title: 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.
authors.affiliation: Department of Pathology, Pakistan Institute of Medical Sciences Islamabad, Pakistan. haque_8888@hotmail.com
authors.forename: Anwar Ul
authors.initials: AU
authors.lastname: Haque
authors.forename: Ambreen
authors.initials: A
authors.lastname: Moatasim
references.citation: Bone. 1995 Aug;17(2 Suppl):87S-91S
references.pmid: 8579904
references.citation: Calcif Tissue Int. 1980;31(1):29-34
references.pmid: 6770971
references.citation: Endocrinology. 1986 Feb;118(2):824-8
references.pmid: 3455914
references.citation: J Bone Joint Surg Br. 1992 Sep;74(5):652-8
references.pmid: 1527108
references.citation: Veroff Pathol. 1984;122:1-195
references.pmid: 6091360
references.citation: Virchows Arch B Cell Pathol. 1973 Mar 30;12(4):318-29
references.pmid: 4196329
references.citation: Am J Pathol. 1994 Oct;145(4):856-67
references.pmid: 7943176
references.citation: Science. 1980 May 2;208(4443):516-8
references.pmid: 6154315
references.citation: Endocrinol Jpn. 1990 Oct;37(5):741-7
references.pmid: 2086204
references.citation: Nature. 1961 Apr 29;190:459-60
references.pmid: 13777407
references.citation: Cancer Genet Cytogenet. 1996 May;88(1):35-8
references.pmid: 8630976
references.citation: Clin Orthop Relat Res. 2005 Sep;438:116-22
references.pmid: 16131879
references.citation: Int J Clin Exp Pathol. 2008 Jan 01;1(1):84-90
references.pmid: 18784826
references.citation: J Interferon Res. 1987 Oct;7(5):619-26
references.pmid: 3479501
references.citation: Mod Pathol. 2004 May;17(5):518-25
references.pmid: 15044915
references.citation: J Pathol. 1984 Dec;144(4):281-94
references.pmid: 6520652
references.citation: Curr Top Pathol. 1989;79:125-50
references.pmid: 2644082
references.citation: Recent Prog Horm Res. 1989;45:507-27; discussion 527-31
references.pmid: 2682847
references.citation: Clin Orthop Relat Res. 1976 Oct;(120):201-31
references.pmid: 975659
references.citation: Kathmandu Univ Med J (KUMJ). 2003 Jul-Sep;1(3):190-2
references.pmid: 16388229
references.citation: Calcif Tissue Int. 1997 Jan;60(1):63-70
references.pmid: 9030482
references.citation: Pediatr Dev Pathol. 2006 Jan-Feb;9(1):38-43
references.pmid: 16808643
references.citation: Lab Invest. 1992 Aug;67(2):166-74
references.pmid: 1501443
references.citation: Diagn Cytopathol. 2002 Dec;27(6):375-8
references.pmid: 12451570
references.citation: Nature. 1975 Nov 27;258(5533):325-7
references.pmid: 1196357
references.citation: Mod Pathol. 2000 Nov;13(11):1206-10
references.pmid: 11106078
references.citation: Int J Oral Surg. 1984 Apr;13(2):92-100
references.pmid: 6430822
references.citation: Mund Kiefer Gesichtschir. 2004 Sep;8(5):316-21
references.pmid: 15480872
references.citation: Pathobiology. 2002-2003;70(6):333-42
references.pmid: 12865629
references.citation: Clin Orthop Relat Res. 1997 May;(338):205-14
references.pmid: 9170381
references.citation: J Bone Joint Surg Am. 1976 Jul;58(5):612-8
references.pmid: 932060
references.citation: Endocrinology. 1991 May;128(5):2324-35
references.pmid: 1850350
references.citation: Ann Rheum Dis. 1996 Jun;55(6):388-95
references.pmid: 8694579
references.citation: J Postgrad Med. 1995 Jul-Sep;41(3):83-4
references.pmid: 10707722
references.citation: Ultrastruct Pathol. 2006 May-Jun;30(3):151-8
references.pmid: 16825116
references.citation: Hand Clin. 2004 Aug;20(3):269-81, vi
references.pmid: 15275686
references.citation: J Bone Miner Res. 2000 Apr;15(4):640-9
references.pmid: 10780856
references.citation: Horm Metab Res. 1987 Nov;19(11):585-9
references.pmid: 2828212
references.citation: Oncol Rep. 2006 Mar;15(3):589-94
references.pmid: 16465417
references.citation: Br J Cancer. 1992 Apr;65(4):523-6
references.pmid: 1562461
references.citation: Endocrinology. 1994 Jun;134(6):2416-23
references.pmid: 8194468
references.citation: Endocrinology. 1998 Oct;139(10):4353-63
references.pmid: 9751519
references.citation: Am J Pathol. 2004 Nov;165(5):1773-80
references.pmid: 15509545
references.citation: Science. 1975 Nov 21;190(4216):784-5
references.pmid: 1105786
references.citation: J Bone Miner Res. 1989 Feb;4(1):29-35
references.pmid: 2541600
references.citation: Proc Natl Acad Sci U S A. 1990 Sep;87(18):7260-4
references.pmid: 2169622
references.citation: Hum Pathol. 2005 Sep;36(9):945-54
references.pmid: 16153456
references.citation: J Clin Endocrinol Metab. 1978 Mar;46(3):425-33
references.pmid: 87400
references.citation: Proc Natl Acad Sci U S A. 1995 May 9;92(10):4562-6
references.pmid: 7753843
references.citation: Br J Oral Maxillofac Surg. 1993 Apr;31(2):89-94
references.pmid: 8471587
references.citation: Science. 1973 May 25;180(4088):875
references.pmid: 4706681
references.citation: J Bone Miner Res. 1996 Jan;11(1):62-71
references.pmid: 8770698
references.citation: Cancer. 1988 Sep 15;62(6):1139-45
references.pmid: 2457425
references.citation: J Clin Invest. 1994 May;93(5):1959-67
references.pmid: 8182127
references.citation: Fetal Pediatr Pathol. 2006 Sep-Oct;25(5):241-8
references.pmid: 17438664
references.citation: Clin Orthop Relat Res. 1986 Mar;(204):59-75
references.pmid: 3006962
references.citation: J Bone Miner Res. 1994 Jul;9(7):1123-30
references.pmid: 7942160
references.citation: Bosn J Basic Med Sci. 2007 Feb;7(1):58-65
references.pmid: 17489771
references.citation: Endocr Rev. 1992 Feb;13(1):66-80
references.pmid: 1555533
references.citation: J Cell Sci Suppl. 1986;4:267-86
references.pmid: 3528195
references.citation: J Cancer Res Clin Oncol. 1993;119(5):301-3
references.pmid: 8440744
references.citation: J Orthop Res. 2005 Jan;23(1):203-9
references.pmid: 15607894
references.citation: J Pathol Bacteriol. 1966 Jul;92(1):163-7
references.pmid: 5956253
references.citation: Ann Surg Oncol. 2007 Oct;14(10):2896-902
references.pmid: 17653593
references.citation: N Engl J Med. 1995 Dec 28;333(26):1757-63
references.pmid: 7491141
references.citation: Histol Histopathol. 2001 Jan;16(1):297-307
references.pmid: 11193206
references.citation: Am J Pathol. 2005 Jul;167(1):117-28
references.pmid: 15972958
references.citation: Acta Cytol. 1990 Nov-Dec;34(6):863-7
references.pmid: 2256421
references.citation: Pathology. 1999 Nov;31(4):373-8
references.pmid: 10643009
references.citation: J Bone Miner Res. 1992 May;7(5):555-61
references.pmid: 1615762
references.citation: Pathol Res Pract. 1999;195(11):753-7
references.pmid: 10605695
references.citation: Endocrinology. 1990 May;126(5):2733-41
references.pmid: 2184023
references.citation: Hum Pathol. 2003 Oct;34(10):983-93
references.pmid: 14608531
references.citation: Endocrinology. 1989 Jul;125(1):20-7
references.pmid: 2544401
references.citation: Cancer. 1995 Mar 1;75(5):1094-9
references.pmid: 7850706
references.citation: Nihon Seikeigeka Gakkai Zasshi. 1994 May;68(5):407-14
references.pmid: 7914219
references.citation: J Clin Pathol. 1992 May;45(5):398-404
references.pmid: 1597517
references.citation: Cell Tissue Res. 1985;241(3):671-5
references.pmid: 2992797
references.citation: J Oral Maxillofac Surg. 1999 Jul;57(7):848-53
references.pmid: 10416634
references.citation: J Cell Biochem. 1998 Jul 1;70(1):121-9
references.pmid: 9632113
references.citation: J Cell Sci. 1984 Aug;70:61-71
references.pmid: 6501437
references.citation: Cancer. 1990 Jun 15;65(12):2697-703
references.pmid: 2340469
references.citation: J Exp Med. 1975 Sep 1;142(3):651-63
references.pmid: 1100763
references.citation: J Assoc Physicians India. 2004 Jul;52:585-6
references.pmid: 15645990
references.citation: J Oral Maxillofac Surg. 1986 Sep;44(9):708-13
references.pmid: 3462363
references.citation: Life Sci. 2003 Aug 1;73(11):1427-36
references.pmid: 12850503
references.citation: J Pathol. 1987 Oct;153(2):121-6
references.pmid: 2961857
references.citation: Endocrinology. 1988 Apr;122(4):1373-82
references.pmid: 3345718
references.citation: J Pathol. 1985 Apr;145(4):297-305
references.pmid: 2987469
references.citation: N Engl J Med. 1974 Nov 14;291(20):1041-6
references.pmid: 4413338
references.citation: J Bone Joint Surg Am. 1990 Feb;72(2):252-8
references.pmid: 1968067
references.citation: J Endocrinol. 1969 Nov;45(3):387-400
references.pmid: 5358264
references.citation: J Bone Miner Res. 1994 Jul;9(7):1013-20
references.pmid: 7942147
references.citation: J Bone Miner Res. 2006 Sep;21(9):1339-49
references.pmid: 16939392
references.citation: Cancer Res. 1987 Aug 1;47(15):4141-5
references.pmid: 3300960
references.citation: Int Orthop. 2006 Dec;30(6):484-9
references.pmid: 17013643
references.citation: Lab Invest. 1994 Oct;71(4):465-71
references.pmid: 7526033
references.citation: Am J Pathol. 1986 Feb;122(2):363-78
references.pmid: 3946557
references.citation: Endocrinology. 1990 Jun;126(6):3153-8
references.pmid: 2161750
references.citation: Diagn Cytopathol. 2004 Jan;30(1):14-8
references.pmid: 14696139
references.citation: J Cell Sci. 1992 Mar;101 ( Pt 3):681-6
references.pmid: 1522150
references.citation: Pathol Res Pract. 1984 May;178(5):431-40
references.pmid: 6462948
references.citation: J Bone Miner Res. 1991 Feb;6(2):183-9
references.pmid: 2028836
references.citation: Cancer Genet Cytogenet. 2005 May;159(1):32-6
references.pmid: 15860354