脂肪肉瘤的临床病理和基因改变的研究进展

doi:10.11904/j.issn.1002-3070.2023.01.015

摘要/Abstract

摘要： 脂肪肉瘤是一种起源于原始间叶细胞的恶性肿瘤,具有显著的组织多样性,由分化和异型程度不同的细胞组成。脂肪肉瘤主要分为四个亚型:以MDM2-HMGA2为关键基因的非典型脂肪源性肿瘤(Atypical lipogenic tumors,ALT)/高分化脂肪肉瘤(Well-differentiated liposarcoma,WDLPS)和去分化脂肪肉瘤(Dedifferentiated liposarcoma,DDLPS),以FUS-CHOP基因融合为主要发生机制的黏液性脂肪肉瘤(Myxoid liposarcoma,MLPS)/圆形细胞脂肪肉瘤(Round cell liposarcoma,RCLPS),以及发病机制复杂且多变的多形性脂肪肉瘤(Pleomorphic liposarcoma,PLPS)。ALT/WDLPS的主要病理变化为多形性成熟脂肪细胞增殖,DDLPS为高级别肉瘤,MLPS/RCLPS主要由非脂质间质细胞组成,而PLPS以异型多空泡脂肪母细胞为特点。这四个亚型所包含的肿瘤基因及临床病理学改变,导致了这四种亚型具有不同的临床行为、治疗敏感性和生物学特性。本文将对这四个亚型的病理及基因改变进行总结和探讨。

关键词: 脂肪肉瘤, 病理学, 免疫组织化学

Abstract: Liposarcoma is a malignant tumor originating from primitive mesenchymal cells,which has remarkable tissue diversity and consists of cells with different degrees of differentiation and atypia.Liposarcoma is mainly divided into four subtypes:atypical lipogenic tumors(ALT)with MDM2-HMGA2 as the key gene/well-differentiated liposarcoma(WDLPS)and dedifferentiated liposarcoma(DDLPS),myxoid liposarcoma(MLPS)/round cell liposarcoma(RCLPS)with FUS-CHOP gene fusion as the main mechanism,and pleomorphic liposarcoma(PLPS)with complex and variable pathogenesis.The main pathological changes of ALT/WDLPS are the proliferation of pleomorphic mature adipocytes,DDLPS is high-grade sarcoma,MLPS/RCLPS is mainly composed of non-lipid stromal cells,and PLPS is characterized by atypical multivacuolar adipocytes.The tumor gene and clinicopathological changes contained in these four subtypes lead to the different clinical behaviors,treatment sensitivity and biological characteristics of these four subtypes.This paper summarizes and discusses the pathological and genetic changes of these four subtypes.

Key words: Liposarcoma, Pathology, Immunohistochemistry

中图分类号:

R738.6

李赛阳, 包俊杰, 曲国蕃. 脂肪肉瘤的临床病理和基因改变的研究进展[J]. 实用肿瘤学杂志, 2023, 37(1): 83-86.

LI Saiyang, BAO Junjie, QU Guofan. Research progress on clinicopathological and genetic alterations of liposarcoma[J]. Journal of Practical Oncology, 2023, 37(1): 83-86.

参考文献

1 Lee ATJ,Thway K,Huang PH,et al.Clinical and molecular spectrum of liposarcoma[J].J Clin Oncol,2018,36(2):151-159.
2 Ray-coquard I,Serre D,Reichardt P,et al.Options for treating different soft tissue sarcoma subtypes[J].Future Oncol,2018,14(10):25-49.
3 Thway K.Well-differentiated liposarcoma and dedifferentiated liposarcoma:an updated review[J].Semin Diagn Pathol,2019,36(2):112-121.
4 Mashima E,Sawada Y,Nakamura M.Recent advancement in atypical lipomatous tumor research[J].Int J Mol Sci,2021,22(3):994.
5 Wang GY,Lucas DR.Dedifferentiated liposarcoma with myofibroblastic differentiation[J].Arch Pathol Lab Med,2018,142(10):1159-1163.
6 Kilpatrick SE.Dedifferentiated liposarcoma:a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification[J].Adv Anat Pathol,2021,28(6):426-438.
7 Baranov E,Black MA,Fletcher CDM,et al.Nuclear expression of DDIT3 distinguishes high-grade myxoid liposarcoma from other round cell sarcomas[J].Mod Pathol,2021,34(7):1367-1372.
8 Mujtaba B,Wang F,Taher A,et al.Myxoid liposarcoma with skeletal metastases:pathophysiology and imaging characteristics[J].Curr Probl Diagn Radiol,2021,50(1):66-73.
9 Abaricia S,Hirbe AC.Diagnosis and treatment of myxoid liposarcomas:Histology matters[J].Curr Treat Options Oncol,2018,19(12):64.
10 Tfayli Y,Baydoun A,Naja AS,et al.Management of myxoid liposarcoma of the extremity[J].Oncol Lett,2021,22(2):596.
11 Nautiyal H,Egiz A,Farajzadeh Asl S,et al.Epithelioid variant of pleomorphic liposarcoma:a rare challenging diagnosis causing severe medial thigh pain[J].Cureus,2021,13(11):e19531.
12 Gjorgova Gjeorgjievski S,Thway K,Dermawan JK,et al.Pleomorphic liposarcoma:a series of 120 cases with emphasis on morphologic variants[J].Am J Surg Pathol,2022,46(12):1700-1705.
13 Anderson WJ,JO VY.Pleomorphic liposarcoma:updates and current differential diagnosis[J].Semin Diagn Pathol,2019,36(2):122-128.
14 Sciot R.MDM2 amplified sarcomas:a literature review[J].Diagnostics(Basel),2021,11(3):496.
15 Yang L,Chen S,Luo P,et al.Liposarcoma:advances in cellular and molecular genetics alterations and corresponding clinical treatment[J].J Cancer,2020,11(1):100-107.
16 Kuusk A,Boyd H,Chen H,et al.Small-molecule modulation of p53 protein-protein interactions[J].Biol Chem,2020,401(8):921-931.
17 Serra S,Chetty R.p16[J].J Clin Pathol,2018,71(10):853-858.
18 Lu J,Wood D,Ingley E,et al.Update on genomic and molecular landscapes of well-differentiated liposarcoma and dedifferentiated liposarcoma[J].Mol Biol Rep,2021,48(4):3637-3647.
19 Wu H,Li X,Shen C.Peroxisome proliferator-activated receptor gamma in white and brown adipocyte regulation and differentiation[J].Physiol Res,2020,69(5):759-773.
20 Thway K,Fisher C.Undifferentiated and dedifferentiated soft tissue neoplasms:immunohistochemical surrogates for differential diagnosis[J].Semin Diagn Pathol,2021,38(6):170-186.
21 Kanojia D,Nagata Y,Garg M,et al.Genomic landscape of liposarcoma[J].Oncotarget,2015,6(40):42429-42444.
22 Owen I,Yee D,Wyne H,et al.The oncogenic transcription factor FUS-CHOP can undergo nuclear liquid-liquid phase separation[J].J Cell Sci,2021,134(17):jcs258578.
23 Scapa JV,Cloutier JM,Raghavan SS,et al.DDIT3 immunohistochemistry is a useful tool for the diagnosis of myxoid liposarcoma[J].Am J Surg Pathol,2021,45(2):230-239.
24 Demetri GD,Antonescu CR,Bjerkehagen B,et al.Diagnosis and management of tropomyosin receptor kinase(TRK)fusion sarcomas:expert recommendations from the World Sarcoma Network[J].Ann Oncol,2020,31(11):1506-1517.
25 Berthold R,Isfort I,Erkut C,et al.Fusion protein-driven IGF-IR/PI3K/Akt signals deregulate Hippo pathway promoting oncogenic cooperation of YAP1 and FUS-DDIT3 in myxoid liposarcoma[J].Oncogenesis,2022,11(1):20.
26 Compton ML,AL-rohil RN.The utility of perilipin in liposarcomas:PLIN1 differentiates round cell liposarcoma from other round cell sarcomas[J].Appl Immunohistochem Mol Morphol,2021,29(2):152-157.
27 Pollack SM.The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients[J].Expert Rev Vaccines,2018,17(2):107-114.
28 Creytens D.What′s new in adipocytic neoplasia?[J].Virchows Arch,2020,476(1):29-39.
29 Creytens D,Folpe AL,Koelsche C,et al.Myxoid pleomorphic liposarcoma-a clinicopathologic,immunohistochemical,molecular genetic and epigenetic study of 12 cases,suggesting a possible relationship with conventional pleomorphic liposarcoma[J].Mod Pathol,2021,34(11):2043-2049.
30 Peng R,Li N,Lan T,et al.Liposarcoma in children and young adults:a clinicopathologic and molecular study of 23 cases in one of the largest institutions of China[J].Virchows Arch,2021,479(3):537-549.
31 Tiemeier GL,Brown JM,Pratap SE,et al.Pleomorphic liposarcoma of bone:a rare primary malignant bone tumour[J].Clin Sarcoma Res,2018,8:2.

[1]	赵宝山, 梁冠盈, 许圣洁, 乔慧, 陈洪霞, 马莹, 鞠学萍, 王麟. PELP1表达与胃癌演进及预后相关性分析[J]. 实用肿瘤学杂志, 2022, 36(1): 31-36.
[2]	王丽娜, 王乐, 靳红, 李奇, 成海燕. UBQLN1在宫颈癌中的表达及其对预后的影响[J]. 实用肿瘤学杂志, 2021, 35(6): 506-510.
[3]	王哲, 祝率, 刘欢, 付蔷, 胡腾龙. SRPX2和Rab31在口腔鳞癌组织中的表达、相关性及临床意义[J]. 实用肿瘤学杂志, 2021, 35(5): 414-419.
[4]	邢志超综述, 麦威审校. 脂肪肉瘤潜在作用靶点的研究进展[J]. 实用肿瘤学杂志, 2019, 33(1): 82-86.
[5]	何煦, 叶尚勉, 董丹丹, 李科. HLA-G在乳腺癌中的表达及意义[J]. 实用肿瘤学杂志, 2018, 32(5): 410-414.
[6]	王佳娜, 沈建军, 张艳红, 王佳天, 李文秀, 潘军英. Ki-67及PTEN在口腔腺样囊性癌中的表达及临床意义[J]. 实用肿瘤学杂志, 2017, 31(6): 489-493.
[7]	石庆宇，李连财，麦威，包俊杰，宋春雨，曲国蕃. SIRT4基因表达与骨肉瘤预后因素相关性研究[J]. 实用肿瘤学杂志, 2016, 30(6): 502-506.
[8]	毛高才，朱其聪，沈宏峰，涂瑞沙，闫庆国. 膀胱与前列腺交界处多向分化癌3例临床病理分析[J]. 实用肿瘤学杂志, 2016, 30(6): 538-542.
[9]	徐俊, 张恩勇, 罗天航, 薛绪潮, 崔航天, 方国恩. 早期胃混合型印戒细胞癌的临床病理因素分析[J]. 实用肿瘤学杂志, 2016, 30(5): 414-419.
[10]	孙燕双,纪军生. 鼻腔原发性移行细胞癌一例并文献复习[J]. 实用肿瘤学杂志, 2015, 29(2): 133-135.
[11]	杨利利, 艾秀清, 贺春钰, 朱相露, 木妮热·木沙江. 621例乳腺浸润性导管癌患者分子分型与临床病理学特征的关系[J]. 实用肿瘤学杂志, 2015, 29(1): 34-38.
[12]	王志超,戴洪双,刘文龙,李效忠,乔忠杰. 平阳霉素对阴茎癌组织c-myc及Ras-P21蛋白表达影响的研究[J]. 实用肿瘤学杂志, 2014, 28(5): 406-409.
[13]	韩鸿彬,韩保卫,李朝辉,董帅军,刘帅锋. 胃食管结合部癌Her-2基因扩增及蛋白表达与临床病理关系[J]. 实用肿瘤学杂志, 2014, 28(5): 410-414.
[14]	朱涛,刘涛,方登攀. 腹膜后巨大脂肪肉瘤1例并文献复习[J]. 实用肿瘤学杂志, 2014, 28(5): 439-441.
[15]	王英炜王宏达朱宏. CK19, HBME-1和MIB-1在甲状腺透明变梁状肿瘤与甲状腺乳头状癌中的表达情况以及鉴别诊断价值[J]. 实用肿瘤学杂志, 2014, 28(4): 326-330.