the giant cell tumor , in which bcl-2 gene was expressed only in its malignant transformation , is a benign , primary skeletal neoplasm with variable biologic aggressiveness .
the correlation between giant cell tumor in hereditary multiple exostosis is still not clearly determined .
a 31-years - old female presented with pain and lump on her left wrist and a coexistence of non tender multiple lump in the right and left knee
. a wide excision of the tumor and reconstruction using non vascularized fibular graft was performed , followed by histopathology and immunohistochemistry of ext-1 and bcl-2 .
giant cell tumor and hereditary multiple exostosis also demonstrated associations of chromosomes 11 with a different pathological process .
giant cell tumor in hereditary multiple exostosis revealed positive ext-1 without bcl-2 expression . it still need more investigation to confirm the relationship between these tumors .
it often characterized by osteolytic destruction at the end of a long bone and large multinuclear cells in its histologic appearance .
it is benign in nature and known to be able to both recur and transform into malignancy , , .
the malignant subtype of gct is usually expressed some genes like the b - cell lymphoma 2 ( bcl-2 ) gene .
the gct was rarely found in coexistence with other benign lesion such as hereditary multiple exostosis ( hme ) , .
the reason behind that coexistence is still unclear , whether caused by either a transformation of hme or only considered as two separated lesions .
hereditary multiple exostosis is an autosomal dominant condition which characterized by the development of multiple exostosis and possess interfamilial and intrafamilial phenotypical variability in severity , size , and number of lesions .
this hme lesions are primarily caused by the presence of exostosin-1 ( ext-1 ) gene that occur in approximately 90% of cases .
the aim of this report is to identify the bcl-2 and ext-1 gene in gct with coexistence of hme .
it also served as a preliminary research to prove that the gct with the expression of ext-1 and bcl-2 in patients with hme tend to be more aggressive with high local recurrence and worse prognosis .
a 31-years - old female presented with pain and lump on her left wrist since 4 months ago . physical examination revealed a lump located on left wrist .
the size of the lump clinically was 5  cm by 6  cm with shiny skin , clear border , firm in consistency , and fixed to the bone ( fig .
her wrist extension and flexion was limited to 10 of flexion and 5 of extension due to pain and mass . on the right and left knees , we found non - tender multiple lumps ( fig .
1b ) . the x ray of left wrist revealed osteolytic lesion with some geographic patterns ( fig .
she had wide surgical excision of the tumor which extended to the wrist joint and 3  cm upper the tumor followed by reconstruction using non vascularized fibular graft .
we found multiple bony masses with clinical characteristics of multiple exostosis on the proximal site of fibular graft ( fig .
the excised part of the radius has replaced with non - vascularized fibular graft , then fixed with plate and screws .
histopathological finding revealed gct with an eosinophilic cytoplasm , round ovals nucleus , vesicular chromatin with small nucleus prominent , and a slight mitosis ( fig .
3 ) . immunochemistry finding revealed existence of ext-1 but no existence of bcl-2 ( fig .
the patient feels no pain , already returned to regular activities , range of motion return to 7599% and the grip strength is 100% ( fig .
the case presented a gct of the left wrist with another lesion of hme on the right and left knee .
this case was very rare because we were not able to find more cases in the literature matching this coexistence .
( 2002 ) mentioning a coexistence of giant cell tumor over the left leg , para - articular osteochondroma over the left hip and an idiopathic thrombocytopenic purpura ( itp ) .
a curettage of gct lesion was performed , followed by washing out the remainder with hot saline , then filled with autogenous iliac bone graft and cement .
( 2015 ) has reported a case of gct of proximal tibia in patient with history of multiple osteochondromatosis .
the tumor was resected , a skeletal reconstruction with gmrs prosthesis was performed , followed by soft tissue reconstruction with rotation flap .
histopathological examination revealed gct with area of fibrohistiocytic pattern and component of aneurysmal bone cyst .
the report also suggested a positive genetic polymorphism in the ext-2 gene . in this case , we suspected the existence of two tumors in one patient .
there was revealed a positive expression of ext-1 gene and negative expression of bcl-2 gene from gct mass of left wrist .
the cells giving positive reaction of anti - ext-1 with b chomogen method ( fig .
positive reaction was pointed by blue arrow , on the other hand , negative reaction was represented by red arrow .
positive control showed coloration on nucleus and cytoplasm , whereas no coloration on nucleus and cytoplasm was found on negative as seen on fig .
currently , ext-1 gene has considered as an important causative factor in hereditary multiple exostosis , , .
hereditary multiple exostosis is genetically heterogeneous with three loci on chromosomes 8q24.1 , 11p13 , and 19q .
the first ext-1 locus that located on chromosome 8 ( 8q24.1 ) was discovered by cook in 1993 , which also linked with chromosome 11q24 .
the distal end of 8q locus is responsible for the formation of hme and was identified as the ext-1 .
later on , a new gene on chromosome 11 ( 11p11 - 13 ) was identified as a locus for hme and named ext-2 .
a third locus on chromosome 19p , suspected of causing hme was named ext-3 , but it is considered to be a minor contributor to the actual formation of hme .
most of the ext-1 and ext-2 genes ( 80% ) prompt to mutation by nonsense , frameshift or splice - site mutations leading to premature termination of the ext proteins .
giant cell tumor of the bone is a benign , primary skeletal neoplasm with variable biologic aggressiveness that demonstrates telomeric associations of chromosomes 11 , 16 , 19 , 20 , and 21 , reduction of telomere length , marker chromosomes , double minutes , chromosome fragments , ring chromosomes , and polyploidy .
some gene that expressed in gct such as ip53 , h - ras , c - myc , mmp-9 , mib-1 and bcl-2 had important rules for malignant transformation   .
we have also performed immunohistochemistry of bcl-2 for finding the apoptosis process in the tumor lesions .
bcl-2 is an anti - apoptosis protein whose overexpression contributes to the uncontrollable proliferation of gliomas and other neoplasm s .
it encodes an integral membrane protein ( 25  kda protein ) , mainly localized to inner mitochondrial membrane , endoplasmic reticulum and nuclear envelope .
the bcl-2 overexpression increases lifespan of b cells , maintains memory b cells , plasma cells and neurons by prolonging life span without cell division .
it also may participates in ion channel formation and alteration of membrane permeability that necessary for initiation of apoptosis .
( 2010 ) in their study reported a higher value of bcl-2 in malignant subtype of gct .
this implies that malignant transformation could trigger gct cells to express this marker more frequently , thus , it could be regarded as an indicator for malignant transformation and unfavorable clinical course .
( 1998 ) studied expression of regulatory apoptotic proteins in peripheral giant cell lesions containing osteoclast - like giant cells that showing only weak positivity for bcl-2 . in this case
the bcl-2 result is negative , revealing that the giant cell tumor was not transformed into malignant .
based on the results of this study , gct characterized as benign aggressive with negative bcl-2 gene expression and showed similarity with hme by a positive ext-1 gene expression .
a data based on ontology between hme and gct assuming that gct may arise from a transformation of hme .
giant cell tumor in hereditary multiple exostosis revealed positive ext-1 without bcl-2 expression . in this case , this coexistence revealed a probability of gct that arised from hme but did not showed malignant transformation .
 highlightsthe giant cell tumor is a benign , primary skeletal neoplasm with variable biologic aggressiveness.a coexistence with hereditary multiple exostosis with expression of ext-1 is very rare.bcl-2 gene is expressed only in malignant transformation of the giant cell tumor.the correlation between giant cell tumor and hereditary multiple exostosis is still not clearly determined.the case revealed giant cell tumor in hereditary multiple exostosis with positive ext-1 without bcl-2 expression . 
Introduction
Presentation of case
Discussion
Conclusion
Introduction
Presentation of case
Discussion
Conclusion