Breakthrough in Epithelioid Sarcoma Research Reveals New Therapeutic Option

Strategic Insights -

Researchers from Ohio State University Wexner Medical Center have reported a significant finding in the field of epithelioid sarcoma, a rare and aggressive type of cancer. The study, published in the journal Genes, Chromosomes and Cancer, describes a case of a 62-year-old woman who presented with a lower abdominal mass and pain. After undergoing a right hemicolectomy, the tumor was found to be positive for CD117, keratins, and a KIT p.V5301 mutation, initially leading to a diagnosis of epithelioid gastrointestinal stromal tumor. However, the patient developed omental relapses while on imatinib and progressive disease persisted despite a change to sunitinib.

The researchers re-reviewed the histopathology of both the hemicolectomy and relapsed omental sites and found marked cellular atypia, increased cellularity, and mitosis in metastatic omental sites. Next-generation sequencing performed on both the primary and relapsed sites revealed the presence of an EWSR1::CREM gene fusion, in addition to the KIT p.V5301 mutation. The tumor was subsequently reclassified as EWSR1::CREM fusion-positive intrabdominal unclassified epithelioid sarcoma with concomitant KIT mutation of unknown significance.

The patient was treated with cytotoxic chemotherapy and radiation therapy, but due to complications and lack of tolerance, treatment was stopped. Pazopanib, a tyrosine kinase inhibitor, was then initiated, and the patient has continued to respond for the past 7 months.

Key Takeaways:

  • The study reports a rare case of EWSR1::CREM fusion-positive intrabdominal unclassified epithelioid sarcoma with concomitant KIT mutation.
  • The tumor showed significant immunophenotypic heterogeneity.
  • The patient's tumor was initially misdiagnosed as epithelioid gastrointestinal stromal tumor due to the presence of CD117 and keratins.
  • Next-generation sequencing revealed the presence of an EWSR1::CREM gene fusion and KIT p.V5301 mutation.
  • The patient responded to pazopanib therapy, a tyrosine kinase inhibitor.
  • The study highlights the need for further research on EWSR1::CREM/FUS fusion-positive tumors.
  • The therapeutic utility of pazopanib as a single agent in this rare group of aggressive sarcomas is underscored.

Statistics:

  • The patient was 62 years old when diagnosed with epithelioid sarcoma.
  • The patient underwent a right hemicolectomy, followed by chemotherapy and radiation therapy.
  • The patient developed omental relapses while on imatinib and progressive disease persisted despite a change to sunitinib.
  • Next-generation sequencing revealed the presence of an EWSR1::CREM gene fusion in addition to the KIT p.V5301 mutation.
  • The patient responded to pazopanib therapy for 7 months.

Sources:

  • Durable Response to Pazopanib (Tyrosine Kinase Inhibitor) in a Patient With EWSR1::CREM Gene Fusion Positive Intra-Abdominal Unclassified Epithelioid Sarcoma. Genes, Chromosomes and Cancer, 2025;64(10).
  • Genes, Chromosomes and Cancer. Wiley, 111 River St, Hoboken 07030-5774, NJ, USA.
  • Ohio State University Wexner Medical Center. Department of Pathology and Laboratory Medicine, Columbus, Ohio, United States.