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Undifferentiated small round cell sarcoma in a young male: a case report.

ABSTRACT: CIC-rearranged sarcomas (CRSs) have recently been characterized as a distinct sarcoma subgroup with a less favorable prognosis compared to other small round cell sarcomas. CRSs share morphologic features with Ewing's sarcoma and prior to 2013 were grouped under undifferentiated sarcomas with round cell phenotype by the WHO classification. In this report, whole-genome sequencing and RNA sequencing were performed for an adolescent male patient with CRS who was diagnosed with undifferentiated pleomorphic sarcoma (UPS) by three contemporary institutions. Somatic mutation analysis identified mutations in IQGAP1, CCNC, and ATXN1L in pre- and post-treatment tissue samples, as well as a CIC-DUX4 fusion that was confirmed by qPCR and DUX4 immunohistochemistry. Of particular interest was the overexpression of the translation factor eEF1A1, which has oncogenic properties and has recently been identified as a target of the investigational agent plitidepsin. This case may provide a valuable waypoint in the understanding and classification of CRSs and may provide a rationale for targeting eEF1A1 in similar soft tissue sarcoma cases.

SUBMITTER: Ricker CA

PROVIDER: S-EPMC6996518 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Undifferentiated small round cell sarcoma in a young male: a case report.

Ricker Cora A CA Berlow Noah E NE Crawford Kenneth A KA Georgopapadakos Todd T Huelskamp Audrey N AN Woods Andrew D AD Dhimolea Eugen E Ramkissoon Shakti H SH Spunt Sheri L SL Rudzinski Erin R ER Keller Charles C

Cold Spring Harbor molecular case studies 20200203 1

<i>CIC</i>-rearranged sarcomas (CRSs) have recently been characterized as a distinct sarcoma subgroup with a less favorable prognosis compared to other small round cell sarcomas. CRSs share morphologic features with Ewing's sarcoma and prior to 2013 were grouped under undifferentiated sarcomas with round cell phenotype by the WHO classification. In this report, whole-genome sequencing and RNA sequencing were performed for an adolescent male patient with CRS who was diagnosed with undifferentiate ...[more]

PMID: 32014859

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Project description:RationaleEwing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) is a rare type of soft tissue sarcomas (STS), especially in infants, with poor prognosis. It is a so-called "small round cell" sarcoma, and has many features of Ewing sarcoma, but lacks rearrangements in EWSR1. The diagnosis and treatment of this kind of STS remains challenging. BCOR genetic abnormalities have been found in some Ewing-like sarcomas.Patient concernsThis report presents an ELS case of a female infant, who was 2 months old when initially diagnosed, with the clinical stage of IIIA (G2T2N0M0). Histologic findings revealed an undifferentiated neoplasm composed of small round tumor cells with round, open chromatic nuclei, and scant cytoplasm in a sheet growth pattern. Fluorescence in situ hybridization (FISH) analysis showed absence of EWSR1 and ETV6 gene rearrangement. Molecular genetic testing found no established variants of clinical significance but variants of unknown significance in APC, KMT2D, and MSH6 were detected. Immunostaining revealed that the tumor cells were positive for TLE1 and BCOR, and negative for cytokeratin (AE1/AE3), Desmin, CD45, S100, CD31, HMB45, and SATB2. INI-1 was retained.DiagnosisEwing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) INTERVENTIONS:: After initial diagnosis, the patient received 4 cycles of combination chemotherapy for 2 months. Radical amputation of left upper extremity was performed 3 months after diagnosis. Postoperative chemotherapy was continued for 6 cycles.OutcomesThe patient died of intracranial metastasis with hemorrhage in 13 months after initial diagnosis, 5 months after the last cycle of chemotherapy.LessonsELS in infancy is extremely rare and has a poorer prognosis than Ewing sarcoma or infantile fibrosarcoma. APC and MSH6 variation might be related with the disease progression and predict a poorer prognosis. This rare case promotes better understanding of the disease and suggests a promising role for the combination chemotherapy regimen in treating infantile ELS. Importantly, it brings to light the possibility of intracranial metastasis, which requires proactive screening for timely detection.

Project description:Small blue round cell tumors (SBRCTs) are a heterogenous group of tumors that are difficult to diagnose because of overlapping morphologic, immunohistochemical, and clinical features. About two-thirds of EWSR1-negative SBRCTs are associated with CIC-DUX4-related fusions, whereas another small subset shows BCOR-CCNB3 X-chromosomal paracentric inversion. Applying paired-end RNA sequencing to an SBRCT index case of a 44-year-old man, we identified a novel BCOR-MAML3 chimeric fusion, which was validated by reverse transcription polymerase chain reaction and fluorescence in situ hybridization techniques. We then screened a total of 75 SBRCTs lacking EWSR1, FUS, SYT, CIC, and BCOR-CCNB3 abnormalities for BCOR break-apart probes by fluorescence in situ hybridization to detect potential recurrent BCOR gene rearrangements outside the typical X-chromosomal inversion. Indeed, 8/75 (11%) SBRCTs showed distinct BCOR gene rearrangements, with 2 cases each showing either a BCOR-MAML3 or the alternative ZC3H7B-BCOR fusion, whereas no fusion partner was detected in the remaining 4 cases. Gene expression of the BCOR-MAML3-positive index case showed a distinct transcriptional profile with upregulation of HOX-gene signature, compared with classic Ewing's sarcoma or CIC-DUX4-positive SBRCTs. The clinicopathologic features of the SBRCTs with alternative BCOR rearrangements were also compared with a group of BCOR-CCNB3 inversion-positive cases, combining 11 from our files with a meta-analysis of 42 published cases. The BCOR-CCNB3-positive tumors occurred preferentially in children and in bone, in contrast to alternative BCOR-rearranged SBRCTs, which presented in young adults, with a variable anatomic distribution. Furthermore, BCOR-rearranged tumors often displayed spindle cell areas, either well defined in intersecting fascicles or blending with the round cell component, which appears distinct from most other fusion-positive SBRCTs and shares histologic overlap with poorly differentiated synovial sarcoma.

Dataset Information

Undifferentiated small round cell sarcoma in a young male: a case report.

Publications

Undifferentiated small round cell sarcoma in a young male: a case report.

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