High-Grade Undifferentiated Small Round Cell Sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 Fusion: Emerging Entities of Soft Tissue Tumors with Unique Histopathologic Features – A Case Report and Literature Review

Abstract

Patient: Female, 36Final Diagnosis: Small cell sarcomaSymptoms: Mass to right upper thighMedication: —Clinical Procedure: Surgical resectionSpecialty: OncologyObjective:Rare diseaseBackground:A subset of undifferentiated small round cell sarcomas (USRCSs) is currently being recognized as emerging entities with unique gene fusions: CIC-DUX4 (the area of focus in this article), BCOR-CCNB3, or CIC-FOXO4 gene fusions. CIC-DUX4 and CIC-FOXO4 fusions have been reported in soft tissue tumors, while BCOR-CCNB3 fusion with an X chromosomal inversion was described in both bone and soft tissue tumors. CIC-DUX4 fusion can either harbor t(4;19)(q35;q13.1) or t(10;19)(q26.3;q13), while t(4;19)(q35;q13.1) is reported more commonly.Case Report:The aim of this study is to share a new case report of a 36-year-old woman who had a rapidly growing mass in her right upper thigh, which was found to be an undifferentiated small round cell sarcoma with t(4;19) (q35;q13.1) CIC-DUX4 fusion was confirmed by cytogenetic testing. Combined modality treatment with surgery, radiation, and chemotherapy was used and achieved a good response. A review of the literature of the reported cases with CIC-DUX4 fusions including both t(4;19) and t(10;19) translocations revealed a total of 44 cases reported. Out of these 44 cases, 33 showed t(4;19)(q35;q13.1) translocation compared to 11 cases with t(10;19)(q26.3;q13).Conclusions:Undifferentiated small round cell sarcomas are aggressive tumors. Their treatment includes surgery, chemo-therapy, and radiation. Resistance to chemotherapy is common. Lung and brain are common sites of metastasis, with associated poor prognosis. Generally, median survival is less than 2 years. Newer techniques have been developed recently which helped identify a subset of previously unclassifiable sarcomas, with promising prognostic value.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

“…Consequently, those tumors showed strong reactivity when investigated for NUTM1 protein expression by immunohistochemistry, while no tumors from any other entity stained positive (Figures 6B and S4A/B). On the basis of CIC fusions present in subgroups of pediatric primitive round cell sarcomas (Haidar et al, 2015) and their distinct transcriptional signature (Specht et al, 2014), we analyzed CNS EFT- CIC tumors for similar gene expression patterns. As observed in peripheral EFT, among the genes specifically upregulated in this group were members of the ETS transcription factor family including ETV1 , ETV4 , ETV5 , FLI1 , and ETS1 (Figure S6C).…”

Clinical management of a unique case of PNET of the uterus during pregnancy, and review of the literature

“…EWSR1 may also match with ETV1, E1AF, or FEV; in other cases, there is no translocation involving EWSR1, such as CIC-DUX4 or BCOR –CCNB3. [ 4 , 7 , 20 – 22 ]…”

CIC‐associated round cell sarcoma of the small bowel

“…Thirdly, the microscopic features include myxoid matrix with prominent stromal edema and heterogenous cytology with mixture of round, spindle and epithelioid cell types are typical of CIC-associated SRCS. 2,4 Finally, localized CIC-associated SRCS showed better outcome with upfront surgery compared to neoadjuvant chemotherapy. 4 However, patients who received neoadjuvant therapy tended to have a larger tumour size with no difference in age or anatomic location.…”