Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Mod Pathol. 2021 Jun;34(6):1203-1212. doi: 10.1038/s41379-021-00744-7. Epub 2021 Feb 11.
Sarcomas with MEIS1-NCOA2 fusions have been so far reported in 2 cases each of primitive renal sarcomas and intraosseous pelvic rhabdomyosarcomas. Their histologic spectrum, anatomic distribution, and clinical behavior remain poorly defined. In this study, we report 6 additional spindle cell sarcomas with MEIS1-NCOA2 or NCOA1 fusions that fall into the same disease spectrum with the previously reported renal sarcomas. The patients' age range was wide (20-76 years, mean 46) and all except one were female. The tumors arose in the kidney (n = 2), and one each in the uterine corpus, vagina, scrotum, and para-rectal region. The consistent morphology was that of monomorphic spindle to ovoid cells in a storiform, whorling, or solid pattern. Alternating cellularity, myxoid stroma, and microcystic changes were seen in some cases. Mitotic activity varied greatly (<1-33/10 high power fields). The immunophenotype was nonspecific, with most cases expressing variable degrees of TLE1, WT1, cyclin D1, CD56, and CD10. Using various platforms of RNA-based targeted sequencing, MEIS1-NCOA2 fusions were recurrently identified in 5 cases, and a novel MEIS1-NCOA1 fusion was found in one renal tumor. The gene fusions were validated by fluorescence in situ hybridization using custom BAC probes. Of the 5 patients with available follow-up (5 months to 8 years), all experienced local recurrences, but no distant spread or death from disease. Our results expand the clinicopathologic spectrum of sarcomas with MEIS1-NCOA2/1 fusions, providing evidence of an undifferentiated spindle cell phenotype with nonspecific immunoprofile and low-grade clinical behavior.
到目前为止，已经在 2 例原始肾肉瘤和骨内盆腔横纹肌肉瘤中分别报告了具有 MEIS1-NCOA2 融合的肉瘤。它们的组织学谱、解剖分布和临床行为仍未得到很好的定义。在这项研究中，我们报告了另外 6 例具有 MEIS1-NCOA2 或 NCOA1 融合的梭形细胞肉瘤，它们属于与先前报道的肾肉瘤相同的疾病谱。患者的年龄范围很广（20-76 岁，平均 46 岁），除 1 例外均为女性。肿瘤发生在肾脏（n=2），子宫体、阴道、阴囊和直肠旁区各 1 例。一致的形态是在漩涡状、盘旋状或实性模式中具有单形性梭形至卵圆形细胞。一些病例中可见交替细胞性、黏液样基质和微囊状改变。有丝分裂活性差异很大（<1-33/10 高倍视野）。免疫表型是非特异性的，大多数病例表达不同程度的 TLE1、WT1、cyclin D1、CD56 和 CD10。使用基于 RNA 的靶向测序的各种平台，在 5 例中反复鉴定出 MEIS1-NCOA2 融合，在 1 例肾肿瘤中发现了一种新的 MEIS1-NCOA1 融合。使用定制的 BAC 探针通过荧光原位杂交验证了基因融合。在有可用随访的 5 例患者中（5 个月至 8 年），所有患者均经历了局部复发，但无远处播散或死于疾病。我们的结果扩展了具有 MEIS1-NCOA2/1 融合的肉瘤的临床病理谱，提供了一种未分化的梭形细胞表型的证据，其免疫表型不特异，临床行为呈低度恶性。
