Clear cell renal cell carcinoma with BAP1 mutation: a report of two cases.

Clear cell renal cell carcinoma is the most common subtype of renal cell carcinomas (RCCs) and accounts for 60%-70% of all RCCs cases in adults. Aberrations in the von Hippel-Lindau (VHL) gene on chromosome 3p occurred in > 90% of clear cell RCCs. Other tumor suppressor genes located on chromosome 3p, such as BAP1, PBRM1, and SETD2, also contribute to tumorigenesis. Clear cell RCCs with both BAP1 and VHL mutations may display distinctive histopathological features. Here, we report two cases of clear cell RCCs with BAP1 mutation. One tumor had VHL, BAP-1, and RAF1 mutations and the tumor nests and alveoli of tumor cells were surrounded by proliferative vessels and the optically clear cytoplasm contained numerous eosinophilic granules and hyaline globules of varying sizes. The other tumor had BAP1 and ATM mutations, and demonstrated clear cells with numerous eosinophilic granules and other typical histopathological features of conventional clear cell RCC. Furthermore, many tumor nodules with dense peripheral lymphocytic infiltrates contained rhabdoid cells. Sarcomatoid cells were also observed. Both tumor cells showed high-grade nuclei. Clear cell RCCs with BAP1 mutation exhibit aggressive clinical behaviors.