FINAL DIAGNOSIS: CHROMOPHOBIC RENAL CELL CARCINOMA
Chromophobic renal cell carcinomas are relatively rare accounting for approximately 6-11% of all renal cell carcinomas (1,6). The male to female ratio is approximately 1 to 1 with a mean age of 59. The tumor usually presents unilaterally with approximately 15% demonstrating multifocality. Radiographically, the tumor may show a hypervascular lesion with a central scar. The tumor is often larger at presentation than conventional clear cell carcinomas of the kidney. Clinically, the patient may present with hematuria , flank pain and or a palpable mass, but most often the patient is asymptomatic.
Chromophobic renal cell carcinomas are thought to arise from the intercalated ducts of the renal cortex. A loss of chromosomes 1 and Y are most often noted. Loss and abnormalities of chromosomes 1,6,10,13,17 , and 21 are also noted (2).
Grossly, the carcinoma may be circumscribed, but very rarely encapsulated. The cut surface is often homogeneous pale and tan. Areas of lobulation with necrosis and hemorrhage are common. A central scar can be present as in an oncocytoma. Multifocality and cyst formation are rare. Gross renal vein involvement is rare although up to one third may show involvement of the perirenal fat.
Histologically the cells usually grow in a solid pattern. However, papillary, trabecular and sarcomatoid patterns are sometimes seen. The cells usually appear round to polygonal with well defined cytoplasmic boarders and pale amphophillic to basophilic granular cytoplasm. Cells with oncocytic features are sometimes seen. The nuclei are usually hyperchromatic, elongated with irregular nuclear contours. Often a peri nuclear clearing is seen. Wrinkled "raisenoid" nuclei as well as binucleated forms can be seen.
Immunohistochemistry shows strong expression of low molecular weight cytokeratins such as AE1 and Cam 5.2(3). EMA is often positive as well. Vimentin is rarely positive. Usually, diffuse and granular cytoplasmic staining of Hale's colloidal iron, as in this case, is noted (4). Ultra structurally, large numbers of cytoplasmic vesicles are seen on electron microscopy (5). These vesicles impart the relatively clear granular cytoplasmic appearance to the cells. Also, they have an affinity toward iron. They are thought to represent either degenerated mitochondria or rough endoplasmic reticulum.
Prognostically, chromophobic renal cell carcinomas have shown better prognosis than other renal cell carcinomas in some studies with a 5 year survival of up to 90% in some series.
Contributed by Raj N Hari, MD, Hong Qu, MD and Rajiv Dhir, MD