Giant cell tumor of bone

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rohan A. Bhimani, M.B.B.S., D.N.B., M.Ch.[2]

Synonyms and keywords: Osteoclastoma; Giant cell myeloma; Giant cell tumor; Giant cell tumor of the bone

Overview

Giant cell tumor of bone is a relatively uncommon tumor of the bone. It is characterized by the presence of multinucleated giant cells (osteoclast-like cells). Giant cell tumor of bone accounts for 4-5% of primary bone tumors and 18.2% of benign bone tumors. Giant cell tumor of bone almost invariably occur when the growth plate has closed and are therefore typically observed in early adulthood, with 80% of cases reported between the ages of 20 and 50, with a peak incidence between 20 and 30. Giant cell tumor of bone typically occur as single lesions. They usually prefers the epiphyses of long bones. Although any bone can be affected, the most common sites are distal femur, proximal tibia, and distal radius. The progression to giant cell tumor of bone usually involves the over-expression in RANK/RANKL signalling pathway with resultant over-proliferation of osteoclasts. On gross pathology, hemorrhage, presence of co-existent aneurysmal bone cyst, and fibrosis are characteristic findings of giant cell tumor of bone. On microscopic histopathological analysis, prominent and diffuse osteoclastic giant cells and mononuclear cells with frequent mitotic figures are characteristic findings of giant cell tumor of bone. Symptoms of giant cell tumor of bone include localized pain, localized swelling, and decreased range of motion. Physical examination findings will depend on the location of the giant cell tumor. Common physical examination findings of giant cell tumor are localized swelling and tenderness at the site of the tumor. Giant cell tumor of bone must be differentiated from aneurysmal bone cyst, chondroblastoma, simple bone cyst, osteoblastoma,giant cell rich osteosarcoma, and brown tumor of hyperparathyroidism. X-ray may be helpful in the diagnosis of giant cell tumor of bone. Common complications of giant cell tumor include malignant transformation, recurrence, and metastasis. Findings on x-ray suggestive of giant cell tumor include metaepiphyseal location of mass and grow to the articular surface of the involved bone with narrow zone of transition. Surgery is the mainstay of treatment for giant cell tumor.

Historical Perspective

  • In 1818, Cooper and Travers first described giant cell tumor (GCT) of bone.[1]
  • In 1845, Par H. Lebert described the first microscopic observations of multinucleated giant cells and fusiform cells as 'tumeur fiblastique'.[2]
  • In 1854, Sir James Paget provided the first description of the giant cell tumor in English literature.[3]
  • In early 1900, Bloodgood a surgeon at Johns Hopkins University, was credited with coining the term "giant-cell tumor" in his publication on radiographic features, conservative treatment, and use of bone grafts.[4]
  • In 1940, Jaffe and Lichtenstein described the clinical-radiographic-histologic identity of giant cell tumor.[5][6]

Classification

  • Giant cell tumor (GCT) can be classified based on imaging findings and on mechanism of origin.

Mechanism of Origin

Based on mechanism of origin, malignant giant cell tumor (MGCT) can be classified into:

Primary Malignant Giant Cell Tumor

  • When MGCT arises de novo, it is called primary MGCT.
  • Metastatizes to lung in 2-5%.

Secondary Malignant Giant Cell Tumor

  • It occurs following radiation or multiple resections of giant cell tumor.

Enneking (MSTS) Staging System

Stages Description
1 Latent: Well demarcated borders
2 Active: Indistinct borders
3 Aggressive: Indistinct borders

Pathophysiology

Genetics

Causes

There are no established causes for giant cell tumor of the bone.[17]

Differentiating Giant cell tumor of bone from other Diseases

Giant cell tumor of bone must be differentiated from:[18]

Epidemiology and Demographics

  • In the United States and Europe, giant cell tumors(GCT) represent approximately 5% of all primary bone tumors and 21% of all benign bone tumors.[9]
  • Giant cell tumors occur most commonly in the third decade of life; less than 5% of GCTs occur in patients who are skeletally immature.[19]
  • GCTs usually occur in patients older than 19 years. [20]
  • Women are more commonly affected than men, with a 1.5:1 ratio.[21]
  • There is no racial predilection to giant cell tumor.

Risk Factors

There are no established risk factors for giant cell tumor.

Screening

There is insufficient evidence to recommend routine screening for giant cell tumor.

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic Study of Choice

Histological appearance: Giant Cell Tumor. Source: Case courtesy of Dr Alexandra Stanislavsky, Radiopaedia.org, rID: 14823
  • Biopsy is the diagnostic study of choice for the diagnosis of giant cell tumor.[23]
  • Gross pathological findings include:
  • Histopathological findings include:
  • Areas of regressive change such as necrosis or fibrosis as well as extensive hemorrhage are frequently present.
  • Frequent mitotic figures in the mononuclear cells may be seen, especially in pregnant women or those on the oral contraceptive pill, due to increased hormone levels.

History and Symptoms

Symptoms of giant cell tumor include:

X-Ray of Femur showing giant cell tumor. Source: Case courtesy of Radswiki, Radiopaedia.org, rID: 11453

Physical Examination

Laboratory Findings

There are no diagnostic laboratory findings associated with giant cell tumor.

Electrocardiogram

There are no ECG findings associated with giant cell tumor.

CT scan of Femur showing giant cell tumor. Source: Case courtesy of Radswiki, Radiopaedia.org, rID: 11453

X Ray

Chest X-Ray

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with giant cell tumor.

CT scan

CT findings for giant cell tumor include:

MRI of Femur showing giant cell tumor. Source: Case courtesy of Radswiki, Radiopaedia.org, rID: 11453

MRI

  • MRI is performed to delineate the extent of the neoplasm.
  • MRI findings of giant cell tumor of bone include:
    • T1: Low to intermediate solid component and Low signal periphery
    • T2: Intermediate to high signal
    • MRI may also reveal an effusion of the joint.

Other Imaging Findings

Bone Scan

  • Increased uptake is observed around the lesion of giant cell tumor, especially around the periphery, with a central photopenic region (doughnut sign).
  • Increased blood pool activity is also observed.

Other Diagnostic Studies

There are no other diagnostic studies associated with giant cell tumor.

Treatment

Medical Therapy

Bone scan showing giant cell tumor. Source: Case courtesy of Radswiki, Radiopaedia.org, rID: 11453

Surgery

Surgery is the mainstay of treatment for giant cell tumor.[28][29]

Extensive Curettage and Reconstruction with adjuvant treatment

Indications

  • Lesions amenable to currettage[6][29]
  • Hand lesion treatment is controversial.
  • If no cortical breakthrough, then treat with curettage and cementing.
  • If significant cortical breakthrough, then intercalary resection with free fibular graft.

Technique

  • The challenge of treatment is to remove lesion while preserving joint and providing support to subchondral joint.
  • Extensive exterioration which is removal of a large cortical window over the lesion is required.
  • Lesion can be filled with bone cement or autograft/allograft bone.
  • Synthetic grafts such as polymethylmethacrylate (PMMA) have improved patient recovery and tumor removal due to the graft's exothermic reaction that causes thermal necrosis of cells and innate inflammatory reaction.[30]

Chemical Adjuvants Used

Outcomes

Amputation

Indications

  • Hand lesions with cortical breakthrough which are not amendable to intercalary resection.[31]

Radiation Therapy

Excision of giant cell tumor of distal radius. Source: Case courtesy by: Dr. Rohan A. Bhimani

Indications

  • Reserved for cases in which surgical treatment is not feasible.[32]
  • Tumors are in locations not amenable to operative treatment.
  • Patients in whom a potential for significant morbidity from tumor relapse or subsequent surgery exists.

Technique

  • Megavoltage radiation is used.
  • Dose: 35 to 70 Gy[33]

Primary Prevention

There are no established measures for the primary prevention of giant cell tumor.

Secondary Prevention

There are no established measures for the secondary prevention of giant cell tumor.







References

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  3. Jaffe HL, Lichtenstein L (1942). "Benign Chondroblastoma of Bone: A Reinterpretation of the So-Called Calcifying or Chondromatous Giant Cell Tumor". Am J Pathol. 18 (6): 969–91. PMC 2032980. PMID 19970672.
  4. Bloodgood JC (1912). "II. The Conservative Treatment of Giant-Cell Sarcoma, with the Study of Bone Transplantation". Ann Surg. 56 (2): 210–39. PMC 1407379. PMID 17862876.
  5. Icihikawa K, Tanino R (2004). "Soft tissue giant cell tumor of low malignant potential". Tokai J Exp Clin Med. 29 (3): 91–5. PMID 15595466.
  6. 6.0 6.1 Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC; et al. (2010). "The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study". J Bone Joint Surg Br. 92 (10): 1475–9. PMID 21089702.
  7. Jawad MU, Scully SP (2010). "In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system". Clin Orthop Relat Res. 468 (7): 2000–2. doi:10.1007/s11999-010-1315-7. PMC 2882012. PMID 20333492.
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  20. Kransdorf MJ, Sweet DE, Buetow PC, Giudici MA, Moser RP (1992). "Giant cell tumor in skeletally immature patients". Radiology. 184 (1): 233–7. doi:10.1148/radiology.184.1.1609086. PMID 1609086.
  21. Picci P, Manfrini M, Zucchi V, Gherlinzoni F, Rock M, Bertoni F; et al. (1983). "Giant-cell tumor of bone in skeletally immature patients". J Bone Joint Surg Am. 65 (4): 486–90. PMID 6833323.
  22. Muheremu, Aikeremujiang; Niu, Xiaohui (2014). "Pulmonary metastasis of giant cell tumor of bones". World Journal of Surgical Oncology. 12 (1): 261. doi:10.1186/1477-7819-12-261. ISSN 1477-7819.
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  28. Puri, Ajay; Agarwal, Manish (2007). "Treatment of giant cell tumor of bone: Current concepts". Indian Journal of Orthopaedics. 41 (2): 101. doi:10.4103/0019-5413.32039. ISSN 0019-5413.
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  30. Oh JH, Yoon PW, Lee SH, Cho HS, Kim WS, Kim HS (2006). "Surgical treatment of giant cell tumour of long bone with anhydrous alcohol adjuvant". Int Orthop. 30 (6): 490–4. doi:10.1007/s00264-006-0154-3. PMC 3172752. PMID 16736146.
  31. Kim Y, Nizami S, Goto H, Lee FY (2012). "Modern interpretation of giant cell tumor of bone: predominantly osteoclastogenic stromal tumor". Clin Orthop Surg. 4 (2): 107–16. doi:10.4055/cios.2012.4.2.107. PMC 3360182. PMID 22662295.
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