儿童骨巨细胞瘤35例临床病理学分析

Pediatric giant cell tumor of bone:a clinicopathological analysis of 35 cases

目的:探讨儿童骨巨细胞瘤(giant cell tumor of bone,GCTB)的临床病理学特征。方法:收集上海交通大学医学院附属第六人民医院2016—2023年诊断的35例儿童GCTB的资料,分析其临床病理特征及影像学特征。结果:35例儿童GCTB占本院同期GCTB患者约4.6%。男患儿11例,女患儿24例。发病年龄9~18岁(平均年龄15岁,中位年龄16岁),8例(8/35,22.9%)术后复发。其中28例(28/35,80%)主要位于长骨,余7例位于小骨和不规则骨。影像学显示肿瘤以溶骨性改变为主,3例骺板未闭合,其中1例肿瘤主体位于干骺端,未跨过骺板。儿童GCTB组织学形态与成人相同,由单核细胞和破骨细胞样巨细胞组成;7例经地诺单抗治疗,表现为巨细胞不同程度消失,间质胶原纤维组织及反应性骨增生。其中1例为儿童多骨性GCTB;3例为儿童原发性恶性GCTB,恶性成分均为骨肉瘤。35例均检测出H3F3A基因突变,其中32例为H3.3 p.G34W突变,1例为H3.3 p.G34V突变,2例为H3.3 p.G34L突变;前两者分别经免疫组织化学染色验证(H3.3 p.G34W抗体与H3.3 p.G34V抗体);后者未行免疫组织化学验证。结论:儿童GCTB女性多见,好发于长骨,尤其膝关节周围;肿瘤主体大多位于骨骺并至干骺端,骺板未闭合者可局限于干骺端内。H3F3A基因突变是诊断与鉴别诊断儿童GCTB的关键。

Objective To investigate the clinicopathological characteristics of giant cell tumor of bone(GCTB)in children.Methods A total of 35 cases of GCTB diagnosed at Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School from 2016 to 2023 were collected,and a retrospective analysis of clinicopathological features and imaging findings was conducted.Results Pediatric GCTB accounted for approximately 4.6%of total GCTB cases during the study period.There were 11 males and 24 females.The onset age ranged from 9 to 18 years(mean age 15 years,median age 16 years),with 8 cases(8/35,22.9%)experiencing postoperative recurrence.Twenty-eight cases(28/35,80%)primarily affected long bones,while 7 cases involved small or irregular bones.Imaging revealed osteolytic changes as the predominant feature,with 3 cases exhibited open physis,one of which had the tumor primarily at the diaphysis without crossing the physis.Histologically,pediatric GCTB resembled adult cases,characterized by mononuclear cells and osteoclast-like giant cells.Seven cases with denosumab treatment demonstrated degrees of giant cell disappearance,increased fibrous tissue and reactive bone proliferation in the stroma.One case was diagnosed as pediatric multicentric GCTB,and three cases as pediatric primary malignant GCTB,with malignant transformation into osteosarcoma.In all 35 cases,mutations in the H3F3A gene were identified,comprising 32 cases with H3.3 p.G34W mutations,one case with H3.3 p.G34V mutation,and 2 cases with H3.3 p.G34L mutations.Notably,the former two categories were successfully validated at the protein level through immunohistochemical staining,utilizing highly specific antibodies tailored for these mutation types:H3.3 p.G34W antibody and H3.3 p.G34V antibody.However,immunohistochemical staining was not available for the last category.Conclusions Pediatric GCTB predominantly affects females and occurs primarily in long bones,mainly around the knee joint,the majority of tumors predominantly arise in the epiphysis and extend into the metaphysis;however,in cases where the epiphyseal plates are still unclosed,the tumors may be restricted to the metaphysis.Detection of H3F3A gene mutation is crucial for the diagnosis and differential diagnosis of pediatric GCTB.