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'''For patient information, click [[Giant cell tumor of bone (patient information)|here]]'''
'''For patient information, click [[Giant cell tumor of bone (patient information)|here]]'''


{{CMG}};{{AE}} {{Rohan}}
{{CMG}}; {{AE}} {{Rohan}}


{{SK}} Osteoclastoma; Giant cell myeloma; Giant cell tumor; Giant cell tumor of the bone
{{SK}} Osteoclastoma; Giant cell myeloma; Giant cell tumor; Giant cell tumor of the bone


==Overview==
==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.<ref name="pmid12579271">{{cite journal |author=Gamberi G, Serra M, Ragazzini P, Magagnoli G, Pazzaglia L, Ponticelli F, Ferrari C, Zanasi M, Bertoni F, Picci P, Benassi MS |title=Identification of markers of possible prognostic value in 57 giant cell tumors of bone |journal=[[Oncology Reports]] |volume=10 |issue=2 |pages=351–6 |year=2003 |pmid=12579271 |doi= |url=http://www.spandidos-publications.com/or/10/2/351 |accessdate=2012-01-18}}</ref> Giant cell tumor of bone almost invariably (97-99%) 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.<ref name=radiopaedia>Giant cell tumor of bone.Dr Henry Knipe and Dr Behrang Amini et al.Radiopaedia.org 2015.http://radiopaedia.org/articles/giant-cell-tumour-of-bone.Accessed on March 11, 2016</ref> 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, osteoid osteoma, [[osteoblastoma]], [[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.<ref name="pmid11553835">{{cite journal |author=Murphey MD, Nomikos GC, Flemming DJ, Gannon FH, Temple HT, Kransdorf MJ |title=From the archives of AFIP. Imaging of giant cell tumor and giant cell reparative granuloma of bone: radiologic-pathologic correlation |journal=[[Radiographics : a Review Publication of the Radiological Society of North America, Inc]] |volume=21 |issue=5 |pages=1283–309 |year=2001 |pmid=11553835 |doi= |url=http://radiographics.rsnajnls.org/cgi/pmidlookup?view=long&pmid=11553835 |accessdate=2012-01-18}}</ref> Surgery is the mainstay of treatment for giant cell tumor.
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==
==Historical Perspective==
*In 1818, Cooper and Travers first described giant cell tumor (GCT) of bone.<ref name="pmid18322700">{{cite journal| author=Balke M, Schremper L, Gebert C, Ahrens H, Streitbuerger A, Koehler G et al.| title=Giant cell tumor of bone: treatment and outcome of 214 cases. | journal=J Cancer Res Clin Oncol | year= 2008 | volume= 134 | issue= 9 | pages= 969-78 | pmid=18322700 | doi=10.1007/s00432-008-0370-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18322700  }} </ref>
*In 1818, Cooper and Travers first described giant cell tumor (GCT) of [[bone]].<ref name="pmid18322700">{{cite journal| author=Balke M, Schremper L, Gebert C, Ahrens H, Streitbuerger A, Koehler G et al.| title=Giant cell tumor of bone: treatment and outcome of 214 cases. | journal=J Cancer Res Clin Oncol | year= 2008 | volume= 134 | issue= 9 | pages= 969-78 | pmid=18322700 | doi=10.1007/s00432-008-0370-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18322700  }} </ref>
*In 1845, Par H. Lebert described the first microscopic observations of multinucleated giant cells and fusiform cells as 'tumeur fiblastique'.<ref name="pmid7004712">{{cite journal| author=McCarthy EF| title=Giant-cell tumor of bone: an historical perspective. | journal=Clin Orthop Relat Res | year= 1980 | volume=  | issue= 153 | pages= 14-25 | pmid=7004712 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7004712  }} </ref>
*In 1845, Par H. Lebert described the first [[microscopic]] observations of [[multinucleated]] [[giant cells]] and fusiform cells as 'tumeur fiblastique'.<ref name="pmid7004712">{{cite journal| author=McCarthy EF| title=Giant-cell tumor of bone: an historical perspective. | journal=Clin Orthop Relat Res | year= 1980 | volume=  | issue= 153 | pages= 14-25 | pmid=7004712 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7004712  }} </ref>
*In 1854, Sir James Paget provided the first description of the giant cell tumor in English literature.<ref name="pmid19970672">{{cite journal| author=Jaffe HL, Lichtenstein L| title=Benign Chondroblastoma of Bone: A Reinterpretation of the So-Called Calcifying or Chondromatous Giant Cell Tumor. | journal=Am J Pathol | year= 1942 | volume= 18 | issue= 6 | pages= 969-91 | pmid=19970672 | doi= | pmc=2032980 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19970672  }} </ref>
*In 1854, Sir James Paget provided the first description of the giant cell tumor in English literature.<ref name="pmid19970672">{{cite journal| author=Jaffe HL, Lichtenstein L| title=Benign Chondroblastoma of Bone: A Reinterpretation of the So-Called Calcifying or Chondromatous Giant Cell Tumor. | journal=Am J Pathol | year= 1942 | volume= 18 | issue= 6 | pages= 969-91 | pmid=19970672 | doi= | pmc=2032980 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19970672  }} </ref>
*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.<ref name="pmid17862876">{{cite journal| author=Bloodgood JC| title=II. The Conservative Treatment of Giant-Cell Sarcoma, with the Study of Bone Transplantation. | journal=Ann Surg | year= 1912 | volume= 56 | issue= 2 | pages= 210-39 | pmid=17862876 | doi= | pmc=1407379 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17862876  }} </ref>
*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]].<ref name="pmid17862876">{{cite journal| author=Bloodgood JC| title=II. The Conservative Treatment of Giant-Cell Sarcoma, with the Study of Bone Transplantation. | journal=Ann Surg | year= 1912 | volume= 56 | issue= 2 | pages= 210-39 | pmid=17862876 | doi= | pmc=1407379 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17862876  }} </ref>
*In 1940, Jaffe and Lichtenstein described the clinical-radiographic-histologic identity of giant cell tumor.<ref name="pmid15595466">{{cite journal| author=Icihikawa K, Tanino R| title=Soft tissue giant cell tumor of low malignant potential. | journal=Tokai J Exp Clin Med | year= 2004 | volume= 29 | issue= 3 | pages= 91-5 | pmid=15595466 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15595466  }} </ref><ref name="pmid21089702">{{cite journal| author=Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC et al.| title=The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study. | journal=J Bone Joint Surg Br | year= 2010 | volume= 92 | issue= 10 | pages= 1475-9 | pmid=21089702 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21089702 }} </ref>
*In 1940, Jaffe and Lichtenstein described the clinical-radiographic-histologic identity of giant cell tumor.<ref name="pmid15595466">{{cite journal| author=Icihikawa K, Tanino R| title=Soft tissue giant cell tumor of low malignant potential. | journal=Tokai J Exp Clin Med | year= 2004 | volume= 29 | issue= 3 | pages= 91-5 | pmid=15595466 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15595466  }} </ref><ref name="pmid21089702">{{cite journal| author=Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC et al.| title=The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study. | journal=J Bone Joint Surg Br | year= 2010 | volume= 92 | issue= 10 | pages= 1475-9 | pmid=21089702 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgidbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21089702  }} </ref>
 
==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===
*The Enneking surgical staging system (also known as the MSTS system) for benign [[Musculoskeletal system|musculoskeletal]] [[Tumor|tumors]] based on [[radiographic]] characteristics of the [[tumor]] host margin.<ref name="pmid20333492">{{cite journal| author=Jawad MU, Scully SP| title=In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. | journal=Clin Orthop Relat Res | year= 2010 | volume= 468 | issue= 7 | pages= 2000-2 | pmid=20333492 | doi=10.1007/s11999-010-1315-7 | pmc=2882012 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20333492 }} </ref>
*It is widely accepted and routinely used [[classification]].
 
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| style="padding: 5px 5px; background: #F5F5F5;" | Aggressive: Indistinct borders
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==Pathophysiology==
==Pathophysiology==
*The exact [[pathogenesis]] of giant cell tumor (GCT) is not fully understood.<ref>{{cite book | last = Peabody | first = Terrance | title = Orthopaedic oncology : primary and metastatic tumors of the skeletal system | publisher = Springer | location = Cham | year = 2014 | isbn = 9783319073224 }}</ref>
*The exact [[pathogenesis]] of giant cell tumor (GCT) is not fully understood.<ref>{{cite book | last = Peabody | first = Terrance | title = Orthopaedic oncology : primary and metastatic tumors of the skeletal system | publisher = Springer | location = Cham | year = 2014 | isbn = 9783319073224 }}</ref><ref name="pmid12579271">{{cite journal |author=Gamberi G, Serra M, Ragazzini P, Magagnoli G, Pazzaglia L, Ponticelli F, Ferrari C, Zanasi M, Bertoni F, Picci P, Benassi MS |title=Identification of markers of possible prognostic value in 57 giant cell tumors of bone |journal=[[Oncology Reports]] |volume=10 |issue=2 |pages=351–6 |year=2003 |pmid=12579271 |doi= |url=http://www.spandidos-publications.com/or/10/2/351 |accessdate=2012-01-18}}</ref>
*Various theories have been proposed concerning the [[pathogenesis]] of giant cell tumor:
*Various theories have been proposed concerning the [[pathogenesis]] of giant cell tumor:
**Over-expression in RANK/RANKL signalling pathway with resultant over-proliferation of osteoclasts.<ref name="pmid15607894">{{cite journal| author=Liao TS, Yurgelun MB, Chang SS, Zhang HZ, Murakami K, Blaine TA et al.| title=Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone. | journal=J Orthop Res | year= 2005 | volume= 23 | issue= 1 | pages= 203-9 | pmid=15607894 | doi=10.1016/j.orthres.2004.06.018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15607894  }} </ref>
**Over-expression in [[RANK]]/[[RANKL]] signalling pathway with resultant over-proliferation of [[osteoclasts]].<ref name="pmid15607894">{{cite journal| author=Liao TS, Yurgelun MB, Chang SS, Zhang HZ, Murakami K, Blaine TA et al.| title=Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone. | journal=J Orthop Res | year= 2005 | volume= 23 | issue= 1 | pages= 203-9 | pmid=15607894 | doi=10.1016/j.orthres.2004.06.018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15607894  }} </ref>
**The stromal cells are believed to be the major neoplastic and proliferative component of giant cell tumor.
**The [[Stromal cell|stromal cells]] are believed to be the major [[neoplastic]] and proliferative component of giant cell tumor.
**The stromal cells often make osteoids, thus have the potential to differentiate into osteoblastic cells.  
**The [[Stromal cell|stromal cells]] often make [[Osteoid|osteoids]], thus have the potential to differentiate into [[Osteoblast|osteoblastic cells]].
**Stromal cells in GCT secrete various chemokines including monocyte chemoattractant protein (MCP)-1 and SDF-1, which attract blood monocytes and stimulate their migration into tumor tissues.  
**[[Monocyte|Monocytes]] derived from [[CD14]] and [[CD34]] positive precursor cells, which also express the chemokine receptor [[CXCR4]].  
*Giant cell tumor of bone typically occur in the epiphyses of long bones. <ref name="ShrivastavaNawghare2008">{{cite journal|last1=Shrivastava|first1=Sandeep|last2=Nawghare|first2=Shishir P|last3=Kolwadkar|first3=Yogesh|last4=Singh|first4=Pradeep|title=Giant cell tumour in the diaphysis of radius – a report|journal=Cases Journal|volume=1|issue=1|year=2008|pages=106|issn=1757-1626|doi=10.1186/1757-1626-1-106}}</ref>  
**[[Stromal cell|Stromal cells]] in GCT secrete various chemokines including [[monocyte]] chemoattractant protein ([[MCP-1|MCP]])-1 and [[Stromal cell-derived factor-1|SDF-1]], which attract blood [[monocytes]] and stimulate their migration into tumor tissues.  
*The bones often involved by epiphyseal GCT are distal femur, proximal tibia, and distal radius.<ref name="pmid1728946">{{cite journal| author=Bridge JA, Neff JR, Mouron BJ| title=Giant cell tumor of bone. Chromosomal analysis of 48 specimens and review of the literature. | journal=Cancer Genet Cytogenet | year= 1992 | volume= 58 | issue= 1 | pages= 2-13 | pmid=1728946 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1728946  }} </ref>
**The over-expression of [[interleukin 6]] (IL6) in GCT has been seen as a further [[autocrine]]/[[paracrine]] factor connected with the formation of multinucleated giant cell.<ref name="pmid14998856">{{cite journal| author=Gamberi G, Benassi MS, Ragazzini P, Pazzaglia L, Ponticelli F, Ferrari C et al.| title=Proteases and interleukin-6 gene analysis in 92 giant cell tumors of bone. | journal=Ann Oncol | year= 2004 | volume= 15 | issue= 3 | pages= 498-503 | pmid=14998856 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14998856  }} </ref>
*Giant cell tumor of bone typically occur in the [[Epiphysis|epiphyses]] of [[Long bone|long bones]]. <ref name="ShrivastavaNawghare2008">{{cite journal|last1=Shrivastava|first1=Sandeep|last2=Nawghare|first2=Shishir P|last3=Kolwadkar|first3=Yogesh|last4=Singh|first4=Pradeep|title=Giant cell tumour in the diaphysis of radius – a report|journal=Cases Journal|volume=1|issue=1|year=2008|pages=106|issn=1757-1626|doi=10.1186/1757-1626-1-106}}</ref>  
*The bones often involved by epiphyseal GCT are distal [[femur]], proximal [[tibia]], and distal [[radius]].<ref name="pmid1728946">{{cite journal| author=Bridge JA, Neff JR, Mouron BJ| title=Giant cell tumor of bone. Chromosomal analysis of 48 specimens and review of the literature. | journal=Cancer Genet Cytogenet | year= 1992 | volume= 58 | issue= 1 | pages= 2-13 | pmid=1728946 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1728946  }} </ref>


===Genetics===
===Genetics===
*Mutation in the histone 3.3 gene H3F3A (p.Gly34)is seen in approximately 92% of giant cell tumours of bone.<ref name="pmid28505000">{{cite journal| author=Amary F, Berisha F, Ye H, Gupta M, Gutteridge A, Baumhoer D et al.| title=H3F3A (Histone 3.3) G34W Immunohistochemistry: A Reliable Marker Defining Benign and Malignant Giant Cell Tumor of Bone. | journal=Am J Surg Pathol | year= 2017 | volume= 41 | issue= 8 | pages= 1059-1068 | pmid=28505000 | doi=10.1097/PAS.0000000000000859 | pmc=5510691 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28505000  }} </ref><ref name="pmid26457357">{{cite journal| author=Cleven AH, Höcker S, Briaire-de Bruijn I, Szuhai K, Cleton-Jansen AM, Bovée JV| title=Mutation Analysis of H3F3A and H3F3B as a Diagnostic Tool for Giant Cell Tumor of Bone and Chondroblastoma. | journal=Am J Surg Pathol | year= 2015 | volume= 39 | issue= 11 | pages= 1576-83 | pmid=26457357 | doi=10.1097/PAS.0000000000000512 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26457357  }} </ref><ref name="pmid8640728">{{cite journal| author=McComb EN, Johansson SL, Neff JR, Nelson M, Bridge JA| title=Chromosomal anomalies exclusive of telomeric associations in giant cell tumor of bone. | journal=Cancer Genet Cytogenet | year= 1996 | volume= 88 | issue= 2 | pages= 163-6 | pmid=8640728 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8640728  }} </ref>
*Mutation in the [[histone]] 3.3 gene [[H3F3A]] (p.Gly34)is seen in approximately 92% of giant cell tumours of bone.<ref name="pmid28505000">{{cite journal| author=Amary F, Berisha F, Ye H, Gupta M, Gutteridge A, Baumhoer D et al.| title=H3F3A (Histone 3.3) G34W Immunohistochemistry: A Reliable Marker Defining Benign and Malignant Giant Cell Tumor of Bone. | journal=Am J Surg Pathol | year= 2017 | volume= 41 | issue= 8 | pages= 1059-1068 | pmid=28505000 | doi=10.1097/PAS.0000000000000859 | pmc=5510691 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28505000  }} </ref><ref name="pmid26457357">{{cite journal| author=Cleven AH, Höcker S, Briaire-de Bruijn I, Szuhai K, Cleton-Jansen AM, Bovée JV| title=Mutation Analysis of H3F3A and H3F3B as a Diagnostic Tool for Giant Cell Tumor of Bone and Chondroblastoma. | journal=Am J Surg Pathol | year= 2015 | volume= 39 | issue= 11 | pages= 1576-83 | pmid=26457357 | doi=10.1097/PAS.0000000000000512 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26457357  }} </ref><ref name="pmid8640728">{{cite journal| author=McComb EN, Johansson SL, Neff JR, Nelson M, Bridge JA| title=Chromosomal anomalies exclusive of telomeric associations in giant cell tumor of bone. | journal=Cancer Genet Cytogenet | year= 1996 | volume= 88 | issue= 2 | pages= 163-6 | pmid=8640728 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8640728  }} </ref>
*A subset of the mutations can be easily detected using a G34W mutation specific antibody.
*A subset of the [[mutations]] can be easily detected using a G34W [[mutation]] specific [[antibody]].


==Causes==
==Causes==
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==Differentiating Giant cell tumor of bone from other Diseases==
==Differentiating Giant cell tumor of bone from other Diseases==
Giant cell tumor of bone must be differentiated from:
Giant cell tumor of bone must be differentiated from:<ref name="pmid10095427">{{cite journal| author=Salzer-Kuntschik M| title=[Differential diagnosis of giant cell tumor of bone]. | journal=Verh Dtsch Ges Pathol | year= 1998 | volume= 82 | issue=  | pages= 154-9 | pmid=10095427 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10095427  }} </ref>
*[[Aneurysmal bone cyst]]
*[[Brown tumor|Brown tumor of hyperparathyroidism]]
**It can look like GCT on radiographs except it occurs as multiple lesions and associated with serum [[calcium]] level abnormalities.
*[[Chondroblastoma]]
*[[Chondroblastoma]]
*Simple bone cyst
**It is [[epiphyseal]] in location
*Osteoid osteoma
**It may also demonstrate [[aneurysmal bone cyst]] formation
*[[Osteoblastoma]]
**It has extensive surrounding [[soft tissue]] and marrow [[edema]]
*[[Osteosarcoma]]
**[[Chondroblastoma]] have sclerotic margin and central [[calcification]] of [[Chondroid chordoma|chondroid]] matrix "ring and arcs" pattern
*Giant cell reparative granuloma
*Giant cell rich [[osteosarcoma]]
*[[Brown tumor]] of hyperparathyroidism
**It occurs in [[metaphysis]] of the bone
*Non-ossifying fibroma
**It has bimodal age distribution; affecting adolescents and elderly.
 
*Chordoma
===Gross Pathology===
**It mimics GCT in [[sacrum]]
*Macroscopically, giant cell tumors are variable in appearance, depending on amount of [[hemorrhage]], presence of co-existent [[aneurysmal bone cyst]], and degree of presence [[fibrosis]].
**It occurs in midline
 
===Microscopic Pathology===
*Giant cell tumor of bone is characterized by the presence of numerous Cathepsin-K producing, CD33 +, CD14 - multinucleated osteoclast-like giant cells and plump spindle-shaped stromal cells that represent the main proliferating cell population.
*The spindle-shaped mononuclear cells are believed to represent the neoplastic population and are characterized at the cytogenetic level by telomeric associations and a peculiar telomere-protecting capping mechanism.
*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 observed, especially in pregnant women or those on the [[oral contraceptive pill]] (due to increased hormone levels).


==Epidemiology and Demographics==
==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.<ref name="pmid12579271">{{cite journal |author=Gamberi G, Serra M, Ragazzini P, Magagnoli G, Pazzaglia L, Ponticelli F, Ferrari C, Zanasi M, Bertoni F, Picci P, Benassi MS |title=Identification of markers of possible prognostic value in 57 giant cell tumors of bone |journal=[[Oncology Reports]] |volume=10 |issue=2 |pages=351–6 |year=2003 |pmid=12579271 |doi= |url=http://www.spandidos-publications.com/or/10/2/351 |accessdate=2012-01-18}}</ref>
*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]].<ref name="pmid12579271">{{cite journal |author=Gamberi G, Serra M, Ragazzini P, Magagnoli G, Pazzaglia L, Ponticelli F, Ferrari C, Zanasi M, Bertoni F, Picci P, Benassi MS |title=Identification of markers of possible prognostic value in 57 giant cell tumors of bone |journal=[[Oncology Reports]] |volume=10 |issue=2 |pages=351–6 |year=2003 |pmid=12579271 |doi= |url=http://www.spandidos-publications.com/or/10/2/351 |accessdate=2012-01-18}}</ref>
*Giant cell tumors occur most commonly in the third decade of life; less than 5% of GCTs occur in patients who are skeletally immature.<ref name="pmid3805057">{{cite journal| author=Campanacci M, Baldini N, Boriani S, Sudanese A| title=Giant-cell tumor of bone. | journal=J Bone Joint Surg Am | year= 1987 | volume= 69 | issue= 1 | pages= 106-14 | pmid=3805057 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3805057  }} </ref>
*Giant cell tumors occur most commonly in the third decade of life; less than 5% of GCTs occur in patients who are skeletally immature.<ref name="pmid3805057">{{cite journal| author=Campanacci M, Baldini N, Boriani S, Sudanese A| title=Giant-cell tumor of bone. | journal=J Bone Joint Surg Am | year= 1987 | volume= 69 | issue= 1 | pages= 106-14 | pmid=3805057 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3805057  }} </ref>
*GCTs usually occur in patients older than 19 years. <ref name="pmid1609086">{{cite journal| author=Kransdorf MJ, Sweet DE, Buetow PC, Giudici MA, Moser RP| title=Giant cell tumor in skeletally immature patients. | journal=Radiology | year= 1992 | volume= 184 | issue= 1 | pages= 233-7 | pmid=1609086 | doi=10.1148/radiology.184.1.1609086 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1609086  }} </ref>
*GCTs usually occur in patients older than 19 years. <ref name="pmid1609086">{{cite journal| author=Kransdorf MJ, Sweet DE, Buetow PC, Giudici MA, Moser RP| title=Giant cell tumor in skeletally immature patients. | journal=Radiology | year= 1992 | volume= 184 | issue= 1 | pages= 233-7 | pmid=1609086 | doi=10.1148/radiology.184.1.1609086 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1609086  }} </ref>
Line 62: Line 92:
*There is no racial predilection to giant cell tumor.
*There is no racial predilection to giant cell tumor.


==Risk Factors==
There are no established risk factors for giant cell tumor.


==Natural History, Complications and Prognosis==
==Screening==
===Complications===
There is insufficient evidence to recommend routine screening for giant cell tumor.
Common complications of giant cell tumor include:
*Malignant transformation
:*Malignant transformation is far more common in men (M:F of ~3:1)
:*Sarcomatous transformation is observed, especially in [[radiotherapy]] treated inoperable tumors.
*Recurrence
:*Local recurrence rate of giant cell tumor of bone is 10 to 40%.
:*Recurrence rates are higher when the tumor bone arises at a surgical inaccessible location locations such as [[spine]] and [[sacrum]].
*Metastasis
:*Giant cell tumor of bone may occasionally metastasize to vital organs such as the lung.<ref name="MuheremuNiu2014">{{cite journal|last1=Muheremu|first1=Aikeremujiang|last2=Niu|first2=Xiaohui|title=Pulmonary metastasis of giant cell tumor of bones|journal=World Journal of Surgical Oncology|volume=12|issue=1|year=2014|pages=261|issn=1477-7819|doi=10.1186/1477-7819-12-261}}</ref>  Hence, this entity has been called benign metastasising giant cell tumor.


===Prognosis===
==Natural History, Complications, and Prognosis==
*The [[prognosis]] of giant cell tumor is generally excellent.
*If left untreated, few patients with giant cell tumor may progress to develop [[lung]] [[metastasis]].<ref name="MuheremuNiu2014">{{cite journal|last1=Muheremu|first1=Aikeremujiang|last2=Niu|first2=Xiaohui|title=Pulmonary metastasis of giant cell tumor of bones|journal=World Journal of Surgical Oncology|volume=12|issue=1|year=2014|pages=261|issn=1477-7819|doi=10.1186/1477-7819-12-261}}</ref>
*Common complications of giant cell tumor include:
**[[Malignant transformation]]
***[[Malignant transformation]] is far more common in men (M:F of ~3:1)
***Sarcomatous transformation is observed, especially in [[radiotherapy]] treated inoperable tumors.
**Secondary [[Aneurysmal bone cyst]] (ABC)
***To differentiate from primary ABC based on enhancing soft-tissue component in GCT; which is not present in primary ABC.
**Recurrence
***Local recurrence rate of giant cell tumor of bone is about 10 to 40%.
***Lucency is seen at bone-cement interface
***It is diagnosed with [[Biopsy|CT guided biopsy]]
**Pathologic [[fracture]]
**[[Infection|Postoperative infection]]
***There is an increased risk with en bloc resection followed by endoprosthesis.
*The [[prognosis]] of giant cell tumor is generally good, despite of recurrences and [[pulmonary metastases]].
*The [[mortality rate]] due to giant cell tumour is about 4%.


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
{| align="right"
|
[[File:Giant-cell-tumour-histology.jpg|300px|thumb| Histological appearance: Giant Cell Tumor. [https://radiopaedia.org/cases/giant-cell-tumour-histology?lang=us 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.<ref name="pmid7497439">{{cite journal| author=Molenaar WM, van den Berg E, Dolfin AC, Zorgdrager H, Hoekstra HJ| title=Cytogenetics of fine needle aspiration biopsies of sarcomas. | journal=Cancer Genet Cytogenet | year= 1995 | volume= 84 | issue= 1 | pages= 27-31 | pmid=7497439 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7497439  }} </ref>
*Gross pathological findings include:
**Giant cell tumors are variable in appearance, depending on amount of [[hemorrhage]], presence of co-existent [[aneurysmal bone cyst]], and degree of presence [[fibrosis]].
*Histopathological findings include:
**Presence of numerous [[Cathepsin K|Cathepsin-K]] producing, [[CD33]] +, [[CD14]] - [[multinucleated]] [[osteoclast]]-like giant cells and plump spindle-shaped [[Stromal cell|stromal cells]] that represent the main proliferating cell population.
**The spindle-shaped [[mononuclear cells]] represents the neoplastic population and are characterized at the [[Cytogenetics|cytogenetic]] level by telomeric associations and a peculiar telomere-protecting capping mechanism.
*Areas of regressive change such as [[necrosis]] or [[fibrosis]] as well as extensive [[Bleeding|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===
===History and Symptoms===
* Patients usually present with pain and limited [[range of motion]] caused by tumor's proximity to the joint space.
Symptoms of giant cell tumor include:
* There may be [[swelling]] as well, if the tumor has been growing for a long time.
*Localized bone [[pain]]
* Some patients may be asymptomatic until they develop a pathologic [[fracture]] at the site of the tumor.
*Localized [[swelling]]
 
*Decreased [[range of motion]] of the affected joint
*[[Limp]]
{| align="right"
|
[[File:Giant-cell-tumour-femur xray.jpg|200px|thumb| X-Ray of Femur showing giant cell tumor. [https://radiopaedia.org/cases/giant-cell-tumour-femur?lang=us Source: Case courtesy of Radswiki, Radiopaedia.org, rID: 11453]]]
|}
===Physical Examination===
===Physical Examination===
Physical examination findings will depend on the location of the giant cell tumor. Most giant cell tumors are located in the long bone of extremities.
*Patients with giant cell tumor usually appears well.
*Common physical examination findings of giant cell tumor include:<ref>{{cite book | last = Peabody | first = Terrance | title = Orthopaedic oncology : primary and metastatic tumors of the skeletal system | publisher = Springer | location = Cham | year = 2014 | isbn = 9783319073224 }}</ref>
**[[Tenderness]] to [[palpation]]
**Soft tissue [[swelling]]
**Decreased [[range of motion]]
**[[Muscle atrophy]]
**Joint effusion
**Involvement of adjacent structures such as peripheral [[nerves]] or [[veins]]


'''Extremities'''
===Laboratory Findings===
There are no diagnostic laboratory findings associated with giant cell tumor.


A palpable firm non tender or tender mass may be appreciated on physical examination. The assessment of giant cell tumor during physical examination include:
===Electrocardiogram===
*Size
There are no [[ECG]] findings associated with giant cell tumor.
*Location
{| align="right"
*Involvement of adjacent structures (such as peripheral [[nerves]] or [[veins]])
|
*[[Edema]]
[[File:CT giant cell tumor.gif|200px|thumb| CT scan of Femur showing giant cell tumor. [https://radiopaedia.org/cases/giant-cell-tumour-femur?lang=us Source: Case courtesy of Radswiki, Radiopaedia.org, rID: 11453]]]
|}


===X Ray===
===X Ray===
X-ray may be helpful in the diagnosis of giant cell tumor of bone. Findings on x-ray suggestive of giant cell tumor include:
*Three views of affected [[bone]] or [[joint]] are recommended.
*Metaphyseal location and grow to the articular surface of the involved bone  
*X-ray findings include:<ref name="pmid11553835">{{cite journal |author=Murphey MD, Nomikos GC, Flemming DJ, Gannon FH, Temple HT, Kransdorf MJ |title=From the archives of AFIP. Imaging of giant cell tumor and giant cell reparative granuloma of bone: radiologic-pathologic correlation |journal=[[Radiographics : a Review Publication of the Radiological Society of North America, Inc]] |volume=21 |issue=5 |pages=1283–309 |year=2001 |pmid=11553835 |doi= |url=http://radiographics.rsnajnls.org/cgi/pmidlookup?view=long&pmid=11553835 |accessdate=2012-01-18}}</ref>
*Narrow zone of transition: a broader zone of transition is observed in more aggressive giant cell tumors
*[[Eccentric Lesion|Eccentric]] [[Metaphysis|metaphyseal]] location and grow to the [[articular surface]] of the involved bone  
*No surrounding sclerosis: 80-85%
*Narrow zone of transition with a broader zone of transition is observed in more aggressive giant cell tumors
*Overlying cortex is thinned, expanded or deficient
*No surrounding [[sclerosis]]
*Periosteal reaction is only observed in 10-30% of cases
*Overlying [[cortex]] is thinned, expanded or deficient
*Soft tissue mass is not infrequent
*[[Periosteal reaction]] usually not seen
*Pathological fracture may be present
*No matrix [[calcification]]/mineralisation
*No matrix [[calcification]]/mineralisation


(Images courtesy of RadsWiki)
'''Chest X-Ray'''
<div align="left">
*Chest [[Radiography|radiograph]] should be done to look for benign [[pulmonary]] [[metastasis]] which may occur with giant cell tumor.
<gallery heights="175" widths="175">
 
Image:Giant-cell-tumor-001.jpg|Giant cell tumor: Distal part of the femur
===Echocardiography or Ultrasound===
Image:Giant-cell-tumor-002.jpg|Giant cell tumor: Distal part of the femur
There are no [[echocardiography]]/[[ultrasound]] findings associated with giant cell tumor.
</gallery>
 
</div>
===CT scan===
CT findings for giant cell tumor include:
*Absence of bone and intralesional [[mineralization]].
{| align="right"
|
[[File:MRI giant-cell-tumour-femur.jpg|200px|thumb| MRI of Femur showing giant cell tumor. [https://radiopaedia.org/cases/giant-cell-tumour-femur?lang=us Source: Case courtesy of Radswiki, Radiopaedia.org, rID: 11453]]]
|}


===MRI===
===MRI===
Typical signal characteristics on MRI of giant cell tumor of bone include:
*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]].


'''T1''':
===Other Imaging Findings===
:*Low to intermediate solid component
 
:*Low signal periphery
===Bone Scan===
:*Solid components enhance, helping distinguish giant cell tumor with [[aneurysmal bone cyst]] from pure aneurysmal bone cyst
*Increased uptake is observed around the lesion of giant cell tumor, especially around the periphery, with a central photopenic region (doughnut sign).
:*Some enhancement may also be observed in adjacent [[bone marrow]]
*Increased blood pool activity is also observed.
'''T2''':
 
:*Heterogenous high signal with areas of low signal intensity (variable) due to haemosiderin or fibrosis
===Other Diagnostic Studies===
:*If an [[aneurysmal bone cyst]] component present, then fluid-fluid levels can be observed
There are no other diagnostic studies associated with giant cell tumor.
:*High signal in adjacent bone marrow thought to represent inflammatory [[edema]]
'''T1 C+ (Gd)''':
:*Solid components will enhance, helping differentiate from aneurysmal bone cyst
===Scintigraphy: Bone Scan===
*Most giant cell tumors demonstrate increased uptake on delayed images, especially around the periphery, with a central photopenic region (doughnut sign).
*Increased blood pool activity is also observed, and can be observed in adjacent bones due to generalised regional hyperaemia.


==Treatment==
==Treatment==
The treatment of giant cell tumor is directed towards local control without sacrificing joint function.<ref name="PuriAgarwal2007">{{cite journal|last1=Puri|first1=Ajay|last2=Agarwal|first2=Manish|title=Treatment of giant cell tumor of bone: Current concepts|journal=Indian Journal of Orthopaedics|volume=41|issue=2|year=2007|pages=101|issn=0019-5413|doi=10.4103/0019-5413.32039}}</ref> Surgery is the mainstay of treatment for giant cell tumor.
 
===Medical Therapy===
*[[Denosumab]]
**It is recommended for the treatment of unresectable GCT of bone (GCTB) in adults and skeletally mature adolescents.<ref name="pmid20149736">{{cite journal| author=Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY et al.| title=Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. | journal=Lancet Oncol | year= 2010 | volume= 11 | issue= 3 | pages= 275-80 | pmid=20149736 | doi=10.1016/S1470-2045(10)70010-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20149736  }} </ref>
**It is a [[monoclonal antibody]] against [[RANKL|RANK-ligand]].
**It decreases the size of the bone defect in giant cell tumor.
**It shows dramatic [[sclerosis]] and reconstitution of [[cortical bone]] after treatment.
 
*[[Bisphosphonates]]
**They are [[osteoclast]] inhibitors which may decrease the size of the defect in giant cell tumors.<ref name="pmid18322700">{{cite journal| author=Balke M, Schremper L, Gebert C, Ahrens H, Streitbuerger A, Koehler G et al.| title=Giant cell tumor of bone: treatment and outcome of 214 cases. | journal=J Cancer Res Clin Oncol | year= 2008 | volume= 134 | issue= 9 | pages= 969-78 | pmid=18322700 | doi=10.1007/s00432-008-0370-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18322700  }} </ref><ref name="pmid17962092">{{cite journal| author=Tse LF, Wong KC, Kumta SM, Huang L, Chow TC, Griffith JF| title=Bisphosphonates reduce local recurrence in extremity giant cell tumor of bone: a case-control study. | journal=Bone | year= 2008 | volume= 42 | issue= 1 | pages= 68-73 | pmid=17962092 | doi=10.1016/j.bone.2007.08.038 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17962092  }} </ref>
{| align="right"
|
[[File:Bone scan giant-cell-tumour-femur.jpg|200px|thumb| Bone scan showing giant cell tumor. [https://radiopaedia.org/cases/giant-cell-tumour-femur?lang=us Source: Case courtesy of Radswiki, Radiopaedia.org, rID: 11453]]]
|}


===Surgery===
===Surgery===
*Classically, treatment is with curettage and packing with bone chips or polymethylmethacrylate (PMMA).
Surgery is the mainstay of treatment for giant cell tumor.<ref name="PuriAgarwal2007">{{cite journal|last1=Puri|first1=Ajay|last2=Agarwal|first2=Manish|title=Treatment of giant cell tumor of bone: Current concepts|journal=Indian Journal of Orthopaedics|volume=41|issue=2|year=2007|pages=101|issn=0019-5413|doi=10.4103/0019-5413.32039}}</ref><ref name="pmid3006962">{{cite journal| author=Goldring SR, Schiller AL, Mankin HJ, Dayer JM, Krane SM| title=Characterization of cells from human giant cell tumors of bone. | journal=Clin Orthop Relat Res | year= 1986 | volume=  | issue= 204 | pages= 59-75 | pmid=3006962 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3006962  }} </ref>
*Local recurrence is from the periphery of the lesion and has historically occurred in up to 40-60% of cases.
 
*Newer intraoperative adjuncts such as thermal or chemical treatment of the resection margins have lowered the recurrence rate to 2.5-10%.
===Extensive Curettage and Reconstruction with adjuvant treatment=== 
*Wide local excision is associated with a lower recurrence rate, but has greater morbidity.
 
'''Indications'''
*Lesions amenable to currettage<ref name="pmid21089702">{{cite journal| author=Gortzak Y, Kandel R, Deheshi B, Werier J, Turcotte RE, Ferguson PC et al.| title=The efficacy of chemical adjuvants on giant-cell tumour of bone. An in vitro study. | journal=J Bone Joint Surg Br | year= 2010 | volume= 92 | issue= 10 | pages= 1475-9 | pmid=21089702 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21089702  }} </ref><ref name="pmid3006962">{{cite journal| author=Goldring SR, Schiller AL, Mankin HJ, Dayer JM, Krane SM| title=Characterization of cells from human giant cell tumors of bone. | journal=Clin Orthop Relat Res | year= 1986 | volume=  | issue= 204 | pages= 59-75 | pmid=3006962 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3006962  }} </ref>
*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 bone|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.<ref name="pmid16736146">{{cite journal| author=Oh JH, Yoon PW, Lee SH, Cho HS, Kim WS, Kim HS| title=Surgical treatment of giant cell tumour of long bone with anhydrous alcohol adjuvant. | journal=Int Orthop | year= 2006 | volume= 30 | issue= 6 | pages= 490-4 | pmid=16736146 | doi=10.1007/s00264-006-0154-3 | pmc=3172752 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16736146  }} </ref>
 
'''Chemical Adjuvants Used'''
*[[Liquid nitrogen]]
*[[Alcohols]]
*[[Phenol]]
*[[Hydrogen peroxide]]
*[[Zinc chloride]]
*[[Argon|Argon Laser]]
 
'''Outcomes'''
*10-30% recurrence with [[curettage]] alone verses 3% with [[adjuvant treatment]]. 
 
===Amputation===
 
'''Indications'''
*[[Hand]] lesions with [[Cortical bone|cortical]] breakthrough which are not amendable to intercalary resection.<ref name="pmid22662295">{{cite journal| author=Kim Y, Nizami S, Goto H, Lee FY| title=Modern interpretation of giant cell tumor of bone: predominantly osteoclastogenic stromal tumor. | journal=Clin Orthop Surg | year= 2012 | volume= 4 | issue= 2 | pages= 107-16 | pmid=22662295 | doi=10.4055/cios.2012.4.2.107 | pmc=3360182 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22662295  }} </ref>
 
===Radiation Therapy===
{| align="right"
|
[[File:Giant cell tumor intra-op.JPG|300px|thumb|Excision of giant cell tumor of distal radius. Source: Case courtesy by: [[User:Rohan Bhimani|Dr. Rohan A. Bhimani]]]]
|}
'''Indications'''
*Reserved for cases in which surgical treatment is not feasible.<ref name="pmid10192357">{{cite journal| author=Nair MK, Jyothirmayi R| title=Radiation therapy in the treatment of giant cell tumor of bone. | journal=Int J Radiat Oncol Biol Phys | year= 1999 | volume= 43 | issue= 5 | pages= 1065-9 | pmid=10192357 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10192357  }} </ref>
*[[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<ref name="pmid8491687">{{cite journal| author=Bennett CJ, Marcus RB, Million RR, Enneking WF| title=Radiation therapy for giant cell tumor of bone. | journal=Int J Radiat Oncol Biol Phys | year= 1993 | volume= 26 | issue= 2 | pages= 299-304 | pmid=8491687 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8491687  }} </ref>
 
===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.


<br><br><br><br><br><br>
==References==
==References==
{{reflist|2}}
{{reflist|2}}

Latest revision as of 21:28, 24 January 2019

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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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