Pediatric Ewing sarcoma as a secondary malignancy following hepatoblastoma: a case report and review of the literature

Markedly improved long-term survival among pediatric cancer patients has led to increased recognition of secondary malignant neoplasms during follow-up. This report presents the rare case of a male patient who developed Ewing sarcoma 10.5 years after successful treatment of primary hepatoblastoma. To our knowledge, this is only the fourth reported case in the literature. A Caucasian male was diagnosed at 3.6 years of age with a high-grade epithelial fetal-type hepatoblastoma and was treated with the SIOPEL-4 chemotherapy protocol followed by surgery, receiving a cumulative anthracycline dose of 300 mg/m 2. At 14 years of age, he presented with intractable left hip pain and was ultimately diagnosed with Ewing sarcoma. The diagnosis was challenging because the lesion was initially suspected to represent recurrent hepatoblastoma, CT-guided biopsy was non-diagnostic, and FISH was negative. RT-PCR ultimately confirmed a type 1 EWSR1-FLI1 fusion transcript. He was initially treated with a modified Euro Ewing 2012 regimen based on the VDC/IE backbone, with actinomycin D substituted for doxorubicin because of prior anthracycline exposure, followed by limb-sparing surgery and adjuvant chemotherapy. The subsequent disease course was aggressive, with local relapse 13 months after completion of initial therapy, followed by thoracic spinal and multifocal osseous metastatic progression requiring multiple salvage regimens. Suspected secondary malignancies may require rigorous molecular confirmation despite misleading conventional workup, prior treatment exposure should directly inform adaptation of subsequent therapy, and heavily pretreated survivors require lifelong oncologic and cardiologic surveillance, as subsequent disease course may remain aggressive despite multimodal management.