Case Presentation: A 61-year-old woman with a history of RA (on methotrexate and adalimumab) and latent TB (previously treated with Rifampin in 2023), presented with a three-month history of cough and shortness of breath. Imaging revealed bilateral pleural effusions and hypodense lesions in the spleen. Thoracentesis was performed, with pleural fluid analysis revealing a lymphocytic exudative effusion. ADA of the pleural fluid was 45U/L (0-30U/L). The differential diagnosis at this stage included malignant pleural effusion, tuberculosis, and RA-related pleural disease. AFB testing on three sputum samples was negative. PET-CT scan demonstrated multiple metabolically active foci in the spleen, along with increased uptake in the omentum, peritoneum, and bilateral pleura, which raised concern for metastatic malignancy of unknown origin. During the four week hospitalization, the patient required three thoracenteses for rapidly accumulating pleural effusions. A pleuroscopy with pleurodesis was done, and pleural biopsies revealed granulomatous inflammation with foci of punctate necrosis. Acid-fast culture of both the pleural fluid and biopsy specimen was positive for Mycobacterium tuberculosis. The patient was started on RIPE therapy (Rifampin, Isoniazid, Pyrazinamide, and Ethambutol) and was discharged with follow-up in the TB clinic.
Discussion: Malignancy and TB are the most common differential diagnoses for lymphocytic-predominant exudative pleural effusions as both conditions share significant clinical and radiological similarities. While FDG PET scans are useful for detecting primary malignancies and distant metastases, they are not definitive in distinguishing between malignancy and TB. This is due to FDG uptake being elevated in both malignant and inflammatory cells, and the overlapping Standardized Uptake Value (SUV) ranges make PET scans unreliable for differentiating between the two conditions. Therefore a biopsy of the affected tissue remains essential for confirming the diagnosis. In our case, the patient had bilateral pleural effusions, three negative AFB sputum samples, and a PET-CT scan showing increased uptake in the pleura, omentum, and spleen, with an SUV max of 12.9 further supporting the suspicion of malignancy. However, pleural biopsies revealed necrotizing granulomatous inflammation, ultimately confirming the diagnosis of TB. This case highlights the diagnostic challenge in distinguishing between TB and malignancy, leading to potential delays in the recognition and treatment of these life-threatening conditions. Latent TB reactivates to active TB in 10% of cases within 2-5 years of initial infection. TB associated with anti-TNF inhibitors is predominantly extrapulmonary, with disseminated TB occurring in 25% of the patients. Given the increased risk of TB in patients receiving treatment with TNF-alpha inhibitors, shared decision-making should be a key part of management when initiating such treatments, ensuring that patients are appropriately screened and monitored for TB reactivation.
Conclusions: TB and malignancy are difficult to distinguish due to similar clinical and radiological characteristics. PET CT scans are also unreliable due to overlapping SUV ranges. A biopsy is required to make a confirmatory diagnosis.Shared decision-making is key prior to initiation of anti-TNF inhibitors due to the increased risk of reactivation of tuberculosis.