Ewing sarcoma of the rib with a rare PTEN mutation

Rib involvement in Ewing sarcoma (ES) is very rare (3-5 %) and may often lead to unique presentations due to mass effect within the thorax. Molecular studies may sometimes offer insights into disease prognosis and possible targeted treatment approaches.

Here we present the case of a 39-year-old female who presented with shortness of breath from a massive primary tumor in the right rib and lung. She was diagnosed with ES, which was confirmed by the presence of EWSR1/FLI-1 rearrangement and received multimodal therapy with neoadjuvant VDC-IE (vincristine-doxorubicin-cyclophosphamide, and ifosfamide-etoposide) followed by surgical excision after partial response, and adjuvant chemoradiation. Unfortunately, the patient experienced histologically confirmed local and distant recurrence after several months. NGS of the recurrent tumor revealed a pathogenic PTEN c.640C>T(p.Q214*) nonsense variant with a very high variant allele frequency (VAF) of 82.6 % but negative germline assessment. She received several lines of chemotherapy but only demonstrated a short response to the oral multi-tyrosine kinase inhibitor cabozantinib before eventually passing away.

PTEN mutations in ES, although rare, may result in a higher likelihood of chemotherapy resistance and poor prognosis. Clinical studies targeting specific molecular traits of these tumors, such as PTEN inactivation, could help improve outcomes in selected cases.