EWSR1-TFCP2 in an adolescent represents an extremely rare and aggressive form of intraosseous spindle cell rhabdomyosarcomas.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Cold Spring Harbor Molecular Case Studies Pub Date : 2022-06-29 DOI:10.1101/mcs.a006209

Agnesa Panferova, Kseniya Yu Sinichenkova, Meriam Abu Jabal, Natalia Usman, Anastasya Sharlai, Vitalii Roshchin, Dmitry Konovalov, Alexander Druy

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Abstract

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.

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一名青少年的 EWSR1-TFCP2 肿瘤是一种极为罕见的骨内纺锤形细胞横纹肌肉瘤，具有侵袭性。

世界卫生组织《软组织和骨肿瘤分类》（WHO Classification of Tumors of Soft Tissue and Bone）将横纹肌肉瘤（RMS）细分为肺泡型、胚胎型、多形性和纺锤形细胞型横纹肌肉瘤。分子基因诊断技术的进步使人们有可能在传统形态实体中发现新的横纹肌肉瘤亚群。其中一个亚群包括罕见的肿瘤，其特征是上皮样和纺锤形细胞形态，具有高度侵袭性的临床病程和明显的骨内生长倾向，并存在病理上的复发性遗传畸变--嵌合基因/转录本 EWSR1::TFCP2、FUS::TFCP2 或 MEIS1::NCOA2。自2018年起，仅有26例报告的RMS病例被归入该亚组。此类肿瘤的罕见性阻碍了解剖病理学家和分子肿瘤学家对其进行正确诊断。在此，我们描述了一例表达 EWSR1::TFCP2 融合基因的骨内纺锤细胞 RMS 临床病例，这是在我们的临床实践中首次遇到，患者是一名 16 岁的女性，出现下颌骨病变。诊断过程花费了大量时间，并涉及到 RNA 测序；这是一种高通量的分子遗传学研究方法。该肿瘤极具侵袭性，对多化疗、放疗和克唑替尼靶向治疗均表现出耐药性，最终导致死亡。

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来源期刊

Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.20

自引率

0.00%

发文量

期刊介绍： Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.