Pižem Jože, Šekoranja Daja, Zupan Andrej, Boštjančič Emanuela, Matjašič Alenka, Mavčič Blaž, Contreras Juan A, Gazič Barbara, Martinčič David, Snoj Žiga, Limpel Novak Katarina A, Salapura Vladka
Institute of Pathology, Faculty of Medicine.
Faculty of Medicine, University of Ljubljana.
Am J Surg Pathol. 2020 Dec;44(12):1623-1634. doi: 10.1097/PAS.0000000000001584.
A simple bone cyst (SBC) is a benign bone lesion of unknown etiology. It can be differentiated from an aneurysmal bone cyst (ABC) by radiologic and histopathologic features, as well as by the absence of fusions of the USP6 gene characteristic of an ABC. In an attempt to differentiate between ABC and SBC in a recurrent bone cyst, we performed targeted RNA sequencing and found an EWSR1-NFATC2 fusion and no fusion of the USP6 gene. We subsequently analyzed additional 10 cysts, consistent with SBCs after radiologic-pathologic correlation, for the presence of an NFATC2 gene fusion, by targeted RNA sequencing, reverse-transcription polymerase chain reaction (RT-PCR) and Sanger sequencing, and fluorescent in situ hybridization. Targeted RNA sequencing showed a FUS-NFATC2 fusion in 4 of 11 SBCs and an EWSR1-NFATC2 fusion in 2 of 11 SBCs. No fusion was identified in 3 SBCs and the analysis was not successful in 2 SBCs because of the low quantity or poor quality of isolated RNA. All the 6 fusions detected by targeted RNA sequencing were confirmed by RT-PCR and Sanger sequencing, and 5 of the 6 fusions by fluorescent in situ hybridization. An additional FUS-NFATC2 fusion was identified by RT-PCR, Sanger sequencing, and fluorescent in situ hybridization in 1 of the 3 cases negative for fusions by targeted RNA sequencing. At least a large subset of SBCs represents cystic neoplasms characterized by FUS-NFATC2 or EWSR1-NFATC2 fusions, which also define a group of distinct, rare "Ewing-like" sarcomas that predominantly arise in long bones. Our results provide additional evidence of the existence of benign lesions with FUS-NFATC2 or EWSR1-NFATC2 fusions. Although they can recur locally in a nondestructive manner, their clinical course and possible relation to sarcoma with EWSR1-NFATC2 or FUS-NFATC2 fusion remains to be elucidated.
单纯性骨囊肿（SBC）是一种病因不明的良性骨病变。它可通过放射学和组织病理学特征，以及缺乏动脉瘤样骨囊肿（ABC）特有的USP6基因融合来与动脉瘤样骨囊肿（ABC）相鉴别。为了在复发性骨囊肿中区分ABC和SBC，我们进行了靶向RNA测序，发现了EWSR1-NFATC2融合，且未发现USP6基因融合。随后，我们通过靶向RNA测序、逆转录聚合酶链反应（RT-PCR）、桑格测序和荧光原位杂交，分析了另外10个经放射学-病理学对照后符合SBC的囊肿，以检测NFATC2基因融合的存在。靶向RNA测序显示，11个SBC中有4个存在FUS-NFATC2融合，11个中有2个存在EWSR1-NFATC2融合。3个SBC未发现融合，2个SBC因分离的RNA量少或质量差而分析未成功。靶向RNA测序检测到的所有6种融合均经RT-PCR和桑格测序证实，6种融合中有5种经荧光原位杂交证实。在靶向RNA测序未发现融合的3例病例中，有1例通过RT-PCR、桑格测序和荧光原位杂交鉴定出另外一种FUS-NFATC2融合。至少很大一部分SBC代表以FUS-NFATC2或EWSR1-NFATC2融合为特征的囊性肿瘤，这也定义了一组主要发生在长骨的独特、罕见的“尤因样”肉瘤。我们的结果为存在具有FUS-NFATC2或EWSR1-NFATC2融合的良性病变提供了更多证据。尽管它们可局部非破坏性复发，但其临床病程以及与具有EWSR1-NFATC2或FUS-NFATC2融合的肉瘤的可能关系仍有待阐明。
