A71-05 Can We Rely on Tissue Polymerase Chain Reaction (PCR)? Diagnostic Accuracy and Predictors in Nontuberculous Mycobacterial Pulmonary Disease

Rationale

The diagnosis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is often challenging, frequently requiring invasive procedures when sputum results are indeterminate. While tissue biopsy is considered one of the definitive diagnostic tools, the diagnostic performance of tissue NTM polymerase chain reaction (PCR) remains questionable. In this context, we aimed to evaluate the diagnostic performance of NTM PCR on formalin-fixed lung tissue, and identify clinical and pathologic predictors of PCR positivity.

Methods

We conducted a retrospective cohort study of patients who underwent lung tissue biopsy with NTM PCR for suspected NTM-PD at a tertiary referral center in South Korea from January 1st, 2018, to December 31st, 2024. We analyzed NTM PCR results from lung tissue and determined whether patients met the ATS/IDSA diagnostic criteria for NTM-PD. Diagnostic accuracy metrics including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Logistic regression analyses were performed to identify independent predictors of positive PCR results among confirmed NTM-PD patients.

Results

During the six-year period, 2,325 patients underwent NTM PCR analysis on formalin-fixed lung tissue. The overall positive rate of NTM PCR was 101/2,325 (4.3%). We identified 75 patients with confirmed NTM-PD according to ATS/IDSA criteria: 27/75 (36.0%) were NTM PCR positive, while 48/75 (64.0%) were negative. The sensitivity, specificity, PPV, and NPV of tissue NTM PCR were 35.6%, 96.9%, 31.7%, and 97.4%, respectively. With a median age of 67.2 years and comparable sex distribution (44.0% female), no significant demographic differences were observed between PCR-positive and PCR-negative groups. Radiologically, fibrocavitary phenotype (63.0% vs. 25.0%; P =  0.002) and the presence of cavities (70.4% vs. 29.2%; P =  0.001) were significantly more frequent in the PCR-positive group. Pathologically, the presence of necrosis was significantly higher in PCR-positive patients (96.3% vs. 52.1%, P < 0.001). Multivariate analysis confirmed that the presence of necrosis was strongly associated with positive NTM PCR results (OR 17.4, 95% CI [1.85, 163.1], P =  0.012).

Conclusions

NTM PCR from formalin-fixed lung tissue exhibits excellent specificity (96.9%) but low sensitivity (35.6%), indicating that a negative result does not reliably exclude NTM-PD. However, histologic necrosis is a robust independent predictor of PCR positivity. Consequently, in patients with negative PCR results, the presence of necrosis should maintain a high clinical index of suspicion for NTM-PD, warranting further evaluation rather than dismissal of the diagnosis.

This abstract is funded by: None