Abstract Introduction Pulmonary mucormycosis is an aggressive fungal infection classically occurring in immunocompromised hosts. In immunocompetent individuals, this disease is exceptionally rare and frequently difficult to diagnose. We describe a unique case of mediastinal and pulmonary mucormycosis in an immunocompetent young adult with heavy marijuana vaping as the only identified risk factor. This case underscores the need to consider invasive fungal infections in atypical presentations of necrotizing thoracic pathology and highlights the challenges of confirming mucormycosis using molecular assays alone. Case Report A 22-year-old previously healthy male presented in October 2023 with pleuritic chest pain. Chest CT revealed enlarged mediastinal and right hilar lymph nodes with a right pulmonary nodule concerning for malignancy at first. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) showed necrotizing caseating granuloma with rare acid-fast bacilli; while MTB PCR was negative. He was lost to follow-up and re-presented in early 2025 with recurrent chest pain and cough unresponsive to corticosteroids and antibiotics. Repeat imaging showed progression of mediastinal lymphadenopathy, with a subcarinal node measuring 2.6 × 5.3 cm. Repeat EBUS-TBNA again demonstrated necrotic tissue without malignancy. Molecular testing at University of Washington was positive for Mucor PCR, while Histoplasma serology was weakly positive. He underwent mediastinal debridement, right lower-lobe wedge resection, and thoracic-duct ligation by thoracic surgery shortly after Pathology revealed necrotizing granuloma without identifiable organisms. He received two weeks of IV liposomal amphotericin B, then oral posaconazole, which was stopped early because of severe nausea.In July 2025, he presented again with recurrent cough and worsening findings on CT imaging, with repeat EBUS-TBNA again showing necrotizing granuloma without evidence of mucormycosis. Follow-up molecular studies, including Karius plasma microbial cell-free DNA, failed to confirm Mucor. The patient remains clinically stable under close Infectious Disease and pulmonology follow-up, with ongoing diagnostic evaluation. Discussion This case illustrates necrotizing mediastinal granulomatous disease with an initial positive Mucor PCR that could not be replicated on subsequent testing. The patient’s only notable exposure was daily marijuana vaping, a possible but unproven conduit for fungal spore inhalation. Although cannabis use has been linked to fungal infections like Aspergillus and Candida infections, mucormycosis associated with marijuana use has not been previously reported. Clinicians should interpret isolated fungal PCR results cautiously and pursue histopathologic correlation and repeat sampling before confirming invasive disease. Persistent thoracic lymphadenopathy in otherwise healthy individuals warrants multidisciplinary evaluation and close follow-up. This abstract is funded by: none
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