Giant Cell-Rich Tumors of Bone

Key points•Multinucleated giant cells can be found in a distinct group of bone tumors and generally represent bystanders of the actual neoplastic population•Most giant cell-rich bone tumors show characteristic molecular alterations that can aid in the differential diagnosis and primarily involve mutations of the H3.3, KRAS, and FGFR1 genes as well as rearrangements of the USP6 gene•Benign fibrous histiocytoma (BFH) is no longer listed as a separate entity in the latest WHO classification and believed to represent giant cell tumor with regressive changes•Giant cell lesion of the small tubular bones has also been eliminated as a distinct entity in the latest WHO classification and thought to represent solid aneurysmal bone cyst•Rearrangements of the USP6 gene are not limited to classical aneurysmal bone cysts but occur in a variety of formerly “difficult to classify” lesions •Multinucleated giant cells can be found in a distinct group of bone tumors and generally represent bystanders of the actual neoplastic population•Most giant cell-rich bone tumors show characteristic molecular alterations that can aid in the differential diagnosis and primarily involve mutations of the H3.3, KRAS, and FGFR1 genes as well as rearrangements of the USP6 gene•Benign fibrous histiocytoma (BFH) is no longer listed as a separate entity in the latest WHO classification and believed to represent giant cell tumor with regressive changes•Giant cell lesion of the small tubular bones has also been eliminated as a distinct entity in the latest WHO classification and thought to represent solid aneurysmal bone cyst•Rearrangements of the USP6 gene are not limited to classical aneurysmal bone cysts but occur in a variety of formerly “difficult to classify” lesions