Giant cell tumor of bone: current review of morphological, clinical, radiological, and therapeutic characteristics

Abstract

Giant cell tumor of bone accounts for about 5% of all primary bone tumors in adults and is still one of the most obscure and intensively examined tumors of bone. This largely results from the lack of uniform clinical, radiographic, histological or morphological aspects that allow prediction of recurrence. Classified by the World Health Organization as “an aggressive, potentially malignant lesion”, the giant cell tumor of bone could give lung metastases, could undergo malignant degeneration or could have multicentric localization. It usually develops in long bones but can also occur in unusual locations. The common presenting symptom is increasing pain at the tumor site. Standard treatment ranges from curettage to wide resection, with reports of varying oncological and functional results. The recurrence rate is high during the first 2-3 years after surgery regardless of pre-operative tumor stage. Herein, we discuss the morphological, clinical, radiological, and therapeutic characteristics of this pathologic entity as well as its differential diagnosis. J Clin Exp Invest 2014; 5 (3): 475-485

Keywords

• Giant cell tumor of bone, diagnosis, treatment, review.

Kemiğin dev hücreli tümörü: Morfolojik, klinik, radyolojik ve tedavi özelliklerinin gözden geçirilmesi

Öz

Kemiğin dev hücreli tümörü erişkinlerdeki tüm primer kemik tümörlerinin %5\'ini oluşturur ve kemik tümörlerinin en güç ve yoğun araştırılanıdır. Bu durum büyük ölçüde tekrarları öngörmeye izin veren tek tip klinik, radyografik, histolojik ve morfolojik özelliklerinin olmayışı nedeniyledir. Dünya Sağlık Örgütü tarafından agresif potansiyeli olan malign bir lezyon olarak sınıflandırılan kemiğin dev hücreli tümörü akciğere metastaz yapar ve malign dejenerasyon veya çok merkezli lokalizasyon gösterir. Tümör genellikle uzun kemiklerde oluşur, ancak alışılmadık lokalizasyonlarda da olabilir. Yaygın semptomu tümör bölgesindeki artan ağrıdır. Standart tedavi küretajdan geniş rezeksiyona kadar değişir ve değişik onkolojik ve fonksiyonel sonuçlar doğurur. Tümör evresine bakılmaksızın, cerrahiyi takip eden ilk 2-3 yılda tekrarlama riski yüksektir. Bu yazıda bu patolojik teşekkülün morfolojik, klinik, radyolojik ve tedavi özellikleri ile ayırıcı tanısı tartışılmıştır.

Anahtar Kelimeler

• Kemiğin dev hücreli tümörü, tanı, tedavi, derleme

References

1. Wülling M, Engels C, Jesse N, et al. The nature of giant cell tumor of bone. J Cancer Res Clin Oncol 2001;127:467-474.
2. Balke M, Schremper L, Gebert C, et al. Giant cell tumor of bone: treatment and outcome of 214 cases. J Can- cer Res Clin Oncol 2008;134:969-978.
3. Goto T, Kawano H, Akiyama T, et al. Serum acid phosphatase can be a useful tumour marker for gi- ant cell tumour of bone. Arch Orthop Trauma Surg 2009;129:1641-1644.
4. Roeder F, Timke C, Zwicker F, et al. Intensity modula- ted radiotherapy (IMRT) in benign giant cell tumors-a single institution case series and a short review of the literature. Radiat Oncol 2010;5:18.
5. Stewart MJ. The histogenesis of myeloid sarcoma. The Lancet 1922;200:1106-1109.
6. Danilov AI. Juxta-epiphyseal osteoblastoclastomas in children. Ortop Travmatol Protez 1973;34:27-30.
7. Murphey MD, Nomikos GC, Flemming DJ, et al. Ima- ging of giant cell tumor and giant cell reparative gra- nuloma of bone: radiologic-pathologic correlation. Ra- diographics 2001;21:1283-1309.
8. Szendröi M. Giant-cell tumour of bone. J Bone Joint Surg Br 2004;86:5-12.

9. Miller IJ, Blank A, Yin SM, et al. A case of recurrent giant cell tumor of bone with malignant transformati- on and benign pulmonary metastases. Diagn Pathol 2010;5:62.
10. Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am 1987;69:106-114.
11. Schajowicz F. Giant-cell tumors of bone (osteoclasto- ma). A pathological and histochemical study. J Bone Joint Surg Am 1961;43:1-29.
12. Kim Y, Nizami S, Goto H, Lee FY. Modern interp- retation of giant cell tumor of bone: predominantly osteoclastogenic stromal tumor. Clin Orthop Surg 2012;4:107-116.
13. Georgiev GP, Landzhov B, Slavchev S, et al. Localiza- tion of matrix metalloproteinase-2 in giant cell tumor of bone. Compt rend Acad bulg Sci 2012;65:1285-1288.
14. Cowan RW, Singh G. Giant cell tumor of bone: a basic science perspective. Bone 2013;52:238-246.
15. Clohisy DR, Vorlicky L, Oegema TR Jr, et al. Histo- chemical and immunohistochemical characterization of cells constituting the giant cell tumor of bone. Clin Orthop Relat Res 1993;287:259-265.
16. Lindeman JH, Hanemaaijer R, Mulder A, et al. Cat- hepsin K is the principal protease in giant cell tumor of bone. Am J Pathol 2004;165:593-600.
17. Khurana JS, McCarthy EF. Giant cell lesions. In: Khu- rana, McCarthy EF, Zhang PJ, editors. Essentials in Bone and Soft-Tissue Pathology. 1st ed. New York Dordrecht Heidelberg London: Springer; 2010. pp. 134-137.
18. Georgiev GP, Georgiev H, Landzhov B. Ultrastructural study of giant cell tumor of bone. Rp./Orthop. Rheu- matol 2012;2-3:13-15.
19. Georgiev GP, Landzhov B, Slavchev S, et al. Compa- rative electron microscopic and immunohistochemical study of stromal cells in giant cell tumor of bone. Sc- ripta Scientifica Medica 2013; 1 suppl 45:19-22.
20. Zheng MH, Robbins P, Xu J, et al. The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts. Histol His- topathol 2001;16:297-307.
21. Miyamoto N, Higuchi Y, Tajima M, et al. Spindle-sha- ped cells derived from giant-cell tumor of bone sup- port differentiation of blood monocytes to osteoclast-li- ke cells. J Orthop Res 2000;18:647-654.
22. Kumta SM, Huang L, Cheng YY, et al. Expression of VEGF and MMP-9 in giant cell tumor of bone and ot- her osteolytic lesions. Life Sci 2003;73:1427-1436.
23. Rabinovich A, Mak IW, Cowan RW, et al. Matrix me- talloproteinase activity in the stromal cell of giant cell tumor of bone. Open Bone J 2009;1:46-52.
24. Kito M, Moriya H, Mikata A, et al. Establishment of a cell line from a human giant cell tumor of bone. Clin Orthop Relat Res 1993;294:353-360.
25. Lausten GS, Jensen PK, Schiİdt T, Lund B. Local recurrences in giant cell tumour of bone. Long-term follow up of 31 cases. Int Orthop 1996;20:172-176.
26. Masui F, Ushigome S, Fujii K. Giant cell tumor of bone: a clinicopathologic study of prognostic factors. Pathol Int. 1998;48:723-729.
27. Turcotte RE, Wunder JS, Isler MH, et al. Giant cell tu- mor of long bone: a Canadian Sarcoma Group study. Clin Orthop Relat Res 2002;397:248-258.
28. Bacchini P, Bertoni F. Giant cell tumor of bone. In: Folpe AL, Inwards CY, editors Bone and soft tissue pathology. 1st ed. Philadelphia: Elsevier Health Scien- ces; 2010. pp. 401-407.
29. McInerney DP, Middlemiss JH. Giant cell tumor of bone. Skeletal Radiol 1978;2:195-204.
30. Kransdorf MJ, Sweet DE, Buetow PC, et al. Giant cell tumor in skeletally immature patients. Radiology 1992;184:233-237.
31. Larsson SE, Lorentzon R, Boquist L. Giant-cell tumor of bone. A demographic, clinical, and histopathologi- cal study of all cases recorded in the Swedish Cancer Registry for the years 1958 through 1968. J Bone Jo- int Surg Am 1975;57:167-173.
32. Eckardt J, Grogan T. Giant cell tumor of bone. Clin Orthop 1986;204:45-58.
33. Manaster BJ, Doyle AJ. Giant cell tumors of bone. Radiol Clin North Am 1993;31:299-323.
34. Kumar R, Guinto FC, Madewell JE, et al. Expan- sile bone lesions of the vertebra. Radiographics 1988;8:749-769.
35. Murari TM, Callaghan JJ, Berrey BJ, Sweet DE. Pri- mary benign and malignant osseous neoplasms of the foot. Foot Ankle 1989;10:68-80.
36. Patel MR, Desai SS, Gordon SL, et al. Management of skeletal giant cell tumors of the phalanges of the hand. J Hand Surg Am 1987;12:70-77.
37. Levine E, DeSmet AA, Neff JR, Martin NL. Scintigrap- hic evaluation of giant cell tumor of bone. AJR Am J Roentgenol 1984;148:343-348.
38. Campanacci M, Giunti A, Olmi R. Giant-cell tumours of bone: a study of 209 cases with long term follow up in 130. Ital J Orthop Traumatol 1975;1:249-277.
39. Lee MJ, Sallomi DF, Munk PL, et al. Pictorial review: giant cell tumours of bone. Clin Radiol 1998;53:481- 489.
40. Hudson TM, Schiebler M, Springfield DS, et al. Radi- ology of giant cell tumors of bone: computed tomog- raphy, arthro-tomography, and scintigraphy. Skeletal Radiol 1984;11:85-95.
41. Van Nostrand D, Madewell JE, McNiesh LM, et al. Radionuclide bone scanning in giant cell tumor. J Nucl Med 1986;27:329-338.
42. Purohit S, Pardiwala DN. Imaging of giant cell tumor of bone. Indian J Orthop 2007;41:91-96.
43. Bertoni F, Bacchini P, Staals EL. Malignancy in giant cell tumor of bone. Cancer 2003;97:2520-2529.
44. Mirra JM. Bone tumors. Clinical, radiologic, and pat- hologic correlations. 1st ed. Philadelphia: Lea & Febi- ger; 1989.
45. Sakkers RJ, van der Heul RO, Kroon HM, et al. Late malignant transformation of a benign giant-cell tu- mor of bone. A case report. J Bone Joint Surg Am 1997;79:259-262.
46. Mori Y, Tsuchiya H, Karita M, et al. Malignant trans- formation of a giant cell tumor 25 years after initial treatment. Clin Orthop Relat Res 2000;381:185-191.
47. Cheng JC, Johnston JO. Giant-cell tumor of bone: prognosis and treatment of pulmonary metastases. Clin Orthop 1997;338:205-214.
48. Prosser GH, Baloch KG, Tillman RM, et al. Does cu- rettage without adjuvant therapy provide low recur- rence rates in giant-cell tumors of bone? Clin Orthop Relat Res 2005;435:211-218.
49. Kivioja AH, Blomqvist C, Hietaniemi K, 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;79:86-93.
50. Lewis JJ, Healey JH, Huvos AG, Burt M. Benign gi- ant-cell tumor of bone with metastasis to mediastinal lymph nodes. A case report of resection facilitated with use of steroids. J Bone Joint Surg Am 1996;78:106- 110.
51. Takanami I, Takeuchi K, Naruke M, Kodaira S. Agg- ressive surgery for treating a pulmonary metastasis of a benign giant cell tumor of the bone: results in four cases. J Thorac Cardiovasc Surg 1998;116:649-651.
52. Goldenberg RR, Campbell CJ, Bonfiglio M. Giant-cell tumor of bone. An analysis of two hundred and eigh- teen cases. J Bone Joint Surg Am 1970;52:619-664.
53. Rock MG, Pritchard DJ, Unni KK. Metastases from histologically benign giant-cell tumor of bone. J Bone Joint Surg Am 1984;66:269-274.
54. Bertoni F, Present D, Enneking WF. Giant-cell tumour of bone with pulmonary metastases. J Bone Joint Surg Am 1985;67:890-900.
55. Sanerkin NG. Malignancy, aggressiveness, and recurrence in giant cell tumor of bone. Cancer 1980;46:1641-1649.
56. Maloney WF, Vangham LM, Jones HH, et al. Benign metastasizing giant-cell tumor of bone: report of th- ree cases and review of the literature. Clin Orthop 1989;243:208-215.
57. Rock MG, Sim FH, Unni KK, et al. Secondary malig- nant giant-cell tumor of bone. Clinicopathological as- sessment of nineteen patients. J Bone Joint Surg Am 1986;68:1073-1079.
58. Tubbs WS, Brown LR, Beabout JW, et al. Benign gi- ant-cell tumor of bone with pulmonary metastases: cli- nical findings and radiological appearance of metasta- ses of 13 cases. AJR Am J Roentgenol 1992;158:331- 334.
59. Schoedel KE, Greco MA, Stetler-Stevenson WG, et al. Expression of metalloproteinases and tissue inhibi- tors of metalloproteinases in giant cell tumor of bone: an immunohistochemical study with clinical correlati- on. Hum Pathol 1996;27:1144-1148.
60. Gamberi G, Benassi MS, Bohling T, et al. Prognostic relevance of Cmyc gene expression in giant-cell tu- mor of bone. J Orthop Res 1998;16:1-7.
61. Kay RM, Eckhardt JJ, Seeger LL, et al. Pulmonary metastasis of benign giant cell tumor of bone: six his- tologically confirmed cases, including one of sponta- neous regression. Clin Orthop 1994;302:219-230.
62. Leggon RE, Zlotecki R, Reith J, Scarborough MT. Giant cell tumor of the pelvis and sacrum: 17 cases and analysis of the literature. Clin Orthop Relat Res 2004;423:196-207.
63. Hoch B, Inwards C, Sundaram M, Rosenberg AE. Multicentric giant cell tumor of bone. Clinicopatho- logic analysis of thirty cases. J Bone Joint Surg Am 2006;88:1998-2008.
64. Wirbel R, Blümler F, Lommel D, et al. Multicentric giant cell tumor of bone: synchronous and metachronous presentation. Case Rep Orthop 2013;2013:756723.
65. Dhillon MS, Prasad P. Multicentric giant cell tumor of bone. Acta Orthop Belg 2007;73:289-299.
66. Bandyopadhyay R, Biswas S, Bandyopadhyay SK, Ray MM. Synchronous multicentric giant cell tumor. J Cancer Res Ther 2010;6:106-108.
67. Wang H, Wan N, Hu Y. Giant cell tumour of bone: A new evaluating system is necessary. Int Orthop 2012;36:2521-2527.
68. Enneking WF. Musculoskeletal tumor surgery. New York: Churchill Livingstone, 1983.
69. Errani C, Ruggieri P, Asenzio MA, et al. Giant cell tu- mor of the extremity: A review of 349 cases from a single institution. Cancer Treat Rev 2010;36:1-7.
70. Klenke FM, Wenger DE, Inwards CY, et al. Giant cell tumor of bone: risk factors for recurrence. Clin Orthop Relat Res 2011;469:591-599.
71. Niu X, Zhang Q, Hao L, et al. Giant cell tumor of the extremity: retrospective analysis of 621 Chinese patients from one institution. J Bone Joint Surg Am 2012;94:461-467.
72. Rock M. Curettage of giant cell tumor of bone: Factors influencing local recurrences and metastasis. Chir Or- gani Mov 1990;75:204-205.
73. Rooney RJ, Asirvatham R, Lifeso RM, et al. Giant cell tumour of bone. A surgical approach to grade III tu- mours. Int Orthop 1993;17:87-92.
74. O’Donnell RJ, Springfield DS, Motwani HK, et al. Re- currence of giant-cell tumors of the long bones after curettage and packing with cement. J Bone Joint Surg Am 1994;76:1827-1833.
75. Blackley HR, Wunder JS, Davis AM, et al. Treatment of giant-cell tumors of long bones with curettage and bone-grafting. J Bone Joint Surg Am 1999;81:811- 820.
76. Malek F, Krueger P, Hatmi ZN, et al. Local control of long bone giant cell tumour using curettage, burring and bone grafting without adjuvant therapy. Int Orthop 2006;30:495-498.
77. Malawer MM, Bickels J, Meller I, et al. Cryosurgery in the treatment of giant cell tumor. A long-term followup study. Clin Orthop Relat Res 1999;359:176-188.
78. Becker WT, Dohle J, Bernd L, et al. Local recurrence of giant cell tumor of bone after intralesional treatment with and without adjuvant therapy. J Bone Joint Surg Am 2008;90:1060-1067.
79. Van der Heijden L, Dijkstra PD, Campanacci DA, et al. Giant Cell tumor with pathologic fracture: should we curette or resect? Clin Orthop Relat Res 2013;471:820-829.
80. Richardson MJ, Dickinson IC. Giant cell tumour of bone. Bull Hosp Jt Dis 1998;57:6-10.
81. Algawahmed H, Turcotte R, Farrokhyar F, Ghert M. High-Speed Burring with and without the Use of Sur- gical Adjuvants in the Intralesional Management of Giant Cell Tumor of Bone: A Systematic Review and Meta-Analysis. Sarcoma. 2010;2010.
82. Vult von Steyern F, Bauer HC, Trovik C, et al. Tre- atment of local recurrences of giant cell tumour in long bones after curettage and cementing. A Scandi- navian Sarcoma Group study. J Bone Joint Surg Br 2006;88:531-535.
83. Van der Heijden L, van de Sande MA, Dijkstra PD. Soft tissue extension increases the risk of local recur- rence after curettage with adjuvants for giant-cell tu- mor of the long bones. Acta Orthop 2012;83:401-405.
84. Ihara K, Doi K, Sakai K, et al. Vascularized fibular graft after excision of giant cell tumor of the distal radius. A case report. Clin Orthop Relat Res 1999;359:189-196.
85. Ben Amor H, Zouari M, Karray S, et al. Giant cell tu- mors of the distal end of the radius treated by resecti- on-arthrodesis. Acta Orthop Belg 1998;64:41-46.
86. Matev B, Georgiev H, Georgiev GP. Giant cell tumor of the fourth metacarpal: case report and literature re- view. J Radiother Med Oncol 2012;18:73-77.
87. Georgiev GP, Slavchev SA. Giant cell tumor of the distal tibia: report of a rare case. J Clin Exp Invest 2013;4:512-516.
88. Yang Q, L Wang, Yang Z, et al. Soft tissue recurrence of giant cell tumor of bone: A report of two cases and literature review. Chin Ger J Clin Oncol 2009;8:642- 646.
89. Xu S, Yu X, Xu M, Fu Z. Inactivated autograft-prosthe- sis composite have a role for grade III giant cell tumor of bone around the knee. BMC Musculoskelet Disord 2013;14:319.
90. Ozaki T, Liljenqvist U, Halm H, et al. Giant cell tumor of the spine. Clin Orthop Relat Res 2002;401:194-201.
91. Deheshi BM, Jaffer SN, Griffin AM, et al. Joint salvage for pathologic fracture of giant cell tumor of the lower extremity. Clin Orthop Relat Res 2007;459:96-104.
92. Dreinhöfer KE, Rydholm A, Bauer HC, Kreicbergs A. Giant-cell tumours with fracture at diagnosis. Curetta- ge and acrylic cementing in ten cases. J Bone Joint Surg Br 1995;77:189-193.
93. Lewis VO, Wei A, Mendoza T, et al. Argon beam co- agulation as an adjuvant for local control of giant cell tumor. Clin Orthop Relat Res 2007;454:192-197.
94. Lackman RD, Hosalkar HS, Ogilvie CM, et al. Intrale- sional curettage for grades II and III giant cell tumors of bone. Clin Orthop Relat Res 2005;438:123-127.
95. Sakayama K, Sugawara Y, Kidani T, et al. Diag- nostic and therapeutic problems of giant cell tumor in the proximal femur. Arch Orthop Trauma Surg 2007;127:867-872.
96. Waldram MA, Sneath RS. Is bone graft necessary? Analysis of twenty cases of giant cell tumour of bone treated by curettage without graft. Int Orthop 1990;14:129-133.
97. Balke M, Ahrens H, Streitbuerger A, et al. Treatment options for recurrent giant cell tumors of bone. J Can- cer Res Clin Oncol 2009;135:149-158.
98. Anract P, De Pinieux G, Cottias P, et al. Malignant giant-cell tumours of bone. Clinico-pathological ty- pes and prognosis: a review of 29 cases. Int Orthop 1998;22:19-26.
99. Leichtle CI, Leichtle UG, Gärtner V, et al. Multiple skeletal metastases from a giant cell tumour of the distal fibula with fatal outcome. J Bone Joint Surg Br 2006;88:396-399.
100. Pals SD, Wilkins RM. Giant cell tumor of bone trea- ted by curettage, cementation, and bone grafting. Ort- hopedics 1992;15:703-708.
101. Labs K, Perka C, Schmidt RG. Treatment of stages 2 and 3 giant-cell tumor. Arch Orthop Trauma Surg 2001;121:83-86.
102. Tse LF, Wong KC, Kumta SM, et al. Bisphosphonates reduce local recurrence in extremity giant cell tumor of bone: a case-control study. Bone 2008;42:68-73.
103. Remedios D, Saifuddin A, Pringle J. Radiological and clinical recurrence of giant-cell tumour of bone after the use of cement. J Bone Joint Surg Br 1997;79:26- 30.
104. Jackson K, Key C, Fontaine M, Pope R. Recurrence of a giant cell tumor of the hand after 42 years: case report. J Hand Surg Am 2012;37:783-786.
105. Zhen W, Yaotian H, Songjian L, et al. Giant-cell tumour of bone. The long-term results of treatment by curettage and bone graft. J Bone Joint Surg Br 2004;86:212-216.
106. Costelloe CM, Kumar R, Yasko AW, et al. Imaging characteristics of locally recurrent tumors of bone. AJR Am J Roentgenol 2007;188:855-863.
107. Pettersson H, Rydholm A, Persson B. Early radio- logic detection of local recurrence after curettage and acrylic cementation of giant cell tumours. Eur J Radiol 1986;6:1-4.
108. Chakravarti A, Spiro IJ, Hug EB, et al. Megavoltage radiation therapy for axial and inoperable giant-cell tumor of bone. J Bone Joint Surg Am 1999;81:1566- 1573.
109. Kostenuik PJ, Nguyen HQ, McCabe J, et al. Deno- sumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in kno- ck-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res 2009;24:182-195.
110. Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-la- bel, phase 2 study. Lancet Oncol 2010;11:275-280.
111. Thomas DM. RANKL, denosumab, and giant cell tu- mor of bone. Curr Opin Oncol 2012;24:397-403.
112. Branstetter DG, Nelson SD, Manivel JC, et al. Deno- sumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res 2012;18:4415-4424.