Extra skeletal Soft Tissue Ewing’s Sarcoma with Variant Translocation of Chromosome t (4; 22) (q35; q12)-A Case Report

Abstract

Introduction:Ewing’s sarcomas is a rare primitive neuroectodermal tumour (PNET) which has an annual incidence of 2.9 /million population in USA 1Jeffery Toretsky et al (2008) They are very uncommon in African and Asian population. It is commonly associated with reciprocal translocation between chromosome 11 and 12 t (11:12) or less frequently the t(21;22)(q22;ql 2) translocation. It is highly aggressive tumor which is PAS- and CD99 (MIC2)-positive relatively few variant translocations have been reported in primary Ewing’s sarcomas (ES).Case Report:We are hereby presenting a case of extra skeletal soft tissue Ewing’s sarcoma with unusual translocation of chromosome t (4, 22) (q35, q12). Patient presented to us in advanced stage with pulmonary metastasis and lower limb neurological deficit. Relatively few variant translocations have been reported in primary Ewing’s sarcomas (ES). To date, 13 variants of the EWS fusion gene have been described in literature. They are extremely rare, representing altogether < 1% of the cases’ 23we are reporting a case of a variant simple translocation of chromosome t (4; 22) (q35;1 2). In our exhaustive literature search we could find only one case of complex translocation which was identified in a dysmorphic 15-year-old girl, t (4:11; 22)(q21; q24; q12) reported by Squire Jet al (1993).Conclusion:This type of translocation is extremely rare and has not been reported in the literature so far. Clinical presentation was initial indolent but later at the time patient presented to our institute he had developed pulmonary metastases and paraplegia due to involvement of spine. Our case report will provide new insight about rare translocation types in Ewing’s sarcoma and understand their clinical behavior of Ewing’s sarcoma with such type of translocation.

Complex/cryptic EWSR1::FLI1/ERG Gene Fusions and 1q Jumping Translocation in Pediatric Ewing Sarcomas

“…Relevant to the second case highlighted, a t(4;22)(q35;q12) reciprocal translocation, it has previously been reported, by conventional chromosome analysis, in an extra-skeletal soft tissue (the distal aspect of right thigh) ES in a patient who presented with pulmonary metastases and paraplegia due to involvement of the spine [ 20 ]. However, FISH or other molecular diagnostic methods for an EWSR1::FLI1 fusion was not performed [ 20 ]. Interestingly, a t(4;22)(q35;q12) translocation has also been reported in a case of embryonal rhabdomyosarcoma and results in the fusion of the EWSR1 gene with the DUX4 gene [ 21 ].…”

“…The t(4;22)(q35;q12) reciprocal translocation in our case involved the distal (near sub-telomere) region of the long arm of chromosome 4 at the 4q35 band, resulting in a cryptic t(4;11;22)(q35;q24;q12) three-way translocation by conventional chromosome analysis. The previously reported ES case with a t(4;22)(q35;q12) reciprocal translocation by conventional chromosome analysis [ 20 ] may also have a cryptic t(4;11;22)(q35;q24;q12) three-way translocation leading to an EWSR1::FLI1 fusion. Therefore, performing FISH or gene fusion-based assays for an EWSR1::FLI1 fusion in these ES cases is vital to rule out a cryptic three-way translocation or other complex rearrangements.…”

Extraskeletal Ewing sarcoma of the sciatic nerve

“…In 85% of EES, a reciprocal translocation between chromosomes 11 and 22 is present, specifically t (11; 22) (q24; q12) resulting in the EWSR1-FLI1 gene [ 7 , 14 , [27] , [28] , [29] ]. About 10% of cases possess a translocation of t (21;22) (q22; q12) to produce the EWSR1-ERG gene [ 4 , [30] , [31] , [32] ]. Both of these chimeric genes encode proteins that induce aberrant oncogenic factors [ 14 , 19 , 32 ].…”

Extraosseous Ewing’s Sarcoma: Pictorial Review of Imaging Findings, Differential Diagnosis, and Pathologic Correlation

“…There has not been any evidence of familial or environmental influence. [11][12][13][14] Radiographs may demonstrate a nonspecific soft-tissue mass in proximity to a bone without gross osseous involvement. 9,15,16 Computed tomography (CT) usually shows a soft tissue mass with similar attenuation as skeletal muscle (►Fig.…”

“…Furthermore, genetic studies have demonstrated reciprocal translocation of t(11; 22)(q24; q12) in approximately 95% of patients, with the remainder demonstrating t(21; 22) (q22; q12) translocation. 11 12 Generally, these tumors are commonly seen in the paravertebral regions or in the deep soft tissues of the extremities, with lower extremities having a higher propensity than upper extremities. 9 Patients with EES often note a rapidly growing soft-tissue mass, with about one-third being painful secondary to compression of adjacent structures.…”