VHL and cyst: Interestingly, CK7 usually shows positive staining in some normal renal tubular epithelium [27], but is generally considered to be negative or focally positive in ccRCC [27–29], which further confirms our hypothesis of cyst-dependent pathway that some normal renal tubular epithelium cells (CK7 + /CA-IX-) may progress to MCRN-LMP cyst‐lining cells (CK7 + /CA-IX +) in the case of VHL gene abnormality, and then may further develop into solid ccRCC tumor cells (CK7-/CA-IX +) because of the overlying of other abnormal genes (Fig. 5).