Differential diagnoses of acute ground-glass opacity in chest computed tomography: pictorial essay

ABSTRACT Ground-glass opacity is a very frequent and unspecified finding in chest computed tomography. Therefore, it admits a wide range of differential diagnoses in the acute context, from viral pneumonias such as influenza virus, coronavirus disease 2019 and cytomegalovirus and even non-infectious lesions, such as vaping, pulmonary infarction, alveolar hemorrhage and pulmonary edema. For this diagnostic differentiation, ground glass must be correlated with other findings in imaging tests, with laboratory tests and with the patients’ clinical condition. In the context of a pandemic, it is extremely important to remember the other pathologies with similar findings to coronavirus disease 2019 in the imaging exams.


❚ INTRODUCTION
The tomographic pattern of ground-glass opacities is a non-specific finding, and may reflect interstitial thickening, partial filling or partial collapse of the einstein (São Paulo). 2021;19:1-8 alveoli, increased blood supply or even a combination of these findings. Radiographically, it is defined as an increase in the lung parenchyma density , but with preservation of the bronchovascular markings, differing from consolidation. (1,2) The causes of ground-glass opacities can be divided into acute and chronic. Among the acute causes are infections (atypical bacterial and viral infections), alveolar hemorrhage, pulmonary edema, diffuse alveolar damage, pulmonary embolism, and some neoplasms. (3)(4)(5)(6)(7)(8)(9) In the context of the pandemic caused by the coronavirus 2 of severe acute respiratory syndrome (SARS-CoV-2), early diagnosis is mandatory to reduce the risk of infection and its spreading.
Despite being a frequent finding in coronavirus 2019 disease (COVID- 19), ground-glass opacities are not pathognomonic of coronavirus infection. Therefore, none of the other causes should be neglected in the differential diagnosis. To help determine a suggestive diagnosis from computed tomography (CT) imaging, this finding should be correlated with the other characteristics of the image and the patients' clinical and laboratory data. (10) The objective of this study was to review and help differentiate pathologies with groundglass opacities in the lung parenchyma on CT, through a literature review based on tomographic images from our service.

Alveolar hemorrhage
Alveolar hemorrhage is bleeding that originates from pulmonary microcirculation. The patient may present with hemoptysis and anemia among the clinical symptoms, and the imaging findings help narrow down the differential diagnosis. The alterations in CT include alveolar infiltrates with central distribution, sparing apices and costophrenic angles and not respecting fissures, and these infiltrates may converge in consolidations. Pulmonary involvement is usually bilateral and diffuse. In its clinical course, when the cause of the hemorrhage ceases, the pulmonary alterations tend to disappear. The definitive diagnosis is established by bronchoscopy and bronchoalveolar lavage (11) (Figure 1).

Pulmonary edema
Pulmonary edema is caused by the accumulation of fluid in the extravascular compartments, according to the capillary membrane permeability and the oncotic pressure. Radiologically, the typical aspect is the batwing sign, characterized by ground-glass opacities associated with bilateral and symmetric smooth septal thickening, sparing the periphery of the lungs. (1,2) When there is an asymmetric distribution of the edema, this is probably related to mitral valve regurgitation or chronic obstructive pulmonary disease. In these cases, tomographic changes predominate, respectively, in the right upper lobe and in the regions least affected by the previous disease. When the pulmonary edema is cardiogenic, pleural effusion may be present (7) (Figure 2).

Viral pneumonia
Viruses are the most common causes of respiratory infection. The imaging findings of viral pneumonias are diverse and overlap with those of non-viral infections and inflammatory conditions. Although a definitive diagnosis cannot be made with imaging findings alone, recognition of viral pneumonia patterns can help differentiate viral pathogens, and reduce the use of antibiotics. (4,12) Cytomegalovirus usually causes an asymptomatic infection or mild flu-like symptoms in immunocompetent patients. However, it can cause life-threatening lung infection in immunocompromised patients. The predominant radiological findings are bilateral and asymmetric ground-glass opacities, small, poorly defined centrilobular nodules, and alveolar consolidations. Thickening of interlobular septa may also be associated with this condition (4) (Figure 3).
The influenza virus (H1N1) causes seasonal infections of the respiratory tract, including trachea and bronchi. These infections can be periodic, endemic or pandemic. The main tomographic findings are unilateral or bilateral ground-glass opacities, which may be associated with focal or multifocal consolidation areas. These changes have a predominantly peribronchovascular and subpleural distribution, with an aspect similar to organizing pneumonia (5) (Figure 4). COVID-19 has become increasingly prevalent worldwide and it reached a pandemic level in March 2020. Ground-glass opacities with bilateral distribution, with or without consolidations, preferably with peripheral distribution and in the posterior segments, are the hallmarks of COVID-19. Other CT imaging findings are crazy paving, reversed halo and consolidation foci (10) (Figure 5). Measles is a cause of infection mainly in childhood. Even with active immunization, a significant number of older patients develop the disease, probably due to vaccine failure or non-immunization and late exposure in adulthood. Tomographic findings of measles pneumonia include ground-glass opacities, halo sign, alveolar consolidations and centrilobular micronodules. Increased hilar lymph nodes and pleural effusion are often associated with this condition (13,14) (Figure 6).

Mycoplasma pneumoniae pneumonia
Mycoplasma pneumonia is one of the most common cause of community-acquired pneumonia in young adults. Histologically, it is characterized by the presence of acute cellular bronchiolitis, which can progress to bronchopneumonia.

Pulmonary infarction
Pulmonary thromboembolism is the main cause of pulmonary infarction. Its diagnosis, during the acute phase, follows a protocol with laboratory and imaging tests. A computed tomography angiography using a dedicated protocol is the gold standard imaging diagnostic method, in which a filling failure is observed in the pulmonary artery and/or its branches. The findings in a pulmonary parenchyma infarction include an reversed halo opacity (peripheral consolidation and a groundglass opacity center), which is wedge-shaped, with the base facing the pleura and the apex facing the hilum (17,18) (Figure 8).

Fat embolism
Fat embolism results in capillaritis induced by fat globules released into the blood after long bone trauma. It manifests as well-demarcated bilateral ground-glass opacities or as poorly defined centrilobular nodules (18) (Figure 9).

Pulmonary contusion
In cases of chest trauma, chest radiography is the first exam performed to assess pneumothorax. In negative cases, further investigation is recommended using chest CT, which has greater sensitivity and specificity for all other changes related to trauma. Pulmonary contusion is the most common lung injury in the context of nonpenetrating chest trauma. It is defined as a traumatic lesion in the alveoli with alveolar hemorrhage, but with no significant alveolar rupture. It appears on tomography in 6 hours after the event, and resolution begins within 24 to 48 hours. Chest CT is characterized by groundglass opacities and/or irregular consolidations, which tend to spare the periphery of the parenchyma close to the pleura (subpleural sparing), located at the site of the trauma or in the opposite side (contrecoup injury), not respecting fissures and/or bronchial distribution (19) (Figure 10).

Lipoid pneumonia
Lipoid pneumonia is an uncommon condition, resulting from the suction of oils into the alveoli. In adults, the most common cause is the use of mineral oil to treat constipation, followed by the use of oily nose drops to treat chronic rhinitis. Computed tomography may show alveolar consolidations, groundglass opacities, interlobular septum and intralobular interstitial thickening, and poorly defined centrilobular micronodules. Crazy paving pattern, which consists of thickening of interlobular septa overlaid with groundglass opacities, is frequently observed. The most characteristic sign of lipoid pneumonia is the presence of pulmonary consolidations with fat attenuation (negative attenuation values) (20) (Figure 11).

Pneumocystis pneumonia
It is caused by Pneumocystis jirovecii, an atypical fungus. It is not commonly found in the lungs of immunocompetent individuals. It is considered an opportunistic infection in immunosuppressed patients, such as patients with HIV/AIDS, cancer, undergoing chemotherapy or in chronic use of corticosteroids. On computed tomography, the main findings are extensive ground-glass opacities, usually with central distribution, relatively sparing the periphery, and there may also be a crazy paving with diffuse distribution. In more advanced disease stages, intralobular lines overlapping groundglass opacities (mosaic pavement) and consolidation may occur. Pulmonary cysts with thick walls, of different shapes and sizes, are observed in approximately one third of patients (8,21) (Figure 12).

E-cigarette, or Vaping, product use-associated lung injury
Electronic cigarettes are devices that aerosolize nicotine concentrates mixed with other solvents and are sold as an alternative to cigarettes. They have become increasingly popular, but they are not innocuous substitutes for traditional cigarettes. Several patterns of lung injury associated with vaping inhalation (Evali, standing for E-cigarette, or Vaping, product use-associated lung injury) have been described. There are several forms of radiological presentation, including hypersensitivity pneumonia, with ground-glass opacity findings, poorly defined centrilobular nodules and, occasionally, mosaic attenuation with predominance in the middle and upper lung fields. In addition, it may present as diffuse alveolar hemorrhage with centrilobular nodules, ground-glass opacities and consolidations, sparing the subpleural region; as acute lung injury, with ground-glass opacities, consolidations, and crazy paving, frequently in a gravity-dependent distribution in the acute phase; as organizing pneumonia characterized by ground-glass opacities, consolidations with peripheral or perilobular distribution, and an reversed halo sign, as well as lipoid pneumonia with ground-glass opacities, consolidations, and crazy paving, with fat attenuation in consolidations (22) (Figure 13).

Organizing pneumonia
The histological pattern is characterized by granulation tissue buds inside the alveoli and alveolar ducts, with chronic inflammation of the adjacent parenchyma. When it has no known cause, it is classified as primary or cryptogenic. When a causal relation can be established, it is classified as secondary. The causes are numerous and include infections, iatrogenic causes (reactions to drugs or radiation therapy), use of illicit drugs, and autoimmune diseases. Typical CT findings include ground-glass opacities, consolidations, and reversed halo images with peribronchovascular distribution (23) (Figure 14).

❚ CONCLUSION
Ground-glass opacities on chest computed tomography are very common and, for the most part, nonspecific. Therefore, for an accurate diagnosis, it is necessary to correlate the patient's clinical and laboratory data with other computed tomography imaging findings.