3,18-20) Sporadic cases of CCRCC typically arise in patients older than 40 years, and men are affected more frequently than women.
Grossly, CCRCC is classically described as a solid, lobulated, well-circumscribed, golden-yellow mass.
Microscopically, CCRCC has highly variable architectural patterns and nuclear/cytoplasmic features.
Notwithstanding the microscopic features seen in difficult cases mentioned above, the diagnosis of CCRCC is straightforward on hematoxylin-eosin (H&E)-stained sections alone in most cases.
At the molecular level, the genetic hallmark of CCRCC is biallelic inactivation of the VHL tumor suppressor gene.
37,38) The knowledge of the importance and interdependence of the VHL/HIF and mTOR pathways in CCRCC tumorigenesis served as the basis for the development of several targeted therapies currently in use.
There is no single marker that is specific for CCRCC and therefore it is generally recommended that a panel of markers be used if immunohistochemistry is necessary in a given case.
Of the stains we often use in difficult cases, the one we most frequently rely upon to support a diagnosis of CCRCC is CA9, a membrane-bound protein that functions in intracellular and extracellular pH regulation and whose expression is driven by hypoxia.
One case had scattered foci of CCRCC with conventional architecture intermixed with areas of anastomosing hemangioma-like vasculature.
Grossly, CCRCC mimicking anastomosing hemangioma had a red-brown color (Figure 1), in contrast to the bright yellow color typically seen in clear cell renal cell carcinoma.
In cases where a hemangioma-like vasculature pattern represents only a fraction of a CCRCC, percutaneous imaging-guided renal needle biopsy could be misinterpreted as a primary vascular neoplasm.