In a patient with a cough lasting more than two weeks, unintentional weight loss, chills, and a chest mass on imaging but negative GeneXpert for Mycobacterium tuberculosis and a normal chest X‑ray, what is the appropriate next step in management?

Management of Suspected TB with Negative GeneXpert and Chest Mass

Given the presence of a chest mass with constitutional symptoms (weight loss, chills, prolonged cough) despite negative GeneXpert, you must directly investigate the mass for malignancy with chest CT followed by tissue diagnosis via bronchoscopy, transthoracic needle aspiration, or surgical biopsy. 1

Immediate Next Steps

Priority: Evaluate the Chest Mass

• Obtain chest CT scan immediately to characterize the mass, as this finding on imaging with constitutional symptoms raises concern for bronchogenic carcinoma or other serious pathology that requires direct investigation 1
• The presence of a mass supersedes the typical algorithmic approach to chronic cough and demands specific evaluation of the mass itself 1
• Do not delay with empiric treatment trials when objective findings like a mass are present, as these indicate established disease requiring specific diagnosis 2

Tissue Diagnosis Required

Following chest CT characterization, proceed with:

• Bronchoscopy with biopsy for central lesions 1
• Transthoracic fine-needle aspiration for peripheral lesions 1
• Video-assisted thoracic surgery (VATS) biopsy if less invasive methods are non-diagnostic 1
• Consider positron emission tomography (PET) scan to further characterize the lesion and assess for metastatic disease 1

Tuberculosis Considerations Despite Negative GeneXpert

GeneXpert Limitations

• GeneXpert sensitivity is not 100% in smear-negative TB, with sensitivity ranging from 66-96% depending on sputum quality 3, 4
• Blood-stained sputum shows particularly low sensitivity (28%), while salivary sputum shows higher sensitivity (66%) 4
• A negative GeneXpert does not definitively exclude TB, especially in high clinical suspicion cases 3, 5

Additional TB Diagnostic Steps

While pursuing mass evaluation, simultaneously:

• Obtain three sputum samples on different days for AFB smear and mycobacterial culture 1, 6
• Culture remains the gold standard and can detect TB missed by GeneXpert 3
• If initial sputum samples are inadequate, consider bronchoscopy with bronchoalveolar lavage (BAL) for both TB diagnosis and mass evaluation 3
• In endemic areas, TB should be considered in any patient with cough >3 weeks regardless of initial negative tests 6

Critical Pitfalls to Avoid

• Do not start single-drug TB treatment until active TB is excluded, as this risks creating drug resistance 1
• Do not rely on chest X-ray alone when a mass is identified—CT is essential for proper characterization 1, 2
• Do not assume negative GeneXpert rules out TB in the presence of high clinical suspicion with constitutional symptoms 3, 5
• Do not empirically treat for common causes of chronic cough (UACS, asthma, GERD) when a mass is present—this delays critical diagnosis 1

If Multidrug TB Treatment is Considered

• Multidrug therapy can be started pending culture results if TB remains highly suspected, but only after obtaining appropriate specimens 1
• This approach prevents delay in treatment while maintaining diagnostic capability through culture 1
• Repeat chest imaging should be obtained to assess for improvement, which would support TB diagnosis even with negative cultures 1

Differential Diagnosis Priority

Given the clinical presentation:

1. Malignancy (lung cancer) - most urgent to rule out given mass and constitutional symptoms 1
2. Tuberculosis - despite negative GeneXpert, culture-positive TB remains possible 3, 5
3. Nontuberculous mycobacteria - can present similarly and may be culture-positive 7
4. Interstitial lung disease - if mass represents consolidation rather than true mass 2