Zhang Bohui, Li Hong, Cao Zhixing, Cao Huihui
Department of Pathology, Zhuhai People's Hospital (The Affiliated Hospital of Beijng Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China.
Department of Pathology, Zhuhai People's Hospital (The Affiliated Hospital of Beijng Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China.
Pathol Res Pract. 2025 Aug;272:156086. doi: 10.1016/j.prp.2025.156086. Epub 2025 Jun 16.
Dedifferentiated liposarcoma (DDLPS) arises from atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) through progression into non-lipogenic sarcomas of varying histological grades, driven by amplification of the chromosome 12q13-15 region containing MDM2, CDK4, DDIT3, STAT6, GLI1, HMGA2, etc. DDLPS demonstrates marked morphological heterogeneity in its dedifferentiated components. We describe two DDLPS cases featuring a prominent arborizing vascular network, myxoid stroma, and STAT6 nuclear expression-features that complicate differentiation from solitary fibrous tumors (SFT), myxoid liposarcoma (MLPS), myxofibrosarcoma (MFS), GLI1-altered tumors, low-grade fibromyxoid sarcoma (LGFMS), soft tissue angiofibroma (STA), etc. Immunohistochemistry (IHC) confirmed STAT6 overexpression, while fluorescence in situ hybridization (FISH) revealed co-amplification of MDM2 and DDIT3. STAT6 amplification in DDLPS leads to detectable protein expression by IHC. DDIT3 amplification in select WDLPS/DDLPS cases correlates with such unique MLPS-like morphology. These observations imply that analogous mechanisms may involve other genes within the 12q13-15 region, underscoring the genomic and phenotypic heterogeneity of DDLPS. Tumor diagnosis requires integrating morphological assessment, immunohistochemistry, molecular testing, clinical context, and imaging findings rather than relying on isolated genetic or immunohistochemical markers. This represents the first reported instance of DDLPS with MLPS-like morphology accompanied by MDM2 and DDIT3 co-amplification and concurrent STAT6 nuclear expression.
去分化脂肪肉瘤（DDLPS）由非典型脂肪瘤性肿瘤/高分化脂肪肉瘤（ALT/WDLPS）进展而来，形成不同组织学分级的非脂肪生成性肉瘤，其驱动因素是12号染色体q13 - 15区域的扩增，该区域包含MDM2、CDK4、DDIT3、STAT6、GLI1、HMGA2等基因。DDLPS在其去分化成分中表现出明显的形态学异质性。我们描述了两例DDLPS病例，其具有显著的树枝状血管网络、黏液样间质和STAT6核表达，这些特征使得与孤立性纤维瘤（SFT）、黏液样脂肪肉瘤（MLPS）、黏液纤维肉瘤（MFS）、GLI1改变的肿瘤、低级别纤维黏液样肉瘤（LGFMS）、软组织血管纤维瘤（STA）等的鉴别变得复杂。免疫组织化学（IHC）证实了STAT6的过表达，而荧光原位杂交（FISH）显示MDM2和DDIT3的共扩增。DDLPS中STAT6的扩增导致通过IHC可检测到蛋白表达。在某些WDLPS/DDLPS病例中，DDIT3的扩增与这种独特的MLPS样形态相关。这些观察结果表明，类似的机制可能涉及12q13 - 15区域内的其他基因，强调了DDLPS的基因组和表型异质性。肿瘤诊断需要综合形态学评估、免疫组织化学、分子检测、临床背景和影像学检查结果，而不是依赖单一的基因或免疫组织化学标志物。这是首次报道具有MLPS样形态、伴有MDM2和DDIT3共扩增以及STAT6核表达同时出现的DDLPS病例。
