Panferova Agnesa, Sinichenkova Kseniya Yu, Abu Jabal Meriam, Usman Natalia, Sharlai Anastasya, Roshchin Vitalii, Konovalov Dmitry, Druy Alexander
Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology;
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Cold Spring Harb Mol Case Stud. 2022 Jun 29;8(5). doi: 10.1101/mcs.a006209.
The WHO Classification of Tumors of Soft Tissue and Bone subdivides rhabdomyosarcomas (RMS) into alveolar, embryonal, pleomorphic, and spindle cell RMS. Advances in molecular genetic diagnostics have made it possible to identify new RMS subgroups within traditional morphological entities. One of these subgroups comprises rare tumors characterized by epithelioid and spindle cell morphology, highly aggressive clinical course with pronounced tendency to intraosseous growth, and the presence of pathognomonic recurring genetic aberrations- chimeric genes/transcripts EWSR1::TFCP2, FUS::TFCP2, or MEIS1::NCOA2. Starting from 2018, only 26 reported cases of RMS have been assigned to this subgroup. The rarity of such tumors hampers their correct diagnostics for both anatomic pathologists and molecular oncologists. Here we describe a clinical case of intraosseous spindle cell RMS expressing EWSR1::TFCP2 fusion gene, encountered for the first time in our practice, in a 16-year-old female patient presenting with mandibular lesion. The diagnostic process took considerable time and involved RNA sequencing; a high-throughput method of molecular genetic research. The tumor was extremely aggressive, showing resistance to polychemotherapy, radiation therapy, and crizotinib targeted therapy, with the fatal outcome.
世界卫生组织软组织和骨肿瘤分类将横纹肌肉瘤（RMS）细分为肺泡型、胚胎型、多形性和梭形细胞RMS。分子遗传诊断技术的进步使得在传统形态学实体中识别新的RMS亚组成为可能。其中一个亚组包括罕见肿瘤，其特征为上皮样和梭形细胞形态、具有明显骨内生长倾向的高度侵袭性临床病程以及存在特征性的复发性基因畸变——嵌合基因/转录本EWSR1::TFCP2、FUS::TFCP2或MEIS1::NCOA2。自2018年以来，仅有26例报告的RMS病例被归入该亚组。此类肿瘤的罕见性给解剖病理学家和分子肿瘤学家的正确诊断带来了阻碍。在此，我们描述了一例骨内梭形细胞RMS的临床病例，该病例表达EWSR1::TFCP2融合基因，这是我们在一名16岁下颌骨病变女性患者的诊疗过程中首次遇到的。诊断过程耗时颇长，涉及RNA测序，这是一种分子遗传研究的高通量方法。该肿瘤极具侵袭性，对多药化疗、放射治疗和克唑替尼靶向治疗均有耐药性，最终导致致命结局。
