, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keller-Ramey
authors.affiliation: Department of Pathology, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Fitzpatrick
authors.affiliation: Department of Pathology, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.|Center for Research Informatics, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
authors.forename: Sabah
authors.initials: S
authors.lastname: Kadri
authors.affiliation: Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, IL, USA.
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Taxy
authors.affiliation: Department of Pathology, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Segal
authors.affiliation: Department of Pathology, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
authors.forename: Larissa V
authors.initials: LV
authors.lastname: Furtado
authors.affiliation: Department of Pathology, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA. Tatjana.Antic@uchospitals.edu.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Antic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008875:Middle Aged; D009006:Monosomy / Q000235:genetics / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D014178:Translocation, Genetic / Q000235:genetics
keywords: Chromosome 8 monosomy; Next-generation sequencing; Renal cell carcinoma; The OncoScan® FFPE assay