A huge gluteal mass diagnosed as CIC-rearranged sarcoma: a rare case report and literature review.

Am J Cancer Res 2025;15(1):195-208 www.ajcr.us /ISSN:2156-6976/ajcr0160209 Case Report A huge gluteal mass diagnosed as CIC-rearranged sarcoma: a rare case report and literature review Zijian Xu, Xinjia Wang, Wanli Wu, Huaitai Lin, Jinhao Zhu, Chenyu Yang, Weidong Wang Department of Bone and Soft Tissue Tumor, Shantou University Medical College Affiliated Cancer Hospital, Shantou, Guangdong, China Received August 30, 2024; Accepted December 31, 2024; Epub January 15, 2025; Published January 30, 2025 Abstract: Capicua transcriptional repressor (CIC)-rearranged sarcoma, also known as CIC-rearranged sarcoma (CRS), is a recently recognized sarcoma subtype characterized by specific molecular features. It is associated with aggressive clinical course and a poor prognosis. Here, we present a rare case of CRS, including a detailed clinical, pathological, and molecular analysis, to enhance understanding of this disease and provide a reference for future diagnosis and treatment. A 15-year-old female adolescent initially presented with a rapidly growing mass in her left buttock, accompanied by intermittent pain. A magnetic resonance imaging (MRI) scan revealed a 12.7 × 8.6 × 11.9 cm mixed-intensity mass, suggesting a mesenchymal sarcoma. After histological and immunohistochemical analysis, a preliminary diagnosis of malignant small round cell tumor was made, which was later confirmed as CRS by Fluorescence in situ hybridization (FISH). A course of VDC/IE regimen was administered as first-line neoadjuvant chemotherapy. However, a follow-up MRI showed a 28% increase in tumor volume. Given the poor response to chemotherapy, we decided to perform a wide resection surgery. Unfortunately, lung metastases developed only one month postoperatively, and local recurrence occurred two months postoperatively. The patient then underwent concurrent chemoradiotherapy. At the time of data cutoff, the patient achieved a stable disease state and retained satisfactory walking function. In conclusion, treatment paradigms for CRS have yet to be defined. For patients with large tumor volumes, preoperative neoadjuvant chemotherapy may be ineffective and could potentially delay more effective treatment. Early surgical resection is probably a more suitable treatment option. Multidisciplinary collaboration is essential in the treatment of CRS, and large studies exploring novel therapeutic options are urgently needed to bring hope to patients with this aggressive disease. Keywords: Capicua (CIC)-rearranged sarcoma (CRS), mesenchymal sarcoma, wide resection surgery, chemotherapy, radiotherapy Introduction The Capicua (CIC) gene functions as a tumor suppressor. It contains a high-mobility group (HMG) box, which recognizes specific DNA sequences, thereby regulating the expression of various target genes. It plays a crucial role in regulating transcription and cell proliferation by acting as a negative regulator of the mitogenactivated protein kinase (MAPK) signaling pathway. This pathway is often associated with cellular processes such as invasion and proliferation, which are pivotal to the development and progression of various cancers [1]. CIC-rearranged sarcoma, previously recognized as an Ewing-like sarcoma characterized by an undifferentiated small round cell sarcoma without the specific FET::ETS gene fusions typical of Ewing sarcoma (ES), is an extremely rare type of soft tissue sarcoma. This tumor entity belongs to the translocation-associated sarcomas, which was established by KawamuraSaito, et al. in 2006 when they identified CIC::DUX4 fusion transcripts in two Ewing-like sarcomas with the t(4;19)(q35;q13) translocation [2]. After fusion with other genes, most commonly DUX4 (in 95% of cases), the transcriptional repressor CIC converts to an oncogene that can promote tumor growth and metastasis. Unlike Ewing sarcoma, CIC-rearranged sarcomas are associated with an aggressive clinical course and a poor prognosis. https://doi.org/10.62347/ZESM2176 CIC-rearranged sarcoma case report Figure 1. Summary of the clinical course. Figure 2. Gross view of the tumor at presentation. CIC-rearranged sarcomas most commonly present in young adults and typically originate from soft tissues of extremities. They often manifest as a lump that gradually increases in size, with or without pain. The clinical symptoms are related to the location of tumor occurrence. Generally, to achieve a precise diagnosis, a combination of pathology, immunohistochemistry and molecular testing is required, including CIC break-apart FISH analysis, to confirm the presence of specific fusion transcripts involving CIC [3]. With the development of genetic testing, nowadays reverse transcription polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS) are also widely used [2]. At diagnosis, about 40% of patients found metastases to lungs or lymph nodes, which indicates the highly aggressiveness of this disease. Currently, there is still no optimal treatment strategy. Due to the similarity in pathological properties, patients with CIC-rearranged sarcomas are commonly treated in the same way as Ewing sarcoma, which combines neoadjuvant and adjuvant anthracycline-based polychemo196 therapy regimen, surgery, and radiotherapy. However, the response is often poor comparing with ES, especially for patients in advanced stage. The 5-year overall survival rate ranges from 17% to 43%, and the median survival is 12 to 18 months [2, 4, 5]. Due to the extreme rarity of this disease, clinical studies are encountering enrollment difficulties and suffer from a lack of investment, resulting in most of them being stuck in the preclinical stage. Thus, to explore an effective, evidence-based therapeutic strategy, more and more clinical data is needed. Herein, we report a case of a 15-year-old patient with CIC-rearranged sarcoma originating from the left buttock. The tumor developed rapidly and, after surgery, it metastasized to the lungs. Subsequently, local recurrence occurred. After standardized treatment according to guidelines, the patient achieved a stable disease state. During the hospital course, informed consent was obtained from the patient’s parents for the inclusion of their child’s medical data, clinical images, and any associated information in this study. The parents were provided with detailed information about the study’s purpose, procedures, potential risks, and benefits. The parents have given their full consent for the publication of their child’s de-identified medical information and images, with the assurance that all identifiable information has been removed to protect the child’s privacy. The clinical course is summarized in Figure 1. Clinical presentation In November 2023, a 15-year-old female adolescent with no significant medical history preAm J Cancer Res 2025;15(1):195-208 CIC-rearranged sarcoma case report Figure 3. A. CT images of the tumor at presentation in coronal, transverse and sagittal position, showing a (...truncated)