慢性过敏性肺炎引起弥漫性肺间质纤维化的病理特征

Pathologic study of diffuse pulmonary interstitial fibrosis caused by chronic hypersensitivity pneumonitis

目的观察慢性过敏性肺炎的病理形态特征，特别是其引起的肺间质纤维化的特点，并比较其与特发性肺间质纤维化的差异和鉴别。方法选择2000年10月至2008年1月间10例慢性过敏性肺炎患者活检组织及临床资料，活检肺组织全部取材，石蜡包埋、HE染色。结果10例慢性过敏性肺炎患者，男性6例、女性4例，年龄23—59岁，平均47．2岁。主要表现为慢性咳嗽，气短等，病程4个月～6年不等。7例表现为普通性间质性肺炎（UIP）样的纤维化，肺组织内斑片状纤维化，病变沿胸膜下、小叶间隔分布，同时又有细支气管周边病变。7例均有纤维母细胞灶，并可见明显的细支气管周边肺泡上皮的细支气管化生和轻度细支气管炎。3例有轻度蜂窝肺。3例为非特异性间质性肺炎（NSIP）样纤维化，表现为肺泡间隔增宽，间质纤维组织和胶原纤维增生，保留肺泡结构。伴中-重细支气管炎，肺泡间隔可见较多淋巴细胞浸润。未见蜂窝肺结构。1例可见Schaumann小体。慢性过敏性肺炎的UIP样的纤维化与特发性UIP相比，除了间质中有松散的肉芽肿和多核巨细胞以外，表现为：（1）发病年龄较轻；（2）慢性过敏性肺炎CT上病变常同时有中、上肺病变，甚至以中、上肺为主，并可见磨玻璃影和马赛克征；（3）二者病变分布不同，特发性UIP的纤维化主要分布在胸膜下和沿小叶周边分布；而慢性过敏性肺炎的UIP样的纤维化常同时累及胸膜下／小叶周边和细支气管周围（小叶中心）；（4）慢性过敏性肺炎的UIP样纤维化蜂窝肺相对较轻；（5）常伴有细支气管上皮化生。慢性过敏性肺炎的NSIP样的肺间质纤维化与特发性NSIP相比，除了间质中有松散的肉芽肿和多核巨细胞以外，二者在病理形态上很难区别。结论慢性过敏性肺炎可以引起UIP样或NSIP样的间质纤维化。按照目前过敏性肺炎的诊断标准，部分表现为NSIP样的肺间质纤维化的慢性过敏性肺炎患者，有可能被误诊为NSIP，值得注意。

Objective To study the pathologic characteristics of chronic hypersensitivity pneumonitis, especially the pattern of pulmonary interstitial fibrosis; and to compare the histologic features with those of idiopathic interstitial pneumonitis. Methods The HE-stained paraffin sections of 10 cases of chronic hypersensitivity pneumonitis encountered during the period from 2000 to 2008 were retrospectively analyzed. Results There were altogether 6 males and 4 females, with age of patients ranging from 23 to 59 years （mean = 47. 2 years）. Clinically, the patients presented with chronic cough and shortness of breath for 4 months to 6 years. Histologically, 7 cases showed usual interstitial pneumonitis （UIP）-like fibrosis. Patchy fibrosis was observed under the pleura, adjacent to interlobular septa and around bronchioles. In all of the 7 cases, foci of fibroblastic proliferation, as well as bronchiolar metaplasia of peribronchiolar alveoli and mild bronchiolitis, were noted. Three cases presented with mild honeycomb changes of lung and 3 cases showed non-specific interstitial pneumonitis （NSIP）-like fibrosis, in which the alveolar septa were expanded by fibrous tissue and collagen, with relative preservation of alveolar architecture. Bronchiolitis and lymphocytic infiltrates in alveolar septa were seen. Schaumann bodies were identified in 1 case. In general,patients with chronic hypersensitivity pneumonitis were younger than patients with idiopathic UIP. Computed tomography often showed upper and middle lobar involvement and mosaic attenuation. Compared with idiopathic UIP, the UIP-like fibrosis of chronic hypersensitivity pneumonitis often occurred not only under the pleura and adjacent to interlobular septa, but also around bronchioles and was accompanied by bronchiolar metaplasia. Conclusions Chronic hypersensitivity pneumonitis can mimic other types of lung conditions with interstitial fibrosis, especially UIP and NSIP. As a result, some cases of chronic hypersensitivity pneumonitis may be misdiagnosed as such.