Therapy-induced neural differentiation in ewing's sarcoma: a case report and review of the literature

Abstract

Ewing's sarcoma (ES) is a small round cell tumor of adolescents or young adults that usually arises in the deep soft tissues of the extremities. The tumor cells have uniform round nuclei, fine powdery chromatin and indistinct nucleoli. CD99 (O13) is a product of the MIC 2 gene that is highly sensitive to ES but not specific. A panel of markers should be used for the differential diagnosis of small round cell tumors because nearly all others, on occasion, show membranous staining for CD99. One of the defining feature of ES is the presence of 22q12 gene rearrangement. The presented case is a 6 year-old boy complaining of swelling on his right leg. The biopsy was compatible with classic ES in terms of histopathological, immunohistochemical and cytogenetic criteria. Wide surgical resection was performed after chemotherapy. The posttreatment specimen was composed of uniformly small round cells mixed with areas of ganglion cells embedded in neurophil-like fibrillary background. Immunohistochemically, neoplastic cells revealed strong CD99 (O13) and NSE staining and the tumor had EWSR1 gene rearrangement. Morphologic alterations due to treatment are commonly seen in pediatric tumors. Single case reports have defined neural differentiation in ES but to the best of our knowledge this is the first report of ES in the literature with all histopathological, immunohistochemical, and cytogenetic criteria evaluated in both pretreatment and posttreatment specimens.Key Words: Ewing's sarcoma, Therapy, FISH, EWSR1, Neural differentiation INTRODUCTIONEwing's sarcoma (ES) represents 6% to 8% of all primary malignant bone tumors. Young adults and children are those most commonly affected. Radiological features include an infiltrative, ill-defined lesion and bone destruction and periosteal reaction of the diaphysis of a long tubular or flat bone. ES is composed of small round cells with scant cytoplasm and indistinct cytoplasmic borders. Nearly all tumors show immunohistochemical positivity for CD99 (O13). This group of tumors contains a 22q12 gene rearrangement (1) and may exhibit rosette-like structures and/or variable markers of neural differentiation (excluding ganglion cells) with a fibrillary background (2). The aim of this case presentation and literature review was to discuss the characteristics and treatment for ES. CASE REPORTA 6-year-old Syrian boy presented to another university hospital with a mass in his right thigh and inability to bear weight for the last 6 months in October 2013. A trucut biopsy was performed and ES without any metastases diagnosed at that center. The patient underwent neoadjuvant chemotherapy with the VIDE protocol for 4 months. After neoadjuvant chemotherapy, the patient had been referred to our center for surgical treatment. Radiological staging of the patient had been done and a lytic-sclerotic lesion of the entire femoral diaphysis causing a partially healed pathological fracture with a massive soft tissue mass which had extensive sunburst-like calcifications of soft tissue and formation ...

Ewing Sarcoma with Ganglion Cells Post-Chemotherapy: A Case Report with Review of Literature

“…Maturation and cytodifferentiation have been documented in neuroblastoma and rhabdomyosarcoma post-chemother-apy showing better prognosis 2,3 ; However, this is a rare phenomenon in ES with only few case reports (►Table 1). [4][5][6][7][8][9] In view of its histomorphology of a malignant small round cell tumor with extensive ganglion cells/neural differentiation, Ewing Sarcoma with Ganglion Cells Post-Chemotherapy Dhandapani et al 215…”

“…It has been shown from the above case reports that such neural differentiation can occur both post-chemotherapy like neuroblastoma, Wilms tumor, and rhabdomyosarcoma or as a part of primary tumor before any adjuvant therapy. [4][5][6][7] From the limited case reports available (11 cases), neural maturation occurs both in bone and soft tissue ES, both preand post-neoadjuvant therapy. Important issue that needs to be addressed from all these case reports is the role of such unusual differentiation in ES and its implication in clinical behavior and outcome that appears to be better in the case reports published till date (►Table 1).…”

“…Maturation and cytodifferentiation have been documented in neuroblastoma and rhabdomyosarcoma post-chemotherapy showing better prognosis 2 3 ; However, this is a rare phenomenon in ES with only few case reports ( Table 1 ). 4 5 6 7 8 9 …”

“…It has been shown from the above case reports that such neural differentiation can occur both post-chemotherapy like neuroblastoma, Wilms tumor, and rhabdomyosarcoma or as a part of primary tumor before any adjuvant therapy. 4 5 6 7 …”

E-26 Transformation-specific Related Gene Expression and Outcomes in Cytogenetically Normal Acute Myeloid Leukemia

“…The ERG , a member of the E-26 transformation-specific ( ETS ) family of transcription factors, plays a major role in multiple cancers, such as Ewing's sarcoma,[ 12 13 ] prostate cancer,[ 14 ] and leukemia. [ 10 15 ] The ERG , which is located on chromosome band 21q22, was involved in cell proliferation, apoptosis, and differentiation.…”