title: Differential diagnosis of renal tumors with clear cytoplasm: clinical relevance of renal tumor subclassification in the era of targeted therapies and personalized medicine.
abstract: BACKGROUND
  The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and-with the exception of some rare tumors-the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies.
  
  
  OBJECTIVE
  To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management.
  
  
  METHODS
  Published literature and personal experience.
  
  
  CONCLUSIONS
  In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains.
authors.affiliation: Department of Pathology, Northwestern Memorial Hospital, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Rajen
authors.initials: R
authors.lastname: Goyal
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gersbach
authors.forename: Ximing J
authors.initials: XJ
authors.lastname: Yang
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rohan
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000175:diagnosis*; D018249:Adenoma, Oxyphilic / Q000175:diagnosis*; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis*; D018207:Angiomyolipoma / Q000175:diagnosis*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D003937:Diagnosis, Differential; D015622:Epithelioid Cells / Q000473:pathology; D005819:Genetic Markers; D006801:Humans; D007680:Kidney Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D058990:Molecular Targeted Therapy; D057285:Precision Medicine; D014178:Translocation, Genetic; D014944:World Health Organization
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers