title: Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity.
abstract: BACKGROUND
  Once believed to represent a uniform malignant phenotype, renal cell carcinoma (RCC) is now viewed as a diverse group of cancers that arise from the nephron.
  
  
  OBJECTIVE
  To review the pathologic characteristics, clinical behavior, molecular biology, and systemic therapy options of recognized RCC histologic subtypes.
  
  
  METHODS
  A systematic review of English-language articles was performed using the Medline and Web of Science databases. Manuscripts were selected with consensus of the coauthors and evaluated using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria.
  
  
  RESULTS
  The major findings of the evaluated manuscripts are discussed with an emphasis on the description of the pathologic features, clinical behavior, prognosis, and therapeutic strategies.
  
  
  CONCLUSIONS
  Classification schemes for kidney cancer have undergone dramatic changes over the past two decades. Improvements in these classification schemes are important, as pathologic variants differ not only in disease biology, but also in clinical behavior, prognosis, and response to systemic therapy. In the era of genomic medicine, further refinements in characterization of RCC subtypes will be critical to the progress of this burgeoning clinical space.
  
  
  RESULTS
  Kidney cancer can be subdivided into related but different cancers that arise from the kidney's tubules. In this article we review current classifications for kidney cancer, discuss their characteristics, and provide an overview of each subtype's clinical behavior and treatment. We stress that each subtype harbors unique biology and thus responds differently to available treatment strategies.
authors.affiliation: Department of Urology, Yale School of Medicine, New Haven, CT, USA. Electronic address: Brian.shuch@yale.edu.
authors.forename: Brian
authors.initials: B
authors.lastname: Shuch
authors.affiliation: Department of Pathology and Laboratory Medicine, Alpert School of Medicine, Brown University, Providence, RI, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Amin
authors.affiliation: Divisions of Urology and Medical Oncology, Departments of Medicine and Surgery, Duke School of Medicine, Durham, NC, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.affiliation: Department of Oncologic, Surgical and Gastrointestinal Sciences, Urologic Unit, University of Padova, Padova, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
authors.affiliation: Unit of Anatomical Pathology, Department of Surgery and Pathology, University of Cordoba, Faculty of Medicine, Cordoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.affiliation: Department of Pathology and Diagnostic, University of Verona and Pederzoli Hospital, Peschiera del Garda, Verona, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.affiliation: Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.affiliation: Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kutikov
mesh_terms: D018249:Adenoma, Oxyphilic / Q000473:pathology* / Q000628:therapy; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D018276:Carcinoma, Medullary / Q000473:pathology* / Q000628:therapy; D002291:Carcinoma, Papillary / Q000473:pathology* / Q000628:therapy; D002292:Carcinoma, Renal Cell / Q000145:classification* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D014178:Translocation, Genetic
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C069203:TFE3 protein, human; C064972:TFEB protein, human
keywords: Kidney cancer; Molecular biology; Pathology; Subtype; Systemic therapy