Introduction
Giant cell tumour (GCT) of bone, or osteoclastoma, is classically described as a locally invasive tumour that occurs close to the joint of a mature bone. It makes 5 to 7% of primary bone tumours according to available literature1-3. It usually occurs around the knee joint and distal radius with incidence of about 75%. It is generally considered to be a benign tumour. The incidence of bone GCT also varies depending on the reporting centre. It involves predominately males in age group of 20 to 40 years after physeal closure. Treatment options include curettage of tumour through a bone window with autologous bone grafting or cementing to fill the gap wherever possible. The reconstruction of the bone defect following wide excision is done depending on site of lesion.
Review
Etiopathogenesis and incidence
Giant cell tumor is described as neoplasm of undifferentiated mesenchymal stromal cells with presence of abundant, mulinucleated giant cells3. it is a benign aggressive tumor which involves the epiphysis and metaphysis of the long bones. Giant cell tumour has a tendency for local aggressiveness and high chances of recurrence. Giant cell tumors are named for the way they look under the microscope. Many "giant cells" are seen. They are formed by fusion of several individual cells into a single, larger complex. Many bone tumors and other conditions (including normal bone) contain giant cells. Giant cell tumor of bone is given its characteristic appearance by the constant finding of a large number of these cells existing in a typical background.
Most bone tumors occur in the flared portion near the ends of long bone (metaphysis), but giant cell tumor of bone occurs almost exclusively in the end portion of long bones next to the joints (epiphysis). Giant cell tumor of bone most frequently occurs around the knee joint in the lower end of the femur or the upper end of the tibia. The most common localization is the distal femur and proximal tibia in 55% to 60% of all the cases, the distal radius is the next place in 10%. Other common locations include the proximal femur and proximal humerus. It is characterized by local aggressive behaviour and frequent recurrence.
Clinico-radiological diagnosis
The clinical picture is that of insidious onset pain. The pain and swelling usually occurs simultaneously in comparison to malignant tumors where pain is the only presenting symptom initially. A history of preceding trivial trauma may be present. The swelling is firm to hard in consistency and gives the feeling of egg shell cracking. Other features are non specific. Radiologically, the tumour appears as an eccentric lytic lesion with cortical thinning and expansion. There is absence of reactive new bone formation. The tumour may erode the cortex and invade the joint. Pathological fracture may also be seen. CT scanning permits accurate delineation of the tumour extent and helps in deciding the line of management.
Histopathology and Treatment
General treatment regimens have not changed much in the past 30 years, in part due to the lack of randomized clinical trials4. Several treatment strategies have been developed for GCT, including surgery, radiotherapy, embolization, cryosurgery, cementation, and chemical adjuvant such as phenol or liquid nitrogen. Surgical management remains the mainstay of the treatment processes. When using the Campanacci or Enneking grading system1,6, the higher the radiographic grading, the more radical surgery. Eckardt and Grogan have recommended intralesional curettage with adjuvant therapy for stage I and II lesions and en bloc resection for stage III lesions7.
GCT is mostly a true neoplastic condition with well-defined clinical, radiological and histopathological features8,9. Radiologically, it is usually lytic and expansile without prominent peripheral sclerosis and periosteal reaction. Some pathologists consider it a low grade or potentially malignant neoplasm10,11. The tumor is locally aggressive and destructive, and it tends to recur after simple curetting. In addition to The histopathology of GCT is characterized by frank and marked hemorrhage, numerous giant cells and stromal cells9,12. The hemorrhage gives rise to the characteristic grossly lytic picture. Many workers have totally ignored this component and did not emphasize the role of multinucleated giant cells in the removal of hemorrhage although such is observed in different pathological lesions such as adenomatous goiter, brown tumor of hyperparathyroidism and giant cells in reparative granulomas. The giant cells are considered reactive while stromal cells are considered “true” neoplastic cells. There had been a lot of debate about the origin of both types of cells. There is now agreement that giant cells are circulating monocytes in origin which have converted into osteoclasts after acquiring some unique features and gene expressions in osseous environment. These conclusions are based on various light, ultrastructural and immunological markers7,13. Giant cells have the characteristic features of several mycobacterial, fungal and parasitic diseases as well as sarcoidosis and foreign bodies. Several non-infectious and non- granulomatous pathological lesions other than GCTB also contain large number of giant cells; most if not all of these are considered reactive rather than neoplastic14,15. Giant cell tumor of the bone is rich in RANK Ligand positive cells, which results in giant osteoclasts that destroy the bone locally.16,17.
Surgery is the treatment of choice if the tumour is determined to be resectable. Curettage is a commonly used technique5,16. The situation is complicated in a patient with a pathological fracture. It may be best to immobilize the affected limb and wait for the fracture to heal before performing surgery. Many authors have reported satisfactory results with intralesional curettage and bone grafting. However, curettage alone has a high rate of recurrence and adjuvants like Methylmethacrylate (bone cement), Cryotherapy and Phenol have been suggested. Various reconstructive procedures have been mentioned in literature. Arthrodesis of the joint is also an alternative option, but considering the young age and level of activity, allograft reconstruction is attractive option.
References
1.Campanacci M, Baldini N, Boriani S, Sudanese A. Giant cell tumour of bone. J Bone Joint Surg Am 1987;69:106–14.
2.Goldenberg RR, Campbell CJ, Bon?glio M. Giant cell tumour of bone. An analysis of two hundred and eighteen cases. J Bone Joint Surg Am 1970;52:619–64.
3.McDonald DJ, Sim FH, McLeod RA, Dahlin DC. Giant cell tumour of bone. J Bone Joint Surg 1986;68:235–42.
4.Thomas DM, Skubitz T. Giant cell tumour of bone. Current Opinion in Oncology 2009;21:338-344
5.Werner M. Giant cell tumour of bone: morphological, biological and histogenetical aspects. Springer-Verlag 2006;30:484-489
6.Enneking WF. A system of staging musculoskeletal neoplasms. Clin Orthop 1986;204:9-24.
7.Eckardt JJ, Grogan TJ. Giant cell tumor of bone. Clin Orthop 1986;204:45-58.
8.Werner M. Giant cell tumour of bone: morphological, biological and histogenetical aspects. Int Orthop 2006;30:484-489.
9.Zheng MH, Robbins P, Xu J, Huang L, Wood DJ and Papadimitriou JM. The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts. Histol Histopathol 2001;16:297-307.
10.Cheng JC and Johnston JO. Giant cell tumor of bone. prognosis and treatment of pulmonary metastases. Clin Orthop Relat Res 1997;338:205-214.
11.McGough RL, Rutledge J, Lewis VO, Lin PP and Yasko AW. Impact severity of local recurrence in giant cell tumor of bone. Clin Orthop Relat Res 2005;438:116-122.
12.Rosai J and Ackerman LV: Bones and Joints. In Rosai J (Ed): Surgical Pathology. Mosby, St Louis, 2004,2169-2172.
13.Gothlin G and Ericsson JLE. The osteoclast: review of ultrastructure, origin, and structure-function relationship. Clin Orthop 1976;120: 201-231
14.Spector WG and Lykke AW. The cellular evolution of inflammatory granulomata. J Pathol Bacteriol 1966;92:163-177.
15.Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350:1655-1664.
16.Fuller K, Wong B, Fox S, Choi Y, Chambers TJ. TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts. J Exp Med. 1998;188:997-1001.
Source(s) of Funding
none
Competing Interests
none
Disclaimer
This article has been downloaded from WebmedCentral. With our unique author driven post publication peer
review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is
completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript
but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before
submitting any information that requires obtaining a consent or approval from a third party. Authors should also
ensure not to submit any information which they do not have the copyright of or of which they have transferred
the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to
the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor
replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the
WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm
that you may suffer or inflict on a third person by following the contents of this website.