Gross Features: Clear cell RCC are characterized by a multinodular and multicolored
tumor mass with a predominantly yellow cut surface and additional gray and white
foci. The yellow ones correspond to well differentiated and the latter ones to less
or undifferentiated tumor areas. Most are solid, but in a few cases there is a
cystic growth pattern composed of multiple cysts varying in size up to 2-3 cm in
diameter. Tumor regression results in white sclerotic septa, focal calcifications,
necrosis, and irregular hemorrhage.
Microscopic Features: Light microscopically, the cytoplasm of the basic clear cell
type usually appears clear and more or less empty with H&E staining. This is the
result of an intensive intracytoplasmic accumulation of glycogen, phospholipids, and
neutral lipids due to increased glucose-6-phosphate levels, activated glycolysis and
reduced gluconeogenesis. As grade increases, the lipid content tends to decrease.
The nuclei of well differentiated tumor cells are condensed and hyperchromatic, while
in less differentiated tumor cells polymorphic nuclei and prominent nucleoli appear.
Ultrastructurally, brush border equivalents and pinocytotic vesicles can be
occasionally found as well as basal infoldings analogous to those observed in the
proximal tubule epithelium. In addition, there are eosinophilic (granular) variants
associated with higher grades of malignancy. They develop cytoplasmic eosinophilia
or cytoplasmic granularity respectively either in the vicinity of the nucleus or more
or less diffusely within the cytoplasm due to increased numbers of mitochondria.
