Objective: The hypodense sign (HyS) on CT imaging is highly suggestive of pulmonary invasive mould disease (IMD) in patients with haematological malignancies, but its diagnostic utility has not been systematically evaluated on contrast-enhanced CT. The objective of this study was to compare the diagnostic performance of the HyS to other common CT findings in a cohort of haematology patients with proven, probable or possible IMD based on European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria.
Methods: We analysed the diagnostic performance of the HyS to other common CT signs among 127 neutropenic patients with haematological malignancies submitted to both non-contrast-enhanced and contrast-enhanced CT scans of the lungs, including CT pulmonary angiography.
Results: The HyS was detected in 15.7% of patients imaged without contrast, and 44.1% after contrast administration. A contrast-aided HyS was detected in 86.6, 78.0 and 15.5% of patients with European Organization for Research and Treatment of Cancer/Mycoses Study Group proven, probable and possible IMD, respectively. When analysed per clinical diagnosis (proven, probable and highly possible IMD-i.e. no alternative diagnosis to mould disease reached), the contrast-enhanced HyS was as sensitive as the halo sign but significantly more specific [halo sign 0.56, 95% CI (0.39-0.71) vs HyS 0.98, 95% CI (0.87-1.00)]. Only the vessel occlusion sign was more sensitive [0.97, 95% CI (0.91-0.99)] and specific [0.97, 95% CI (0.86-0.99)] than the HyS for IMD diagnosis.
Conclusion: The high specificity of the HyS strongly supports the diagnosis of pulmonary IMD in neutropenic patients, and is highly suggestive breakthrough fungal disease in patients on mould-active antifungal prophylaxis. Advances in knowledge: This is the first systematic analysis of the hypodense sign on contrast-enhanced CT; the sign can support the diagnosis of IMD when other CT signs are uncertain.