LOT and HOT … or not. The proliferation of clinically insignificant and poorly characterised types of renal neoplasia

Abstract

The classification of malignant tumours is influenced by both immunohistochemical and molecular genetic findings. This is highlighted in the latest World Health Organization classification of renal neoplasia, which has a tumour category of 'tumours that are molecularly defined'. This implies that the defining molecular features are integral to tumourigenesis, which may not necessarily be the case. Renal oncocytoma is recognised as a benign tumour with variable morphology and immunoexpression. A variant of these tumours is hybrid oncocytic chromophobe tumour, which has features of both oncocytoma and chromophobe renal cell carcinoma and may, on rare occasions, show malignant behaviour. Recent reports have proposed two further entities with eosinophilic cytoplasm and varying nuclear pleomorphism, designated low grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT), formally known as high grade oncocytic tumour (HOT). The diagnosis of these apparently benign tumours was made on the basis of morphological and immunohistochemical features. More recently it has been claimed that the mutations in the mTOR pathway are also a diagnostic feature and it is further suggested that these mutations are key to the pathogenesis of these tumours. As is seen in oncocytoma, immunohistochemical expression of tumours included in series of LOT and EVT is variable. The mutations in the mTOR pathway, where detected, were not constant, with any combination of mTOR, TSC1 and/or TSC2 being involved. A major issue is that in many of the studies full comparative genomic hybridisation results are not presented. In addition it is well recognised that mTOR mutations are seen in a variety of renal tumours. In view of these conflicting results, the rarity of these tumours and their apparent benign nature, raises questions as to why these tumours should be considered specific entities.

Keywords: Renal tumour; chromophobe renal cell carcinoma; oncocytoma.