ewing 's sarcoma ( ews ) is an aggressive osteolytic tumor of bone and rapidly disseminates to other sites .
it shares the histological features with other malignant small round cell tumors ( msrct ) .
therefore the defining cytogenetic abnormality is a balanced translocation t(11;22 ) expressing the ews / friend leukemia integration-1 ( fli-1 ) chimeric fusion protein .
metastatic ews should be diagnosed early as it is difficult to control and treatment needs a multimodality approach constituting chemotherapy , surgery and radiotherapy .
the case we present here is a 14-year - old female child who presented with low backache since 1 year followed by right eye proptosis for 4 months and swelling over right side chest wall since 3 months [ figure 1a ] .
magnetic resonance imaging revealed involvement of posterior element of the sacrum with l5 vertebra and a presacral soft tissue mass measuring 11.8 cm  7.5 cm .
large abdominal soft tissue mass in pancreatic region measuring 6.2 cm  4.8 cm was seen indicating a possibility of nodal involvement .
venous invasion with tumor thrombus in left internal and common iliac veins and lower inferior vena cava was noticed .
fine needle aspiration smears from orbital mass were highly cellular showing cells arranged both in clusters and singly dispersed [ figure 1c ] .
cells were both light and dark types with a thin rim of pale cytoplasm and small round nuclei having small inconspicuous nucleoli .
rosette like structures , but no true rosettes were seen . considering the clinical presentation , a provisional diagnosis of msrct possibly ews was given .
two tru - cut biopsy samples were taken from the same mass . from one sample , paraffin block was prepared .
histologically the tumor cells were arranged in irregular nests separated by dense fibrous stroma [ figure 2a ] .
the cells were 1 - 2 times larger than small lymphocytes with scant eosinophilic or clear cytoplasm , centrally placed round nuclei with finely distributed chromatin and inconspicuous nucleoli [ figure 2b ] .
mitotic figures were few ; necrosis scanty and rosettes were not seen indicating the absence of neural differentiation .
the paraffin block was subjected to cd99 immunohistochemical marker and was strongly and diffusely positive [ figure 2c ] .
other sample was preserved in trizol reagent for molecular genetic analysis to look for ews - fli-1 translocation .
total ribonucleic acid ( rna ) was extracted from snap frozen tumor tissue using trizol reagent .
reverse transcription - polymerase chain reaction ( rt - pcr ) was performed with abl oligonucleotide primer to check for the quality of the rna isolated , which amplified a 300 bp product .
the ews - fli-1 product was type 1 fusion ( 330 bp ) [ figure 2d ] .
( c ) cytology of orbital mass ( h and e 100 ) ( a ) photomicrograph showing small round cells in tissue section ( h and e 100 ) .
ews is a primary nonosteogenic malignant tumor of bone with peak incidence in second decade of life .
we report the above case in a 14-year - old girl with involvement of l5 vertebra and sacral bone with metastasis to multiple sites at the time of presentation
. early and correct diagnosis of ews is essential for clinical management since it belongs to the group of primary msrct .
this group includes neuroblastoma , lymphoma , desmoplastic small round cell tumor and rhabdomyosarcoma besides ews and peripheral neuroectodermal tumor where neural differentiation is seen in addition to all the features of ews .
since the morphologic features in all these tumors are more or less similar , one takes the help of special stains in addition to other ancillary techniques for differentiation of one from the other .
pas stain detects the presence of large amounts of intracellular glycogen , but it is a nonspecific finding since many childhood tumors contain it and up to 35% of ews may not contain detectable glycogen .
cd99 is a useful marker in the differential diagnosis of these tumors as 90% of ews / peripheral neuroectodermal tumors stain positive .
though neuroblastoma , the main tumor in the differential diagnosis is not positive for cd99 , it is seen to be positive in other malignant small cell tumors such as small cell osteosarcoma , lymphoblastic lymphoma , mesenchymal chondrosarcoma , and alveolar rhabdomyosarcoma .
the chromosome 22q12 breakpoints are clustered within a single gene designated ews and chromosome 11q24 are within a gene called fli-1 .
this translocation results in the expression of an aberrant hybrid protein in which the n - terminal part of ews is linked to deoxyribonucleic acid binding domain ( ets domain ) of the fli-1 transcription factor .
the ews - fli-1 protein is thought to be responsible for the origin of ews .
kelleher and thomas have suggested some promising therapeutics like ews - fli-1 gene silencing , growth factor - i receptor antagonists , mammalian target of rapamycin inhibition , kit oncoprotein targeting , etc . although cytogenetic analysis can detect a wide variety of chromosomal translocations , it is time consuming , technically difficult and success rate is variable .
hence , we used the reverse transcription followed by pcr assay for detecting the presence and type of ews / fli-1 fusion transcript .
the specific genetic alterations among other small round cell tumors can establish the genotypic diagnosis of these tumors .
the most common site to which ews spreads , or metastasizes , is the lungs .
metastatic ewing 's sarcoma is typically difficult to control , though patients with lung metastases have a better prognosis than patients with other distant metastases .
following diagnosis by tru - cut biopsy and cd99 immunopositivity ( which was confirmed by rt - pcr analysis ) , our patient received three cycles of chemotherapy and no radiotherapy .
after one cycle of chemotherapy , the right eye proptosis and swelling over the chest wall disappeared [ figure 1b ] . however after receiving next two cycles , she became bedridden and before receiving the 4 course of chemotherapy , the patient expired ( within 1 year of diagnosis ) .
this case exemplifies the idea that every new lesion in a patient with ews should be considered as a possible metastasis .
 ewing 's sarcoma ( ews ) is an undifferentiated sarcoma of bone . 
 its morphologic appearance resembles many other malignant small round cell tumors . due to the morphologic overlap 
 , there is diagnostic difficulty and for accurate diagnosis , requires special studies such as immunohistochemistry , electron microscopy , cytogenetics , and molecular genetic analysis . 
 we report a case of metastatic ews from orbital mass in a 14-year - old female child diagnosed by cytology after clinicopathologic evaluation . 
 she presented with low back ache of 1 year followed by proptosis of the right eye and swelling of the right side chest wall . 
 cytosmear and tru - cut biopsy was taken from the orbital mass showed features of ews . 
 it was confirmed later by further studies including demonstration of ews / friend leukemia integration-1 fusion gene by molecular genetic analysis . 