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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

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Address all correspondence 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