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).
Well-circumscribed, solid, beige or light brown (image A).
Eosinophilic type can be mahogany-brown and ~1/5 has central scar (similar to oncocytoma).
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).
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+