儿童胸膜肺母细胞瘤13例临床病理及分子遗传学特征分析

Pleuropulmonary blastoma: a clinicopathologic and genetic analysis of 13 cases

目的探讨胸膜肺母细胞瘤(pleuropulmonary blastoma,PPB)的临床病理及基因学特征。方法回顾性分析13例PPB的临床病理资料,完善随访资料,并复习相关文献,对3例明确有甲状腺肿瘤家族史典型患儿的肿瘤组织进行全外显子测序。结果13例患儿中,Ⅰ型PPB 2例、Ⅱ型3例、Ⅲ型8例,截至随访有2例Ⅰ型患儿和1例近期就诊的Ⅲ型患儿存活,其余10例患儿均死亡。镜检:囊性区良性上皮下可见似“生发层”样密集的间叶细胞,实性区由成片异型间叶细胞组成,具有多种分化潜能。肿瘤细胞vimentin阳性,并根据不同的分化表达不同的免疫组化标记。3例有家族史的患儿均存在DICER1基因突变。结论Ⅰ型PPB预后较好,进展为Ⅱ、Ⅲ型预后差。PPB是家族性肿瘤易感综合征的一部分,DICER1基因是PPB关键致病基因,基因检测或能帮助早期发现PPB。

Purpose To investigate the clinicopathological and genetic features of pleuropulmonary blastoma(PPB).Methods The clinicopathological data were collected in thirteen cases of PPB.Follow-up was conducted and the literature was reviewed.Whole exon sequencing of formalin-fixed and paraffin-embedded(FFPE)tumor tissue was performed in 3 cases with family history remarkable for thyroid diseases.Results Thirteen patients were observed(2 cases of typeⅠ,3 typeⅡand 8 typeⅢ).All the typeⅠpatients survived,typeⅡand typeⅢpatients died except for one typeⅢpatient who was just recently diagnosed.Microscopically,cystic area consisted of condensed primitive mesenchyme beneath the cyst lining.The solid area consisted of atypia sarcomatous cells with various differentiations.Immunohistochemically,different immunohistochemical markers were expressed according to the differentiations.Vimentin was positive in all the cases.All the 3 cases with family history harbored DICER1 mutations(missense,frameshift or nonsense mutation).Conclusion Type I PPB has a better prognosis than typeⅡand typeⅢ.PPB is a part of DICER1-associated syndrome.Genetic testing may assist in early detection of PPB.