Zhang Yahan, Qiu Yan, Zhang Xianliang, He Xin, Chen Chen, Chen Min, Zhang Hongying
Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Front Oncol. 2023 Jan 16;12:1065071. doi: 10.3389/fonc.2022.1065071. eCollection 2022.
Among those tumors with consistent USP6 rearrangement, some arise from soft tissue and show bone metaplasia, including myositis ossificans (MO), fibro-osseous pseudotumor of digits (FOPD), soft tissue aneurysmal bone cyst (ST-ABC) and fasciitis ossificans (FO). These lesions are easily confused with malignancies because they show a rapid growth rate and brisk mitoses. Here, we aim to clarify the clinicopathologic and genetic characteristics of this entity and analyze the correlations among the different subtypes in one of the largest cohorts.
The clinicopathologic features of 73 cases of MO, FOPD, ST-ABC and FO diagnosed at West China Hospital, Sichuan University from January 2010 to December 2021 were retrospectively analyzed. Forty-three undecalcified samples were analyzed by systematic genetic studies, including fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), Sanger sequencing and next-generation-based sequencing were performed.
This series included 40 males and 33 females aged 2 to 80 years old (median: 31 years). FOPD occurred in extremal soft tissue, while lower extremities (38/58, 65.5%) were the most commonly involved lesions in the other three subgroups. Histologically, proliferative myofibroblasts/fibroblasts with varying degrees of osteoid tissue were present. Fluorescence in situ hybridization (FISH) results indicated that 22 cases (22/27, 81.5%) were positive for USP6 rearrangement, and 5 cases were negative. Among those cases with positive FISH results, 18 underwent reverse transcription-polymerase chain reaction (RT-PCR) detection that successfully detected common USP6 fusion types. Thirteen cases showed COL1A1::USP6 fusion, one showed MYH9::USP6 fusion, and 4 were negative for common fusion types. Next-generation-based sequencing technology was performed on two lesions with negative RT-PCR results and novel fusion partners SNHG3 and UBE2G1 were discovered.
Our findings revealed that COL1A1 is the most common fusion partner in this entity, unlike primary aneurysmal bone cysts and nodular fasciitis. Notably, we believed that FO may demonstrate more similar clinicopathologic and genetic manifestations with MO/FOPD and ST-ABC instead of nodular fasciitis for involving lower limbs most frequently and showing recurrent COL1A1::USP6 fusion. Additionally, this study also found two novel USP6 fusion partners, which further expanded our knowledge of this neoplastic spectrum.
在那些具有一致USP6重排的肿瘤中，有些起源于软组织并表现出骨化生，包括骨化性肌炎（MO）、指纤维骨性假瘤（FOPD）、软组织动脉瘤样骨囊肿（ST-ABC）和骨化性筋膜炎（FO）。这些病变很容易与恶性肿瘤混淆，因为它们生长速度快且有活跃的核分裂象。在此，我们旨在阐明这一实体的临床病理和基因特征，并在最大的队列之一中分析不同亚型之间的相关性。
回顾性分析2010年1月至2021年12月在四川大学华西医院诊断的73例MO、FOPD、ST-ABC和FO的临床病理特征。对43例未脱钙样本进行了系统的基因研究，包括荧光原位杂交（FISH）、逆转录聚合酶链反应（RT-PCR）、桑格测序，并进行了基于二代测序。
该系列包括40例男性和33例女性，年龄2至80岁（中位数：31岁）。FOPD发生于四肢软组织，而其他三个亚组中下肢是最常受累的部位（38/58，65.5%）。组织学上，可见不同程度类骨组织的增生性肌成纤维细胞/成纤维细胞。荧光原位杂交（FISH）结果显示，22例（22/27，81.5%）USP6重排阳性，5例阴性。在FISH结果阳性的病例中，18例进行了逆转录-聚合酶链反应（RT-PCR）检测，成功检测到常见的USP6融合类型。13例显示COL1A1::USP6融合，1例显示MYH9::USP6融合，4例常见融合类型为阴性。对2例RT-PCR结果阴性且有新融合伙伴SNHG3和UBE2G1的病变进行了基于二代测序技术检测，发现了新的融合伙伴。
我们的研究结果显示，与原发性动脉瘤样骨囊肿和结节性筋膜炎不同，COL1A1是该实体中最常见的融合伙伴。值得注意的是，我们认为FO可能在临床病理和基因表现上与MO/FOPD和ST-ABC更为相似，而不是结节性筋膜炎，因为FO最常累及下肢并显示复发性COL1A1::USP6融合。此外，本研究还发现了两个新的USP6融合伙伴，这进一步扩展了我们对这一肿瘤谱系的认识。
