Giant Cell Tumor Treatment & Management
- Author: Valerae O Lewis, MD; Chief Editor: Harris Gellman, MD more...
The presence of tumor is the indication for surgery.
Radiation therapy and embolization generally are reserved for cases in which surgical treatment is not feasible. Radiation therapy has been proposed for patients who are not surgical candidates, for those whose tumors are in locations not amenable to operative treatment, and for those in whom a potential for significant morbidity from tumor relapse or subsequent surgery exists.[57, 58]
Many authors have reported a strong association between radiation therapy and malignant transformation of the giant cell tumor (GCT).[3, 7, 9, 59, 60, 61, 19] However, much of this information was derived during the era of orthovoltage radiation. Subsequent studies have examined the effect of megavoltage radiation and have shown it to be well tolerated and not associated with malignant transformation. GCTs that have undergone malignant transformation are treated as sarcomas.[62, 63, 57, 64, 58]
Although megavoltage radiation now is used, recommendations regarding radiation dose and fractionation schedules vary in the literature. Dose recommendations range from 35 to 70 Gy.[62, 63, 65, 57, 64] Recurrence rates in these series ranged from 10-15%, and malignant transformation was uncommon. However, long-term follow-up still is warranted.
In June 2013, the FDA approved denosumab for the treatment of unresectable GCT of bone (GCTB) in adults and skeletally mature adolescents. Approval was based on positive results from two open-label trials involving 305 patients with GCTB that was either recurrent, unresectable, or for which planned surgery was likely to result in severe morbidity. Of the 187 patients with measurable tumors, 47 experienced a reduction in tumor size after 3 months of treatment with the drug. Of these patients with an objective response, 24 (51%) had a duration of response lasting at least 8 months.[66, 67]
Pulmonary metastases have been cited as the cause of death in 16-25% of reported cases.[10, 21, 68] The need for early detection and treatment of these metastases has been emphasized. Pulmonary metastases have been treated with wide resection, chemotherapy, radiation therapy, and interferon alfa. When possible, wide surgical resection is the treatment of choice.[20, 9, 10, 21, 14]
When the pulmonary metastases cannot be completely surgically excised, adjuvant treatment, such as chemotherapy or radiation therapy, has been advocated. In addition, in situations when the metastases are unresectable, both chemotherapy and radiation have been used as solitary agents.[69, 70, 21, 71, 72, 73] At University of Texas MD Anderson Cancer Center, interferon has been used with promising results.
Spontaneous malignant transformation of GCT is not uncommon. Malignant transformation has been defined as a sarcoma associated with a benign typical GCT at presentation or as a sarcoma arising at the site of a preexisting GCT. Malignant transformations have resulted in osteosarcoma, fibrosarcoma, or malignant histiocytoma.[74, 75, 60] Periods of 4-40 years for malignant transformation have been reported.[75, 59, 60, 23]
In the past, GCTs were treated with amputation or with wide resection and reconstruction. However, with the knowledge that GCT is a locally aggressive yet benign disease, the surgical treatment of GCTs is intralesional for most locations.
Various treatment options have been advocated, including the following:
Curettage and bone grafting
Curettage and insertion of polymethylmethacrylate (PMMA) 
Embolization of the feeding vessels
Although intralesional procedures remain the treatment of choice for most GCTs, wide en-bloc resection offers the lowest recurrence rate and can be performed in expandable bone. In the proximal fibula, wide resection without reconstruction is often performed. Similarly, GCTs of the distal radius often are resected and reconstructed with autograft or allograft (see the images below).
However, in the long bones, resection necessitates prosthetic or allograft reconstruction and is generally reserved for grade III lesions.[78, 79, 80, 81]
Intralesional curettage and bone grafting is a limb-sparing option that is associated with good functional and oncologic outcomes. However, simple curettage with or without bone grafting has recurrence rates of 27-55%.[7, 75, 9, 12, 13, 82] The high risk of recurrence led several surgeons to replace bone graft packing of the lesion with PMMA packing (see the images below). The heat given off by the hardening PMMA is thought to lead to thermal necrosis of the remaining tumor cells in the curetted cavity.[83, 84]
The PMMA technique, compared with bone grafting, offers the advantages of lack of donor-site morbidity, an unlimited supply, immediate structural stability, low cost, and ease of use. In addition, the barium contained in the methylmethacrylate results in a radiopaque substance that sharply contrasts with the surrounding bone (see the image below). Local recurrences are more readily apparent than in cases in which bone graft is used.
The disadvantages of using cement include difficulty in removing it when revision is needed and the possibility that subchondral cement may predispose the joint to early degenerative osteoarthritis.[85, 86] The latter is a theory that remains to be proved.[87, 88, 89, 90] In fact, using a canine model, Frassica et al showed that subchondral PMMA did not cause joint degeneration. However, in a later study, Frassica et al showed that subchondral bone grafts are superior to cement for restoration of the normal subchondral anatomy.
Investigators have shown no differences in recurrence when comparing bone graft with PMMA.
Several authors have added the technique of high-speed burring of the cavity after simple intralesional curettage. A large cortical window is necessary to expose the entire tumor and tumor cavity, allowing thorough curettage and burring of the cavity (see the first image below). This has been found to reduce the recurrence rates to 12-25%. The high-speed burr (see the second image below) not only adds a thermal component to eradication of the tumor but also allows more thorough removal of the tumor. High-speed burring of the cavity then may be followed by a chemical or physical adjuvant and packing of the lesion with PMMA or a bone graft.[92, 83]
Adjuvant therapies, such as phenol, liquid nitrogen, or H2O2 and argon beam coagulation, all have advantages and disadvantages. However, they all offer a method for eradication of microscopic disease. Many authors suggest that phenol is an effective means of decreasing the recurrence rate of GCTs. After curettage is performed and all perforations in the bone are sealed, phenol is poured into the cavity. This results in a cellular death at a depth of approximately 1-2 mm. The use of 5% phenol has been advocated.[93, 94, 95, 96, 87, 68]
Recurrence rates with curettage and phenol and packing with PMMA or bone grafts are 5-17%. Phenol is systemically toxic. Preventing exposure to the surrounding tissues while at the same time allowing exposure to the entire curetted cavity is difficult. It can cause a serious chemical burn, and it is also readily absorbed through the skin and mucosa. The material has a hazardous effect on the nervous system, heart, kidneys, and liver. It damages the DNA, coagulates protein, and causes cellular necrosis. Several authors have raised the concern of the rapid absorption of the phenol through cancellous bones.[93, 94, 95, 96, 87, 68]
Many authors advocate cryosurgery as an adjuvant. Liquid nitrogen is a chemical reagent used in cryosurgery. In the direct-pour technique, after the curettage is performed and after all perforations in the bone are sealed, liquid nitrogen is poured through a stainless steel funnel into the cavity (see the image below).[97, 98, 99, 100, 101, 102]
The liquid nitrogen is left in the cavity until it all evaporates. The surrounding tissues are irrigated with warm sodium chloride solution in an attempt to prevent or minimize thermal injury to the surrounding tissues. The process is repeated two or three times, resulting in cellular death at a depth of approximately 1-2 cm. The cavitary defect is then reconstructed with PMMA or bone grafts.
Recurrence rates with cryosurgery have been reported to be in the range of 2-12%. The disadvantages of cryosurgery include the need for wide exposure, the need to protect the soft tissues, skin necrosis, osteonecrosis, and fracture. Fracture is the most commonly reported and gravest complication.[97, 92, 98, 99, 100, 101, 102]
Malawer et al noted that internal fixation with Steinmann pins and reconstruction of the cavitary defect with PMMA significantly reduced the incidence of fracture and suggested that all patients who undergo cryosurgery receive internal stabilization as well (see the images below).
Some authors, as an alternative to cryosurgery and phenol therapy, have advocated argon-beam coagulation. This modality lacks the application hazards identified with both phenol and liquid nitrogen. Thermal coagulation applied through a concentrated argon gas is used to paint the tumor cavity (see the images below).
The penetration is approximately 2-3 mm. Reported recurrence rates for this procedure when paired with PMMA are approximately 7%. No acute complications were noted. Long-term follow-up is warranted to assess the effect of argon beam coagulation on joint and/or subchondral physiology and on the incidence of pathologic fracture.
A review of the literature reveals that adjuvant treatment, when paired with intralesional curettage, offers excellent recurrence-free survival. Successful treatment of GCTs depends more on the thoroughness of intralesional curettage than on the specific adjuvant employed. The adequacy of tumor removal is influenced by tumor location, associated fracture, soft-tissue extension, and an understanding of the functional consequences of resection. The specific adjuvant treatment used appears to be at the surgeon's discretion; each option has advantages and disadvantages.
After treatment, patients with GCT should be monitored with serial physical examinations and radiography of the involved site and of the chest. Relapses may be associated with new pain or swelling. Tumor recurrences have been noted many years after initial treatment, and long-term observation of at least 5 years is recommended.
In summary, GCTs of bone are benign but locally aggressive primary bone tumors. Local control is most closely related to complete tumor removal. However, the functional consequences and good long-term results often dictate intralesional (curettage) procedures.
Cooper AS, Travers B. Surgical Essays. London, England:. Cox Longman & Co. 1818: 178-9.
McDonald SG. Surgery for Bone and Soft Tissue Sarcomas. NY:. Lippincott Williams & Wilkins. 1998:756.
Campanacci M, Baldini N, Boriani S. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987 Jan. 69(1):106-14. [Medline].
Cheng JC, Johnston JO. Giant cell tumor of bone. Prognosis and treatment of pulmonary metastases. Clin Orthop. 1997 May. (338):205-14. [Medline].
Connell D, Munk PL, Lee MJ, et al. Giant cell tumor of bone with selective metastases to mediastinal lymph nodes. Skeletal Radiol. 1998 Jun. 27(6):341-5. [Medline].
Dahlin DC. Caldwell Lecture. Giant cell tumor of bone: highlights of 407 cases. AJR Am J Roentgenol. 1985 May. 144(5):955-60. [Medline].
Dahlin DC, Cupps RE, Johnson EW Jr. Giant-cell tumor: a study of 195 cases. Cancer. 1970 May. 25(5):1061-70. [Medline].
Fitz GR, Carter HK. Giant cell tumor of bone: review and presentation of two unusual cases. J Am Osteopath Assoc. 1966 Nov. 66(3):292-302. [Medline].
Goldenberg RR, Campbell CJ, Bonfiglio M, et al. Giant-cell tumor of bone. An analysis of two hundred and eighteen cases. J Bone Joint Surg Am. 1970 Jun. 52(4):619-64. [Medline].
Kay RM, Eckardt JJ, Seeger LL, et al. Pulmonary metastasis of benign giant cell tumor of bone. Six histologically confirmed cases, including one of spontaneous regression. Clin Orthop. 1994 May. (302):219-30. [Medline].
Kitano K, Shiraishi T, Okabayashi K, et al. A lung metastasis from giant cell tumor of bone at eight years after primary resection. Jpn J Thorac Cardiovasc Surg. 1999 Dec. 47(12):617-20. [Medline].
Kreicbergs A, Lonnqvist PA, Nilsson B. Curettage of benign lesions of bone. Factors related to recurrence. Int Orthop. 1985. 8(4):287-94. [Medline].
McDonald DJ, Sim FH, McLeod RA, et al. Giant-cell tumor of bone. J Bone Joint Surg Am. 1986 Feb. 68(2):235-42. [Medline].
Mirra JM, Ulich T, Magidson J, et al. A case of probable benign pulmonary "metastases" or implants arising from a giant cell tumor of bone. Clin Orthop. 1982 Jan-Feb. (162):245-54. [Medline].
Mnaymneh WA, Dudley HR, Mnaymneh LG. Giant-cell tumor of bone. An analysis and follow-up study of the forty-one cases observed at the Massachusetts General Hospital between 1925 and 1960. J Bone Joint Surg Am. 1964. 46A:63-75.
Present DA, Bertoni F, Springfield D, et al. Giant cell tumor of bone with pulmonary and lymph node metastases. A case report. Clin Orthop. 1986 Aug. (209):286-91. [Medline].
Riley LH Jr, Hartmann WH, Robinson RA. Soft-tissue recurrence of giant-cell tumor of bone after irradiation and excision. J Bone Joint Surg Am. 1967 Mar. 49(2):365-8. [Medline].
Shifrin LZ. Giant cell tumor of bone. Clin Orthop. 1972 Jan-Feb. 82:59-66. [Medline].
Unni KK. Dahlin's bone tumors: general aspects and data on 11,087 cases. New York, NY:. Lippincott-Raven. 1996: 463.
Bertoni F, Present D, Sudanese A, et al. Giant-cell tumor of bone with pulmonary metastases. Six case reports and a review of the literature. Clin Orthop. 1988 Dec. (237):275-85. [Medline].
Maloney WJ, Vaughan LM, Jones HH, et al. Benign metastasizing giant-cell tumor of bone. Report of three cases and review of the literature. Clin Orthop. 1989 Jun. (243):208-15. [Medline].
Szyfelbein WM, Schiller AL. Cytologic diagnosis of giant cell tumor of bone metastatic to lung. A case report. Acta Cytol. 1979 Nov-Dec. 23(6):460-4. [Medline].
Rock MG, Pritchard DJ, Unni KK. Metastases from histologically benign giant-cell tumor of bone. J Bone Joint Surg Am. 1984 Feb. 66(2):269-74. [Medline].
Tubbs WS, Brown LR, Beabout JW, et al. Benign giant-cell tumor of bone with pulmonary metastases: clinical findings and radiologic appearance of metastases in 13 cases. AJR Am J Roentgenol. 1992 Feb. 158(2):331-4. [Medline].
Nojima T, Takeda N, Matsuno T, et al. Case report 869. Benign metastasizing giant cell tumor of bone. Skeletal Radiol. 1994 Oct. 23(7):583-5. [Medline].
Sanerkin NG. Malignancy, aggressiveness, and recurrence in giant cell tumor of bone. Cancer. 1980 Oct 1. 46(7):1641-9. [Medline].
Sung HW, Kuo DP, Shu WP, et al. Giant-cell tumor of bone: analysis of two hundred and eight cases in Chinese patients. J Bone Joint Surg Am. 1982 Jun. 64(5):755-61. [Medline].
Niu X, Xu H, Inwards CY, Li Y, Ding Y, Letson GD, et al. Primary Bone Tumors: Epidemiologic Comparison of 9200 Patients Treated at Beijing Ji Shui Tan Hospital, Beijing, China, With 10 165 Patients at Mayo Clinic, Rochester, Minnesota. Arch Pathol Lab Med. 2015 May 15. [Medline].
Frassica FJ, Sanjay BK, Unni KK, et al. Benign giant cell tumor. Orthopedics. 1993 Oct. 16(10):1179-83. [Medline].
Schajowicz F, Granato DB, McDonald DJ. Clinical and radiological features of atypical giant cell tumours of bone. Br J Radiol. 1991 Oct. 64(766):877-89. [Medline].
Kransdorf MJ, Sweet DE, Buetow PC, Moser RP. Giant cell tumor in skeletally immature patients. Radiology. 1992 Jul. 184(1):233-7. [Medline].
Picci P, Manfrini M, Zucchi V. Giant-cell tumor of bone in skeletally immature patients. J Bone Joint Surg Am. 1983 Apr. 65(4):486-90. [Medline].
Puri A, Agarwal MG, Shah M, Jambhekar NA, Anchan C, Behle S. Giant cell tumor of bone in children and adolescents. J Pediatr Orthop. 2007 Sep. 27(6):635-9. [Medline].
Bogumill GS, Johnson LC. Giant cell tumor: a metaphyseal lesion. J Bone Joint Surg Am. 1972. 54:1558.
Campanacci M, Giunti A, Olmi R. [Metaphyseal and diaphyseal localization of giant cell tumors]. Chir Organi Mov. 1975. 62(1):29-34. [Medline].
Fain JS, Unni KK, Beabout JW, et al. Nonepiphyseal giant cell tumor of the long bones. Clinical, radiologic, and pathologic study. Cancer. 1993 Jun 1. 71(11):3514-9. [Medline].
Peison B, Feigenbaum J. Metaphyseal giant-cell tumor in a girl of 14. Radiology. 1976 Jan. 118(1):145-6. [Medline].
Sherman MA. Giant cell tumors in the metaphysis of a child. J Bone Joint Surg Am. 1961. 43:1225-9.
Wilkerson JA, Cracchiolo A 3rd. Giant-cell tumor of the tibial diaphysis. J Bone Joint Surg Am. 1969 Sep. 51(6):1205-9. [Medline].
Errani C, Ruggieri P, Asenzio MA, Toscano A, Colangeli S, Rimondi E, et al. Giant cell tumor of the extremity: A review of 349 cases from a single institution. Cancer Treat Rev. 2010 Feb. 36(1):1-7. [Medline].
Karpik M. Giant Cell Tumor (tumor gigantocellularis, osteoclastoma) - epidemiology, diagnosis, treatment. Ortop Traumatol Rehabil. 2010 May-Jun. 12(3):207-15. [Medline].
Cummins CA, Scarborough MT, Enneking WF. Multicentric giant cell tumor of bone. Clin Orthop. 1996 Jan. (322):245-52. [Medline].
Hindman BW, Seeger LL, Stanley P, et al. Multicentric giant cell tumor: report of five new cases. Skeletal Radiol. 1994 Apr. 23(3):187-90. [Medline].
Kadir S, Hudson TM. Multicentric giant cell tumors of bone. ROFO Fortschr Geb Rontgenstr Nuklearmed. 1978 Jun. 128(6):769-70. [Medline].
Kaufman SM, Isaac PC. Multiple giant cell tumors. South Med J. 1977 Jan. 70(1):105-7. [Medline].
Madhuri V, Sundararaj GD, Babu NV, et al. Multicentric giant cell tumour of bone--a report of two cases. Indian J Cancer. 1993 Sep. 30(3):135-9. [Medline].
Peimer CA, Schiller AL, Mankin HJ, et al. Multicentric giant-cell tumor of bone. J Bone Joint Surg Am. 1980. 62(4):652-6. [Medline].
Sanghvi V, Lala M, Desai S, et al. Synchronous multicentric giant cell tumour: a case report with review of literature. Eur J Surg Oncol. 1999 Dec. 25(6):636-7. [Medline].
Sim FH, Dahlin DC, Beabout JW, et al. Multicentric giant-cell tumor of bone. J Bone Joint Surg Am. 1977 Dec. 59(8):1052-60. [Medline].
Hoch B, Inwards C, Sundaram M, Rosenberg AE. Multicentric giant cell tumor of bone. Clinicopathologic analysis of thirty cases. J Bone Joint Surg Am. 2006 Sep. 88(9):1998-2008. [Medline].
Ennecking W. Musculoskeletal Tumor Surgery. New York, NY:. Churchill Liningstone. 1983.
Hudson TM, Schiebler M, Springfield DS, et al. Radiology of giant cell tumors of bone: computed tomography, arthro- tomography, and scintigraphy. Skeletal Radiol. 1984. 11(2):85-95. [Medline].
Matsubayashi S, Nakashima M, Kumagai K, Egashira M, Naruke Y, Kondo H, et al. Immunohistochemical analyses of beta-catenin and cyclin D1 expression in giant cell tumor of bone (GCTB): A possible role of Wnt pathway in GCTB tumorigenesis. Pathol Res Pract. 2009 Mar 24. [Medline].
Salerno M, Avnet S, Alberghini M, Giunti A, Baldini N. Histogenetic characterization of giant cell tumor of bone. Clin Orthop Relat Res. 2008 Sep. 466(9):2081-91. [Medline].
Frassica FJ, Sim FH, Pritchard DJ. Subchondral replacement: a comparative analysis of reconstruction with methyl methacrylate or autogenous bone graft. Chir Organi Mov. 1990. 75(1 Suppl):189-90. [Medline].
Seider MJ, Rich TA, Ayala AG. Giant cell tumors of bone: treatment with radiation therapy. Radiology. 1986 Nov. 161(2):537-40. [Medline].
Malone S, O''Sullivan B, Catton C, et al. 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 Oct 15. 33(3):689-94. [Medline].
Schwartz LH, Okunieff PG, Rosenberg A. Radiation therapy in the treatment of difficult giant cell tumors. Int J Radiat Oncol Biol Phys. 1989 Nov. 17(5):1085-8. [Medline].
Hefti FL, Gachter A, Remagen W. Recurrent giant-cell tumor with metaplasia and malignant change, not associated with radiotherapy. A case report. J Bone Joint Surg Am. 1992 Jul. 74(6):930-4. [Medline].
Mori Y, Tsuchiya H, Karita M. Malignant transformation of a giant cell tumor 25 years after initial treatment. Clin Orthop. 2000 Dec. (381):185-91. [Medline].
Rock MG, Sim FH, Unni KK. Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients. J Bone Joint Surg Am. 1986 Sep. 68(7):1073-9. [Medline].
Bennett CJ Jr, Marcus RB Jr, Million RR, et al. Radiation therapy for giant cell tumor of bone. Int J Radiat Oncol Biol Phys. 1993 May 20. 26(2):299-304. [Medline].
Chen ZX, Gu DZ, Yu ZH. Radiation therapy of giant cell tumor of bone: analysis of 35 patients. Int J Radiat Oncol Biol Phys. 1986 Mar. 12(3):329-34. [Medline].
Nair MK, Jyothirmayi R. Radiation therapy in the treatment of giant cell tumor of bone. Int J Radiat Oncol Biol Phys. 1999 Mar 15. 43(5):1065-9. [Medline].
Harwood AR, Fornaster VL, Rider WD. Supervoltage irradiation in the management of giant cell tumor of bone. Radiology. 1977 Oct. 125(1):223-6. [Medline].
Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar. 11(3):275-80. [Medline].
Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15. 18(16):4415-24. [Medline].
Rock M. Adjuvant management of benign tumors; basic concepts of phenol and cement use. Chir Organi Mov. 1990. 75(1 Suppl):195-7. [Medline].
Kutchemeshgi AD, Wright JR, Humphrey RL. Pulmonary metastases from a well-differentiated giant cell tumor of bone. Report of a patient with apparent response to cyclophosphamide therapy. Johns Hopkins Med J. 1974 Apr. 134(4):237-45. [Medline].
Ladanyi M, Traganos F, Huvos AG. Benign metastasizing giant cell tumors of bone. A DNA flow cytometric study. Cancer. 1989 Oct 1. 64(7):1521-6. [Medline].
Stargardter FL, Cooperman LR. Giant-cell tumour of sacrum with multiple pulmonary metastases and long- term survival. Br J Radiol. 1971 Dec. 44(528):976-9. [Medline].
Stewart DJ, Belanger R, Benjamin RS. Prolonged disease-free survival following surgical debulking and high- dose cisplatin/doxorubicin in a patient with bulky metastases from giant cell tumor of bone refractory to "standard" chemotherapy. Am J Clin Oncol. 1995 Apr. 18(2):144-8. [Medline].
Vanel D, Contesso G, Rebibo G, et al. Benign giant-cell tumours of bone with pulmonary metastases and favourable prognosis. Report on two cases and review of the literature. Skeletal Radiol. 1983. 10(4):221-6. [Medline].
Benjamin RS. Interferon a2b as anti-angiogenesis therapy of giant cell tumors of bone: implications for the study of newer angiogenesis-inhibitors. Proc Am Soc Clin Oncol. 1999. 18:548a.
Gitelis S, Mallin BA, Piasecki P. Intralesional excision compared with en bloc resection for giant-cell tumors of bone. J Bone Joint Surg Am. 1993 Nov. 75(11):1648-55. [Medline].
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 Sep. 134(9):969-78. [Medline].
Wysocki RW, Soni E, Virkus WW, Scarborough MT, Leurgans SE, Gitelis S. Is intralesional treatment of giant cell tumor of the distal radius comparable to resection with respect to local control and functional outcome?. Clin Orthop Relat Res. 2015 Feb. 473 (2):706-15. [Medline].
Clohisy DR, Mankin HJ. Osteoarticular allografts for reconstruction after resection of a musculoskeletal tumor in the proximal end of the tibia. J Bone Joint Surg Am. 1994 Apr. 76(4):549-54. [Medline].
Kocher MS, Gebhardt MC, Mankin HJ. Reconstruction of the distal aspect of the radius with use of an osteoarticular allograft after excision of a skeletal tumor. J Bone Joint Surg Am. 1998 Mar. 80(3):407-19. [Medline].
Mankin HJ, Doppelt SH, Sullivan TR, et al. Osteoarticular and intercalary allograft transplantation in the management of malignant tumors of bone. Cancer. 1982 Aug 15. 50(4):613-30. [Medline].
Mankin HJ, Fogelson FS, Thrasher AZ. Massive resection and allograft transplantation in the treatment of malignant bone tumors. N Engl J Med. 1976 Jun 3. 294(23):1247-55. [Medline].
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(2):129-33. [Medline].
Leeson MC, Lippitt SB. Thermal aspects of the use of polymethylmethacrylate in large metaphyseal defects in bone. A clinical review and laboratory study. Clin Orthop. 1993 Oct. (295):239-45. [Medline].
Mjoberg B, Pettersson H, Rosenqvist R. Bone cement, thermal injury and the radiolucent zone. Acta Orthop Scand. 1984 Dec. 55(6):597-600. [Medline].
Campanacci M, Capanna R, Fabbri N, et al. Curettage of giant cell tumor of bone. Reconstruction with subchondral grafts and cement. Chir Organi Mov. 1990. 75(1 Suppl):212-3. [Medline].
Persson BM, Wouters HW. Curettage and acrylic cementation in surgery of giant cell tumors of bone. Clin Orthop. 1976. 00(120):125-33. [Medline].
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. [Medline].
Quint U, Vanhofer U, Harstrick A. Cytotoxicity of phenol to musculoskeletal tumours. J Bone Joint Surg Br. 1996 Nov. 78(6):984-5. [Medline].
Wilkins RM, Okada Y, Sim FH, et al. Methyl methacrylate replacement of subchondral bone: a biomechanical, biochemical, and morphologic analysis. In: Enneking WF, et al. Limb Salvage in Musculoskeletal Oncology. New York, NY:. Churchill Livingstone. 1987: 479-86.
Willert HG. Clinical results of the temporary acrylic bone cement plug in the treatment of bone tumors: a multicentric study. In: Enneking WF, ed. Limb Salvage in Musculoskeletal Oncology. New York, NY:. Churchill Livingstone. 1987: 445-58.
Turcotte RE. Giant cell tumor of bone. Orthop Clin North Am. 2006 Jan. 37(1):35-51. [Medline].
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 Jun. 81(6):811-20. [Medline].
Capanna R, Sudanese A, Baldini N. Phenol as an adjuvant in the control of local recurrence of benign neoplasms of bone treated by curettage. Ital J Orthop Traumatol. 1985 Sep. 11(3):381-8. [Medline].
Durr HR, Maier M, Jansson V. Phenol as an adjuvant for local control in the treatment of giant cell tumour of the bone. Eur J Surg Oncol. 1999 Dec. 25(6):610-8. [Medline].
Gitelis S, Wang JW, Quast M, et al. Recurrence of a giant-cell tumor with malignant transformation to a fibrosarcoma twenty-five years after primary treatment. A case report. J Bone Joint Surg Am. 1989 Jun. 71(5):757-61. [Medline].
O''Donnell RJ, Springfield DS, Motwani HK, et al. Recurrence of giant-cell tumors of the long bones after curettage and packing with cement. J Bone Joint Surg Am. 1994 Dec. 76(12):1827-33. [Medline].
Aboulafia AJ, Rosenbaum DH, Sicard-Rosenbaum L, et al. Treatment of large subchondral tumors of the knee with cryosurgery and composite reconstruction. Clin Orthop. 1994 Oct. (307):189-99. [Medline].
Malawer MM, Bickels J, Meller I, et al. Cryosurgery in the treatment of giant cell tumor. A long-term followup study. Clin Orthop. 1999 Feb. (359):176-88. [Medline].
Malawer MM, Dunham W. Cryosurgery and acrylic cementation as surgical adjuncts in the treatment of aggressive (benign) bone tumors. Analysis of 25 patients below the age of 21. Clin Orthop. 1991 Jan. (262):42-57. [Medline].
Marcove RC. A 17-year review of cryosurgery in the treatment of bone tumors. Clin Orthop. 1982 Mar. (163):231-4. [Medline].
Marcove RC, Weis LD, Vaghaiwalla MR, et al. Cryosurgery in the treatment of giant cell tumors of bone. A report of 52 consecutive cases. Cancer. 1978 Mar. 41(3):957-69. [Medline].
Pogrel MA. The management of lesions of the jaws with liquid nitrogen cryotherapy. J Calif Dent Assoc. 1995 Dec. 23(12):54-7. [Medline].
Grogan TJ, Eckardt J. Phenol cauterization versus liquid nirogen cryosurgery: extent of cellular necrosis in a dog model. Trans Orthop Res Soc. 1984. 9(291):184.
Lewis VO, Wei A, Mendoza T, et al. Argon Beam Coagulation as an Adjuvant for Local Control of Giant Cell Tumor. Clin Orthop Relat Res. 2007 Jan. 454:192-197. [Medline].
Carrasco CH, Murray JA. Giant cell tumors. Orthop Clin North Am. 1989 Jul. 20(3):395-405. [Medline].
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 Nov. 81(11):1566-73. [Medline].
Ghert MA, Rizzo M, Harrelson JM, Scully SP. Giant-cell tumor of the appendicular skeleton. Clin Orthop Relat Res. 2002 Jul. 201-10. [Medline].
Goto T, Kawano H, Akiyama T, Shinoda Y, Okuma T, Kobayashi H, et al. Serum acid phosphatase can be a useful tumour marker for giant cell tumour of bone. Arch Orthop Trauma Surg. 2009 Mar 25. [Medline].
Jaffe HL, Lichtenstien L, Portis RB. Giant cell tumor of bone. Its pathologic appearance, grading, supposed variants and treatment. Arch Pathol. 1940. 30:993-1031.
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 Mar. 57(2):167-73. [Medline].
McCarthy EF. Giant-cell tumor of bone: an historical perspective. Clin Orthop. 1980 Nov-Dec. (153):14-25. [Medline].
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. [Medline].
Muscolo DL, Ayerza MA, Calabrese ME. The use of a bone allograft for reconstruction after resection of giant- cell tumor close to the knee. J Bone Joint Surg Am. 1993 Nov. 75(11):1656-62. [Medline].
Vidal J, Mimran R, Allieu Y, et al. Plastic de comblement par metacrylate de methyle traitement de certaines tumeurs osseous benignes. Montpellier Chirurgical Tome. 1969. 15:389-97.