patients with eos usually present in the fourth and fifth decades of life unlike skeletal osteosarcoma patients who present in the fifth and sixth decades of life .
there are also reports of eos involving the face , breast , abdominal wall , soft tissues of the back and retroperitoneum , and site of a vaccination scar .
found that 10% of the patients had previous irradiation and 13% of the patients had history of trauma related to the site of eos .
the genetic change most commonly associated with osteosarcoma is the loss of the p53 tumor suppressor gene on chromosome 17 and loss of retinoblastoma gene rb1 on chromosome 13 .
a genetic association between paget 's disease and osteosarcoma has also been identified on chromosome 18q .
other genomic changes , such as loss on 13q and 15q and gain on 1q and 8q , have been detected in patients with eos .
the contribution of the major susceptibility genes on chromosome 10q ( ret proto - oncogene ) is well established in hd .
in addition , potential modifying associations exist with chromosomes 2 , 9 , 13 , 20 , 21 , and 22
. variations of main ret proto - oncogene account for as much as 50% of familial and 2030% of sporadic cases .
the etiology of the majority of sporadic cases is not clear , appearing to arise from combined cumulative effects of susceptibility loci on other chromosomes controlling the mechanism of cell proliferation , differentiation , and maturation .
presence of genitourinary abnormalities in the form of horse - shaped kidney and azoospermia , and sporadic hd pointed toward a genetic abnormality in our patient .
hence , we performed genetic screening at the common sites for both hd and osteosarcoma on chromosome 10 ( ret proto - oncogene ) and chromosome 17 ( p53 tumor suppressor gene ) .
however , we found no abnormalities at both these loci , suggesting a role of combined cumulative effects of susceptibility genes on other chromosomes .
inactivation or alteration of a gene located at this susceptibility loci could have been an early event in the development of eos in our patient .
the cornerstone of treatment consists of radical surgery and polychemotherapy . due to the rare nature of this disease ,
no data from randomized studies concerning the type of chemotherapeutic combinations are available . in a small retrospective study , goldstein - jackson et al . reported favorable results when eoss were treated as conventional osteosarcomas .
active chemotherapeutic agents for skeletal osteosarcoma consist of a combination of doxorubicin and cisplatin , with or without the addition of other drugs such as methothrexate , ifosfamide , and etoposide .
the use of multi - agent chemotherapy has extensively improved the outcome for skeletal osteosarcoma . however , these treatments are very intensive , and therefore acute and delayed toxicities can be expected .
doxorubicin can cause bone marrow toxicity and cardiotoxicity , whereas cisplatin can cause nephro - and ototoxicity .
adjuvant radiotherapy does not increase the survival when patients are treated with effective surgery and chemotherapy , and increase the risk for secondary tumors .
however , radiation should be considered in the setting of an unresectable or incompletely resected primary tumor . in this case ,
the tumor was completely resected , but the resection margins were close due to the orbital localization of the tumor , making wide resection impossible .
the first case was an 11-year - old boy who developed an eos of the orbit following radiotherapy for retinoblastoma in infancy .
the second patient was a 22-year - old otherwise healthy male with no predisposing factor .
our case is the oldest patient ever detected with an eos in the orbit with no history of previous radiotherapy or trauma .
one could suggest a possible association between eos and patients known hd , but this has never been reported in the literature before .
 primary extraskeletal osteosarcoma ( eos ) is an extremely rare malignancy . in this report 
 , the clinical course of a 32-year - old man presenting with proptoses is described . 
 medical history included hirschsprung disease ( hd ) , horseshoe kidney , azoospermia , and vertebral anomalies . 
 imaging of the orbit showed an oval , well - defined heterogeneous mass adjacent to the lateral wall of the orbit . 
 the patient underwent a lateral orbitotomy and complete excision of the mass . 
 the mass was not attached to the bone . 
 histopathologic and immunohistochemical examination confirmed the diagnosis of an eos . 
 the patient received chemotherapy and radiotherapy and is free of the disease 3 years after the diagnosis . 
 genetic screening showed no mutations for both the ret proto - oncogene for hd and the p53 tumor suppressor gene for osteosarcoma . 
Discussion