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| IJCEP Copyright © 2007-All rights reserved. |
| International Journal of Clinical and Experimental Pathology |
Int J Clin Exp Pathol 1(6):489-501;2008
Review Article
Giant Cell Tumor of Bone: A Neoplasm or a Reactive Condition?
Anwar Ul Haque and Ambreen Moatasim
Department of Pathology, Pakistan Institute of Medical Sciences, Islamabad
Received 13 Sept 2007; Revision received 9 Oct 2007; Accepted and available online 1 January 2008
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. (IJCEP708007).
Key Words: Giant cell tumor, bone, osteoclastoma, aneurysmal bone cyst, osteoclast, hemorrhage, bone matrix, telomerase
Full Text PDF
Address all correspondences to: Anwar Ul Haque, MD, Department of Pathology, Pakistan Institute of Medical Sciences (PIMS) G 8/3
Islamabad 44000 Pakistan. Phone 2294099. Email: haque_8888@hotmail.com & haque8888@gmail.com
Review Article
Giant Cell Tumor of Bone: A Neoplasm or a Reactive Condition?
Anwar Ul Haque and Ambreen Moatasim
Department of Pathology, Pakistan Institute of Medical Sciences, Islamabad
Received 13 Sept 2007; Revision received 9 Oct 2007; Accepted and available online 1 January 2008
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. (IJCEP708007).
Key Words: Giant cell tumor, bone, osteoclastoma, aneurysmal bone cyst, osteoclast, hemorrhage, bone matrix, telomerase
Full Text PDF
Address all correspondences to: Anwar Ul Haque, MD, Department of Pathology, Pakistan Institute of Medical Sciences (PIMS) G 8/3
Islamabad 44000 Pakistan. Phone 2294099. Email: haque_8888@hotmail.com & haque8888@gmail.com