The most appropriate next step in management is to perform a bronchoscopic biopsy of the mediastinal lymph nodes and lung. The diagnosis is most likely sarcoidosis. Sarcoidosis is a multiorgan inflammatory disease characterized by tissue infiltration by mononuclear phagocytes, lymphocytes, and noncaseating granulomas. The cause remains unknown, but there is increasing evidence to suggest it is the end result of interactions among a persistent antigen, HLA class II molecules, and T-cell receptors. Ninety percent of patients with sarcoidosis have pulmonary involvement; however, diagnosis is often difficult because symptoms can be nonspecific. Pulmonary function tests often show restriction, but obstruction can be seen as well; these findings are not specific to sarcoidosis. Sarcoidosis is a diagnosis of exclusion based on multisystem involvement and histologic evidence of noncaseating granulomas when all other causes are ruled out. Bronchoscopy with transbronchial biopsies combined with endobronchial biopsies has been shown to have sensitivities as high as 90% for diagnosing sarcoidosis. Most patients require a tissue diagnosis, but there are some exceptions that do not warrant histologic confirmation. These include classic clinical presentations of known sarcoid syndromes such as Löfgren syndrome (hilar lymphadenopathy, acute oligoarthritis, and erythema nodosum) and Heerfordt syndrome (uveitis, parotid gland enlargement, and fever).

Sarcoidosis often spontaneously resolves and the decision to treat is based on symptoms. Glucocorticoids are the treatment of choice, but in this patient the decision to treat should be made only after confirming a diagnosis and then assessing the risks and benefits of treatment.

The Centers for Disease Control and Prevention endorses the use of interferon-γ release assays (IGRAs) in all clinical settings in which the tuberculin skin test (TST) is recommended. IGRAs are as sensitive as but more specific than the TST in diagnosing tuberculosis. Testing for tuberculosis with both an IGRA and TST is generally not recommended, and this patient's recent negative TST makes a diagnosis of tuberculosis an unlikely cause of his clinical findings.

Although serum angiotensin-converting enzyme levels are elevated in 75% of patients with chronic sarcoidosis, the test lacks specificity and is therefore of limited use diagnostically.