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Chromophobe Renal Cell Carcinoma

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  • 3rd most common subtype of RCC.
  • Morphologically has "classic" and eosinophilic types, the later has significant overlap with oncocytoma and often poses a diagnostic problem.
  • Cytogenetics: multiple chromosomal losses involving 1, 6, 10, 13, 17, 21 and Y (more than in oncocytoma).
  • Gross:
    • Well-circumscribed, solid, beige or light brown (image A).
    • Eosinophilic type can be mahogany-brown and ~1/5 has central scar (similar to oncocytoma).
  • Histology:
    • Classic chromophobe RCC cells have flocculent cytoplasm (pale or reticulated, not-optically clear as in clear cell RCC) that condenses around the edges, giving the appearance of thick prominent cell borders ("plant cell-like") (image B).
    • Cells grow in larger nests (larger than in renal oncocytoma and without the "chicken wire" vessels of clear cell RCC).

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    • Nuclei tend to be much more pleomorphic than in clear cell RCC or oncocytoma. (Fuhrman grading not used because of this innate "high-grade" appearance in this mostly low-grade tumor).
      • Other grading approaches being introduced.
    • Characteristic nuclei have koilocyte-like or raisin-like appearance, sometimes binucleated and with perinuclear halo (image C).
    • Eosinophilic type cells have abundant eosinophilic cytoplasm like oncocytoma, but in contrast have larger nests.
  • Immunohistochemistry: CD117 (c-kit)+ (image D), Ksp-cadherin+, and CK7+ (diffuse).
  • Relatively higher proportion of high-grade sarcomatoid change (2-9%).
  • Better survival than clear cell and papillary RCCs (5 year survival of >90%).
  • DDX: (Morphologic differences as above)
    • Clear cell RCC: CAIX+, CD117- or KSP-cadherin-
    • Renal oncocytoma: CK7– or focal+