病理组织中的病原学检查对结核病的诊断价值

Diagnostic value of pathogenic detection in pathological tissue for tuberculosis

目的探讨病理组织中的病原学检查对结核病的诊断价值。方法选择2016年5月至2019年5月深圳市第三人民医院收治的190例疑似或确诊为结核病患者的病理标本,将190份标本按照病理形态分为4组:组1为坏死性肉芽肿组(109份),组2为非坏死性肉芽肿组(20份),组3为普通炎症组(45份),组4为非结核病变组(16份)。比较各种病原学检测方法在4组病理标本中检出结核分枝杆菌(Mycobacterium tuberculosis,MTB)的阳性率,同时比较不同抗结核治疗时间对病原学检查结果的影响。统计学方法采用x^(2)检验或Fisher确切概率法。结果在组1、组2、组3和组4患者的组织病理标本中抗酸染色的阳性率分别为17.4%(19/109)、5.0%(1/20)、4.4%(2/45)、0(0/16),MTB培养的阳性率分别为32.0%(32/100)、4/19、4.8%(2/42)、0(0/16),结核分枝杆菌/利福平耐药实时荧光定量核酸扩增检测体系(Mycobacterium tuberculosis/rifampin resistance real-time quantitative nucleic acid amplification detection system,Xpert MTB/RIF)检测的MTB阳性率分别为74.3%(81/109)、15.0%(3/20)、13.3%(6/45)、0(0/16),荧光定量聚合酶链反应(fluorescent quantitative polymerase chain reaction,FQ-PCR)检测的MTB阳性率分别为63.0%(58/92)、0(0/15)、2.6%(1/38)、0(0/10),实时荧光核酸恒温扩增检测(simultaneous amplification and testing,SAT)的MTB阳性率分别为32.4%(24/74)、0(0/10)、0(0/15)、0(0/10),各种病原学方法检测4组标本中的MTB阳性率差异均有统计学意义(均P<0.05)。Xpert MTB/RIF检测组1标本中MTB的阳性率高于抗酸染色、MTB培养和SAT,差异均有统计学意义(x^(2)=71.016、37.162、35.679,均P<0.01),但与FQ-PCR比较差异无统计学意义(x^(2)=2.517,P=0.112),联合病原学检查MTB的阳性率为85.3%(93/109),高于Xpert MTB/RIF的74.3%(81/109),差异有统计学意义(x^(2)=4.100,P=0.043)。各种病原学检查抗结核治疗时间≤1个月与>1个月的组1病理标本MTB阳性率分别为:抗酸染色为14.3%(7/49)比20.0%(12/60)(x^(2)=0.612,P=0.434),MTB培养为48.9%(22/45)比18.2%(10/55)(x^(2)=10.721,P=0.001),Xpert MTB/RIF为69.4%(34/49)比78.3%(47/60)(x^(2)=1.131,P=0.287),FQ-PCR为55.0%(22/40)比69.2%(36/52)(x^(2)=1.965,P=0.161),SAT为43.3%(13/30)比25.0%(11/44)(x^(2)=2.736,P=0.098)。结论MTB病原学检查结果与典型的结核病病理形态学存在一致性。病理组织的各种病原学检查方法中以Xpert MTB/RIF检出率最高,且不受早期抗结核治疗时间的影响,而联合病原学检查能提高检出率,可在标本量足够时采用。

Objective To understand the diagnostic value of tuberculosis(TB)pathogenic detection methods(TPDM)in pathological tissue for TB.Methods A retrospective study was conducted with 190 pathological specimens from different tissues suspected with TB from Third People′s Hospital of Shenzhen during May 2016 and May 2019.Specimens were divided into four groups according to histomorphology:group one,necrotizing granulomatous inflammation(109 cases);group two,non-necrotic granulomatous inflammation(20 cases);group three,non-granulomatous inflammation(45 cases);group four,non-tuberculous lesions(16 cases).The positive rates of each TPDM among specimens from four groups were compared.The positive rates of all TPDM for specimens from group one were compared.Meanwhile,the influence of antituberculosis treatment course on the TPDM was analyzed.Chi-square test or Fisher′s exact test was used for statistical analysis.Results The positive rates of Ziehl-Neelsen acid-fast staining among the four groups were 17.4%(19/109),5.0%(1/20),4.4%(2/45)and 0(0/16),respectively.The positive rates of Mycobacterium tuberculosis(MTB)complex culture were 32.0%(32/100),4/19,4.8%(2/42)and 0(0/16),respectively.The positive rates of Mycobacterium tuberculosis/rifampin resistance real-time quantitative nucleic acid amplification detection system(Xpert MTB/RIF)were 74.3%(81/109),15.0%(3/20),13.3%(6/45)and 0(0/16),respectively.The positive rates of fluorescent quantitative polymerase chain reaction(FQ-PCR)were 63.0%(58/92),0(0/15),2.6%(1/38)and 0(0/10),respectively.The positive rates of simultaneous amplification and testing(SAT)were 32.4%(24/74),0(0/10),0(0/15)and 0(0/10),respectively.The differences of each TPDM among four groups were all statistically significant(all P<0.05).The positive rate of Xpert MTB/RIF in group one specimens was significantly higher than those of acid-fast staining,MTB culture and SAT(x^(2)=71.016,37.162 and 35.679,respectively,all P<0.01),while the difference was not statistically significant when compared with FQ-PCR(x^(2)=2.517,P=0.112).The positive rate of combined TPDM(85.3%(93/109))was significantly higher than Xpert MTB/RIF(74.3%(81/109))(x^(2)=4.100,P=0.043).The positive rates of acid-fast staining group 1A(anti-tuberculosis treatment course was less than one month)and group 1B(anti-tuberculosis treatment course was longer than one month)were 14.3%(7/49)and 20.0%(12/60),respectively(x^(2)=0.612,P=0.434);those of MTB culture were 48.9%(22/45)and 18.2%(10/55),respectively(x^(2)=10.721,P=0.001);those of Xpert MTB/RIF were 69.4%(34/49)and 78.3%(47/60),respectively(x^(2)=1.131,P=0.287);those of FQ-PCR were 55.0%(22/40)and 69.2%(36/52),respectively(x^(2)=1.965,P=0.161);those of SAT were 43.3%(13/30)and 25.0%(11/44),respectively(x^(2)=2.736,P=0.098).Conclusions The results of TPDM correlate closely with the typical histomorphological features of tuberculosis.Xpert MTB/RIF possesses significantly higher sensitivity than any other single TPDM,and is not attenuated by early anti-tuberculosis treatment.Combined TPDM could significantly improve the sensitivity of TB pathogenic detection,which is suggested to be applied when the tissue specimen is sufficient.