梭形细胞/硬化性横纹肌肉瘤20例临床病理学观察

目的:探讨梭形细胞/硬化性横纹肌肉瘤(spindle cell/sclerosing rhabdomyosarcoma,SRMS)的临床病理学特征、免疫表型,及MyoD1表达与基因突变的关系。方法:收集2009至2019年20例空军军医大学(第四军医大学)西京医院SRMS病例资料和切片。对肿瘤切除标本进行组织学形态和免疫组织化学EnVision染色,对12例进行MYOD1基因Sanger法测序分析。结果:20例包括儿童12例和成人8例,其中男性11例,女性9例,年龄8个月至85岁,平均22岁。患者临床主要表现为逐渐增大的无痛性肿块。发生于头颈部7例,腹盆腔7例(腹腔4例、盆腔2例、左侧胸腹腔1例),上肢5例(左肩部2例、右腋下1例、右肱骨1例、左前臂1例),背部1例。肿瘤直径2.5~20.0 cm,平均6.2 cm。病理组织学观察,肿瘤主要由梭形细胞组成,呈束状排列,其中7例至少部分区域呈鱼骨样或人字形的束状排列,似成人型纤维肉瘤;4例可见不同程度明显的间质硬化,2例局部可见血管外皮细胞瘤样结构,4例出现疏松黏液样区域,9例可见不同程度的坏死灶。有3例在梭形细胞之间有少量的梭形或多角形的横纹肌母细胞。在该组病例中,16例为纯梭形细胞,2例为纯硬化性,2例为梭形细胞/硬化性混合性横纹肌肉瘤。免疫组织化学显示,梭形细胞均为结蛋白阳性,以及Myogenin和/或MyoD1不同程度阳性;而其他标志物,如广谱细胞角蛋白、间变性淋巴瘤激酶1、CD34、上皮细胞膜抗原、HMB45、H-cald、平滑肌肌动蛋白和S-100蛋白均阴性。12例测序病例中,有4例(4/12)检测到MYOD1基因p.L122R位点突变。有效随访12例,时间1~51个月,3例因多发转移死亡,3例复发,2例带瘤生存。结论:SRMS是少见类型的横纹肌肉瘤,好发于头颈部,多见于儿童,成人较少见。有MYOD1基因突变的SRMS通常有弥漫的MyoD1核阳性,与更具有侵袭性的生物学行为有关。

Spindle cell/sclerosing rhabdomyosarcoma:a clinicopathological study of 20 cases

Objective To study the clinicopathological features and immunophenotype of spindle cell/sclerosing rhabdomyosarcoma(SRMS)in adults and children,as well as its correlation with the expression and gene-mutations of MYOD1.Methods Twenty cases of SRMS were collected at Xijing Hospital,Fourth Military Medical University from 2009 to 2019.These cases were evaluated for clinical,pathological,and immunohistochemical features.MYOD1 gene sequencing was performed on 12 cases with available tissue and sufficient DNA quantity using Sanger sequencing.Results The 20 patients included 12 children and 8 adults,11 males and 9 females,with an age range of 8 months to 85 years(mean 22 years).Most of them presented with a painless,progressively enlarged solid mass.The tumors occurred in head and neck(7 cases),abdominal and pelvic cavity(7 cases,including 4 in abdominal cavity,2 in pelvic cavity,1 in abdominal and left thoracic cavity),upper limb(5 cases,including 2 in left shoulder,1 in right armpit,1 in right humerus,and 1 in left forearm),and the back(1 case).The diameter of these tumors ranged from 2.5 to 20 cm,with a mean of 6.2 cm.Histologically,all of the tumors were mainly composed of spindle cells arranged in fascicles,and in 7 cases,at least in part,arranged in herringbone pattern,resembling adult fibrosarcoma.Foci reminiscent of interstitial sclerosing were presented in 4 cases,pseudovascular structures in 2 cases,loosely myxoid stroma in 4 cases,and varying degree of necrosis in 9 cases.A various number of spindled or polygonal rhabdomyoblasts were observed between spindle cells in 3 cases.Among them,16 cases showed spindle cell morphology,2 cases showed scleroisng morphology,and 2 cases showed a hybrid phenotype of spindle,sclerosing and primitive undifferentiated areas.Immunohistochemically,the tumor cells were positive for desmin,Myogenin and/or MyoD1,but negative for CKpan,ALK1,CD34,EMA,HMB45,SMA,H-cald and S-100.Four cases(4/12)harbored a homozygous or heterozygous MYOD1(p.L122R)mutation.MYOD1-mutant SRMS usually had diffuse and strong nuclear MyoD1 positivity.Follow-up was available in 12 cases,ranged from 1 to 51 months.At the end of follow-up period,3 patients died of the disease,3 patients developed local recurrences,2 patients survived with disease.Conclusions SRMS is a rare type of rhabdomyosarcoma,and more commonly occurs in the head and neck of children than adults.MYOD1-mutant SRMS usually had diffuse and strong nuclear MyoD1 positivity,frequently associated with a more aggressive behavior.