Abstract Histoplasma capsulatum, an endemic dimorphic fungus, can mimic primary or metastatic malignancy both metabolically and radiographically. Pulmonary and adrenal involvement may produce PET-avid lesions indistinguishable from cancer, often prompting invasive evaluation. This case illustrates disseminated histoplasmosis presenting as presumed metastatic lung cancer in an immunocompetent host. A 69-year-old male with a 50-pack-year smoking history and seasonal residence in the American Southwest was referred for evaluation of bilateral adrenal masses incidentally discovered after trauma. He denied fever, weight loss, or night sweats, and his examination was unremarkable. Chest CT showed asymmetric reticulonodular opacities, greater on the right, with mediastinal adenopathy and focal pleural thickening, findings concerning for metastatic disease. Abdominal CT revealed bilateral adrenal masses up to 4.5 cm with minimal (10%) contrast washout, a pattern typically associated with metastases. Given his smoking history and imaging, metastatic lung carcinoma was favored, though atypical infection remained possible. Positron emission tomography (PET) demonstrated diffuse hypermetabolic activity in both lungs and intense FDG uptake in the adrenal glands, findings indicative of a metabolically active systemic process and initially interpreted as metastatic malignancy. Bronchoscopy with bronchoalveolar lavage was negative for malignant cells or infectious organisms. CT-guided biopsy of the left adrenal mass showed necrotizing granulomatous inflammation without malignancy. Grocott methenamine silver staining identified numerous yeast forms consistent with Histoplasma capsulatum, while acid-fast bacilli staining was negative. Serum and urine fungal antigen assays confirmed markedly elevated Histoplasma antigens with cross-reactive Blastomyces antigen positivity; Coccidioides testing was negative. Disseminated histoplasmosis involving the lungs and adrenal glands was diagnosed. The patient began oral itraconazole 200 mg three times daily for three days, then 200 mg twice daily for a 12-month course. Serial fungal antigens declined by 90%, and follow-up CT showed resolution of pulmonary infiltrates and interval reduction of adrenal lesions, confirming therapeutic response. Disseminated histoplasmosis can mimic metastatic malignancy, particularly in endemic regions or in patients with risk factors such as heavy smoking. Bilateral adrenal involvement with low washout and intense PET avidity may appear indistinguishable from metastases. In such cases, fungal infection should remain high on the differential for PET-avid pulmonary or adrenal lesions. Prompt tissue sampling and fungal antigen testing are essential to confirm diagnosis and prevent unnecessary oncologic therapy. Serial antigen monitoring and follow-up imaging objectively track response, while awareness of antigen cross-reactivity reinforces the need for clinical-pathologic correlation. Early recognition of histoplasmosis can transform a presumed metastatic malignancy into a treatable infection. This abstract is funded by: None
Nazir et al. (Fri,) studied this question.