外科肺活检病理诊断过敏性肺炎47例临床病理学分析

Hypersensitivity pneumonia diagnosed by excisional lung biopsy:a clinicopathological features of 47 cases

目的分析外科肺活检病理诊断过敏性肺炎(hypersensitivity pneumonia,HP)病例的临床病理特征及免疫组织化学特点,提高对HP的诊断水平。方法收集中国医学科学院北京协和医学院北京协和医院2000年1月至2020年6月近20年外科肺活检病理诊断HP病例47例的临床病理资料,通过光镜及免疫组织化学染色分析其临床病理及免疫组织化学CD3、CD4、CD8、CD20等表达情况。结果47例HP病例,年龄15~68岁,男女比例22∶25,症状主要为气短和咳嗽,32例有过敏原接触史。大部分患者出现肺限制性通气功能障碍和弥散功能障碍。85.3%(29/34)患者肺泡灌洗液中淋巴细胞比例增高,31.3%(10/32)患者CD4^(+)/CD8^(+)T淋巴细胞≤0.8。镜下表现上,59.6%(28/47)的病例出现小灶性肉芽肿/间质内多核巨细胞,40.4%(19/47)仅见间质内多核巨细胞。93.6%(44/47)的病例可见细支气管上皮化生,70.2%(33/47)的病例可见局部富细胞性炎性病变。44例(93.6%)伴纤维化,表现为寻常型间质性肺炎(UIP)样纤维化(47.7%,21例)、非特异性间质性肺炎(NSIP)样纤维化(29.5%,13例)、单纯细支气管中心性纤维化(6.8%,3例)和混合性纤维化(15.9%,7例)。免疫组织化学结果显示55.8%(24/43)的病例组织中CD4^(+)T淋巴细胞占比<CD8^(+)T淋巴细胞占比,14.0%(6/43)的病例两者占比大致相等。32例患者有随访资料,均存活,7例病情好转,12例病情平稳,13例加重。结论外科肺活检病理诊断HP的病例主要为慢性HP病例,临床特点以病程较长、出现限制性通气障碍和弥散功能障碍伴肺泡灌洗液中淋巴细胞比例增高为主,近1/3患者无明确过敏原接触史。镜下纤维化程度较重,纤维化类型多样,以UIP样和/或NSIP样纤维化为主,免疫组织化学半数以上病例肺组织中CD4^(+)/CD8^(+)T淋巴细胞<1。部分慢性HP患者治疗后纤维化仍持续加重。

Objective To analyze the clinicopathological and immunohistochemical characteristics of the hypersensitivity pneumonia(HP)cases that were diagnosed by excisional lung biopsy,to improve the diagnosis accuracy of HP.Methods The data of 47 HP cases diagnosed by excisional lung biopsy during the last 20 years were collected in Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,from January 2000 to June 2020.The clinicopathological features and the immunohistochemical profiles of CD3,CD4,CD8 and CD20 were analyzed using light microscopy and immunohistochemical stains.Results The age of the patients ranged from 15 to 68 years,while the ratio of male to female was 22∶25.The main symptoms were shortness of breath and cough,and 32 cases had a history of allergen exposure.Most of the patients had restrictive impaired ventilatory function,and impaired diffusion function.The proportion of lymphocytes in bronchoalveolar lavage fluid(BALF)increased in 85.3%(29/34)of the patients,and the CD4+/CD8+T cell ratio was not higher than 0.8 in 31.3%(10/32)of the patients.Microscopically,59.6%(28/47)of the cases showed nonnecrotizing granuloma/giant cells in the stroma,and 40.4%(19/47)of the cases had only giant cells.Ninety-three-point six percent of the cases(44/47)had peribronchiolar metaplasia,while 70.2%(33/47)had focal cell-rich inflammation.Forty-four cases(93.6%,44/47)had fibrosis,which was manifested as usual interstitial pneumonia-like fibrosis(47.7%,21 cases),nonspecific interstitial pneumonia-like fibrosis(29.5%,13 cases),purely peribronchiolar fibrosis(6.8%,3 cases)and mixed fibrosis(15.9%,7 cases).Immunohistochemistry showed that CD4+T cells were fewer than CD8+T cells in 24 cases(55.8%,24/43)of HP.Thirty-two HP patients had follow-up data.Among them,7 patients had improved symptoms,12 patients were stable,and 13 patients had worsening symptoms.Conclusions The most common type of HP diagnosed by excisional lung biopsy is chronic HP.The clinical characteristics are long course of disease,restricted ventilation disorder and impaired diffusion function with the increase of lymphocyte proportion in BALF.Nearly 1/3 of the patients have no known history of allergen contact.The degree of fibrosis in HP patients diagnosed by excisional lung biopsy is severe,and the histologic types of fibrosis varies,but the UIP-like and/or NSIP-like fibrosis is most common.The CD4^(+)/CD8^(+)T cell ratio in lung tissues is less than 1 in more than half of the cases.Pulmonary fibrosis continued to increase in some of the patients with chronic HP,even after treatment.