肺移植治疗终末期肺疾病合并神经内分泌癌的临床病理分析

Clinicopathological analysis of lung transplantation in the treatment of end-stage lung disease complicated with neuroendocrine carcinoma

目的探讨肺移植治疗终末期肺疾病合并神经内分泌癌的临床病理特征。方法中日友好医院2017年4月至2021年12月间确诊终末期肺疾病行肺移植手术且经HE染色及免疫组织化学染色确诊神经内分泌癌5例,对其临床及随访资料、组织学特征和免疫表型进行回顾性分析。结果5例受者男女比例为4∶1;平均年龄64岁,范围在56~73岁。其中,3例为特发性肺纤维化合并小细胞癌(包括1例复合型小细胞癌),1例为支气管扩张合并类癌,1例为结缔组织病相关性肺纤维化合并类癌。HE染色结果显示,合并类癌的支气管扩张受者移植病肺中可观察到从神经内分泌细胞增生到类癌的形态学谱系变化。免疫组织化学染色结果显示,小细胞癌及类癌神经内分泌标记物CgA、Syn、CD56和上皮标记物AE1/AE3和TTF-1均呈阳性表达。2例小细胞癌和1例复合型小细胞癌Ki-67指数为80%,2例类癌Ki-67指数≤1%。截至完稿,5例中,3例存活,余2例分别于移植术后33 d和196 d死于全耐药肺炎克雷伯菌、纹带棒杆菌及鲍曼不动杆菌感染并发重症肺炎和气道狭窄。结论移植肺合并神经内分泌癌多见于老年男性,临床终末期肺疾病以特发性肺纤维化居多;神经内分泌癌类型以小细胞癌为主,均表达特异性神经内分泌标记物和TTF-1,有助于神经内分泌癌的诊断;术后感染是影响预后的重要因素。

Objective To explore the clinicopathological features of end-stage lung disease complicated with neuroendocrine carcinoma after lung transplantation(LT).Methods From April 2017 to December 2021,5 cases of neuroendocrine cancer were diagnosed as end-stage lung disease by hematoxylin-eosin(HE)and immunohistochemical stain.Clinical follow-up data,histological characteristics and immunophenotyping were analyzed retrospectively.Results The ratio of male-to-female in five recipients was 4:1 and the average age 64(56-73)years.Three cases were idiopathic pulmonary fibrosis concomitant with small cell carcinoma(including 1 case of combined small cell carcinoma),bronchiectasis plus carcinoid carcinoma(n=1)and connective tissue disease-related fibrosis plus carcinoid carcinoma(n=1).HE stain indicated that morphological spectrum changed from neuroendocrine cell hyperplasia to carcinoid in transplanted lung of bronchiectasis.Immunohistochemical stain indicated that neuroendocrine markers CgA,Syn,CD56 and epithelial markers AE1/AE3,TTF-1 were positive for small cell carcinoma and carcinoid.Ki-67 index of small cell carcinoma(n=2)and combined small cell carcinoma(n=1)was 80%and Ki-67 index of carcinoid(n=2)was≤1%.Until the last follow-up,3/5 patients survived and the remaining 2 died of Klebsiella pneumoniae,Corynebacterium striatus and Acinetobacter baumannii infections at Days 33 and 196 post-transplantation.Conclusions Neuroendocrine carcinoma in transplanted lung is more common in elderly males and end-stage lung disease is mostly idiopathic pulmonary fibrosis.Small cell carcinoma is a major type of neuroendocrine carcinoma.Specific neuroendocrine markers and TTF-1 aid in a definite diagnosis of neuroendocrine carcinoma.Postoperative infection is an important prognostic factor.