“…Papillary type II is more heterogeneous and may be associated with silencing of CDKN2A, mutations in SETD2 and NRF2-ARE pathways, TFE3 fusions, as well as some CpG island methylator phenotypes. Cytogenetics shows allelic imbalance of one or more chromosomes, including 1p, 3p, 5, 6, 8, 9p, 10, 11, 15, 18 and 22 (48,54,58,60,61,64,65). Patients with hereditary papillary renal cancer (HPRC) develop bilateral multifocal type I tumors, while those with HLRCC, which is caused by a germline mutation of the fumarate hydratase gene, develop papillary type II tumors that characteristically have eosinophilic cytoplasm and large inclusion-like nucleoli (66,67).…”