CIC-DUX4 sarcomas

Abstract

Purpose of reviewCIC-DUX4 sarcoma (CDS) is a high-grade undifferentiated round cells sarcoma that belongs to the undifferentiated round cell sarcomas family. It represents less than one percent of sarcomas, defining a rarest among rare malignancies. It affects young adults, displaying soft tissue mass. Considered very aggressive, a high proportion of cases display an advanced disease with lung metastasis at diagnosis. Here we discuss recent progress in molecular characterization of CDS, the main tracks of CDS biology and the current and future prospects of therapeutic approaches.Recent findingsCDS is characterized by a specific oncogenic translocation CIC::DUX4 that induce ETV4 overexpression. Patients with CDS show an aggressive clinical course and have a significantly unfavorable outcome compared to Ewing sarcoma. As of today, there is a lack of consensus on whether they should be treated with an Ewing-like approach, as currently done by most sites, or regarded as high-grade soft tissue sarcoma (STS). Anyway, when feasible, combination regimens including anthracycline and alkylating agents should be favored and patients should not benefit from a therapeutic de-escalation. Overall, registration within clinical trials and prospective registries is recommended.SummaryOverall, CDS showed a poor prognosis regardless of the patterns of treatment that warrant biological studies to better understand the disease.

Case Report: Colon malignant tumor caused by retroperitoneal small round cell undifferentiated sarcoma

“…Small round cell undifferentiated sarcoma is a highly invasive malignant tumor that shares morphological similarities and partially overlaps with other types of small round cell tumors in immunohistochemical detection ( 7 , 24 ). It is extremely rare in clinical practice, with few reports in the literature, a high misdiagnosis rate, and poor prognosis ( 18 ).…”

“…Therefore, a more proactive approach to the treatment of this rare disease is required. Unfortunately, there are currently no standardized guidelines for its diagnosis and treatment both domestically and internationally ( 24 ). Small round cell undifferentiated sarcoma is morphologically similar to Ewing’s sarcoma, so the treatment is often modeled after Ewing’s sarcoma ( 29 ).…”

CIC-Rearranged Sarcomas: An Intriguing Entity That May Lead the Way to the Comprehension of More Common Cancers

“…Currently, patients with CIC-rearranged sarcoma are routinely treated in the same way as EWS, with a neoadjuvant and adjuvant anthracycline-based polychemotherapy regimen, surgery, and radiotherapy. Although some sporadic cases of good response to chemotherapy or radiation therapy have been reported [ 15 , 16 ], the prognosis of CIC sarcomas is poor. The 5-year overall survival is around 50%, which is significantly lower than the 80% 5-year overall survival of EWS patients [ 4 , 14 , 17 ].…”