Table 2:

Tools for recognition of MIT family translocation-associated RCC

Clinical: Young age raises suspicion (but occurrence in age 50+ may be more common due to rarity of RCC in young patients) Morphology: Mixture of clear and eosinophilic cells Mixture of papillary and nested architecture Psammoma bodies Hyalinized stroma Unusually voluminous cytoplasm Pigment deposition Immunohistochemistry: TFE3 or TFEB protein – strong nuclear labelling in a clean background (but can be technically challenging) Carbonic anhydrase IX – minimal or negative staining Melanocytic markers – often positive Cathepsin K – often positive (but depends on gene fusion) Cytokeratin or vimentin – may be minimal or decreased (but variable) Molecular: Break-apart FISH – will detect most rearrangements (but certain fusions by chromosomal inversion may be subtle or false-negative) Polymerase chain reaction or next generation sequencing – will detect rearrangements with false-negative FISH (depending on method, may require knowledge of both partners)