Renal Neoplasia: Diagnostic Problems and Recently Recognized Entities
Case 3 -
Eosinophilic Variant of Chromophobe Renal Cell Carcinoma
John N Eble, M.D.
Holger Moch, M.D.
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.
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
|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
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
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|
|Positive in part of cytoplasm: ||Not chromophobe|
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.