The flip-flop fungus sign: an FDG PET/CT sign of benignity

Benign granulomatous processes such as fungal infection may mimic metastatic lung cancer on FDG PET/CT. We found that these processes often have draining lymph node(s) with equal or greater FDG activity than associated lung nodule(s), a "flip-flop" of what is commonly seen in lung cancer. The aim of this study was to examine the utility of this "flip-flop fungus" (FFF) sign for diagnosing benign pulmonary disease. FDG PET/CT scans performed between 9/09-3/13 for the indications of pulmonary nodule or mass were reviewed. Scans with at least one hilar or mediastinal FDG avid draining node were included. Patients with a history of cancer, lack of pathologic confirmation, or without at least two years of imaging follow-up were excluded. A total of 209 FDG PET/CT exams were included and reviewed in a blinded fashion. A positive FFF sign had a sensitivity of 60.0% (95% CI: 47.6-71.5%) and specificity of 84.9% (95% CI: 77.8-90.4%) (P<0.0001) for benign disease. With additional strict imaging criteria applied, the FFF sign had a specificity of 98.6% (95% CI: 94.9-99.8%) (P<0.0001) and a positive predictive value of 90.0% (95% CI: 68.3-98.5%). A positive FFF sign was predominately due to granulomatous disease (91%), mostly histoplasmosis (73%). A positive FFF sign combined with positive fungal serology (n=16) had a specificity of 100% for benign disease. The FFF sign predicts benign disease in patients with a lung nodule(s) and an FDG avid draining lymph node(s) that would otherwise be considered worrisome for cancer.