Xpert® MTB/RIF assay on formalin-fixed paraffin-embedded tissues in the diagnosis of extrapulmonary tuberculosis

Background: Diagnosis of extrapulmonary tuberculosis continues to be a challenge due to the complexity of the causative organism and the wide array of pathologic features seen in this infection. Xpert MTB/RIF can be used on fresh or frozen tissue specimens for diagnosis of tuberculosis with good results. However, there is little data on its use with formalin-fixed paraffin-embedded (FFPE) tissues. Objectives: The aim of this study was to demonstrate the potential utility of Xpert MTB/RIF and to compare its performance to Ziehl-Neelsen staining for the detection of Mycobacterium tuberculosis from FFPE tissues using histological features from haematoxylin and eosin staining as the gold standard. Methods: Eighty randomly selected archival FFPE tissues exhibiting histological features of tuberculosis were included in the study. After deparaffinisation and lysis, all the tissue specimens were subjected to the Xpert (R) MTB/RIF assay. The outcome measures were proportions of positively identified cases by each test. Results: Using histology as the gold standard, the sensitivity of Ziehl-Neelsen staining was 20.3% (95% confidence interval: 12% - 30.8%), and the sensitivity of the Xpert (R) MTB/RIF assay was 53.2% (95% confidence interval: 41.6% - 64.9%); the difference was statistically significant (p = 0.002). None of the cases tested positive for rifampicin resistance. Conclusion: With prior deparaffinisation and lysis, FFPE tissues are amenable to testing by Xpert (R) MTB/RIF assay. A validation study to determine the clinical utility, analytical optimisation and cost implications of this assay for FFPE tissues is recommended.