Gruel Nadège, El Zein Sophie, Tzanis Dimitri, Nicolas Nayla, Maraval Aurélien, Fieffe Christelle, Bonvalot Sylvie, Caly Martial, Fuhrmann Laetitia, Ait Rais Khadija, Jovelin Sylvie, Bonnet Clément, Pierron Gaëlle, Watson Sarah
INSERM U830, Équipe Labellisée Ligue Nationale Contre le Cancer, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Center, Paris, France.
Department of Translationnal Research, Institut Curie Research Center, Paris, France.
Genes Chromosomes Cancer. 2023 Jun;62(6):367-372. doi: 10.1002/gcc.23130. Epub 2023 Feb 21.
Adipocytic tumors are the most common mesenchymal tumors in soft tissues. Among them, a diagnostic challenge relies in the distinction between lipoma and atypical lipomatous tumor (ALT)/well differentiated liposarcoma (WDLPS), as both entities are often undistinguishable not only from a radiological point of view, but also at the microscopic level and particularly when dealing with small tumor specimen. Thus, detection of recurrent MDM2 amplifications may be the only criteria to discriminate malignant tumors from lipomas. In this study, we report the case of a patient diagnosed with a well differentiated, adipocytic tumor located in the inferior limb and lacking MDM2 amplification, whose diagnosis was reclassified for ALT/WDLPS after identification of an alternative MDM4 amplification by comparative genomic hybridization profiling, whole exome sequencing and fluorescence in situ hybridization (FISH). Screening of a cohort of 37 large, deep-seated, well-differentiated adipocytic tumors previously classified as lipomas using RT-qPCR and FISH failed to detect other cases of MDM4-amplified ALT/WDLPS. This report shows that MDM4 amplification is an exceptional molecular event alternative to MDM2 amplification in ALT/WDLPS. This alteration should be considered and looked for in suspicious adipocytic tumors to optimize their surgical management.
脂肪细胞性肿瘤是软组织中最常见的间叶组织肿瘤。其中，诊断难题在于区分脂肪瘤和非典型脂肪瘤性肿瘤（ALT）/高分化脂肪肉瘤（WDLPS），因为这两种实体不仅在放射学角度常常难以区分，在显微镜下也是如此，尤其是处理小肿瘤标本时。因此，检测MDM2基因的反复扩增可能是区分恶性肿瘤与脂肪瘤的唯一标准。在本研究中，我们报告了一例患者，其被诊断为位于下肢的高分化脂肪细胞性肿瘤且缺乏MDM2基因扩增，在通过比较基因组杂交分析、全外显子测序和荧光原位杂交（FISH）鉴定出另一种MDM4基因扩增后，其诊断被重新分类为ALT/WDLPS。使用逆转录定量聚合酶链反应（RT-qPCR）和FISH对一组先前被归类为脂肪瘤的37例大型、深部、高分化脂肪细胞性肿瘤进行筛查，未检测到其他MDM4基因扩增的ALT/WDLPS病例。本报告表明，MDM4基因扩增是ALT/WDLPS中一种罕见的替代MDM2基因扩增的分子事件。在可疑的脂肪细胞性肿瘤中应考虑并寻找这种改变，以优化其手术治疗。
