Case 3 -

Eosinophilic Variant of Chromophobe Renal Cell Carcinoma John N Eble, M.D. Holger Moch, M.D.

Case History: A 60 year-old man complained of hematuria. CT scan showed an 8 cm mass in the upper pole of his left kidney. This was removed by radical nephrectomy. Macroscopic findings: The nearly spherical, well-circumscribed tumor had a brown cut surface. Diagnosis: Eosinophilic variant of chromophobe renal cell carcinoma Renal tumors with abundant eosinophilic cytoplasm are fairly common and can pose problems because their differential diagnosis includes both benign and malignant neoplasms and because the literature contains conflicting and confusing information about their properties. While papillary renal cell carcinoma, type 2, urothelial carcinoma, and collecting duct carcinoma may have eosinophilic cytoplasm, their architectural patterns, nuclear characteristics, and other features remove them from serious consideration in the differential diagnosis of tumors with the appearance shown by the present case. The differential diagnosis of this histologic appearance is summarized in the box below. Diagnostically Problematic Renal Tumors with Abundant Eosinophilic Cytoplasm and Their Frequencies Oncocytoma 5% Eosinophilic Variant of Chromophobe Renal Cell Carcinoma 0.5% Renal Cell Carcinoma, Unclassified 0.5% Clear Cell Renal Cell Carcinoma with Predominance of Eosinophilic Cytoplasm <<0.5% Oncocytoma-like Angiomyolipoma <<0.1% By most estimates, renal oncocytoma is by far the most common tumor with this appearance. Following oncocytoma are the eosinophilic variant of chromophobe renal cell carcinoma and renal cell carcinoma, unclassified. Clear cell renal cell carcinoma with predominance of eosinophilic cytoplasm and oncocytoma-like angiomyolipoma are rare. Not only do these tumors all have abundant eosinophilic cytoplasm, they often have similar architectural and nuclear features. That renal oncocytoma has long been known to occasionally extend into perirenal fat and sometimes into blood vessels compounds the problem. In some cases, there are gross or microscopic features which weigh strongly against the diagnosis of renal oncocytoma. When any of these is present it is highly likely that another diagnosis is correct. Microscopic invasion of fat is more common than microscopic invasion of blood vessels. In most cases of renal oncocytoma, no mitotic figures are detectable. Occasionally a few mitotic figures may be found with careful scrutiny of multiple sections. More numerous mitotic figures than this strongly suggest that one of the other diagnoses is correct. Occasionally, an oncocytoma may show pseudopapillae because of incipient necrosis or fixation artifact. If you are convinced that the papillae are real, it is not an oncocytoma. Poor fixation and tissue processing can rarely make the cytoplasm of oncocytomas lighter or almost clear. However, in a properly prepared specimen, areas of cells with clear cytoplasm should not be seen in oncocytoma. Spindle cell sarcomatoid change is not seen in oncocytoma. Features Which Should Give You Pause In Diagnosing Renal Oncocytoma Gross Invasion of Perirenal Fat or Vessels Mitotic figures Papillary architecture Clear or Spindle Cells To render a precise diagnosis, additional procedures can be extremely helpful. Thoenes and associates early recognized the diagnostic utility of the Hale's colloidal iron stain and it remains essential to solving these problems. The stain should be interpreted as outlined in the box below Interpretation of Hale's Colloidal Iron Stain Diffusely negative: Could be oncocytoma Not a chromophobe Diffusely positive: Chromophobe renal cell carcinoma Not oncocytoma Positive in part of cytoplasm: Not chromophobe Not oncocytoma Renal cell carcinoma, unclassified Immunohistochemistry for cytokeratin 7 can also be helpful. A strongly positive reaction in all or nearly all of the neoplastic cells, with accentuation of the staining at the plasma membrane suggest that the tumor is a chromophobe renal cell carcinoma. Single cells or small cluster of cells with positive cytoplasmic reactions is typical of oncocytoma but not entirely specific.