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Metastatic sporadic paraganglioma with EWSR1::CREM gene fusion: A unique molecular profile that expands the phenotypic diversity of the molecular landscape of the EWSR1::CREM gene fusion positive tumors |
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| Authors: | Sehrish Javaid Ashley Patton Gabriel Tinoco Steve Oghumu Obiajulu Hans Iwenofu |
| Institution: | 1. Division of Oral and Maxillofacial Pathology, College of Dentistry, The Ohio State University, Columbus, Ohio, USA;2. Department of Pathology & Laboratory Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA;3. Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Medical Center, Columbus, Ohio, USA
The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA;4. Division of Oral and Maxillofacial Pathology, College of Dentistry, The Ohio State University, Columbus, Ohio, USA The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA |
| Abstract: | Chromosomal translocations with gene fusions are uniquely rare events in paraganglioma, mostly involving UBTF::MAML3 gene fusion. Precedent literature suggests that tumors involving MAML3 gene fusion correlate with poor clinical outcomes. Herein, we report a case of metastatic sporadic paraganglioma harboring EWSR1::CREM gene fusion in a 36-year-old male, that has not been previously described. The patient presented with large paraspinal mass that was resected the same year. Tumor recurred 3-years later and on further work-up, patient was found to have metastases involving both lungs. Histopathologic evaluation of the original primary tumor showed tightly packed irregular nests and cords of cells containing palely eosinophilic cytoplasm. Features considered atypical included: areas of solid growth pattern, coagulative tumor necrosis, focal cellular atypia and angiolymphatic invasion were also identified. By immunohistochemistry, the tumor cells were positive for synaptophysin and chromogranin and negative for keratin. The S100 stain highlights the sustentacular cells and the Ki-67 proliferation index of 15%. The recurrence specimen was similar but showed increased cellularity, atypia, necrosis, and proliferative activity (Ki-67 proliferation index of 35%). CT guided biopsy of the right lung lesion was consistent with metastasis. Next generation sequencing identified EWSR1::CREM fusion. The breakpoints were found in chromosome 22: 29683123 for EWSR1 exon 7 (NM_005243.3) and at chromosome 10:35495823 for CREM exon 6 (NM_001267562.1). Fluorescence in situ hybridization for EWSR1 gene rearrangement was positive. In summary, we report a case of metastatic paraganglioma with EWSR1::CREM gene fusion, not previously described in this entity, and expands on the phenotypic diversity within the genetic landscape of EWSR1::CREM gene fusion positive tumors. |
| Keywords: | EWSR1::CREM metastatic paraganglioma molecular genetics sporadic type |