肺胎儿型腺癌临床病理特征分析

Clinicopathologic features and genetic differences between high-grade and low-grade fetal adenocarcinomas of the lung

目的探讨低级别肺胎儿型腺癌(L-FLAC)和高级别肺胎儿型腺癌(H-FLAC)临床病理特征、诊断及分子遗传学特点异同点。方法回顾性分析华北理工大学附属医院病理科诊断5例FLAC的临床资料、组织学特点、免疫表型、分子特点、随访及预后情况,并复习相关文献。结果3例L-FLAC平均发病年龄37.7岁,与性别和吸烟史无关,常为早期病变(Ⅰ~Ⅱ期);2例H-FLAC均为老年吸烟男性,确诊时多晚期。镜下L-FLAC细胞核轻度异型,伴核上或核下空泡,局灶见桑葚样小体,核分裂象少见。H-FLAC细胞核异型显著伴坏死,核分裂象易见,可与其他类型腺癌混合存在。免疫表型:β-catenin在L-FLAC中呈胞核/质阳性,H-FLAC则呈胞膜阳性;p53在L-FLAC中呈低水平表达,H-FLAC为突变型表达模式;L-FLAC还可灶状表达神经内分泌标记物和SALL-4;Ki-67增殖指数为20%~70%。5例FLAC均行EGFR、KRAS及BRAF基因突变检测,结果为阴性。5例均予手术治疗,随访5.3~43.8个月,无复发及转移。结论FLAC属极为罕见的肺部恶性肿瘤,除了形态学及免疫表型差异外,L-FLAC和H-FLAC在分子遗传学特征方面尚有区别,因此更倾向视H-FLAC为普通型肺腺癌的亚型,而非从属于肺胎儿型腺癌。

Objective To investigate the clinicopathologic,immunohistochemical(IHC),and mutational differences between the low-grade fetal lung adenocarcinoma(L-FLAC)and high-grade fetal adenocarcinoma(H-FLAC).MethodsThe clinical data,histological features,immunophenotype,and genetic alteration were retrospectively reviewed and compared between L-FLAC and H-FLAC.Results Patients with H-FLAC were elderly male smokers at advanced TNM stages,whereas most patients with L-FLAC tended to be much younger and at an early TNM stage.Morphologically,L-FLACs had a pure pattern with complex glandular architecture composed of cells with subnuclear and supranuclear vacuoles,mimicking a developing fetal lung.In contrast,H-FLACs contained both fetal lung-like(FLL)and conventional lung adenocarcinoma(CLA)components.With regard to IHC markers,β-catenin exhibited a nuclear/cytoplasmic staining pattern in L-FLACs but a membranous staining pattern in H-FLACs.Furthermore,p53 was expressed diffusely and strongly in H-FLACs,whereas in L-FLACs,p53 staining was completely absent.All cases showed no mutation of EGFR,KRAS and BRAF.Conclusion The morphologic,IHC,and genetic features of HG-FLAC indicate that it is a variant of conventional lung adenocarcinoma rather than a subset of FLAC.