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Bilateral pleural masses in an immunocompromised patient. We present a case of persistent pleural masses with mediastinal adenopathy in an immunocompromised patient initially biopsied, diagnosed and treated for Pneumocystis jiroveci pneumonia, ultimately requiring surgical thoracoscopy to diagnose pulmonary histoplasmosis. We discuss the diagnostic approach for pleural masses in immunocompromised patients, the limitations of tissue sampling, interpretation and methodology, and pitfalls of testing in making a pathogen-specific diagnosis.