In the 2020 WHO classification of soft tissue and bone tumors, undifferentiated small round cell sarcomas are classified into four categories: Ewing sarcoma (ES), round cell sarcoma with EWSR1-non-ETS fusions, CIC-rearranged sarcomas (CRS), sarcoma with BCOR gene alterations [1]. ES constitutes the most common group in this group. It is the second most frequent malignant bone tumor in the first two decades. It is slightly more common in males than females with a ratio of 1.4:1 and rare after 30 years of age [1,2]. Although most of the cases are encountered in bone, soft tissue localization is more common in patients over 30 years [3]. ES consists of the fusions between the FET and the ETS gene families. Most common fusion is EWSR1::FLI1(t[11;22][q24;q12]) [1,4]. Classic ES is characterized by monotonous histopathologic features such as a small round/ovoid nucleus, fine chromatin, and narrow eosinophilic/clear cytoplasm [5].

CRS makes up approximately two-thirds of EWSR1-negative undifferentiated small round cell sarcomas [6]. Most of the cases are encountered in the soft tissues of extremities and trunks of patients in the 3rd to 4th decades. Although histopathologic features resemble to ES, the nuclear atypia is usually more prominent along with vesicular chromatin and prominent mitoses. Also, some of the cases have myxoid stroma which is extremely rare in ES and immunohistochemical expression profiles are different. Currently, CRS are treated with ES protocols; unfortunately, the response of treatment is poor with an aggressive clinical course [7,8]. DUX4 is the partner gene in nearly 95 % of CRS, followed by FOXO4, LEUTX, NUTM1, and NUTM2A genes [1].

Cyclin E1 is responsible for the transition of the G1/S phase in the cell cycle with Cyclin-Dependent Kinase 2 (CDK2). Deregulation of cyclin E1 activity and increased cyclin E1 expression result in replication stress and chromosomal and genomic instability which play a role in tumorigenesis [9]. An experimental mouse model conducted by Okimoto et al. elucidated that increased cyclin E1 activity is related to tumorigenesis in CRS and treatments targeting the cyclin E1/CDK2 pathway turn out to decrease tumor volume. Therefore, they put forward the idea that these treatment modalities may be effective in CRS [10].

In our study, we aimed to demonstrate whether the immunohistochemical cyclin E1 expression is correlated with the clinicopathologic features in small round cell tumors, especially in CRS.