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In histoplasmosis-endemic regions, pulmonary nodules often raise concern for malignancy. Distinguishing benign infectious granulomas from neoplastic lesions while limiting invasiveness is a major diagnostic challenge.

We report a case series of 11 patients diagnosed with nodular pulmonary histoplasmosis at the University Hospital of Guadeloupe, a French West Indies institution located in an endemic area. Clinical, radiologic, microbiologic, and histopathologic data were retrospectively reviewed.

All 11 patients presented with solid pulmonary nodules associated with mediastinal and/or hilar lymphadenopathy, mimicking locally advanced lung cancer. Among the nine patients who underwent 18F-FDG PET/CT, all but one showed hypermetabolic activity in the nodule. Five patients were immunocompromised, and notably, four of the eleven patients were treated for rheumatoid arthritis. Diagnosis was established through surgical resection in five cases, percutaneous or lymph node biopsy in another five, and bronchoalveolar lavage (BAL) alone in one patient. Serologic testing was positive in all five patients tested, and H. capsulatum PCR on BAL was positive in two of the four cases tested. Exposure history and clinical context supported the diagnosis in several cases, but noninvasive tests alone were generally insufficient to exclude malignancy.

This series illustrates the diagnostic difficulty of pulmonary nodules in histoplasmosis-endemic areas and the frequent need for invasive procedures. The development of improved, noninvasive diagnostic strategies is essential to avoid unnecessary surgery while ensuring timely cancer diagnosis.