非结核分枝杆菌肺病的病理学特征及分子病理在其诊断中的价值

Pathological Characteristics and Molecular Diagnosis of Non-tuberculosis Mycobacterium Lung Disease

目的探讨非结核分枝杆菌肺病的临床病理学特征和分子病理学方法在其诊断中的价值。方法分析首都医科大学附属北京胸科医院2016年2月至2019年8月石蜡包埋标本诊断肺部非结核分枝杆菌(NTM)感染的45例患者病理组织学形态、抗酸杆菌形态特征及临床、影像、细菌学资料:荧光PCR方法检测结核分枝杆菌特异基因序列IS6110;探针熔解曲线方法行分枝杆菌菌种鉴定:选取同期确诊肺结核病例50例进行比较分析。结果NTM肺病病理组织学表现为坏死性肉芽肿34例(75.6%,34/45)。非坏死性肉芽肿1例(2.2%,1/45),非肉芽肿病变10例(22.2%,10/45);坏死为粉染坏死、富于核碎片的嗜碱性坏死及化脓性坏死,与肺结核比较,后者更多表现为粉染坏死及嗜碱性坏死,差异有统计学意义(χ^(2)=10.270,P-0.001;χ^(2)=7.449,P 0.006);17例(37.8%,17/45)NTM肺病中观察到巨大奇异形多核巨细胞,与肺结核组比较差异有统计学意义(χ^(2)=13.446.P<0.01)。抗酸杆菌数量多少不一。形态多样,胞内分枝杆菌常见大量抗酸杆菌,堪萨斯分枝杆菌奇异形抗酸杆菌易见。胞内分枝杆菌18例(40.0%,18/45).蟾蜍分枝杆菌8例(17.8%,8/45).鸟、堪萨斯、龟分枝杆菌各6例(13.3%,6/45),猿猴分枝杆菌1例(2.2%,1/45)。结论NTM肺病的诊断和鉴别诊断值得病理医师关注,仅靠组织形态学特征和抗酸杆菌形态特点不能明确诊断,分子病理学方法是确诊结核病和NTM肺病的重要手段。

Objective To investigate the clinicopathological features of non-tuberculosis mycobacterial lung disease and the role of molecular pathology in diagnosis.Methods Forty-five formalin-fixed,paraffin embedded(FFPE)specimens were collected from the Department of Pathology,Beijing Chest Hospital from February 2016 to August 2019.The clinical,imaging and histopathologic features,bacteriologic data and morphologic characteristics of acid fast bacilli(AFB)were analyzed retrospectively.Specific gene sequence IS6110 of Mycobacterium tuberculosis(MTB)was detected by fluorescence PCR.Identification of Mycobacteria was by melting curve method.Fifty cases of pulmonary tuberculosis were selected in the same period as control.Results The NTM lung cases included 18 cases(40.0%,18/45)of M.intracellulare,eight cases(17.8%,8/45)of M.xenopi,six cases(13.3%,6/45)of M.avium,six cases(13.3%,6/45)of M.kansasii,six cases(13.3%,6/45)of M.chelonae and one case(2.2%,1/45)of M.simiae.Histopathologically,there were necrotizing granulomas in 34 cases(75.6%,34/45),non-necrotizing granuloma in one case(2.2%,1/45)and non-granulomatous lesions in 10 cases(22.2%,10/45).The necrosis was pink necrosis,basophilic necrosis rich in nuclear fragments and suppurative necrosis.Pulmonary TB showed more pink necrosis and basophilic necrosis,the difference was statistically significant(χ^(2)=10.270,P=0.001;χ^(2)=7.449,P=0.006).Seventeen cases(37.8%,17/45)of NTM lung disease showed giant multinucleated giant cells,which were significantly different from those in pulmonary tuberculosis group(χ^(2)=13.446,P=O.Ol).The number and morphology of AFB were also different.More AFB were found in M.intracellular cases and significant AFB were easily seen in M.kansasii infection.Conclusions M.tuberculosis and NTM cannot be reliably differentiated by histologic features or by AFB morphology.Molecular assays are important to distinguish tuberculosis from NTM lung disease.