Earlier Diagnosis of Angioinvasive Pulmonary Mold Disease: Is Computed Tomography Pulmonary Angiography a New Step?

Molds are a frequent causeofmorbidity and mortality in allogeneic hematopoietic stem cell transplant recipients and in patients with hematologicalmalignancies. Themost frequent molds involved in this setting are Aspergillus spp. and Zygomycetes [1]. Aspergillus and Zygomycetes infect the lower or upper respiratory tract after inhalation of spores. When host defenses are failing, the spores germinate and the hyphae invade the tissue. Because they also invade the vessels (Figure 1) and occlude them, thrombosis results in infarction of the tissues, and necrosis is a hallmark of the disease whatever the localization. Most of the clinical and radiological signs are explained by tissue infarction. High-resolution computed tomography (CT) scan allows earlier detection of pulmonary lesions in high-risk febrile patients. The typical CT scan aspects of invasive aspergillosis are presence of nodules. The lesions can bemodified by presence of a halo sign (early phase), an air crescent sign (usually after recovery from neutropenia), or a cavity. The halo sign indicates a rim of ground glass opacity around a nodule with a progressive attenuation. At pathologic examination, the nodules represent foci of infarction, and the halo of ground glass opacity results from alveolar hemorrhage [2]. Presence of a halo sign around nodules was first described in invasive pulmonary aspergillosis [3]. It has also been reported in non-Aspergillus fungal infections, nonfungal infections, primary or metastatic neoplasms, inflammatory or systemic diseases, and iatrogenic injury such as transbronchial lung biopsy [4]. Based on data from a large clinical trial [5], Greene et al showed that nodules were present at baseline in 94% of the cases of invasive aspergillosis and that at least one macronodule (.1 cm) was surrounded by a halo sign in 64% of the cases with nodular lesions [6]. These results supported the decision by the European Organisation for Research and Treatment of Cancer/Mycosis Study Group (EORTC/ MSG) consensus group to consider a nodule with a halo sign a strong radiological signal in favor of invasive aspergillosis in a patient with host factors predisposing to this infection [7]. However, a limitation of the analysis by Greene et al is that the presence of a nodule with a halo sign was a criterion for inclusion in the clinical trial, and therefore there might have been an overestimation of the rates of nodular lesion as well as of halo sign. In our local series of 208 consecutive cases of invasive pulmonary aspergillosis [8], 155 (75%) patients had at least one nodule on the first CT scan, and only 51% of them had a halo sign around the nodule. The consensus definitions for invasive fungal diseases have appropriately been updated in 2008 and have accepted that patients with a dense well-circumscribed lesion may qualify for invasive pulmonary fungal disease [7, 9]. Although not clearly stated, dense well-circumscribed lesions include nodules, non-nodular infarcts, and consolidations. Whether alveolar infiltrates are also included remains a debate, and clarification is expected from the next update. Despite recent improvements in diagnosis and treatment of invasive aspergillosis, the mortality rate remains high, in the range of 30%–40% [5]. Because earlier onset of treatment has been associated with better outcome, any new diagnostic method can help to further improve the outcome. In 2005, Sonnet et al suggested that high-resolution multidetector CT angiography allows direct detection of angioinvasion in aspergillosis or mucormycosis by showing the vascular occlusion at a peripheral level [10]. Vascular occlusion has been defined as an interruption of a pulmonary artery at the border of a focal lesion without depiction of the vessel inside the lesion or peripheral to the lesion. Vascular occlusion was Received 23 October 2011; accepted 28 October 2011; electronically published 14 December 2011. Correspondence: Raoul Herbrecht, MD, Department of Oncology and Hematology, Hôpital de Hautepierre, 67098 Strasbourg, France (raoul.herbrecht@chru-strasbourg.fr). Clinical Infectious Diseases 2012;54(5):617–20 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/cir894