Update on the molecular pathology of the distinctive giant cell, fibro-osseous and bone forming lesions of the jaws.

In the 5th edition World Health Organisation (WHO) classification of head and neck tumours, lesions that are distinctive in the jaws for reasons of presentation, behaviour or molecular changes are separated from the bone tumour classification and listed with head and neck tumours in a section on odontogenic and maxillofacial bone tumours. The molecular characterisation of these lesions has advanced recently and this narrative review discusses critically the genetic alterations in the odontogenic tumours that form bone/cementum (variable findings), giant cell-rich lesions of the jaws (sporadic giant cell granulomas with mutually exclusive TRPV4, KRAS or FGFR1 mutations, brown tumours with KRAS mutations and cherubism with SH3BP2 mutations), and bone cysts (aneurysmal bone cyst with USP6 rearrangements and simple bone cyst lacking NFATC2 rearrangement). Additionally, fibro-osseous lesions are discussed, with fibrous dysplasia harbouring GNAS mutations, familial florid cemento-osseous dysplasia, familial gigantiform cementoma and gnathodiaphyseal dysplasia sharing ANO5 mutations and psammomatoid ossifying fibroma showing SATB2 rearrangements. In most cases the changes support the current classification, but areas of uncertainty are described and differences between jaw lesions and similar lesions elsewhere in the skeleton are highlighted.