The Usefulness of Nested Polymerase Chain Reaction(PCR) for M. tuberculosis in Differential Diagnosis of Solitary Pulmonary Nodule

Shim, Jae Jeong; Lee, So Ra; Lee, Sang Youb; Lee, Sang Hwa; Suh, Jung Kyung; Cheong, Hee Jin; Cho, Jae Yun; Kim, Woo Joo; Kang, Eun Young; In, Kwang Ho; Yoo, Se Hwa; Kang, Kyung Ho

Abstract

OBJECTIVES
The evaluation and management of a patient with solitary pulmonary nodule(SPN) are guided by principles that were derived from earlier surgical studies. SPN has a relatively good prognosis even if it is a malignant lesion. In Korea, where there is a high incidence of pulmonary tuberculosis, approximately 40% to 70% of clinically encountered solitary pulmonary nodules are tuberculous lesions. SPNs can be diagnosed by clinical findings and chest imaging techniques, but confirmed only by pathologic or cytologic studies. Transthoracic needle aspiration biopsy(TNAB) or cytology will be diagnostic in 80% to 95% of malignant nodules, but will identify the benign nature in 50% to 90% of benign nodules; such results imply lower accuracy of TNBA or cytology in diagnosing benign nodules. Differential diagnosis of SPNs can be difficult in tuberculosis endemic areas, such as in Korea, Nested polymerase chain reaction(PCB) is the widely used method to test very small amount of pathogene and to detect M, tuberculosis in fine needle aspirates.
METHODS
33 patients with SPN found on chest radiographs were evaluated by chest CT, mycobacteriologic and cytologic studies from sputum, bronchial washing fluids, and transthoracic fine needle aspirates, 17 cases were malignant SPNs(51.5%), consisting af 14 primary lung cancers and 3 metastatic SPNs, 18 cases were benign SPNs(48.5%), consisting of 8 tuberculous, 4 localized pneumonia, 1 pulmonary sequestration, and 3 radiologically suspected tuberculous lesions without response to anti-TB drugs. Nested PCR for detecting M. tuberculosis using TB-1, TB-2, TB-28, and TB-29C was carried out on fine needle aspirates from 33 patients with SPN.
RESULTS
Among the pathologically proven 17 malignant SFNs, 15(88.5%) cases were detected as cancer on chest CT. 15(88.5%) cases were confirmed by transthoracic needle aspiration cytology, among which 3(17.7%) cases showed positive on sputum cytology, and other 3(17.7%) cases yielded positive on bronchial washing cytology as well. Two cases of malignant nodules were confirmed by open resection. In 8 tuberculous SPNs, Neither AFB stain of sputum, bronchial washings, nor transthoracic needle aspirates showed positive. However, mycobacterium was cultured in 1 (9.l%) case from sputum, in 3 (27.3%) cases from bronchial washing fluids, and in 2 (18.2%) cases from transthoracic needle aspirates. Thus, five cases were confirmed bacteriologically; one case had positive culture results on both bronchial washing and transthoracic needle aspirates. Three out of 8 tuberculous cases were radiologically suspected and showed response to anti-TB drugs, but were not bacteriologically confirmed. Chest CT could detect 72.7% of tuberculous nodules. Aspirates from malignancy, pneumonia, and sequestration were negative on nested PCR for tuberculosis, One of the 3 radiologically suspected tuberculous nadules without response to anti-TB drugs yielded positive results on nested PCR for M, tuberculosis. In contrast, 7 out of 8(87.5%) aspirates from proven tuberculous nodules showed positive results on nested PCR for M. tuberculous, which included 4 bacteriologically proven tuberculous nodules and 3 radiologically suspected tuberculous nodules with response to anti-TB drugs.
CONCLUSION
Nested PCR could be used to detect M. tuberculosis in fine needle aspirates from tuberculous SPN with good sensitivity (87.5%) and specificity(96.0%). Therefore, nested PCR for detecting M. tuberculosis in fine needle aspirates may be useful in the differential diagnosis of solitary pulmonary nodules.