Hypodense Sign in Lungs on CT in Immunocompromised Patient

We read with interest the article entitled “Imaging Approach to Pulmonary Infections in the Immunocompromised Patient” by Grover et al.[1] We would like to add a “hypodense sign” (HyS) to the list of radiological findings described by the authors. The HyS was described by Horger et al as[2] the presence of a central area of hypodensity seen on narrow window settings (width: 110–140 Hounsfield Units [HU]; level: 15–40 HU). This sign can be seen in consolidation or nodule and can be appreciated on unenhanced scans, computed tomography pulmonary angiography (CTPA), and contrast-enhanced scans. This sign has been reported to be associated with invasive pulmonary aspergillosis, mucormycosis, and fusariosis.[3] [4] The hypodense nodule sign has been described in the context of immunocompromised patients. The underlying pathogenesis is infarction secondary to angioinvasion by fungal elements.[3] [4] This sign may be a precursor for forming a cavity.[2] [5] Some studies have described the importance of hypodense sign in diagnosing invasive mold disease ([Table 1]). Hence, it is a helpful sign in arriving at the diagnosis of invasive mold disease with a sensitivity of 23% on high-resolution CT (HRCT) and 64% on CTPA, and a specificity of 100% on HRCT and 98% on CTPA.[3] This sign can help to differentiate between bacterial and fungal diseases in immunocompromised individuals.[2] [3] This sign has also been described in some bacterial infections, particularly in tuberculosis, i.e., a cavity filled with central mucous within or in case of a pulmonary abscess; however, leukocytes play a vital role in abscess formation, and immunocompromised individuals usually have neutropenia.[3] [6] Hence, we would like to add the hypodense sign as a useful diagnostic sign in CTs of immunocompromised individuals.

Table 1 Studies describing hypodense sign in immunocompromised patients

Study	Sample size	Type of scan	Patient population
Horger et al[2]	43	Unenhanced scan	Neutropenic patients
Sassi et al[3]	127	HRCT and contrast-enhanced CT	Hematological Malignancies
Qin et al[5]	25	CT chest with intravenous contrast and without intravenous contrast	Liver transplant patients
Stanzani et al[6]	44	Unenhanced scan and CTPA	Hematological malignancies
Schulze et al[7]	17	Noncontrast CT and volume perfusion CT	Hematological malignancies

Publication History

Article published online:
20 December 2022

• References

• 1 Grover SB, Grover H, Antil N, Patra S, Sen MK, Nair D. Imaging approach to pulmonary infections in the immunocompromised patient. Indian J Radiol Imaging 2022; 32 (01) 81-112
• 2 Horger M, Einsele H, Schumacher U. et al. Invasive pulmonary aspergillosis: frequency and meaning of the “hypodense sign” on unenhanced CT. Br J Radiol 2005; 78 (932) 697-703
• 3 Sassi C, Stanzani M, Lewis RE. et al. The utility of contrast-enhanced hypodense sign for the diagnosis of pulmonary invasive mould disease in patients with haematological malignancies. Br J Radiol 2018; 91 (1083): 20170220
• 4 Alexander BD, Lamoth F, Heussel CP. et al. Guidance on imaging for invasive pulmonary aspergillosis and mucormycosis: from the imaging working group for the revision and update of the Consensus Definitions of Fungal Disease from the EORTC/MSGERC. Clin Infect Dis 2021; 72 (Suppl 2): S79-S88
• 5 Qin J, Meng X, Fang Y. et al. Computed tomography and clinical features of invasive pulmonary aspergillosis in liver transplant recipients. J Thorac Imaging 2012; 27 (02) 107-112
• 6 Stanzani M, Sassi C, Lewis RE. et al. High resolution computed tomography angiography improves the radiographic diagnosis of invasive mold disease in patients with hematological malignancies. Clin Infect Dis 2015; 60 (11) 1603-1610
• 7 Schulze M, Vogel W, Spira D, Sauter A, Hetzel J, Horger M. Reduced perfusion in pulmonary infiltrates of high-risk hematologic patients is a possible discriminator of pulmonary angioinvasive mycosis: a pilot volume perfusion computed tomography (VPCT) study. Acad Radiol 2012; 19 (07) 842-850