Ultrastructural spectrum of oncocytic and chromophobe renal tumors: Insights from osmium maceration-based scanning electron microscopy of formalin-fixed tissues

Ultrastructural analysis has declined in diagnostic pathology since the advent of immunohistochemistry for formalin-fixed paraffin-embedded tissues. To reevaluate the utility of ultrastructural analysis, we adopted the osmium maceration method for scanning electron microscopy (SEM) of formalin-fixed surgical specimens: renal oncocytoma, chromophobe renal cell carcinoma (ChRCC), and tumors categorized as other oncocytic tumors of the kidney (OOT). Light microscopy and immunohistochemistry have revealed that these tumors have overlapping features. SEM observation of the formalin-fixed tumors highlighted distinct morphological features: The oncocytomas contained large mitochondria with vesicular cristae; ChRCCs harbored small mitochondria with microvesicles, and OOTs showed abundant but small mitochondria with lamellar cristae. Quantitative morphometry confirmed that the number of mitochondria in oncocytomas and OOTs exceeded that of non-neoplastic lesions, whereas ChRCCs contained fewer mitochondria. In addition, mitochondria in ChRCCs and OOTs were smaller than those of non-neoplastic lesions, whereas mitochondria in oncocytomas were larger. Thus, SEM of formalin-fixed tissues, optimized by osmium maceration, can provide diagnostically valuable information beyond conventional histology and immunohistochemistry that may help to clarify the biology of challenging oncocytic and chromophobe renal tumors.