Giant Cell Tumor of Bone - an Overview

Document Type: CURRENT CONCEPTS REVIEW

Authors

1 Department of Orthopaedics, P.D Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai, India

2 Head of Surgey & Orthopaedics, Consultant in Orthopaedics Trauma & Arthroplasty, P.D Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg Mahim, Mumbai, India

3 Consultant in Orthopaedic Oncology & Soft Tissue Tumors, Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg Mahim, Mumbai, India

Abstract

 
Giant Cell tumors (GCT) are benign tumors with potential for aggressive behavior and capacity to metastasize. Although rarely lethal, benign bone tumors may be associated with a substantial disturbance of the local bony architecture that can be particularly troublesome in peri-articular locations. Its histogenesis remains unclear. It is characterized by a proliferation of mononuclear stromal cells and the presence of many multi- nucleated giant cells with homogenous distribution.
There is no widely held consensus regarding the ideal treatment method selection. There are advocates of varying surgical techniques ranging from intra-lesional curettage to wide resection. As most giant cell tumors are benign and are located near a joint in young adults, several authors favor an intralesional approach that preserves anatomy of bone in lieu of resection. Although GCT is classified as a benign lesion, few patients develop progressive lung metastases with poor outcomes. Treatment is mainly surgical. Options of chemotherapy and radiotherapy are reserved for selected cases. Recent advances in the understanding of pathogenesis are essential to develop new treatments for this locally destructive primary bone tumor.

Keywords


  1. Turcotte RE. Giant cell tumor of bone. Orthop Clin North Am. 2006; 37(1):35–51.
  2. Eckardt JJ, Grogan TJ. Giant cell tumor of bone. Clin Orthop Relat Res. 1986; 204(2):45–58.
  3. McGrath PJ. Giant-cell tumour of bone: an analysis of fifty-two cases. J Bone Joint Surg Br. 1972; 54(2): 216–29.
  4. Bertoni F, Present D, Sudanese A, Baldini N, Bacchini P, Campanacci M. Giant-cell tumor of bone with pulmonary metastases. Six case reports and a review of the literature Clin Orthop Relat Res. 1988; 237(2):275–85.
  5. Siebenrock KA, Unni KK, Rock MG. Giant-cell tumour of bone metastasising to the lungs. A long-term follow-up. J Bone Joint Surg Br. 1998; 80(1):43–7.
  6. Hoeffel JC, Galloy MA, Grignon Y, Chastagner P, Floquet J, Mainard L, et al. Giant cell tumor of bone in children and adolescents. Rev Rhum Engl Ed. 1996; 63(9):618–23.
  7. Shih HN, Hsu RW, Sim FH. Excision curettage and allografting of giant cell tumor. World J Surg. 1998; 22(5):432–7.
  8. Bridge JA, Neff JR, Mouron BJ. Giant cell tumor of bone. Chromosomal analysis of 48 specimens and review of the literature. Cancer Genet Cytogenet. 1992; 58(1):2–13.
  9. Osaka S, Toriyama S. Surgical treatment of giant cell tumors of the pelvis. Clin Orthop Relat Res. 1987; 222(3):123–31.
  10. Sanjay BK, Frassica FJ, Frassica DA, Unni KK, McLeod RA, Sim FH. Treatment of giant-cell tumor of the pelvis. J Bone Joint Surg Am. 1993; 75(10):1466–75.
  11. Tornberg DN, Dick HM, Johnston AD. Multicentric giant-cell tumors in the long bones. A case report. J Bone Joint Surg Am. 1975; 57(3):420–2.
  12. Goldenberg RR, Campbell CJ, Bonfiglio M. Giant-cell tumor of bone. An analysis of two hundred and eighteen cases. J Bone Joint Surg Am. 1970; 52(4):619–64.
  13. Larsson SE, Lorentzon R, Boquist L. Giant-cell tumor of bone. A demographic, clinical, and histopathological study of all cases recorded in the Swedish Cancer Registry for the years 1958 through 1968. J Bone Joint Surg Am. 1975; 57(2):167–73.
  14. Dreinhöfer KE, Rydholm A, Bauer HC, Kreicbergs A. Giant-cell tumours with fracture at diagnosis. Curettage and acrylic cementing in ten cases. J Bone Joint Surg Br. 1995; 77(2):189–93.
  15. Turcotte RE, Wunder JS, Isler MH, Bell RS, Schachar N, Masri BA, et al. Giant cell tumor of long bone: a Canadian Sarcoma Group study. Clin Orthop Relat Res. 2002; 397(2):248–58.
  16. Sung HW, Kuo DP, Shu WP, Chai YB, Liu CC, Li SM. Giant-cell tumor of bone: analysis of two hundred and eight cases in Chinese patients. J Bone Joint Surg Am. 1982; 64(5):755–61.
  17. Jeys LM, Suneja R, Chami G, Grimer RJ, Carter SR, Tillman RM. Impending fractures in giant cell tumours of the distal femur: incidence and outcome. Int Orthop. 2006; 30(2):135–8.
  18. Lewis VO, Wei A, Mendoza T, Primus F, Peabody T, Simon MA. Argon beam coagulation as an adjuvant for local control of giant cell tumor. Clin Orthop Relat Res. 2007; 454(1):192–7.
  19. Pereira HM, Marchiori E, Severo A. Magnetic resonance imaging aspects of giant-cell tumours of bone. J Med Imaging Radiat Oncol. 2014; 58(6):674–8.
  20. Cavanna L, Biasini C, Monfredo M, Maniscalco P, Mori M. Giant cell tumor of bone. Oncologist. 2014; 19(11):1207.
  21. Chakarun CJ, Forrester DM, Gottsegen CJ, Patel DB, White EA, Matcuk GR Jr. Giant cell tumor of bone: review, mimics, and new developments in treatment. Radiographics. 2013; 33(1):197–211.
  22. James IE, Walsh S, Dodds RA, Gowen M. Production and characterization of osteoclast-selective monoclonal antibodies that distinguish between multinucleated cells derived from different human tissues. J Histochem Cytochem. 1991; 39(7):905–14.
  23. Wulling M, Delling G, Kaiser E. The origin of the neoplastic stromal cell in giant cell tumor of bone. Hum Pathol. 2003; 34(10):983–93.
  24. Huang L, Teng XY, Cheng YY, Lee KM, Kumta SM. Expression of preosteoblast markers and Cbfa-1 and Osterix gene transcripts in stromal tumour cells of giant cell tumour of bone. Bone. 2004; 34(3):393–401.
  25. Wulling M, Engels C, Jesse N, Werner M, Delling G, Kaiser E. The nature of giant cell tumor of bone. J Cancer Res Clin Oncol. 2001; 127(8):467–74.
  26. Liao TS, Yurgelun MB, Chang SS, Zhang HZ, Murakami K, Blaine TA, et al. Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone. J Orthop Res. 2005; 23(1):203–9.
  27. Hanaoka H, Friedman B, Mack RP. Ultrastructure and histogenesis of giant-cell tumor of bone. Cancer. 1970; 25(6):1408–23.
  28. Yoshida H, Akeho M, Yumoto T. Giant cell tumor bone. Enzyme histochemical, biochemical and tissue culture studies. Virchows Arch A Pathol Anat Histol. 1982; 395(3):319–30.
  29. Ueda Y, Imai K, Tsuchiya H, Fujimoto N, Nakanishi I, Katsuda S, et al. Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant cells of human giant cell tumor of bone and is associated with vascular invasion. Am J Pathol. 1996; 148(2):611–22.
  30. Middleton J, Arnott N, Walsh S, Beresford J. The expression of mRNA for insulin-like growth factors and their receptor in giant cell tumors of human bone. Clin Orthop Relat Res. 1996; 322(2):224–31.
  31. Schwartz HS, Dahir GA, Butler MG. Telomere reduction in giant cell tumor of bone and with aging. Cancer Genet Cytogenet. 1993; 71(2):132–8.
  32. Wu PF, Tang JY, Li KH. RANK pathway in giant cell tumor of bone: pathogenesis and therapeutic aspects. Tumour Biol. 2015; 36(2):495–501.
  33. Rock M. Curettage of giant cell tumor of bone. Factors influencing local recurrences and metastasis. Chir Organi Mov. 1990; 75(1 Suppl):204–5.
  34. Rock MG, Sim FH, Unni KK, Witrak GA, Frassica FJ, Schray MF, et al. Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients. J Bone Joint Surg Am. 1986; 68(7):1073–9.
  35. Lausten GS, Jensen PK, Schiodt T, Lund B. Local recurrences in giant cell tumour of bone. Long-term follow up of 31 cases. Int Orthop. 1996; 20(3):172–6.
  36. Campanacci M, Capanna R, Fabbri N, Bettelli G. Curettage of giant cell tumor of bone. Reconstruction with subchondral grafts and cement. Chir Organi Mov. 1990; 75(1 Suppl):212–3.
  37. Miller G, Bettelli G, Fabbri N, Capanna R. Curettage of giant cell tumor of bone. Introduction--material and methods. Chir Organi Mov. 1990; 75(1 Suppl):203.
  38. Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987; 69(1):106–14.
  39. McDonald DJ, Sim FH, McLeod RA, Dahlin DC. Giant-cell tumor of bone. J Bone Joint Surg Am. 1986; 68(2):235–42.
  40. Gitelis S, Mallin BA, Piasecki P, Turner F. Intralesional excision compared with en bloc resection for giant-cell tumors of bone. J Bone Joint Surg Am. 1993; 75(11):1648–55.
  41. Liu HS, Wang JW. Treatment of giant cell tumor of bone: a comparison of local curettage and wide resection. Changgeng Yi Xue Za Zhi. 1998; 21(1):37–43.
  42. Oda Y, Miura H, Tsuneyoshi M, Iwamoto Y. Giant cell tumor of bone: oncological and functional results of long-term follow-up. Jpn J Clin Oncol. 1998; 28(5):323–8.
  43. Prosser GH, Baloch KG, Tillman RM, Carter SR, Grimer RJ. Does curettage without adjuvant therapy provide low recurrence rates in giant-cell tumors of bone? Clin Orthop Relat Res. 2005; 435(1):211–8.
  44. Persson BM, Ekelund L, Lovdahl R, Gunterberg B. Favourable results of acrylic cementation for giant cell tumors. Acta Orthop Scand. 1984; 55(2):209–14.
  45. Khan MT, Gray JM, Carter SR, Grimer RJ, Tillman RM. Management of the giant-cell tumours of the distal radius. Ann R Coll Surg Engl. 2004; 86(1):18–24.
  46. von Steyern FV, Kristiansson I, Jonsson K, Mannfolk P, Heinegard D, Rydholm A. Giant-cell tumour of the knee: the condition of the cartilage after treatment by curettage and cementing. J Bone Joint Surg Br. 2007; 89(3):361–5.
  47. Hisatome T, Yasunaga Y, Ikuta Y, Fujimoto Y. Effects on articular cartilage of subchondral replacement with polymethylmethacrylate and calcium phosphate cement. J Biomed Mater Res. 2002; 59(3):490–8.
  48. Chen TH, Su YP, Chen WM. Giant cell tumors of the knee: subchondral bone integrity affects the outcome. Int Orthop. 2005; 29(1):30–4.
  49. Niu XH, Cai YB, Hao L, Zhang Q, Ding Y, Liu WS, et al. Allograft replacement in management of giant cell tumor of bone: a report of 77 cases. Zhonghua Wai Ke Za Zhi. 2005; 43(16):1058–62.
  50. Trieb K, Bitzan P, Lang S, Dominkus M, Kotz R. Recurrence of curetted and bone-grafted giant-cell tumours with and without adjuvant phenol therapy. Eur J Surg Oncol. 2001; 27(2):200–2.
  51. Marcove RC, Weis LD, Vaghaiwalla MR, Pearson R. Cryosurgery in the treatment of giant cell tumors of bone: a report of 52 consecutive cases. Clin Orthop Relat Res. 1978; 134(1):275–89.
  52. Nelson DA, Barker ME, Hamlin BH. Thermal effects of acrylic cementation at bone tumour sites. Int J Hyperthermia. 1997; 13(3):287–306.
  53. Quint U, Muller RT, Muller G. Characteristics of phenol. Instillation in intralesional tumor excision of chondroblastoma, osteoclastoma and enchondroma. Arch Orthop Trauma Surg. 1998; 117(1-2):43–6.
  54. Nicholson NC, Ramp WK, Kneisl JS, Kaysinger KK. Hydrogen peroxide inhibits giant cell tumor and osteoblast metabolism in vitro. Clin Orthop Relat Res. 1998; 347(3):250–60.
  55. Boriani S, Sudanese A, Baldini N, Picci P. Sarcomatous degeneration of giant cell tumours. Ital J Orthop Traumatol. 1986; 12(2):191–9.
  56. Chakravarti A, Spiro IJ, Hug EB, Mankin HJ, Efird JT, Suit HD. Megavoltage radiation therapy for axial and inoperable giant-cell tumor of bone. J Bone Joint Surg Am. 1999; 81(11):1566–73.
  57. Malone S, O’Sullivan B, Catton C, Bell R, Fornasier V, Davis A. Long-term follow-up of efficacy and safety of megavoltage radiotherapy in high-risk giant cell tumors of bone. Int J Radiat Oncol Biol Phys. 1995; 33(3):689–94.
  58. Manaster BJ, Doyle AJ. Giant cell tumors of bone. Radiol Clin North Am. 1993; 31(2):299–323.
  59. Saiz P, Virkus W, Piasecki P, Templeton A, Shott S, Gitelis S. Results of giant cell tumor of bone treated with intralesional excision. Clin Orthop Relat Res. 2004; 424(2):221–6.
  60. Ghert MA, Rizzo M, Harrelson JM, Scully SP. Giant-cell tumor of the appendicular skeleton. Clin Orthop Relat Res. 2002; 400(2):201–10.
  61. Jacobs PA, Clemency RE Jr. The closed cryosurgical treatment of giant cell tumor. Clin Orthop Relat Res. 1985; 192(1):149–58.
  62. Sheth DS, Healey JH, Sobel M, Lane JM, Marcove RC. Giant cell tumor of the distal radius. J Hand Surg Am. 1995; 20(3):432–40.
  63. Zhen W, Yaotian H, Songjian L, Ge L, Qingliang W. Giant-cell tumour of bone. The long-term results of treatment by curettage and bone graft. J Bone Joint Surg Br. 2004; 86(2):212–6.
  64. Kivioja AH, Blomqvist C, Hietaniemi K, Trovik C, Walloe A, Bauer HC, et al. Cement is recommended in intralesional surgery of giant cell tumors: a Scandinavian Sarcoma Group study of 294 patients followed for a median time of 5 years. Acta Orthop. 2008; 79(1):86–93.
  65. Frassica FJ, Gorski JP, Pritchard DJ, Sim FH, Chao EY. A comparative analysis of subchondral replacement with polymethylmethacrylate or autogenous bone grafts in dogs. Clin Orthop Relat Res. 1993; 293(1):378–90.
  66. Welch RD, Berry BH, Crawford K, Zhang H, Zobitz M, Bronson D, et al. Subchondral defects in caprine femora augmented with in situ setting hydroxyapatite cement, polymethylmethacrylate, or autogenous bone graft: biomechanical and histomorphological analysis after two-years. J Orthop Res. 2002; 20(3):464–72.
  67. Saibaba B, Chouhan DK, Kumar V, Dhillon MS, Rajoli SR. Curettage and reconstruction by the sandwich technique for giant cell tumours around the knee. J Orthop Surg (Hong Kong). 2014; 22(3):351–5.
  68. Jain K, Sunila RR, Mruthyunjaya CS, Ravishankar R, Rupakumar CS, Gadiyar HB, et al. Bone tumors in a tertiary care hospital of south India: A review 117 cases. Indian J Med Paediatr Oncol. 2011; 32(2):82–5.
  69. Niu X, Zhang Q, Hao L, Ding Y, Li Y, Xu H, et al. Giant cell tumor of the extremity: retrospective analysis of 621 Chinese patients from one institution. J Bone Joint Surg Am. 2012; 94(5):461–7.
  70. van der Heijden L, Dijkstra PD, van de Sande MA, Kroep JR, Nout RA, van Rijswijk CS, et al. The clinical approach toward giant cell tumor of bone. Oncologist. 2014; 19(5):550–61.
  71. Chang SS, Suratwala SJ, Jung KM, Doppelt JD, Zhang HZ, Blaine TA, et al. Bisphosphonates may reduce recurrence in giant cell tumor by inducing apoptosis. Clin Orthop Relat Res. 2004; 426(1):103–9.
  72. Cheng YY, Huang L, Lee KM, Xu JK, Zheng MH, Kumta SM. Bisphosphonates induce apoptosis of stromal tumor cells in giant cell tumor of bone. Calcif Tissue Int. 2004; 75(1):71–7.
  73. Tse LF, Wong KC, Kumta SM, Huang L, Chow TC, Griffith JF. Bisphosphonates reduce local recurrence in extremity giant cell tumor of bone: a case-control study. Bone. 2008; 42(1):68–73.
  74. Fujimoto N, Nakagawa K, Seichi A, Terahara A, Tago M, Aoki Y, et al. A new bisphosphonate treatment option for giant cell tumors. Oncol Rep. 2001; 8(3):643–7.
  75. Nishisho T, Hanaoka N, Miyagi R, Sakai T, Toki S, Takahashi M, et al. Local administration of zoledronic acid for giant cell tumor of bone. Orthopedics. 2015; 38(1):e25–30.
  76. Balke M, Schremper L, Gebert C, Ahrens H, Streitbuerger A, Koehler G, et al. Giant cell tumor of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol. 2008; 134(9):969–78.
  77. Balke M, Ahrens H, Streitbuerger A, Koehler G, Winkelmann W, Gosheger G, et al. Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol. 2009; 135(1):149–58.
  78. Vult von Steyern F, Bauer HC, Trovik C, Kivioja A, Bergh P, Holmberg Jorgensen P, et al. Treatment of local recurrences of giant cell tumour in long bones after curettage and cementing. A Scandinavian Sarcoma Group study. J Bone Joint Surg Br. 2006; 88(4):531–5.
  79. Feigenberg SJ, Marcus RB Jr, Zlotecki RA, Scarborough MT, Enneking WF. Whole-lung radiotherapy for giant cell tumors of bone with pulmonary metastases. Clin Orthop Relat Res. 2002; 401(1):202–8.
  80. Wray CC, Macdonald AW, Richardson RA. Benign giant cell tumour with metastases to bone and lung. One case studied over 20 years. J Bone Joint Surg Br. 1990; 72(3):486–9.
  81. Bertoni F, Present D, Enneking WF. Giant-cell tumor of bone with pulmonary metastases. J Bone Joint Surg Am. 1985; 67(6):890–900.
  82. Chan CM, Adler Z, Reith JD, Gibbs CP Jr. Risk factors for pulmonary metastases from giant cell tumor of bone. J Bone Joint Surg Am. 2015; 97(5):420–8.
  83. Lopez-Pousa A, Martin Broto J, Garrido T, Vazquez J. Giant cell tumour of bone: new treatments in development. Clin Transl Oncol. 2015; 17(6):419-30.
  84. Matcuk GR Jr, Patel DB, Schein AJ, White EA, Menendez LR. Giant cell tumor: rapid recurrence after cessation of long-term denosumab therapy. Skeletal Radiol. 2015; 44(7):1027-31.
  85. Lewin J, Thomas D. Denosumab: a new treatment option for giant cell tumor of bone. Drugs Today (Barc). 2013; 49(11):693–700.
  86. Dufresne A, Derbel O, Cassier P, Vaz G, Decouvelaere AV, Blay JY. Giant-cell tumor of bone, anti-RANKL therapy. Bonekey Rep. 2012; 149(1):1-8.