Analysis of EWSR1-CREM fusion sarcoma with ALK protein overe xpression and response to alectinib therapy

Abstract The molecular changes in soft tissue sarcomas are complex. It has numerous fusion partners, and different fusion partner diseases exhibit different histological morphologies and biological behaviors. A 53-year-old female patient had sarcoma in the left thigh. Imaging revealed a sarcoma shadow in the intermuscular soft tissue of the medial left thigh, suggestive of malignancy. The patient underwent a left thigh mass resection and inguinal lymph node dissection. Pathological histology revealed sarcoma with epithelioid morphology and lymph node metastasis. Immunohistochemistry showed ALK (D5F3) and ALK1 proteins were strongly expressed. NGS and FISH detection confirmed the fusion of exon 7 of EWSR1 and exon 6 of CREM in sarcoma. Without ALK molecular changes was observed. Five months after the visit, lung imaging revealed multiple lung masses suggestive of tumor metastasis. Despite the current insufficiency in the theoretical foundation for the experimental diagnosis of ALK targeted therapy in this particular case, patients afflicted with severe anemia are unable to endure chemotherapy, thus opting for oral alectinib treatment. The results of a 21-month follow-up revealed that the patient's lung nodules exhibited a slight increase in size compared to their initial measurements, indicating a gradual growth pattern. The present findings suggest that alectinib exhibits ineffectiveness in the treatment of soft tissue sarcoma characterized by EWSR1-CREM fusion and abnormal ALK protein expression. Consequently, the exploration of novel targeted medications, such as pazopanib, is warranted.