Electron microscopy: the gold standard in the differential diagnosis of chromophobe renal cell carcinoma and oncocytoma.

o the Editors: We read the article “Classification and Reclassification of Adult Renal Epithelial Tumors,” by Mazzucchelli and colleagues,1 with great interest. The authors underlined that sometimes the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma can be very difficult. Renal oncocytoma is always a benign lesion,2 while at other sites (salivary glands, thyroid, breast, etc.) it has a malignant counterpart. Consequently, conclusive diagnostic criteria must be acquired to diagnose renal oncocytoma definitively because the treatment should be conservative (wait and see or tumorectomy). Immunohistochemistry is not conclusive.3 Because ultrastructurally the oncocytes contain numerous mitochondria, the majority of which are of normal size and shape, the use of monoclonal antibody against human mitochondria should theoretically be conclusive in the diagnosis of the tumor. Unfortunately, chromophobe renal cell carcinoma also expresses this antibody, as do all the oncocytic lesions. This finding is in contrast to the ultrastructural characteristics of chromophobe renal cell carcinoma. In fact, the cytoplasm of neoplastic cells is crowded by loose glycogen deposits and numerous, sometimes invaginated vesicles (Table I). Therefore, electron microscopy is the gold standard for documenting oncocytic cell origin. In our experience this procedure may be used on formalin-fixed material and demonstrates that the oncocytes have rounded nuclei with compact nucleoli and numerous cytoplasmic mitochondria (Figure 1), while chromophobe renal cell carcinoma shows miocrovescicles in the cytoplasm (Figure 2). In conclusion, we think that electron microscopy on formalin-fixed material should be considered the choice procedure in the differential diagnosis of chromophobe renal cell carcinoma and oncocytoma.