Nonspecific airspace opacities are the most frequent radiologic findings found with any pulmonary infectious process. Alveolar, “patchy,” “air-space,” or “mass-like” opacities have been identified in many fungal diseases, often progressing to areas of consolidation in the lung. Alveolar opacities have been noted in both endemic and opportunistic fungal infections. Airspace opacities have been noted as a frequent initial pattern in invasive pulmonary aspergillosis (IPA). Opacities may be unifocal or multifocal and then progress to diffuse consolidation, though segmental areas of consolidation have been noted as one of the most common CT patterns in IPA [41, 42] (Fig. 6.6). Other disease processes resulting from Aspergillus infection such as bronchopneumonia, hypersensitivity pneumonitis, chronic necrotizing aspergillosis, and semi-invasive aspergillosis have also presented with alveolar opacities, often progressing to consolidation [38, 41, 43]. Patchy, ill-defined opacities progressing to more diffuse, bilateral airspace consolidation are common findings in blastomycosis (seen with a prevalence of 26–76 %) [21].

Interstitial, “reticular,” “reticulonodular,” and “linear” opacities have also been observed in many fungal infections. Diffuse bilateral interstitial opacities in a perihilar distribution [37, 44, 45] are the most common pattern seen in Pneumocystis infection (Fig. 6.7). Chest CT often reveals perihilar ground-glass opacity in a mosaic pattern with patchy distribution of affected lung interspersed with areas of normal lung, and noted thickening of the interlobular septa [38]. Interstitial opacities are also the most common pattern seen in cryptococcosis [46]. Ground-glass attenuation may be seen in AIDS patients with this infection. Aspergillus is able to affect the lung in a variety of ways, most of which can present in an interstitial pattern. These range from nodular opacities of invasive and semi-invasive disease, mimicking the radiologic findings of reactivation tuberculosis (TB), to coarse reticulation found in chronic hypersensitivity pneumonitis [38, 41]. A miliary or reticulonodular pattern is commonly seen in Blastomyces infection. Coccidioides pneumonia has been noted with diffuse reticulonodular lesions, especially in the setting of AIDS. Heavy exposure to Histoplasma can similarly present with diffuse reticulonodular opacities, such as those found in acute disseminated disease [47]. Other organisms commonly demonstrating interstitial opacities include Penicillium marneffei in the setting of HIV infection and paracoccidioidomycosis. In Paracoccidioides infection, the “reversed halo sign” of ground-glass opacity surrounded by denser airspace consolidation of crescent and ring shapes, has been reported in 10 % of patients [48, 49]. The lesions predominate in the mid to lower lungs, particularly in the periphery [49]. The reversed halo sign has also be described in zygomycosis and IPA, as well as histoplasmosis and Pneumocystis jiroveci pneumonia. In an immunosuppressed patient with reversed halo sign, invasive fungal infection should be considered until proven otherwise [50].

Distribution and location of opacities are also nonspecific. Opacities may be confined to a lobe or they may be diffuse as seen in disseminated disease. Hematogenous candidal spread can manifest as perivascular pulmonary opacities [51]. Allergic bronchopulmonary aspergillosis often presents with fleeting or migratory upper lobe opacities [41]. Phantom opacities which resolve in one segment then reappear in another lung field have also been seen in coccidioidomycosis [51].

The shape of infiltrates can sometimes aid in the diagnosis. Wedge-shaped opacities, reflecting invasion of blood vessels with subsequent lung infarction, are suggestive of invasive Aspergillus or Mucorales [52].

Uncommon pathogens which can cause infections presenting with nonspecific pulmonary opacities include Fusarium, Trichosporon, Malassezia furfur, and the phaeohyphomycetes [53].

A well-defined nodule, either single or multiple, has been reported as a frequent initial radiographic pattern of IPA [54]. This nodular lesion may be surrounded by a rim of hemorrhage from thrombosis of fungi within pulmonary vessels [55]. Days to weeks after treatment of neutropenia, patients infected with Aspergillus may present with ground-glass attenuation around the nodules recognized as the “halo sign” [41, 56, 57] (Fig. 6.8). The “halo sign” is highly suggestive of angioinvasive aspergillosis, but is nonspecific. It is thought that the surrounding ground-glass opacity may be related to hemorrhage from the vascular involvement. Other infectious processes including the mucormycosis, Candida, herpes simplex virus, and cytomegalovirus infections, as well as noninfectious processes such as Wegener’s granulomatosis, Kaposi’s sarcoma, and hemorrhagic metastatic malignancies have also been presented with “halo signs” [58–60]. Nodular lesions may also be observed with branching linear opacities recognized as the “tree-in-bud” pattern seen in Aspergillus bronchiolitis [38]. “Tree-in-bud” pattern suggests a small airways process; a disease process which may be spread endobronchially. Similar lesions are found in endobronchial spread of mycobacterial, viral, and mycoplasma pneumonia. Nodules from Mucorales can be indistinguishable from IPA. The most common finding in pulmonary cryptococcosis are nodules, solitary or multiple, with or without cavitation, ranging from 5 to 20 mm in size with smooth or irregular margins, associated with other parenchymal findings such as masses and consolidation [61–63]. Miliary nodules are less commonly found in the AIDS patient with cryptococcosis [64]. Other organisms which can present with diffuse nonspecific nodular lesions include disseminated Candida and Histoplasma. Nodules can turn to “buck shot” calcifications in pulmonary histoplasmosis [52]. Approximately 5 % of those who develop Coccidioides pneumonia may develop solitary pulmonary nodules. Infections with Pneumocystis, Scedosporium, and Paracoccidioides have also demonstrated pulmonary nodules.

Parenchymal masses may include aspergillomas, 3–5 cm mobile, round or oval masses, usually solitary, and seen in the upper lobe within a preexisting cavity (Fig. 6.9) or ectatic bronchus. These masses may be partially surrounded by a radiolucent crescent (Monod’s sign) of varying thickness [41, 65, 66]. This is the pattern most often seen in immunocompetent hosts [66]. Occasionally, coccidioidal infections may leave persistent chest X-ray lesions, most common being the coccidioidoma and the peripheral cavity [51]. The occasional “fungus ball” can form inside the cavity, rupture into the pleural space and produce an air–fluid level on an upright chest X-ray. Nonspecific mass lesions have been reported in infections with Cryptococcus, Pneumocystis, and the Mucorales. As fungal infections may present with nodules and masses which may have irregular or speculated borders, it is not uncommon to mistake them for malignancy. Fungal infections mimicking malignancy include coccidiomycosis, histoplasmosis, aspergillosis, blastomycosis, and cryptococcus. Some have advocated for use of fluorodeoxyglucose (FDG)/positron emission tomography (PET) to differentiate between infection and malignancy; however, there is a high rate of false positives secondary to hypermetabolic nature of fungal infections. However, PET/CT does have a high negative predictive value [67].

Nonparenchymal masses may be seen in the hilar or mediastinal areas. Chronic pulmonary blastomycosis might present with a single large perihilar mass that often warrants a thoracotomy to rule out possible carcinoma. In fact, up to 31 % of patients present with paramediastinal or perihilar masses, which unlike histoplasmosis, rarely contain calcification [21]. Other findings of cryptococcosis in AIDS patients include mediastinal masses.

Virtually any nodular lesion has the potential to cavitate. Nodular lesions seen in Aspergillus and Mucorales infections may progress to cavitate to what is recognized as the “air crescent sign” [41, 57, 58, 68]. The air crescent sign represents cavitation of nodules caused by resorption of necrotic tissue by returning neutrophils [55] (Fig. 6.10). It is usually unilateral and frequently in the upper lobes [38]. Other nodules, single or multiple, can cavitate and then proceed to either diffuse pulmonary consolidation or abrupt development of large wedge-shaped pleural-based lesions mimicking bland infarction. Thin- or thick-walled cavities as well as cavitary infiltrates can appear in subacute invasive aspergillosis and chronic progressive coccidioidomycosis, both of which can mimic TB [52]. Approximately 5 % of those who develop Coccidioides pneumonia develop thin-walled solitary cavities, typically near the pleura (Fig. 6.11). A chronic form of Coccidioides pneumonia presents as a slowly progressive fibrocavitary process of biapical fibronodular lesions with retraction and cavitation. In pulmonary histoplasmosis, upper lobe cavities are common, except in those with HIV infection. Cavitary infiltrates have also been demonstrated in disseminated disease. Fibrotic apical infiltrates with cavitation have been reported in chronic pulmonary histoplasmosis which can be confused with TB infection or co-infection on chest X-ray [52]. Other fungal infections reported to cause cavitary disease include sporotrichosis and paracoccidioidomycosis; nodular areas are sometimes confluent, often in the lower lobes; cavitation occurs in one third of cases. Cavitation from blastomycosis is unusual and not as commonly seen as in mycobacterial or Histoplasma infections. Cryptococcal infection may present with cavitary masses or nodules, though this is uncommonly seen in the setting of AIDS infection. In cancer patients infected with Pneumocystis previously given prophylactic aerosolized pentamidine, upper lobe infiltrative disease suggestive of tuberculosis may be seen, but cavitary lesions are very uncommon.