Histones and their practical application in bone tumors: Do I always need them?

Historically, the diagnosis of giant cell-rich neoplasms arising in bone has been challenging owing to overlapping clinical and radiographic findings resulting in the difficult separation of several neoplasms, particularly when biopsy material is limited. However, with the discovery of the driver histone mutations in giant cell tumor of bone (GCTB) and chondroblastoma, as well as USP6 rearrangements in aneurysmal bone cyst, pathologists now have objective ancillary tools to aid in the separation of several histologically similar giant cell-rich neoplasms. Furthermore, the recognition of histone mutations has allowed pathologists to revisit several entities, such as "malignant chondroblastoma," and furthered our understanding of phenomena such as "aneurysmal bone cyst-like change," formerly recognized as "secondary aneurysmal bone cyst." Herein, the evolution of testing for histone mutations in bone tumors is considered; the sensitivity and specificity of the histone antibodies is reviewed; and a practical guide for the use of these ancillary tests is offered.