肺黏液性微乳头型腺癌7例临床病理分析

Lung mucinous micropapillary adenocarcinoma:a clinicopathological study of 7 cases

目的探讨肺黏液性微乳头型腺癌的临床病理特征。方法回顾性分析7例手术切除的黏液性微乳头型腺癌的临床病理资料、组织形态学和免疫组化结果,并应用免疫组化、ARMS法和FISH检测EGFR、KRAS、EML4-ALK、BRAF等主要驱动基因。结果 7例患者平均年龄57. 4岁,男女比为4∶3,3例有吸烟史,5例获得随访的病例中4例死亡。组织学方面,所有病例主要由微乳头构成并含有丰富的细胞内/外黏液,表现为彼此游离的黏液性微乳头和实性细胞团"漂浮"在黏液池中。肿瘤细胞呈多角形,异型性明显,有时含有黏液柱状细胞和印戒细胞。部分病例肺泡壁的结构保持完整,肺泡腔内充满黏液及肿瘤性微乳头。所有病例弥漫性表达CK7(7/7),不同程度表达TTF-1(4/7)、Napsin A(2/7)、p53(4/7)、MUC5B(4/7)、MUC5AC(3/7)和ROS1(2/7),1例表达ALK(D5F3),不表达p63、CK5/6、GATA3、CK20、CDX2和PAX8。2例有KRAS突变,1例表达ALK(D5F3)的病例经FISH证实阳性,未检测出EGFR、BRAF(V600E)和ROS1突变。结论肺黏液性微乳头型腺癌罕见,在组织和细胞学特征、免疫表型和常见驱动基因改变方面与经典的微乳头型腺癌有不同之处,该肿瘤的生物学行为具有高度侵袭性,预后较差。

To evaluate the clinicopathological characteristics of lung mucinous micropapillary adencarcinoma(ADC).Methods The clinicopathological data,histomorphology and immunophenotype of 7 cases of lung mucinous micropapillary ADC that underwent complete resection were retrospectively studied.The major driver mutations of lung ADC,including EGFR,KRAS,EML4-ALK,BRAF and ROS1 were tested by immunohistochemistry(IHC),amplification refractory mutation system(ARMS)and fluorescence in situ hybridization(FISH).Results The patients’mean age was 57.4 years and the male-to-female ratio was 4∶3.Three patients were former or current smokers.Four of the 5 patients died during the follow-up.His-tologically,all tumors predominantly consisted of discohesive mucinous micropapillary tufts and tumour cell islands floating into pools of mucin-rich matrix.The tumour cells were usually polygonal with prominent nuclear atypia,and admixed more or less columnar cells with cytoplasmic mucin and signet ring cells.In some tumors the pre-existing alveolar structures were observed,which were filled with abundant intracytoplasmic mucin and micropapillary structures.All cases(7/7)strongly expressed CK7.Some cases were positive for TTF-1(4/7),p53(4/7),MUC5B(4/7),MUC5AC(3/7),Napsin A(2/7),ROS1(2/7)and ALK(D5F3)(1/7).All tumors were negative for p63,CK5/6,GATA3,CK20,CDX2 or PAX8.Two cases harboured KRAS mutation and 1 positive for ALK(D5F3)antibody was confirmed ALK rearrangement by FISH testing.No EGFR,BRAF(V600E)or ROS1 mutation was detected in all tumours.Conclusion Compared with the common subtype,mucinous micropapillary ADC is rare and exhibits different histo-cytological characteristics,immunophenotypes and molecular genetic alterations with an aggressive behaviour and poor prognosis.