Diagnostic Performance of Coccidioidomycosis PCR Testing in Lung Nodules: A Retrospective Study in Central California

Coccidioidomycosis is an endemic fungal infection in the southwestern United States that can present as solitary lung nodules, mimicking malignancy on imaging. Molecular testing, such as PCR, offers rapid diagnosis but its performance in this clinical setting remains unclear.

We conducted a retrospective analysis of patients evaluated for lung nodules at a tertiary care community-based lung nodule clinic in Central California between 2011 and 2025. Coccidioides PCR in patients with proven or probable Coccidioidomycosis was compared to those with biopsy-proven lung cancer. Diagnostic yield of Coccidioides PCR was assessed across biopsy methods and benchmarked against histology and fungal cultures.

Among 122 patients with Coccidioidomycosis, PCR demonstrated low sensitivity (range: 20-41%) but high specificity (100%) across all biopsy modalities. Histology and fungal cultures outperformed PCR, detecting additional cases missed by molecular testing. Notably, 9 PCR-negative cases were confirmed on histology, and PCR was only positive in 71.4% of culture-confirmed cases.

Coccidioides PCR testing has high specificity but limited sensitivity for diagnosing lung nodules in endemic regions, limiting its utility as a single test. Histology and fungal culture remain essential. Selective use of PCR may enhance diagnostic efficiency and reduce unnecessary costs in regions burdened by Coccidioidomycosis.