Giant cell tumour of bone: morphological, biological and histogenetical aspects

Abstract

The giant cell tumour of bone (GCT) is a locally aggressive intraosseous neoplasm of obscure biological behaviour. Although well defined in clinical, radiological and histological terms, detailed information on its biological development is still relatively incomplete. The tumoral tissue consists of three cell types--the neoplastic giant cell tumour stromal cells (GCTSC), representing the proliferative fraction, secondarily recruited mononuclear histiocytic cells (MNHC) and multinuclear giant cells (MNGC). These cellular components interact together with factors that have a role in regulating osteoclast function in normal bone tissue (e.g. RANK, RANKL, OPG, M-CSF). Recent publications suggest that the neoplastic stromal cells express differentiation features of mesenchymal stem cells. Further research of the pathogenesis of GCT as well as the complex interactions of its cellular populations may provide the knowledge necessary for developing approaches for a biological-based therapy of this neoplasm.

Fig. 1

Distribution of giant cell tumours (GCTs) in the Bone Tumour Registry Hamburg according to localisation, age and sex. Note the epiphyseal localisation of most tumours at the ends of the long bones

Fig 2

a Typical X-ray of a giant cell tumour in the distal femur situated in the epi- and metaphysis (growth plates are closed), b typical histology with multinuclear giant cells (MNGC, arrows) between numerous mononuclear cells without nuclear atypia (H&E stain, original magnification 200×), c a portion of the mononuclear cells (MNHC, arrows) reacts with an antibody against the histiocytic marker CD68 (original magnification 400×), d in this part of the tumour the MNHC are fused to the MNGC, the CD68-negative cells represent the neoplastic stromal cells (GCTSC, arrows, original magnification 400×)