| Abstract: |
Undifferentiated sarcomas characterized by a primitive monomorphic round to spindle cell phenotype and often non-specific immunoprofile remain difficult to subclassify outside molecular analysis. The increased application of RNA sequencing in clinical practice led to significant advances and discoveries of novel gene fusions that furthered our understanding and refined classification of otherwise undifferentiated neoplasms. In this study, we report an undifferentiated round to spindle cell sarcoma arising in the femur of a 34-year-old female. The round to spindle tumor cells were arranged in short fascicles, with focal rosette formation, within a hyalinized stroma. The tumor immunoprofile included diffuse reactivity for CD99, SATB2, and TLE1 and patchy positivity for Cyclin D1, Keratin AE1/AE3, synaptophysin, and chromogranin. Other markers, such as EMA, SMA, desmin, S100, ERG, and WT1, were negative. Fluorescence in situ hybridization analysis for EWSR1 gene alterations showed a break-apart signal and targeted RNA sequencing revealed an EWSR1::SSX3 gene fusion. The patient received neoadjuvant chemotherapy followed by surgery and subsequently relapsed in less than a year with lung metastasis. Larger series are needed to determine if this fusion defines a novel subset of undifferentiated tumors or represents a genomic variant of already existing primitive round cell sarcoma categories, such as Ewing sarcoma or synovial sarcoma. © 2023 Wiley Periodicals LLC. |
| Keywords: |
immunohistochemistry; adult; clinical article; human tissue; protein expression; cancer surgery; unclassified drug; exon; genetics; case report; doxorubicin; cancer combination chemotherapy; cancer radiotherapy; drug megadose; molecular genetics; nuclear magnetic resonance imaging; follow up; ki 67 antigen; cell proliferation; in situ hybridization, fluorescence; computer assisted tomography; multiple cycle treatment; etoposide; transcription factor; cyclophosphamide; vincristine; tumor biopsy; pathology; tumor marker; histology; ifosfamide; transcription factors; ewing sarcoma; sarcoma; cancer genetics; lung metastasis; fluorescence in situ hybridization; gene rearrangement; chromatin; tumor protein; tumor cell; gene fusion; fusion gene; oncogene proteins, fusion; cytoplasm; spindle cell; mitosis rate; cell nucleus; neoadjuvant chemotherapy; spindle cell sarcoma; cyclin d1; rna binding protein ews; chromogranin; ewsr1 protein, human; soft tissue neoplasms; soft tissue tumor; cd99 antigen; cytokeratin ae1; cytokeratin ae3; synaptophysin; rna-binding protein ews; lung nodule; bone sarcoma; eosinophil; maximum standardized uptake value; undifferentiated; sarcoma, ewing; ewsr1; humans; human; female; article; rna sequencing; round cell; biomarkers, tumor; positron emission tomography-computed tomography; femoral head; oncogene fusion protein; rna-based next-generation sequencing; ssx3; undifferentiated sarcoma of bone; protein satb2; protein tle1; ewsr1 ssx3 fusion gene; femoral sarcoma; femur diaphysis
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