Erdheim-Chester病肺累及患者的临床表现和病理特征及基因突变

Clinical and pathological characteristics of Erdheim-Chester disease involving the lungs

目的 探讨Erdheim-Chester病（ECD）肺累及患者的临床表现、病理特征及基因突变状态.方法 回顾性分析北京协和医院2014年10月至2016年8月收治的4例ECD肺累及患者的临床资料、胸部影像学表现、病理组织形态、免疫表型（EnVision法）和BRAFV600E基因突变情况,并复习相关文献.结果 4例中男3例,女1例,年龄7~47岁,平均34.5岁.以胸闷、气短及骨痛为主要临床表现.胸部CT显示胸膜增厚或胸腔积液（4/4）、小叶间隔增宽（3/4）、支气管血管束增粗（3/4）、双肺多发性斑片状磨玻璃和实变影（4/4）及囊状影（1/4）等.多发性骨病变是主要的肺外表现,4例均有多处骨病变,累及长骨、颅骨及椎骨等,均表现为多发性骨摄取增高及骨硬化.4例均经胸部组织外科活检证实,取材部位胸膜1例,肺组织2例,前上纵隔肿物1例.病理检查见较多泡沫样组织细胞弥漫浸润,伴纤维组织增生及散在淋巴细胞和浆细胞浸润;免疫组织化学染色示CD68阳性,CD1a阴性.4例实时荧光定量PCR检测BRAFV600E基因突变,结果均为阳性.结论 该病罕见,临床表现为胸闷、气促,也可无明显的呼吸系统症状.ECD肺累及时病理可见弥漫性沿淋巴管分布的泡沫样组织细胞浸润及纤维化,需要与弥漫性间质性肺疾病及转移性肿瘤相鉴别.常出现胸膜增厚及胸腔积液,同时有多骨硬化病变,检测到BRAFV600E基因突变有助于ECD的诊断.

Objective To explore the clinical manifestations, pathological features, differential diagnosis and gene mutation status in patients with pulmonary involvement of Erdheim-Chester disease （ECD）.Methods The clinical data of 4 cases of Erdheim-Chester disease admitted to Peking Union Medical College Hospital from October 2014 to August 2016 were examined for imaging, microscopic and immunohistochemitry findings,and BRAFV600E mutation.The related literatures were reviewed.ResultsAmong the 4 cases,there were 3 males and 1 female,aging from 7 to 47 years,and the average age was 34.5 years.They complained of chest tightness, shortness of breath and bone pain.They all had multiple bone lesions, involving the long bones, skulls and vertebrae, and imaging showed increased bone uptake and bone sclerosis.CT scan showed pleural thickening or pleural effusion（4/4）, widened lobular septa（3/4）, bronchial vascular bundle thickening（3/4）, multiple patchy ground glass and solid shadows（4/4）, and cystic shadows（1/4）.Multiple bone lesions were the main extrapulmonary manifestations.All the cases had multiple bone lesions, involving the long bones, skulls and vertebrae, and showed increased bone uptake and bone sclerosis.Surgical biopsy of the thoracic tissue was performed in all 4 cases （pleural in 1 case, lung in 2, anterior mediastinal mass in 1）.Microscopically, the lesion was composed of spindle-shaped fibroblasts and foamy histiocytes enmeshed in reactive fibrous tissue.Lymphocytes and plasma cells were also found.Immunohistochemically, all the histiocytes were positive for CD68, and none of them expressed CD1a.All cases were detected by real-time quantitative PCR for BRAFV600E gene mutation.ConclusionsThe pulmonary involvement of Erdheim-Chester disease is rare, with clinical manifestations of chest tightness, shortness of breath, and some have no obvious respiratory symptoms.Pulmonary involvement in Erdheim-Chester disease has important manifestations, in which foam-like tissue cells with diffuse distribution along the lymphatic enmeshed in reactive fibrous tissue.It should be differentiated from diffuse interstitial lung diseases and metastatic tumors.The clinical features are often manifested as pleural thickening and pleural effusion, with multiple bone sclerosis lesions.BRAFV600E mutation detection is helpful for the diagnosis.