Division of Oral and Maxillofacial Pathology, College of Dentistry, The Ohio State University, Columbus, Ohio, USA.
Department of Pathology & Laboratory Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Genes Chromosomes Cancer. 2023 Feb;62(2):85-92. doi: 10.1002/gcc.23094. Epub 2022 Oct 31.
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.
染色体易位与基因融合在副神经节瘤中是极为罕见的事件，主要涉及 UBTF::MAML3 基因融合。先前的文献表明，涉及 MAML3 基因融合的肿瘤与不良的临床结局相关。在此，我们报告了一例 36 岁男性的转移性散发性副神经节瘤，其携带 EWSR1::CREM 基因融合，这在该实体中尚未被描述。患者表现为巨大的脊柱旁肿块，同年进行了切除。3 年后肿瘤复发，进一步检查发现患者有双肺转移。对原始原发性肿瘤的组织病理学评估显示，细胞排列紧密，呈不规则巢状和条索状，胞质淡嗜酸性。被认为是非典型的特征包括：实性生长模式、凝固性肿瘤坏死、局灶性细胞异型性和血管淋巴管侵犯。免疫组化染色显示，肿瘤细胞阳性表达突触素和嗜铬粒蛋白，阴性表达角蛋白。S100 染色突出支持细胞，Ki-67 增殖指数为 15%。复发病例标本相似，但细胞密度增加、异型性、坏死和增殖活性增加（Ki-67 增殖指数为 35%）。右肺病变的 CT 引导活检与转移一致。下一代测序鉴定出 EWSR1::CREM 融合。断点位于染色体 22：29683123 处 EWSR1 外显子 7（NM_005243.3）和染色体 10：35495823 处 CREM 外显子 6（NM_001267562.1）。EWSR1 基因重排的荧光原位杂交呈阳性。总之，我们报告了一例转移性副神经节瘤伴 EWSR1::CREM 基因融合的病例，该病例在该实体中尚未被描述，并扩展了 EWSR1::CREM 基因融合阳性肿瘤的遗传景观内的表型多样性。
