Abstract Introduction Fibrosing mediastinitis is a rare but severe late complication of granulomatous infections, most commonly Histoplasma capsulatum. Its imaging features — dense mediastinal calcification and extrinsic compression of mediastinal structures — can overlap with sarcoidosis, leading to misdiagnosis and inappropriate corticosteroid therapy. We report a case of progressive calcified pulmonary nodules and mediastinal fibrosis initially attributed to sarcoidosis but ultimately diagnosed as chronic histoplasmosis-associated fibrosing mediastinitis. Case Presentation A 52-year-old woman with diabetes, hypertension, and hyperlipidemia was diagnosed with stage II pulmonary sarcoidosis in 2015 based on bilateral hilar lymphadenopathy and scattered perilymphatic nodules. She was treated with prednisone 10 mg daily but was subsequently lost to follow-up. She resides in the Tennessee Valley, an area endemic for histoplasmosis. Over the last six months, she experienced worsening dyspnea, chronic cough, intermittent fevers, and unintentional weight loss. Repeat CT chest demonstrated innumerable bilateral calcified nodules, densely calcified mediastinal lymph nodes, and marked mediastinal architectural distortion with narrowing of the right main bronchus and pulmonary artery — findings highly suggestive of fibrosing mediastinitis. The distribution of random, heavily calcified nodules was atypical for sarcoidosis, prompting re-evaluation. Her workup revealed a positive Histoplasma urine antigen and elevated complement fixation titers. Autoimmune testing (ACE, ANA, ANCA) was normal, and tuberculosis testing (AFB smear/culture and QuantiFERON-Gold) was negative. HIV testing was also negative. EBUS- guided lymph node sampling and CT-guided biopsy of a calcified nodule showed necrotizing granulomas with dense calcification, and fungal staining demonstrated organisms morphologically consistent with Histoplasma. A diagnosis of chronic histoplasmosis with fibrosing mediastinitis was made, representing likely longstanding misclassification as sarcoidosis. Corticosteroids were discontinued, and itraconazole therapy was initiated. Her respiratory symptoms improved modestly, although mediastinal fibrosis remained structurally irreversible. Discussion This case highlights the difficulty of distinguishing sarcoidosis from granulomatous infections in histoplasmosis-endemic regions. While sarcoidosis typically presents with non-caseating granulomas and non-calcified perilymphatic nodules, chronic histoplasmosis more often produces calcified micronodules, dense mediastinal calcification, and progressive fibrosing mediastinitis with airway and vascular compression. Misdiagnosis is clinically significant: corticosteroid therapy can exacerbate fungal disease, delay appropriate antifungal treatment, and allow irreversible fibrosis to progress. Careful review of imaging patterns, attention to geographic risk, and early microbiologic evaluation are essential to avoid this pitfall. This abstract is funded by: None
Qasim et al. (Fri,) studied this question.