Giant cell tumor of bone: a neoplasm or a reactive condition?

Abstract

Giant cell tumor of bone (GCTB) is a benign but locally aggressive bone tumor of young adults. It typically presents as a large lytic mass at the end of the epiphysis of long bones. Grossly it is comprised of cystic and hemorrhagic areas with little or no periosteal reaction. Microscopically areas of frank hemorrhage, numerous multinucleated giant cells and spindly stromal cells are present. Telomeric fusions, increased telomerase activity and karyotypic aberrations have been advanced as a proof of its neoplastic nature. However such findings are not universal and can be seen in rapidly proliferating normal cells as well as in several osseous lesions of developmental and/or reactive nature, and the true neoplastic nature of GCTB remains controversial. The ancillary studies have generally not reached to the point where these alone can be taken as sole diagnostic and discriminatory criteria. While giant cells and stromal cells have been extensively studied, little attention has been paid to the overwhelming hemorrhagic component. If examined carefully intact and partially degenerated red blood cells are almost invariably seen in many giant cells as well as in the stroma. While hemorrhage in many patients may be resolved without leaving any trace over time, in some it gives rise to giant cell formation, and in others it may lead to proliferation of fibroblasts and histiocytes. At times one sees xanthomatous cells due to intracytoplasmic cholesterol deposits and sharp cholesterol clefts. Individual genetic makeup, local tissue factors as well as the amount of hemorrhage may play a key role in the final effects and outcome. Malignancy usually does not occur in GCTB and when discover, it usually represents primary bone sarcomas missed at original diagnosis. Embolization therapy to curtail hemorrhage and insertion of cement substance to support matrix are helpful in reducing recurrences. Aneurysmal bone cyst (ABC) shares many features with GCTB. There had been unique karyotypic changes in some aneurysmal bone cysts making it distinct from GCTB. However these changes may be in the endothelial cells which are quite different from stromal or giant cells. It had been concluded that the poor matrix support to the vessels may lead to frequent and profuse intraosseous hemorrhage attracting blood-derived monocytes with active conversion into osteoclasts, resulting in GCTB formation. On the other hand, dilatation of the thin-walled blood vessels results in formation of ABCs. If hemorrhagic foci are replaced by proliferation of fibroblasts and histiocytes, then a picture of fibrous histiocytic lesion is emerged. Enhanced telomerase activity and karyotypic aberrations may be necessary for rapid division of the nuclei of the giant cells in order to be able to deal with significant in situ intraosseous hemorrhage.

Keywords: Giant cell tumor; aneurysmal bone cyst; bone; bone matrix; hemorrhage; osteoclast; osteoclastoma; telomerase.

Figure 1

A lytic expansile lesion with multiple septae involving the first metacarpal bone. The tumor was histologically proven GCTB.

Figure 2

Tibia showing a lytic expansile lesion with septae consistent with aneurysmal bone cyst.

Figure 3

Hemorrhage in GCTB giving rise to myriads of pathological lesions (Reproduced with permission from International Journal of Pathology).

Figure 4

A. GCTB showing the three important components, i.e., multinucleated giant cells, stromal cells and large foci of hemorrhages (H&E × 100). B. Many multinucleated giant cells sipping blood at a hemorrhagic bay in a GCTB (H&E × 100). C. Small aneurysmally dilated vessels with areas of hemorrhages and scattered multinucleated giant cells around in a GCTB (H&E × 100). D. Red cells ingested by the giant cells in a GCTB (H&E × 400). E. Interaction between hemorrhage and giant cells (H&E × 400). F. Fine needle aspiration cytology of a GCTB. Multinucleated giant cells with engulfed red blood cells. Also note several single nucleated giant cells (monocytes) (H&E × 400).

Figure 5

Proposed mechanism of conversion of monocytes into active osteoclasts in GCTB.