Pulmonary Cryptococcosis During Osimertinib Treatment for Epidermal Growth Factor Receptor (EGFR) L858R-Mutant Lung Adenocarcinoma: A Case Report

Pulmonary cryptococcosis is a rare but important opportunistic fungal infection that may occur during epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy for lung cancer. We describe the case of a woman in her 60s receiving osimertinib for EGFR L858R-mutant lung adenocarcinoma who developed new pulmonary lesions. A CT-guided biopsy confirmed pulmonary cryptococcosis despite negative serum cryptococcal antigen results, with markedly elevated serum β-D-glucan levels, an atypical finding in cryptococcal infections. The patient was also receiving dexamethasone for brain metastases. Although her lymphocyte count was within the normal range, functional immunosuppression was suspected due to the combined effects of EGFR-TKI therapy and corticosteroid use. This case highlights the limitations of serological testing in immunocompromised patients undergoing molecular-targeted therapy and underscores the importance of early pathological evaluation. The patient responded well to induction therapy with amphotericin B and flucytosine, followed by fluconazole consolidation. While causality cannot be definitively established, this case suggests the need for vigilance for opportunistic infections in similar clinical settings.