Oncocytic Tumors in the Kidney: A Tri-Focal Review - Integrated Pathological, Cytopathological, and Molecular Perspectives. Part 2

: This second of two parts review is devoted to the practical aspects of FNAB diagnosis of renal oncocytoma and the interesting biology underlying the morphologic transformation of oncocytes. In the first section, we describe the most useful cytologic variables for the recognition of oncocytoma, since its first cytologic description 44 years ago. The usefulness of the recently introduced cytologic diagnostic category of "low-risk oncocytic neoplasm" is discussed, as well as the known problems of differential diagnosis. These are so relevant that they may limit the possibility of an accurate diagnosis in small specimens, such as FNA and core biopsies. However, this must be compatible with the possibility of making a useful diagnosis for the therapeutic management of the patient. The second section deals with the molecular aspects of oncocytes, with special emphasis on correlating it with the peculiar morphology of oncocytic tumors and their less aggressive behavior. Firstly, why does this accumulation of abnormal mitochondria occur, and secondly, what are the consequences? Regarding oxidative phosphorylation, oncocytes show a dysfunctional respiratory complex that makes them unable to respond adequately to the hypoxia so typical of the neoplastic environment. We discuss the genes and molecules responsible for mitochondrial dysfunction, and, finally, the molecular differences between sporadic oncocytomas and those associated with a hereditary context.