At the crossroad between Ewing sarcoma and neuroblastoma: a report of two cases of Ewing sarcoma with post treatment neuroblastoma-like differentiation.

Abstract

Background: Ewing sarcoma (ES) is the second most frequent sarcoma of bone, often affecting young patients and pursuing an aggressive clinical course. Among therapeutic choices, radio- and chemotherapy are employed in neoadjuvant setting, and they yield variable histological changes in neoplastic tissue, which mainly include necrosis and fibrosis. Cytodifferentiation is seldom observed in pediatric tumors such as nephroblastoma and rhabdomyosarcoma following treatment. Nevertheless, it represents an extremely rare phenomenon in ES.

Case presentation: In this study we present the clinico-pathologic and molecular features of two cases of ES undergoing neuroblastoma-like differentiation after treatment. Both tumors were primarily located in bone and presented the histologic and immunohistochemical features of classic ES in needle biopsies. They were treated with standard chemotherapy protocols followed by surgical resection. The resection specimens of the primary tumor of patient 1 and pleural metastases of patient 2 presented foci of eosinophilic fibrillary stroma resembling neuropil and containing cellular elements with wide granular eosinophilic cytoplasm, eccentric nuclei containing vesicular chromatin and prominent nucleoli, reminiscent of ganglion cells. These cells were positive for chromogranin, synaptophysin and CD56, while CD99 was negative. Molecular confirmation of EWSR1 rearrangement was provided in both cases by next generation sequencing and FISH analysis.

Conclusions: Evidence of neural differentiation in ES unravels interesting hints about its controversial histogenesis. Furthermore, awareness of this event must be increased to avoid misdiagnosis with neuroblastoma, which shows significant morphological overlap.