X-Rays and Computed Tomography

Radiology is the science of studying anatomy and pathology using x-rays—electromagnetic waves (like visible light, only with a much shorter wavelength) capable of penetrating the tissues. In computed tomography (CT), the widely recognized imaging standard of reference for assessment of most pulmonary abnormalities, a collimated fan beam of radiation is generated by an x-ray tube inside a gantry (Fig. 3-1).

Figure 3-1 The figure summarizes conceptually the steps of a computed tomography examination, from the acquisition of the images in the gantry (1) to their displaying on a monitor (4). In the computer, the information about a set of volume units of body (voxels) (2) is rendered on the monitor on a scale of grays, according to their average attenuation (3).

The beam is quite homogeneous when entering the body (ingoing radiation) but, point by point, inhomogeneous when exiting (outgoing radiation) because of different attenuations produced by the tissues. The attenuation highly depends on the characteristics of the tissue, calcium being at the highest and air at the lowest end of a scale with soft tissue densities (e.g., organs, muscles, blood vessels, interstitium) and fat in between (see Fig. 3-1).

Always point by point, the outgoing radiation activates a matrix of tiny sensible elements (detectors) during a continuous spiral movement of the tube-detectors system around the body (scan), and the information acquired is stored in a computer. At the end of the process, the system contains a digital three-dimensional map of single unitary elements (voxels) composing the scanned volume (see Fig. 3-1).

Computed Tomography, Spiral Computed Tomography, and High-Resolution Computed Tomography

For viewing, CT is able to return the values of a two-dimensional matrix of voxels on a monitor over a scale of grays (gray-scale), where the brightest (white) spots represent the elements with higher attenuation and the darkest (black) the ones of lower attenuation. Although spiral CT is able to show images of equal quality along planes in any direction, the axial (transverse), frontal (coronal), and sagittal (lateral) views are used more commonly (Figs. 3-2 to 3-4). For each view, a stack of images may be seen in sequence simply by browsing at the workstation through the volumetric data set; at the end of the diagnostic process, the entire volume is investigated from multiple points of view.

Figure 3-2 Computed tomography transverse (axial) view of the lungs at the level of the heart (sun) (case with lung pathology). In the axial images, it is as if the patient were seen from below. Consequently, the right lung is to the left of the viewer. R, right; L, left.

Figure 3-3 Computed tomography frontal (coronal) view of the lungs at the level of the descending aorta (sun) (case with lung pathology). Again, the right of the patient is to the left of the viewer. The patient is always seen vis-à-vis. R, right; L, left.

Figure 3-4 Computed tomography sagittal (lateral) view of the right lung (case with lung pathology). In the sagittal images, the anteroposterior and the craniocaudal directions are explored. A, anterior; P, posterior.

With a diffuse lung disease (DLD), the high-resolution option is used. An actual collimation of 0.5 to 2 mm and a high spatial frequency reconstruction algorithm (edge enhancing) generate the final images.¹ The narrow collimation reduces the voxel size, thereby minimizing the averaging of densities (attenuations) inside them, and this allows the rendering of subtle anatomical details (down to 0.1–0.2 mm in the most favorable conditions¹). A limit is the noise of the image because of the reduced radiation penetrating such small voxels. However, at the pulmonary level, the difference of attenuation (contrast) between lung structures and air is high; thus, the signal is high, and the final signal-to-noise ratio remains adequate for diagnostic purposes.

Terminology

In general, the structures that attenuate more are whiter (thus, more opaque or dense or also hyperdense) than the structures that attenuate less (thus, more transparent or lucent or also hyperlucent). Therefore, the concept of density/opacity/attenuation of an element is a relative one, and for the object of interest it should be expressed in comparison with a reference structure, usually the surrounding background. The mediastinal vessels, for example, are denser than the fat in which they are embedded, but in turn this fat is denser than the tracheal lumen containing air (Fig. 3-5).

Figure 3-5 Effect of different window settings on the same image at the level of the aortic arch (sun). The upper figure has been documented with a mediastinal window that optimizes the contrast on the details at the soft tissue level. The azygos vein (arrow), for example, and a couple of small lymph nodes in the anterior mediastinum (arrowhead) are nicely seen. The lung window (lower image), on the contrary, optimizes the contrast at the lung level and allows recognition of small hyperlucencies (curved arrows) inside faint peripheral lung opacity.

In CT, the observed attenuations also can be described using a quantitative scale measured in Hounsfield units (HUs), where the zero value is given to water. Most common densities are air (−1000 HU), fat (−120 HU), water (0 HU), muscle (+40 HU), radiologic contrast medium (+130 HU), and bone (+400 or more HU).

If a special iodinated substance (contrast medium) is injected intravenously before the examination, the visibility of the tissues is enhanced (contrast enhancement) because iodine is a powerful absorber of radiation (see Fig. 3-5). A contrast medium is used rarely in the studies performed for a suspected DLD but frequently when a mass or a vascular condition is under investigation.

The body structures are best observed on monitors or films where the brightness/contrast is optimized to bring out the details of the image. However, human eye limitations do not allow a real-time appreciation of these details over the entire dynamic range of chest attenuations. Fortunately, all pertinent data are available to the machine, and the operator needs only to press a button to switch, through a dedicated processing referred to as windowing and leveling, from a mediastinal window (where the details in the lung are squeezed down to the absolute blackness) to a lung window (where the soft tissues are leveled out but the lung structures stand out with maximal detail) (see Fig. 3-5).

Arteries, Veins, and Bronchi

When examined using a lung window, the lungs appear as overall grayish structures delineated by the mediastinum and thoracic cage. Their shape depends on how they are cut by the plane of the section (see Figs. 3-2 to 3-4). The homogeneously whitish elements standing out over this background are blood vessels, which appear roundish or linear depending on the plane of section. Their size should be appropriate to their position within the lung (central versus peripheral) (Fig. 3-6). Each artery is joined by a companion airway, characterized longitudinally as a pair of tapering whitish lines separated by air, which branch regularly (“railway track” appearance). The airways appear as white rings when cut transversally (see Fig. 3-6). Actually, the visibility of bronchial structures within an aerated parenchyma is far below the visibility of companion vessels because of the mostly air-containing nature of the former. Consequently, when looking at a normal lung, the general feeling is of a predominance of blood vessels with only sporadic visibility of bronchioles within the outer third of the lungs.

Figure 3-6 Frontal view of a normal right lung, inferiorly delimitated by the diaphragmatic dome (above the sun). White lines and dots within the pulmonary parenchyma are vessels (arrows). Black lines and rings are bronchi (arrowheads). The figure also shows a pleural fissure (curved arrow).

The outer wall of the arteries and both the outer and inner surface of the bronchial walls should present a sharply defined interface with the surrounding parenchyma (Fig. 3-7). As a rule, bronchial walls in corresponding regions of both lungs should be similar in thickness. Moreover, coupled bronchi and arteries should present roughly the same diameter, and this in turn depends on their position (central or peripheral).¹ The arteries tend to divide dichotomously, whereas the veins often present a monopodial branching with several smaller branches flowing into a main collection drain. Arteries and veins also have a different course that becomes almost perpendicular at the level of the vein entrance into the mediastinum and right heart (see Fig. 3-7).

Figure 3-7 Arteries (arrows) and bronchi (arrowheads) run parallel to each other, and they are approximately the same size at every level. The right inferior pulmonary vein (curved arrow) enters the left atrium (sun).

Mediastinal and thoracic pleura are invisible when normal. However, they can appear as subtle tiny linear opacities at the fissural level, where two layers fuse radiologically (see Fig. 3-7). When normal, lymphatics are not visible at any level, their size being inadequate to be perceptible radiologically.

Secondary Lobule

At the periphery of the lung, after 28 generations of arteries and 23 generations of bronchi,² arteries and bronchi become so small that they become invisible. As a consequence, the far peripheral pulmonary parenchyma should have no visible vessels, and the same and even more is true for the bronchi (see Figs. 3-6 and 3-7). Thus, the appreciation of vessels immediately below the pleural surface should point at an abnormality. However, exceptions are possible in the most dependent areas (Fig. 3-8), where the hydrostatic pressure is higher and the vessels larger.

Figure 3-8 Close-up detail of the posterior portion of the right lung in an axial view at the level of the intermediate bronchus (sun). Here we are facing the lobular level, with the centrilobular artery (arrow) and bronchiole (arrowhead) and a perilobular vein (curved arrow).

The centrilobular bronchioles, in particular, should not be visible, and also, when normal, the interstitial framework at the lobular level should not be appreciable per se. Consequently, when an intralobular network of white lines and/or the walls of bronchioles become visible, this means that they are thickened and hence abnormal. In general, under normal circumstances, the lobular architecture is discernible only here and there when fragments of centrilobular arteries and perilobular veins are identified; this is more frequent in the dependent portions of the lung (see Fig. 3-8).

Increasing Visibility

Curved Multiplanar Reformation

Having the entire volume available and working digitally makes it possible to reconstruct objects traveling in and out of a two-dimensional plane along curved reformatted images (curved MPR). This allows a structure to be traced and displayed as if it lay along a single plane. For example, an intuitive visualization of the entire course of a bronchus from a cavitated lesion to its origin can be achieved by displaying it along a manually or automatically generated centerline of the bronchial lumen (Fig. 3-9). The curved reformatted images are not real, but they are effective and easy to generate and therefore suitable for practical purposes (e.g., “virtual” bronchoscopy).

Figure 3-9 Axial view (left) and curved reformatted image (right) of the right paramediastinal region in a patient with emphysema and a cavitary lesion of the lung. The axial image is in a plane. The right is artificially reconstructed along the drainage bronchus (arrows); however, it is effective in showing the bronchial ramifications from the hilum to the periphery. MPR, multiplanar reformation.

Increasing Ambience

Maximum Intensity Projection

When averaging, no information from the patient is lost, but averaging requires a millimetric slice thickness. Otherwise, the details of interest are lost because the operator averages them in with the background. However, in doing so the operator loses the ambience (e.g., where pathologic lesions exist in space, which is of extraordinary significance for the diagnostic process). Increasing the thickness of the slice lowers resolution and results in the superimposition of too many elements in the same image. For this reason, a number of techniques have been implemented.

The maximum intensity projection (MIP) technique renders only the voxels with higher attenuation in a thick slice (0.5–2 cm). The technique is suitable to render tridimensionally the vascular tree standing against a black background; moreover, with MIP, it is possible to obtain a comprehensive representation of the position of various lesions inside the lobular framework³ (Fig. 3-10). In selected cases, MIP images are useful for distinguishing between vessels and nodules and, when nodules are present, to assess their profusion.

Figure 3-10 The image to the left (Ave.) is an axial view of the right lung in a patient with multiple nodular lesions. The maximum intensity projection (MIP) image to the right shows a thicker axial slab at the same level and in a way that the relationships between the lesions and the vessels are more easily appreciated, as in a tridimensional environment.

Minimum Intensity Projection

The minimum intensity projection (minIP) technique renders only the voxels with lower attenuation in a thick slice (0.5–2 cm). This technique is useful for improving the visualization of hyperlucent elements (bronchi, emphysema, bullae, honeycombing) and some opacities, allowing a more precise study of their attributes and distribution. The minIP technique is also ideal for investigating bronchial caliper and course, particularly within areas of increased density (Fig. 3-11).

Figure 3-11 Sagittal view (minIP image) of a lung in a patient with patchy areas of increased opacity (suns). Note how easily the extension of the opacities is grasped with this technique and how precisely the bronchial elements inside them are depicted.

Volume Rendering

Volume rendering (VR) techniques may be also used in the assessment of DLD. When implemented, the machine renders only the structures within a specific range of attenuations and contained within a chosen volume. Volume rendering may be useful for studying a volume of lung in three dimensions from within or for inspecting its surface from outside (external volume rendering) (Fig. 3-12). This is particularly useful for concisely looking at the pulmonary surface and its abnormalities and for helping to make medical decisions (e.g., determining the site of a surgical biopsy).

Figure 3-12 Tridimensional external lateral view of a lung in a patient with patchy hyperlucencies due to idiopathic UIP (arrows). With this technique (tridimensional volume rendering), it is possible to obtain synthetic and effective visions of both lung surfaces from different points of view. A, anterior; P, posterior.

Prone and Expiratory Computed Tomography

CT examinations are routinely performed on supine patients at the end of inspiration. Then, the higher content of air in the lungs allows better contrast (hence, better visibility) of anatomy and pathology.

However, in supine patients, some whiter atelectatic lung is frequently seen in the most dependent posterior areas (see Fig. 3-8), where it may simulate pathology or, alternatively, hide it. These normal densities disappear with prone positioning (Fig. 3-13), and indeed some experts suggest the routine use of prone scans when diseases under consideration characteristically involve posterior lung (e.g., asbestosis).⁴

Figure 3-13 Supine (top) and prone (bottom) axial views of the right lung approximately at the same level. In the supine scan, there is an area of faint increased attenuation in the subpleural region (arrow). The opacity disappears in the prone position, so it should be functional and not due to lung pathology.

In normal subjects, an expiratory scan shows a uniform reduction in size of the lungs together with a homogeneous increase of their density, due to the reduced amount of air within the alveoli. When an arterial obstructive or a bronchial stenotic disease is present, variable portions of lung become darker than normal because of the reduced blood supply caused directly by hampered vascular filling or indirectly caused by hypoxemic vasoconstriction. However, in the expiratory CT, the hyperlucent areas due to vascular obstruction physiologically increase their density, whereas in the case of bronchial stenosis they do not because the air does not exit from the alveoli (air trapping) (Fig. 3-14). When arterial obstructive or bronchial stenotic diseases are suspected, supplementary expiratory scans should then be added to complete the investigative process.

Figure 3-14 Frontal view of the right lung of a patient with constrictive bronchiolitis. The existence of patchy areas of different density due to air trapping is better demonstrated by the expiratory scan (arrowheads). Insp., inspiratory scan; Exp., expiratory scan.

Interstitial Hydrostatic Pulmonary Edema

The septal lines of pulmonary edema are usually associated with smooth subpleural and peribronchovascular interstitial thickening (peribronchial cuffing). Patchy lobular GGO often coexists, due to minimal alveolar edema⁹ (Fig. 3-23). There is a tendency for the hydrostatic edema to show a symmetrical basal and posterior distribution (in supine patients) (Fig. 3-24), but patchy nongravitational distributions are not impossible.¹⁰

Figure 3-23 This coronal view shows bilateral smooth perilobular, peribronchovascular, and subpleural thickening in a patient with hydrostatic pulmonary edema (Fig. 3-22 is a close-up of this image). Areas of faint GGO are also present (arrows).

Figure 3-24 Supine patient, axial scan at the lung bases. The image reveals the posterior (gravitational) prevalence of bronchial cuffing (curved arrows) and bilateral pleural effusion (arrows) in a patient with congestive heart failure. Note also the enlarged heart (sun).

Heart enlargement and bilateral pleural effusion are common findings in cardiogenic pulmonary edema (see Fig. 3-24), and in a number of patients also a pericardial effusion may coexist. When the flow of the lymph to the systemic veins decreases, an enlargement of mediastinal lymph nodes due to fluid stagnation may occur¹¹ (Fig. 3-25).

Figure 3-25 Axial scan (mediastinal window) in a patient with congestive heart failure. Subcarinal enlarged lymph nodes are visible in the mediastinum (curved arrows). A small bilateral pleural effusion coexists (arrows).

Lymphangitic Carcinomatosis

Lymphangitic carcinomatosis may present with a fully smooth subset¹² (Fig. 3-26), but not infrequently nodular irregularities (beaded appearance of septa and fissures) and random micronodules in areas of thickening occur. Nodules result from focal growth of cells within the lymphatics and local extensions into the parenchyma.^6,13 Subpleural thickening, when present, may also be smooth or nodular. Pleural effusion is unilateral in 50% of cases.

Figure 3-26 Sagittal view in a patient with lymphangitic carcinomatosis. The image shows smooth thickening of interlobular septa in the right upper lobe (curved arrows) and a thickening of the peribronchovascular interstitium, resulting in an increased thickness of bronchial walls and increased size of companion arteries (arrows). A pleural effusion is also present, with basal (sun) and intrafissural distribution.

The lesions of lymphangitic carcinomatosis are typically patchy, often unilateral, and not gravity-dependent¹² (Fig. 3-27). Hilar lymphadenopathy is visible in 50% of patients. Enlarged mediastinal lymph nodes can be also seen in a number of cases (25% to 50%).¹³ Dedicated CT window settings may demonstrate metastatic lesions elsewhere (Fig. 3-28).

Figure 3-27 This coronal view shows a unilateral lymphangitic carcinomatosis. Note the non–gravity-dependent smooth septal thickening in the right upper lobe (arrowhead), the thickening of the peribronchovascular interstitium (curved arrow), and a pleural effusion (sun), together with lower lobe atelectasis.

Figure 3-28 Sagittal view at the level of the midline in a patient with multiple skeletal metastases. The image has been documented with bone window settings and shows multifocal spotty white areas in the sternum (arrow) and thoracic vertebrae (arrowheads).

Veno-occlusive Disease

The presentation of veno-occlusive disease is similar to that of hydrostatic pulmonary edema. Smooth septal lines, bronchial cuffing, and patches of GGO related to alveolar wall thickening and pulmonary edema are apparent^14,15 (Fig. 3-29).

Figure 3-29 Pulmonary veno-occlusive disease in a 25-year-old man. The axial CT image shows widespread smoothly thickened interlobular septa (curved arrow), bronchial cuffing in the centrilobular area (arrowhead), and a right pleural effusion (arrow). The sun indicates the heart.

The lesions present a geographical appearance with variable localization. They are always bilateral and may have a gravitational preference¹⁵ (Fig. 3-30).

Figure 3-30 An axial scan of the same patient as in Figure 3-29 confirms the gravitational distribution of the lesions.

A key radiologic sign is a coexisting enlargement of the central pulmonary arteries compatible with arterial pulmonary hypertension¹⁶ (Fig. 3-31). The right side of the heart also may be dilated without evidence of left atrial or ventricular enlargement. In addition, pericardial or pleural effusion and enlargement of the mediastinal lymph nodes may be visible.¹⁴

Figure 3-31 A contrast-enhanced axial scan (mediastinal window) of the same patient as in Figure 3-29 reveals a dilated central pulmonary artery (arrowhead) and a right pleural effusion (curved arrow). Compare the size of the main pulmonary artery with the diameter of the ascending aorta (arrow): they should be the same in a normal individual.

Erdheim-Chester Disease

Erdheim-Chester disease is a non–Langerhans cell systemic histiocytosis that produces smooth septal and subpleural interstitial thickening, with more-or-less regular contours (Fig. 3-32). Multifocal areas of ground glass attenuation, small centrilobular nodular opacities, and pleural effusion may be also present.^17,18

Figure 3-32 Computed tomography scan of a patient with Erdheim-Chester disease. The image shows a caricatural bilateral smooth thickening of interlobular septa (curved arrow) and subpleural interstitium along the costal margins (arrowheads) and the fissures.

The septal lesions of Erdheim-Chester disease involve both lungs diffusely (Fig. 3-33), but in some cases they may predominate in the upper or lower lobes.¹⁸ In addition, the pleura and the mediastinal structures may be involved (Fig. 3-34). The superior vena cava, along with the pulmonary trunk and main arteries, may be “coated” by anomalous tissue, and in case of severe involvement, a reduction of the vascular lumen is also possible. The cardiac involvement may be endocardial or myocardial (not visible with HRCT) or pericardial, the latter being the most frequent and best visible on images, thanks to the contrast provided by the adjacent pericardial fat¹⁹ (see Fig. 3-34).

Figure 3-33 Widespread basal septal thickening in the same patient as in Figure 3-32.

Figure 3-34 Axial scan (mediastinal window) of the same patient as in Figure 3-32. An abnormal dense tissue thickens the subpleural spaces (curved arrows) and infiltrates the mediastinal fat (arrowheads).

Diffuse Interstitial Amyloidosis

The diffuse interstitial form of amyloidosis is characterized by smooth or nodular septal, peribronchovascular, and subpleural thickening, frequently (50%) associated with well-defined subpleural nodules that are often calcified (Fig. 3-37).^22,23 The lesions of diffuse pulmonary amyloidosis show a basal and peripheral prevalence²⁴ (Fig. 3-38).

Figure 3-37 Diffuse interstitial amyloidosis. This axial scan at the level of the heart (sun) shows both smooth and nodular septal thickening (arrowheads) associated with well-defined subpleural nodules (curved arrow).

Figure 3-38 This is a more basal scan from the same patient as in Figure 3-37. Bull’s-eye, liver; sun, heart.

The key to the diagnosis is the existence of subpleural, confluent, calcified consolidations (Fig. 3-39). Associated findings are lymph node enlargement and unilateral or bilateral pleural effusions.²⁵ Tracheobronchial involvement may be also present, with thickening of the tracheal and bronchial walls due to deposition of amyloid.

Figure 3-39 Mediastinal window at the level of the great vessels (bull’s-eyes) in the same patient as Figure 3-37. The image shows patchy peripheral calcified consolidations in both lungs (arrowheads).

Asbestosis

The early lesions of this disease are a combination of centrilobular dotlike and branching³⁰ opacities, which are often arranged in clusters or connected in form of subpleural curvilinear lines³¹ (Fig. 3-48). These nodular opacities correspond to peribronchiolar nodular fibrosis responsible also for hyperlucent areas (mosaic perfusion) of lobular size from air trapping.³¹ The subsequent evolution may lead to an irregular interlobular and intralobular reticulation with bronchiectasis, architectural distortion, and honeycombing.³²

Figure 3-48 Axial scan at the level of the heart (sun) in a patient with asbestosis. Areas of advanced fibrosis with honeycombing (arrowhead), but also more initial subpleural lines with beaded appearance (arrow) are evident. The pattern is completed in this case by patchy areas of mosaic oligemia (curved arrows).

The lesions are predominantly or exclusively located in the subpleural lobules of the posterior regions of the lower lobes in the early phases of disease,³⁰ but they may become more extensive as the disease progresses (Fig. 3-49).

Figure 3-49 Axial scan at the carinal level in the same patient as in Figure 3-48. At this transversal level, the fibrotic involvement of the lung is only initial, and the honeycomb changes are confined in restricted areas (arrow). Bilaterally, there are pleural plaques of typical aspect (arrowheads).

Diffuse parietal pleural thickening and pleural plaques with or without calcifications (Fig.3-50; see also Figs. 3-48 and 3-49) are considered typical of the asbestos-related disease, but not all patients with asbestosis show pleural abnormalities.² Parenchymal bands are also characteristic of this disease (see Fig. 3-50) and may reflect thickening of interlobular septa, fibrosis along bronchovascular sheaths, coarse scars, or areas of atelectasis adjacent to pleural plaques or visceral pleural thickening.^32,33

Figure 3-50 Calcified pleural plaques (curved arrows), subpleural lines (arrowhead), and parenchymal bands (arrows) are variably distributed in this patient with initial parenchymal asbestosis.

Chronic Hypersensitivity Pneumonitis

Fibrotic GGO and irregular reticulation with traction bronchiectasis and bronchiolectasis are the most common features of hypersensitivity pneumonitis, but honeycombing is also a frequent finding. Characteristically, the fibrotic lesions may be associated to a mixture of lobular areas with decreased attenuation, centrilobular nodules, and cysts inside the GGO³⁴ (Fig. 3-51).

Figure 3-51 Mixed densities pattern in a patient with chronic hypersensitivity pneumonitis. Coarse irregular linear opacities (arrowhead) coexist with patchy honeycombing (arrow) and areas of hyperlucent lung with reduced vascularity (curved arrow).

Both reticulation and honeycombing may prevail in the periphery of the lung and may show upper lung predominance (Fig. 3-52). However, a random distribution is also common. Lower lobe predominance is uncommon.³⁴

Figure 3-52 The lesions of chronic HP tend to prevail in the upper regions of the lung (arrows), and this is true also for honeycombing. In this sagittal view of the left lung, the base of the lung is relatively free of lesions, and this is an important element in the differential diagnosis with idiopathic UIP.

Accompanying signs of retraction on the pleural surfaces and on the mediastinal profiles are generic consequences of the underlying fibrosis. Some volume loss may occur, particularly in the upper lungs³⁵ (Fig. 3-53).

Figure 3-53 In chronic HP, interface signs, and evidence of architectural derangement are prevalently located in shrunken upper lobes, indicated here by the upward bowing of the major fissures (arrows).

Idiopathic Usual Interstitial Pneumonia (Clinical Idiopathic Pulmonary Fibrosis)

Patchy areas of dense irregular reticulation and macro,³¹ as well as micro²⁸ honeycombing alternating with normal lung (morphologic heterogeneity), are the most specific feature. Some focal areas of only slightly increased attenuation (due to uneven fibrosis) interspersed with relatively normal alveoli may coexist.²⁸ Rugged pleural surfaces (due to the tendency for fibrosis to occur in the periphery of the secondary lobule) are very frequent.²⁸ Characteristically, the patches of fibrosis are intermingled and sharply marginated with areas of normal parenchyma³⁶ (Fig. 3-54).

Figure 3-54 Axial scan at the level of the right liver dome (bull’s-eye) and of the heart base (sun) in a patient with idiopathic UIP. Areas of patchy honeycombing alternating with normal lung are present (arrowheads) and are typical of this disease.

The disease is typically subpleural,^29,37 with some extension to the inner lung in connection with thickened vessels and ectatic bronchi.²⁸ The longitudinal distribution of the lesions is interesting. Although the more complex lesions with traction bronchiectasis and honeycombing show middle and lower predominance,³⁴ a contemporary irregular reticulation is frequently seen in the upper peripheral lung³⁸ (Fig. 3-55). Especially in advanced fibrosis, the lung becomes smaller and the indirect signs of retraction and remodeling striking.

Figure 3-55 The peripheral regions of both lungs in this frontal view of a patient with idiopathic UIP show an irregular reticulation superiorly (arrows), and typical honeycombing is present at the basal level (arrowheads).

Focal emphysematous hyperlucencies in the upper zones of the lung²⁸ but also inside the basal lesions are possible,³⁹ and these may create diagnostic problems of differential diagnosis with honeycombing.⁴⁰ A mild enlargement of mediastinal lymph nodes is present in approximately 70% of cases.⁴¹ Occasionally, small nodular foci of calcification²⁵ or a disseminated dendriform pulmonary ossification⁴² may be found. Associated solitary pulmonary opacities from lung cancer are possible,⁴³ as much as in all fibrotic disorders.

Some CVDs⁴⁴ and, more rarely, drug reactions⁴⁵ may present with aspects indistinguishable from the idiopathic UIP. Consequently, the suspicion of the underlying disorder may be formulated only on clinical grounds, but occasionally specific signs of the original disease are also seen radiologically^46–48 (Fig. 3-56).

Figure 3-56 Patchy honeycombing alternating with normal lung (UIP subset) in a patient with systemic sclerosis. In this axial scan at the subcarinal level, an enlarged esophagus with air-fluid level is visible (arrowhead) between the intermediate bronchus to the right and the junction of the upper and lower lobe bronchus to the left (arrows).

Idiopathic Fibrotic Nonspecific Interstitial Pneumonia

Characteristic features of disease include reticular/GGO opacities with homogeneous aspect in affected areas. Inside the lesions, traction bronchiectasis and bronchiolectasis are common, and their extent has been shown to be a reliable indicator of fibrosis⁵⁰ (Fig. 3-59). Dense consolidations, on the contrary, are uncommon, and their presence should raise the suspicion of another disease (such as OP, chronic eosinophilic pneumonia, or bronchioloalveolar carcinoma) or, in the appropriate clinical setting, of an acute exacerbation (see Alveolar Pattern, subsets Acute and Chronic).⁴⁹ Honeycombing, if present, is mild and otherwise should raise the suspicion of UIP⁵¹; however, it has been reported that, over time, a number of NSIP originally presenting with NSIP pattern progress to UIP pattern.⁵²

Figure 3-59 This is a patient with a typical fibrotic NSIP subset, possibly from systemic sclerosis because the esophagus is enlarged. Mainly the periphery of both lungs is involved by a subtle reticular GGO (arrows) without significant honeycombing. A shrunk right lower lobe (arrowhead) is more extensively involved, and it contains some bronchiectasis.

The disease is bilateral and symmetric,⁴⁹ involving mainly the lower lungs in more than 90% of the cases⁵¹ (Fig. 3-60), otherwise equally distributed. On the contrary, primarily upper lobe lesions are very rare.⁴⁹ Axially, the pattern is diffuse in more than 50% of the cases or predominantly peripheral subpleural, but in a number of cases (20% to 43% according to some authors^27,51) the immediate subpleural regions are relatively spared.

Figure 3-60 Frontal view of both lungs at the level of the descending aorta (sun). A basal fibrotic GGO with reticulation and bronchiectasis and bronchiolectasis is indicated by the arrows. In this patient, several areas of mosaic oligemia are also present (bull’s-eyes).

Volume loss, mostly of the lower lobes, is fairly common,⁵¹ usually in conjunction with other indirect signs of fibrosis. Lymphadenopathy is possible at the mediastinal level,⁴⁹ usually mild and involving not more than two nodal stations.⁴¹

Several CVDs⁴¹ and adverse reactions to therapeutic drugs^53,54 may present with aspects indistinguishable from the idiopathic NSIP. Consequently, the suspicion of the underlying disorder should be formulated on clinical grounds. Occasionally, specific signs of the original disease are visible radiologically^46–49 (Fig. 3-61).

Figure 3-61 Supine and prone scans at a same axial level (costophrenic angles) in a patient with systemic sclerosis. In the supine image, there is some faint increased attenuation with irregular reticulation in the subpleural lung (arrows). In the prone scan, the GGO is gone (hence reversible) but the reticulation persists (arrows). In both images, the esophagus is enlarged (arrowheads).

Sarcoidosis

Fibrosis may present early in the history of the disease, when nodular elements are fairly well visible. Irregularities of the margin of the nodules, distortion of fissures, bronchial irregularities, traction bronchiectasis, and more-or-less coarse linear opacities corresponding to the fibrotic component of the disease.⁵⁵ The elements of the bronchovascular bundle become crowded and show a zigzagging course with angulations^55,56 (Fig. 3-64). Progressive fibrosis leads to central conglomeration of parahilar bronchi embedded in a dense agglomerate of tissue radiating from the center to the periphery.⁵⁶ Honeycombing and cystic abnormalities may be also seen, but rarely the honeycombing involves mainly the lower lung zones, mimicking UIP/IPF.⁵⁷

Figure 3-64 Axial scan of a patient with mild fibrosing sarcoidosis. There are some white irregular lines outstretched between the hilum and the periphery (arrows). Slightly ectatic bronchi with thickened wall (curved arrows) contribute to the feeling of a tug-of-war fibrosis. Calcified lymph nodes can be seen inside the mediastinum.

The disease shows parahilar predominance between the central and the peripheral middle and upper lung, with patchy accentuation of parenchymal distortion and severity of the lesions^55,58 (Fig. 3-65).

Figure 3-65 Frontal scan of a patient with sarcoidosis. The tug-of-war aspect of the fibrosing component of the disease is well appreciable in the upper lung fields. Several micronodules are also identifiable, in particular in the right middle lung field (arrow).

Mediastinal lymphadenopathy frequently coexists, often calcified. CT findings suggestive of pulmonary hypertension are possible in the late disease.² Cavitation of conglomerated masses may be seen in patients with necrotizing sarcoid granulomatosis, the entity first described by Liebow characterized by sarcoid-like granulomas and vasculitis associated with variable degrees of necrosis⁵⁶ (Fig. 3-66).

Figure 3-66 Necrotizing sarcoid granulomatosis. Here the lesions extending between the hila and the periphery are dense opacities containing air hyperlucencies from cavitation (arrows). Large bronchi stand out; they are embedded and irregularly stretched inside the opacities (arrowhead).

Airway-Centered Interstitial Fibrosis

The main findings of airway-centered interstitial fibrosis are peribronchovascular interstitial thickening with traction bronchiectasis, thickened airway walls, and surrounding dense tissue with irregular margins (Fig. 3-69). Bronchiolectasis and honeycombing may also occur in a limited number of cases. GGO, poorly defined centrilobular micronodules, and lobular air trapping with the mosaic attenuation of the dark lung pattern are lacking.⁵⁹

Figure 3-69 At a first glance, the lesions in this patient with ACIF mimic a nodular disease. Actually, the faint opacities scattered throughout the lungs are due to thickening of bronchial walls (better seen in the inset, where an enlarged view of the area between the curved arrows is shown).

(Courtesy of Fabrizio Luppi, MD, Modena, Italy.)

The lesions show a central rather than a peripheral distribution. They consistently show scarring around the airways⁶⁰ (Fig. 3-70).

Figure 3-70 Another image of the same patient as in Figure 3-69. In the posterior left lung (curved arrows), the insistent thickening of the peripheral airways is well evident (inset).

(Courtesy of Fabrizio Luppi, MD, Modena, Italy.)

Follicular Bronchiolitis

The basic features of follicular bronchiolitis consist of bilateral well-defined or ill-defined small centrilobular nodules (Fig. 3-76). In some patients, the centrilobular opacities may present a branching appearance reflecting the morphology of the small airways involved, thereby with aspects mimicking an aspect called tree-in-bud^66–68 (see Fig. 3-76).

Figure 3-76 Axial view of a patient with follicular bronchiolitis. Innumerable small nodules are scattered throughout both lungs, but they spare the subpleural region (arrowheads), which indicates a centrilobular distribution. In the periphery of the lungs, there are also branching structures with tree-in-bud aspect (curved arrows).

The lesions are bilateral and diffuse (Fig. 3-77), sometimes with a predominant involvement of the lower zones.⁶⁶

Figure 3-77 Sagittal view of the same patient as in Figure 3-76. This computed tomography plane highlights the visibility of the fissures (arrowheads) that are not involved by the nodules. This view also shows the craniocaudal distribution of the lesions that prevail in the right upper (sun) and middle (bull’s-eye) lobes.

Patchy areas of GGO are present in 75% of patients, and mild bronchial wall thickening often exists⁶⁸ (Fig. 3-78). Rare subpleural nodules also may be present (20%), and thin-walled cysts may occur due to “check-valve” obstruction of small bronchioles by lymphoid tissue.^69,70

Figure 3-78 Coronal view of the same patient as in Figure 3-76. Bronchial wall thickening is visible in both parahilar zones (curved arrows).

Subacute Hypersensitivity Pneumonitis

The hypersensitivity pneumonitis pattern is defined by the presence of numerous centrilobular nodules with low-density and ill-defined margins (nodular GGO), usually less than 5 mm in diameter (Fig. 3-79).³⁵ The key to the diagnosis is the coexistence of sporadic lobular areas of air trapping appearing as patches of black lung (see Fig. 3-79). These regions of lobular air trapping are caused by concomitant bronchiolar inflammation and obstruction.⁷¹

Figure 3-79 Subacute hypersensitivity pneumonitis. The axial scan at the level of the heart (sun) shows low-density, ill-defined, uniformly distributed nodules. In terms of their aspect, the nodules are similar to snowflakes. A few dark areas of lobular size due to air trapping are also visible in the middle lobe and in the lingula (arrowheads).

The lesions are uniformly distributed, with possible middle-lower predominance^35,71 (Fig. 3-80).

Figure 3-80 This axial scan of the same patient as in Figure 3-79, but at a lower level, confirms a high prevalence of lesions in the basal lung. The heart is indicated by the sun, the hepatic dome by the bull’s-eye.

Areas of GGO often coexist. These are usually bilateral and symmetric, but sometimes they can be patchy. Another significant diagnostic finding is the combination of patchy GGO, normal lung, and dark lung from air trapping. This mixture of densities gives the lung a distinctive appearance that has been nicknamed “head cheese” because of its resemblance to the variegated cross-sectional appearance of sausage made from parts of the head of a hog⁷² (Fig. 3-81).

Figure 3-81 Another patient with hypersensitivity pneumonitis in the subacute phase. The image shows a patchy mixture of normal parenchyma (arrow), areas of GGO (curved arrow), and dark lobules (arrowhead), resulting in the so-called “head cheese” aspect.

Bronchiolar wall thickening may also occur, and lung cysts have been found occasionally. The latter are probably caused by partial obstruction of bronchioles (“check-valve” mechanism).⁷¹ Mediastinal lymph node enlargement has been described in approximately 30% of patients. In patients with an insidious onset of disease, focal areas of consolidation may be occasionally present, presumably representing OP or superimposed unrelated processes such as aspiration injury or infectious pneumonia.

Respiratory Bronchiolitis–Interstitial Lung Disease

The typical presentation of respiratory bronchiolitis–interstitial lung disease (RB-ILD) is that of centrilobular nodularity (Fig. 3-82), often in combination with areas of GGO and moderate centrilobular emphysema. The nodules present low-density and ill-defined margins (nodular GGO) and may be tiny and difficult to recognize^73,74 (see Fig. 3-82). Centrilobular nodules reflect accumulation of macrophages and inflammation in and around the respiratory bronchioles.

Figure 3-82 RB-ILD in a heavy smoker with cough. The axial image, obtained through the upper lungs, shows diffuse centrilobular nodules bilaterally. The tiny nodules have a very low density; hence, they are difficult to recognize unless a narrow radiologic window is set.

The nodules have an even uniform distribution in the axial plane, and they predominate in the upper lobes⁷⁶ (Fig. 3-83). The areas of GGO involve the lung zones diffusely with a patchy distribution; this sign is thought to reflect the macrophage accumulation in the alveoli and alveolar ducts.⁷⁵

Figure 3-83 Sagittal view of another patient with RB-ILD. Scattered small opacities of faint density (arrows) are present, predominantly in the upper lobes.

Another common finding in RB-ILD is central and peripheral bronchial wall thickening caused by airway inflammation (90%) (Fig. 3-84). Areas of hypoattenuation are noted in 38% of patients and are most likely related to air trapping.^75,77 Sometimes signs of other smoking-related interstitial lung diseases may coexist (i.e., desquamative interstitial pneumonitis, pulmonary Langerhans cell histiocytosis, smoking-related pulmonary fibrosis), creating mixed patterns.⁷⁶

Figure 3-84 Sagittal view of the same patient as in Figure 3-83. The findings range from barely visible micronodular GGOs to a more convincing bronchial wall thickening (arrowheads) and some centrilobular emphysema (curved arrow).

Sarcoidosis

The most characteristic abnormality in patients with sarcoidosis is the presence of small, high-density nodules with well-defined margins, sometimes with shaggy profiles (see Fig. 3-74). The nodules are distributed along the costal margins and the fissures, but they are also concentrated along the bronchovascular sheath^56,78 (Fig. 3-86). They may coalesce to form large nodules or pseudoplaques along the pleural margins⁶² (see Fig. 3-86).

Figure 3-86 Sarcoidosis. Several small nodules with well-defined margins and high density are distributed along the costal margins (curved arrows) and the bronchovascular bundle (arrowhead).

The distribution of the lesions is patchy, with a parahilar predominance (see Fig. 3-86). A predilection for the upper-dorsal lung zones is often present^56,78 (Fig. 3-87).

Figure 3-87 Sagittal view of a patient with sarcoidosis. A middle-upper predominance of the nodules is evident.

Lymphadenopathy is the most common finding in sarcoidosis, and typically it is hilar, bilateral, and symmetrical. In addition, mediastinal lymph node enlargement is often present, especially in the right paratracheal and subcarinal node groups (Fig. 3-88). Lymph node calcifications are visible in 25% to 50% of cases, and these may be amorphous, punctate, dense, or eggshell and suggest chronic disease.⁷⁸

Figure 3-88 Contrast-enhanced frontal view through the middle of the mediastinum in a patient with sarcoidosis. Large subcarinal (arrowhead) and hilar (curved arrows) adenopathies are present. They are quite typical of this disease.

Occasionally, the confluence of several interstitial granulomas may result in large, irregular, masslike nodules without or with air bronchogram, resembling air-space consolidations. Small satellite nodules may be present at the periphery of these opacities, an occurrence referred to as the “galaxy sign,” given its resemblance to collections of stars.⁷⁹ In some cases, on the contrary, the nodules can be so small that they are not distinctly visible, but their attenuation produces patchy areas of finely granular increased opacity (granular GGO). Finally, granulomas situated in the small airways can cause lobular air trapping.⁸⁰

Lymphoid Interstitial Pneumonia

Lymphoid interstitial pneumonia is a multifaceted disease that may present with different patterns depending at least in part on the underlying disease. In patients with acquired immunodeficiency syndrome (AIDS), HRCT most often shows nodular aspects along lymphatic routes. The well-defined nodules range from 1 to 3 mm (Fig. 3-89). This pattern may be associated with thickening of the bronchovascular bundles, mild interlobular septal thickening, and tiny ill-defined centrilobular nodules.⁸¹

Figure 3-89 This axial image in a patient with LIP shows subpleural micronodules (curved arrow) and nodular thickening of interlobular septa (arrows). In this case, the lesions prevail to the right.

The lesions involve mainly the lower lung zones⁸² (Fig. 3-90).

Figure 3-90 Same patient as in Figure 3-89. The axial scan at a lower level shows some prevalence of the nodules in the lower lung.

In Sjögren syndrome, lymphoid interstitial pneumonia is typically associated with round or oval thin-walled cysts of variable size (Fig. 3-91). They may be seen in up to 80% of patients and are typically few in number, and they measure less than 3 cm in diameter. They presumably result from air trapping due to peribronchiolar lymphoid infiltration.^83,84

Figure 3-91 Axial scan at the level of the heart (sun) in a patient with Sjögren syndrome. The image shows several cysts in both lungs; they appear as small, black, rounded lesions with very thin walls (arrows).

Other possible findings include bilateral areas of ground glass attenuation and poorly defined centrilobular nodules, most often in congenital immunodeficiency syndromes. Lymphadenopathy is variably associated with lymphoid interstitial pneumonia, according to different series (0% to 68%).^81,83,85

Silicosis and Coal Worker’s Pneumoconiosis

The characteristic feature of silicosis and coal worker’s pneumoconiosis (CWP) is the presence of multiple nodules with a lymphatic distribution. Usually the nodules predominate in the subpleural regions, but they are also observed in the centrilobular regions (Fig. 3-92). The high-density nodules often have well-defined margins, sometimes with calcification. Subpleural nodules have a rounded or triangular configuration, and if they are confluent, they may resemble pleural plaques (pseudoplaques)⁸⁶ (see Fig. 3-92).

Figure 3-92 Axial thin-section computed tomogram in a patient with silicosis. The image shows numerous small nodules in both lungs. Note also the pseudoplaques that represent aggregates of several subpleural nodules (arrowheads).

The lesions of pneumoconiosis mainly involve the upper and posterior lung zones. Bilateral and symmetrical distributions may be observed, although a right-sided predominance is common^86,87 (Fig. 3-93).

Figure 3-93 Axial scan of a patient with silicosis. The image shows a posterior predominance of the nodules and a higher profusion to the right (arrow).

Hilar and mediastinal lymph node enlargement may precede the appearance of parenchymal nodular lesions. Calcification of lymph nodes is common (Fig. 3-94) and may occur at the periphery of the node, producing an “eggshell” appearance. This so-called “eggshell calcification pattern” is highly suggestive of silicosis.⁸⁷

Figure 3-94 The computed tomography scan, documented with a mediastinal window, shows tiny calcifications in the pretracheal lymph nodes (arrow).

The appearance of large parenchymal opacities or hyperdense areas greater than 1 cm in diameter indicates the presence of complicated silicosis/CWP (progressive massive fibrosis). These masses are often bilateral, symmetrical, and calcified, and they can demonstrate cavitations.⁸⁸

Hematogenous Metastases

The nodules, usually dense and well defined, tend to appear evenly distributed. Individual nodules may have “feeding vessels” consistent with their hematogenous origin (Fig. 3-96). Nodules with poorly defined margins can be identified in 16% to 30% of cases; these may reflect lepidic growth of tumor.^64,89 Nodules may also be cavitated and/or surrounded by a “halo” of ground glass attenuation, which is typical of hemorrhage.^89,90

Figure 3-96 Metastatic nodules. The image shows random nodules of different size, and one of them seems to present a “feeding vessel” (curved arrow). Note also enlarged hilar (arrow) and subcarinal (arrowhead) lymph nodes.

A basilar predominance is typically noted due to preferential blood flow to the lung bases. When limited in number, metastatic nodules may be seen primarily in the lung periphery. In patients who have innumerable metastases, a uniform distribution throughout the lung is common⁸⁹ (Fig. 3-97).

Figure 3-97 The axial image taken through the middle lung zone shows innumerable nodules with uniform random distribution in this patient with metastatic disease.

Macronodules, carcinomatous lymphangitis, and enlarged lymph nodes also may be present (Fig 3-98; see also Fig. 3-96). Occasionally, intravascular tumor emboli may result in nodular or beaded enlargement of the peripheral pulmonary arteries with a tree-in-bud appearance⁹¹ (see Fig. 3-98).

Figure 3-98 Axial image in a patient with metastatic breast carcinoma. A micronodularity is intuitable in the middle lobe, where some lesions assume a tree-in-bud appearance (arrowheads). Note also the mediastinal and hilar soft tissue density due to enlarged lymph nodes (curved arrows).

Miliary Tuberculosis

Numerous dense 1- to 3-mm nodules that are uniform in size, either sharply or poorly defined, are characteristic of this disease (Fig. 3-99). The nodules may be observed in the subpleural regions or along the fissures, but the general impression is of a random distribution. At times, a relationship may be observed with the most peripheral vessels.^92,93 Macronodules resulting from the fusion of several granulomas are sometimes seen. GGOs are common in these patients and may represent areas of edema or multiple microgranulomas.^94,95 The nodules are distributed uniformly throughout the lungs without cephalocaudal or central-to-peripheral preference⁹² (Fig. 3-100).

Figure 3-99 Miliary tuberculosis. The axial image shows innumerable noncalcified nodules of miliary size scattered throughout both lungs with random distribution. The nodules are dense and uniform in size.

Figure 3-100 Sagittal view of the same patient as in Figure 3-99. The tiny nodules are scattered quite uniformly all through the lungs. In the upper lobe, there are also signs of bronchogenic spread of the disease with a tree-in-bud pattern (curved arrows).

Associated findings that may suggest the diagnosis are present in up to 30% of affected persons and include consolidation, cavitation, and signs of bronchogenic spread of the disease with tree-in-bud pattern (see Fig. 3-100) and lymphadenopathy.⁹² Necrotic lymph nodes may be observed in 70% of seropositive patients and in 20% of seronegative patients.⁹³ Diffuse or localized GGO is sometimes seen, and it may herald acute respiratory distress syndrome.^94,95 Changes from previous tuberculosis are seen in 50% of the patients and provide an aid in the differential diagnosis. Such changes often occur in the upper lobes as fibrotic bands with traction bronchiectasis, apical calcified nodules, and areas of oligemia due to previous bronchiolitis obliterans^95,96 (Fig. 3-101).

Figure 3-101 Coronal view of the same patient as in Figure 3-99. Patchy areas of oligemic dark lung (arrowheads) are present in the upper lung fields.

Fungal infection may produce diffuse interstitial lung disease characterized by small nodules with random distribution like miliary tuberculosis.⁹⁷ Also in this type of infection, signs of bronchiolar spreading with bronchioles filled with infected material are often present and result in a tree-in-bud appearance.⁹⁸ All these aspects are most commonly seen in immunocompromised patients.⁹⁹ The presence of cavitation inside the nodules and large nodules with a halo sign are both suggestive of fungal infection. The nodules may be associated with areas of air-space consolidation.^62,100

Acute Interstitial Pneumonia/Acute Respiratory Distress Syndrome

Areas of GGO (100%) and patchy air-space consolidation (92%)¹¹⁸ with air bronchogram¹¹⁹ are the main findings in patients with both acute respiratory distress syndrome and acute interstitial pneumonia¹²⁰ (Fig. 3-109). Interlobular septal thickening (89%) and intralobular reticulation (78%)¹¹⁸ with aspects of crazy paving,^102,103 thickening of the bronchovascular bundle (86%), and nodular (86%) opacities¹¹⁸ are also very frequent. Similar findings with variants have been described in acute eosinophilic pneumonia^121–123 and acute reactions to therapeutic^{45,53,54,124,125} and illicit¹²⁶ drugs.

Figure 3-109 Acute respiratory distress syndrome. Bilateral patchy areas of GGO with crazy paving aspect and an air bronchogram are visible. A bilateral pleural effusion coexists in this patient (arrowheads).

The distribution of the lesions is variable, a specific predominance either in the craniocaudal or axial directions being possible in single cases.¹¹⁸ During the progression of disease, the extent of GGO tends to increase, and more homogeneous, gravity-dependent consolidative opacities appear^118,120 (Fig. 3-110).

Figure 3-110 Extensive bilateral opacification of the lung in a patient with ARDS. The opacities are denser posteriorly, due to progressively atelectatic parenchyma. Note the air bronchogram inside the consolidations, which is typical of the injury edema. There are also abnormal collections of air at the mediastinal (arrowhead) and soft tissue (arrow) level, from barotrauma.

Moving from the acute and subacute to the chronic fibrotic phase, a distortion of the interstitial and bronchovascular markings is frequent (Fig. 3-111), and beyond the first week or two, a dramatic increase of subpleural cysts and bullae also occurs.¹²⁷ On the contrary, if signs of retraction and remodeling are evident in the early phases of disease, an acute exacerbation (acceleration) of a fibrosing disorder should be suspected (see Acceleration of Fibrosing Diseases). Late radiologic features of both acute interstitial pneumonia/acute respiratory distress syndrome are a piling up of findings from original disease, atelectasis, inflammation, and side effects of mechanical ventilation.

Figure 3-111 Late phase of ARDS. An alveolar opacity is still present in the left pericardial region (curved arrow); elsewhere (arrows), there is a network of irregular linear opacities due to residual fibrotic processes.

Acceleration (Acute Exacerbation) of Fibrosing Diseases

The radiologic presentation of accelerated fibrosing diseases (also called acute exacerbation) is a coexistence of more-or-less extensive GGO with or without consolidation and signs of the underlying disorder (Fig. 3-112). In patients with UIP, irregular reticulation with patchy areas of honeycombing^128,129 is visible. In contrast, in patients with NSIP, irregular reticulation and bronchiectasis, as well as increasing of previous GGO, are present.¹³⁰

Figure 3-112 Accelerated UIP. Areas of opacity and GGO prevalent to the right are superimposed to a fine reticulation with subtle honeycombing (arrow). The mediastinum is enlarged, due to traction fibrosis testified by interface signs (arrowhead).

The distribution of the alveolar densities may be multifocal, diffuse (Fig. 3-113) (and when multifocal it tends to evolve rapidly to the diffuse form), or peripheral. In a series of accelerated UIP, multifocal and diffuse disease corresponded to pathologic diffuse alveolar damage, whereas peripheral disease is mainly correlated with OP and numerous fibroblastic foci.¹³¹

Figure 3-113 Accelerated fibrosing disease. There is an intense opacification of most lung parenchyma at this basal level, with a “scratched” aspect due to underlying fibrosing disease. Several ectatic bronchi coexist (arrowheads), and there is also a collection of mediastinal air from barotrauma due to mechanical ventilation (arrows).

The possibility of an acute exacerbation (Fig. 3-114) has been described for idiopathic UIP (clinical IPF), idiopathic NSIP, and both UIP and NSIP associated with connective tissue disorders.^131,132 The specific aspect of the two leading subsets has been described in detail in Fibrotic Pattern.

Figure 3-114 An extensive honeycombing (arrow) prevails at the basal level of this patient with accelerated usual interstitial pneumonia. The rest of the lung is extensively opacified, pointing to an acutely exacerbated fibrosing disorder.

Diffuse Alveolar Hemorrhage

Whatever the underlying cause (e.g., vasculitides, drug reactions, coagulopathies), limited free blood within the lobular boundaries gives origin to ill-defined centrilobular nodules. Larger amounts of fluid flooding the alveoli cause more-or-less extended opacities, ranging in intensity from vague GGO (Fig. 3-115) to intense consolidation.¹³³

Figure 3-115 Patient with microscopic polyangiitis. There is a diffuse granular GGO with some discrete ill-defined nodules that seem connected to small vessels (arrows).

The distribution of the lesions is variable and depends on both the anatomical location and the mechanism by which the hemorrhage occurs. Extended areas of opacification may be patchy or uniform, tend to spare lung apices, and often show parahilar predominance¹³⁴ (Fig. 3-116).

Figure 3-116 The alveolar opacities in this patient with alveolar hemorrhage show neat parahilar predominance.

Within days of an acute episode, the interlobular thickening due to hemosiderin-laden macrophages accumulating in the interstitium may give a crazy paving aspect to the opacities (Fig. 3-117). After repeated episodes, a persistent irregular reticular pattern with traction bronchiectasis, sometimes even with honeycombing, may be seen.¹³³

Figure 3-117 Long-standing alveolar hemorrhage. There is a fine reticular pattern intermingled with the alveolar opacities (arrowhead) and a modest distortion of bronchiolar elements (curved arrow).

Hydrostatic Pulmonary Edema

GGOs accompanied by visible interlobular septa and thickened peribronchovascular bundle are the most common findings^10,135 (Fig. 3-118). Frank parenchymal consolidations may coexist, but they are more typical of advanced cases. Usually, they are not investigated with CT (frank alveolar edema is simply diagnosed with radiography). The specific aspects of the interstitial involvement in pulmonary edema are described in detail in Septal Pattern, subset Smooth.

Figure 3-118 Patient with mild pulmonary edema. In this axial plane, there are patchy areas of GGO (arrowheads) and septal lines (curved arrow), highlighting the lobular boundaries. Some pleural effusion coexists to the right (arrow).

The opacities are diffuse or patchy and bilateral if no reasons for unilaterality exist (e.g., patient’s lateral decubitus, fibrosing mediastinitis).¹³⁵ The lesions often show gravitational or parahilar predominance related to pressure dynamics⁹ (Fig. 3-119). However, in these early phases of edema, the gravitational predominance may be subtle, and in selected cases even an upper lobe distribution of lesions may occur.¹⁰ A characteristically asymmetrical involvement of right middle and upper lobes is the rule in case of myocardial infarction, papillary muscle rupture, and mitral valve insufficiency.¹⁰

Figure 3-119 Pulmonary edema. In this patient, a hazy GGO from partial alveolar filling shows a noticeable central predominance (arrowheads) with sparing of the most peripheral lung.

Unilateral or bilateral pleural effusion and thickening of the interlobar fissures are common in hydrostatic pulmonary edema¹⁰ (Fig. 3-120). In addition, mediastinal lymphadenopathy is not rare at all in patients with left-sided heart failure.¹¹

Figure 3-120 In this patient with patchy parahilar GGO from pulmonary edema, a pleural effusion is also visible on both sides posteriorly (arrows) and inside the fissures (arrowheads).

Infectious Diseases

A mixture of lobular or diffuse GGO/consolidation, centrilobular ill-defined nodules, and thickened interlobular septa may be seen, with a prevalence depending on the specific disease and its severity. The lesions reflect the variable extent of underlying histopathologic features: bronchial and bronchiolar participation, interstitial and alveolar inflammatory cell infiltration, intra-alveolar hemorrhage, and diffuse alveolar damage^134,136 (Fig. 3-121).

Figure 3-121 Patient with H1N1 influenza virus pneumonia. The pattern is dominated by dense homogeneous parahilar consolidations and peripheral nodules of hazy GGO (arrowheads) in centrilobular position.

More than 60% of patients with Mycoplasma pneumoniae pneumonia have lower zone predominance, whereas 50% of patients with fungi have upper zone predominance of the lesions.¹³⁷ In influenza pneumonia, the opacities may show a preference for perivascular (Fig. 3-122) and subpleural areas.¹³⁶ Pneumocystis presents a striking upper lobe predominance of GGO.¹³⁸

Figure 3-122 Patient with H1N1 influenza virus pneumonia. In this frontal view, the consolidations tend to aggregate in the parahilar areas along the bronchovascular bundles.

Nodules are frequent in patients with fungal (65%), viral (77%), and M. pneumoniae pneumonia (89%), and they are much less common in patients with bacterial pneumonia (17%).¹³⁹ In varicella-zoster virus pneumonia, well-defined and ill-defined nodules of 1 to 10 mm diameter are diffusely scattered throughout the lungs (Fig. 3-123); coalescence of nodules and patches of GGO are also possible.¹³⁶ In immunocompromised subjects, especially HIV patients, the presence of extensive, diffuse, bilateral GGO is suggestive (although not specific) for Pneumocystis jiroveci pneumonia;^139,140 it becomes very typical if cystic lesions are contemporarily present.¹³⁷ On the contrary, nodules are absent.¹³⁹

Figure 3-123 External view of the lungs in a subject with varicella-zoster virus pneumonia. The nodular lesions characteristic of this virus are well evident on the surface of the pulmonary parenchyma.

Bronchioloalveolar Carcinoma

The diffuse form of bronchioloalveolar carcinoma is a mixed densities disease. Patchy areas of GGO/consolidation and/or multifocal macronodular lesions with a halo sign are the most common presentations.^141–143 A skeletal, stretched, air bronchogram is frequently seen inside the opacities¹⁴⁴ (Fig. 3-126). Crazy paving aspects and collections of air within consolidations (known as cystic bronchioloalveolar carcinoma) (see Fig. 3-105) are also possible.^143,145 When nodules are present at the lobular level, they assume the aspect of centrilobular ill-defined opacities or, rarely, a tree-in-bud appearance.¹⁴¹

Figure 3-126 Bronchioloalveolar carcinoma. A large consolidation to the right possibly points at the origin of the disease, and elsewhere there are the signs of diffuse spreading. The arrow points to a narrowed and stretched bronchus inside the main opacity.

Central or peripheral, a quite characteristic aspect is that of a more dense consolidation (possibly, the origin of the neoplasm), with GGO nearby. There are scattered patches of GGO and/or consolidation with a halo sign elsewhere, ipsilaterally and/or contralaterally¹⁴³ (Fig. 3-127). Bulging of fissures is possible in the presence of dense lobar consolidation¹⁴⁴ (Fig. 3-128), and pleural effusion and mediastinal lymph node enlargement are also possible.¹⁴³

Figure 3-127 Axial scan in a patient with multifocal bronchioloalveolar carcinoma. To the left, there is a homogeneous alveolar opacity posteriorly (arrow) and a GGO with crazy paving anteriorly (sun). To the right, a focal lesion (arrowhead) has the typical aspect of a roundish consolidation surrounded by a rim of GGO (halo sign). Note the presence of low-density material (mucus) inside the left main bronchus (curved arrow).

Figure 3-128 Bronchioloalveolar carcinoma. The dense, homogeneous opacity in the right cardiophrenic angle is an entire consolidated lobe. Note the bulging of the fissure posteriorly (arrow). Note also the black remnants of bronchi stretched inside the opacities.

Chronic Eosinophilic Pneumonia

Chronic eosinophilic pneumonia is a mixed densities disease. In the early phases, bilateral homogenous air-space consolidations are the most frequent modality of presentation (65%). However, GGO may also be the predominant pattern (35%), and septal lines often coexist (72%)¹⁴⁶ (Fig. 3-129). In the later stages, GGO, nodules, some reticulation and, after weeks, linear bandlike opacities parallel to the pleural surface can be seen.¹²² The opacities are quite characteristically arranged in the periphery of the upper lung zones in 50% of the cases,¹²² with a less frequent “hinging on the bronchi” appearance compared with OP lesions (Fig. 3-130).

Figure 3-129 Chronic eosinophilic pneumonia. Inhomogeneous consolidation with septal lines to the right and spotty areas of GGO bilaterally are the modality of presentation of the disease in this axial scan.

Figure 3-130 The opacities of this CEP are essentially peripheral, and to the right there is also a bizarre connecting trail (arrowheads) between two main foci of consolidation.

In drug-induced eosinophilic pneumonia, areas of ground glass attenuation, air-space consolidation, nodules, and interlobular septal thickening are common.^123,147 The clinical response to corticosteroids is usually excellent and, typically, accompanied by rapid clearing of the opacities¹¹⁷ (Fig. 3-131). Pleural effusion is possible in 10% of cases.¹²²

Figure 3-131 CEP in the same patient as in Figure 3-129. This is a comparable axial image of the patient after a brief period of steroid therapy: the parenchymal opacities have simply disappeared.

Desquamative Interstitial Pneumonia

Desquamative interstitial pneumonia is a GGO disease. Quite extensive areas of pure GGO are indeed the dominant finding^148,149 (Fig. 3-132). Centrilobular nodules are uncommon,¹⁴⁹ and consolidative and reticular opacities are also uncommon.¹⁴⁸

Figure 3-132 Desquamative interstitial pneumonia. Patches of GGO are visible at the level of the lower lungs in this axial CT scan. At this time, no opacities were visible at the upper levels.

The lesions start typically in the lower lungs and peripherally^149,150 (Fig. 3-133).

Figure 3-133 Coronal view of both lungs in a patient with DIP. This minIP image allows better recognition of patchy areas of GGO in the lower lung fields. The arrowheads point to small areas of paraseptal emphysema.

Emphysema (Fig. 3-134; see also Fig. 3-133) has been reported in about 50% of patients with desquamative interstitial pneumonia.¹⁵¹ In late disease, signs of fibrosis may superimposed, with interstitial irregular lines, interface signs, and cystic hyperlucencies inside the GGO^149,152 (see Fig. 3-134).

Figure 3-134 This is the same patient as in Figure 3-132, but after several years of a disease poorly managed. Now there are several patches of GGO in the upper lungs (this is an axial view at the level of the aortic arch). Some paraseptal emphysema is appreciable in the anterior paramediastinal area, but also tiny hyperlucencies inside the GGO are visible (arrow).

Infectious and Inflammatory Diseases

These are mixed densities and tree-in-bud entities. Single or multiple areas of consolidation/GGO alert to the existence of an alveolar disorder.⁶⁷ Signs of bronchial and bronchiolar involvement (bronchiectasis and bronchial wall thickening, bronchiolectasis with tree-in-bud or centrilobular nodules) often coexist and at times are the dominant pattern.^66,67,70 In areas of bronchiolar involvement, expiratory air trapping is frequently evident.^67,70 Cavitated opacities should raise the possibility of mycobacterial disease, and a surrounding (but also at a distance) tree-in-bud pattern should raise the suspicion of an aerogenous spread of disease (Fig. 3-135).

Figure 3-135 Disseminated tuberculosis. To the left, there is a cavitated process surrounded by bronchi with thickened walls (arrow). To the right, anteriorly, there is a triangular consolidation with air bronchogram (arrowhead) and in the posterior area of the same lobe there are tree-in-bud opacities (curved arrow), indicating a bronchial spread of the process. Enlarged lymph nodes are present in the mediastinum, to the left of the aortic arch (sun).

Bronchiolitis of infectious origin often has a patchy distribution, whereas noninfectious, inflammatory bronchiolitis tends to have a more uniform, bilaterally symmetrical involvement. Diffuse panbronchiolitis, in particular, presents with centrilobular nodules, tree-in-bud pattern, bronchiectasis, and bronchiolectasis with a dominant symmetrical lower lobe distribution.⁶⁷ If signs of bronchial involvement (including bronchiectasis) and/or alveolar opacities are found predominantly in the right middle lobe and lingula, an infection from nontuberculous mycobacteria (“Lady Windermere” syndrome) should be suspected^153–155 (Fig. 3-136).

Figure 3-136 “Lady Windermere” syndrome. Several ectatic bronchi with thickened walls are visible in the anterior segment of the right upper lobe (upper arrowhead) and in the middle lobe (lower arrowhead). A patchy hyperlucent lung and some tree-in-bud opacities (arrow) are visible in the lower lobe in this sagittal scan.

Unresolving consolidative opacities with low CT attenuation values (or frankly fatty densities) point to the possibility of an exogenous lipoid pneumonia^156,157 (see Fig. 3-105). In chronic mycobacterial infections, signs of retraction at the segmental or lobar level may be seen¹⁵⁵ (Fig. 3-137).

Figure 3-137 Some GGO and several ectatic bronchi with thickened walls are visible bilaterally in this axial scan, due to a tubercular process. Both the mediastinum (arrowhead) and the major fissure to the left (arrow) are retracted in connection with the parenchymal process.

Mucosa-Associated Lymphoid Tissue Lymphoma

Mucosa-associated lymphoid tissue lymphoma (MALToma) is a mixed densities disease. Air-space consolidations with air bronchogram, from unifocal or multifocal lesions to pneumonic-like opacities of lobar size, are the most common findings^158–160 (Fig. 3-138). In the surrounding area, spreading of disease along lymphatic routes may be responsible for a GGO with septal lines, some bronchial thickening, and micronodules with lymphatic distribution.^158,161,162 Centrilobular nodules are also possible.¹⁵⁹

Figure 3-138 Pulmonary MALT lymphoma. In this case, the lesion is in form of a mass in the right lung, in contact with the pleural surface. Note a stretched bronchus entering the mass (arrow): this is uncommon in lung cancer so it might arouse the suspicion of a different lesion.

The disease may be unilateral or bilateral, seemingly with no vertical or horizontal zonal predominance.¹⁵⁸ The infiltration along bronchovascular bundles may result in focal lesions typically centered on the bronchi^159,162 (Fig. 3-139).

Figure 3-139 Pulmonary MALT lymphoma. This tumor assumes the aspect of a pulmonary consolidation that determines a modest attraction of the mediastinum to which it adheres. An air bronchogram is well recognizable inside the opacity.

The lesions show a temporally indolent nature¹⁶⁰ and do not present a tendency to cavitation.¹⁶² Significant hilar and mediastinal lymphadenopathies or pleural effusion are not a characteristic feature of the disease^159,162 (Fig. 3-140).

Figure 3-140 MALT lymphoma in the same patient as in Figure 3-139. Small lymph nodes are visible in the paratracheal area and at the level of the aortopulmonary window (arrows), but no definite adenopathic masses are present.

Cellular Nonspecific Interstitial Pneumonia

Cellular NSIP is a GGO disease. The opacities involve the lungs more-or-less extensively and are homogeneous. Significant reticulation, traction bronchiectasis, or other signs of architectural distortion should be minimal or absent^49,163 (Fig. 3-141), and honeycombing is typically absent.¹⁶⁴

Figure 3-141 The scan is an axial view at the level of the costophrenic angles in a patient with NISP. The liver is evident (sun). The transparency of the basal lung is inhomogeneous because of the presence of patchy areas of pure GGO. Some slightly ectatic bronchi are recognizable (arrows).

The disease is bilateral and symmetrical,¹⁶³ involving mainly the lower lung in more than 90% of cases⁵¹ (else equally distributed). The opacities may show some tendency to distribute along the bronchovascular bundles.⁵⁰ Axially, the disease is diffuse in more than half of the cases or predominantly peripheral and subpleural. However, in a number of cases (20% to 43%), the extreme subpleural lung is relatively spared^27,51 (Fig. 3-142).

Figure 3-142 Axial scan at the level of the costophrenic angles in a subject with NSIP. There is quite homogeneous peripheral GGO; however, it spares the most subpleural lung (curved arrows). The opacities are more extensive to the left.

Several CVDs⁴⁴ and chronic drug reactions¹⁶⁵ may present with aspects indistinguishable from idiopathic NSIP. Consequently, a search for a nonidiopathic underlying disorder should be always undertaken clinically, although occasionally other signs of the original disease are visible radiologically^46,49 (Fig. 3-143).

Figure 3-143 The pulmonary window shows NSIP-compatible lesions in this patient with rheumatoid arthritis, and this mediastinal window shows a chronic pleural effusion to the left (arrow). The heart (sun) is severely shifted ipsilaterally.

Organizing Pneumonia

OP is a mixed densities disease. The classic presentation (60% to 80% of cases²⁷) of the cryptogenic OP but also of other OP reactions (e.g., from pulmonary infection, connective tissue disease, drug toxicity) is characterized by unilateral or bilateral areas of patchy consolidation in which an air bronchogram is often recognizable¹⁶⁶ (see Fig. 3-124). Areas of GGO attenuation (60%) with septal lines (40%) may coexist.^27,146 Several variants of the classic presentation have been described for this protean disease, including multiple nodules (Fig. 3-144) that may cavitate; solitary focal lesions that may resemble a lung cancer; and a peripheral distribution of disease in the context of the secondary lobule, thereby mimicking a linear septal pattern (see Fig. 3-106). All are detailed in the excellent review by Oikonomou.¹⁶⁶

Figure 3-144 Organizing pneumonia presenting in nodular form. Note also the presence of mediastinal enlarged lymph nodes, especially in the paratracheal area (arrowheads). This is not the most typical aspect of this protean disease. The most frequent, mixed densities presentation is illustrated in Figure 3-124.

The consolidative lesions are often (60% to 80%) peripheral and/or centered on bronchial branches,²⁷ with the latter being a striking feature in a number of cases (17%)¹⁶⁷ (Fig. 3-145). Cryptogenic OP often involves the lower lung zones to a greater degree than the upper ones.²⁷ When focal, the lesions are often located in the upper lobes and they may be cavitary, thus creating problems of differential diagnosis with lung cancer.¹⁶⁸

Figure 3-145 The consolidations of OP are often centered on the bronchial elements, as in the case shown (arrows).

The opacities of OP vary in size from a few centimeters to an entire lobe.¹⁶⁸ Most patients respond to corticosteroid therapy (Fig. 3-146) or, in cases due to drug toxicity, to cessation of therapy. On occasion, the lesions may disappear spontaneously, only to reappear elsewhere (migrating disease).¹⁶⁹

Figure 3-146 Healed OP after corticosteroid therapy. Only a minimal GGO (arrows) with some bronchial rigidity (arrowhead) persists. Usually, the response of the opacities to the therapy is striking; however, the possibility of a relapse is high.

Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis is a GGO disease with crazy paving. The typical presentation of the disease (100% of cases) is dominated radiologically by crazy paving,¹⁰³ often in the form of sharply marginated areas with a geographical distribution¹⁷⁰ (Fig. 3-147). The extension of the pulmonary abnormalities is often impressive in comparison with the mild respiratory conditions of the patient. This clinicoradiologic discrepancy is considered quite typical of this disease.¹⁷¹

Figure 3-147 Pulmonary alveolar proteinosis. This patient presents very typical patchy areas of GGO with superimposed septal pattern (crazy paving).

The areas of crazy paving are more often bilateral and symmetrical, sparing apices and costophrenic angles. Some central predominance has been suggested, but extensive or multifocal asymmetrical distributions without zonal preference are possible¹⁷¹ (Fig. 3-148).

Figure 3-148 In this case, the areas of crazy paving are more-or-less extended throughout the lung without considerable geographical preferences.

The natural course of disease is an evolution of the opacities over a period of months or years¹⁷¹ (Fig. 3-149). Pleural effusion and cardiomegaly are absent.¹⁷¹

Figure 3-149 In this image, the lung involved by the crazy paving is intermingled with normal lung. There are no signs of pulmonary parenchymal distortion or of pleural effusion, and the heart (sun) is of normal size.

Centrilobular Emphysema

In the early stage of disease, the cysts appear as tiny roundish black holes with invisible walls, and they are surrounded by normal lung parenchyma (Fig. 3-156). The lesions are homogeneously lucent. However, sometimes a central nodular or branching opacity representing the centrilobular artery is seen, and this finding may be helpful for distinguishing emphysema from other diffuse cystic diseases.¹⁷⁵ When emphysema enlarges and involves the entire secondary lobule, remnants of vessels and septa may simulate the appearance of thin walls, usually incomplete.²

Figure 3-156 Centrilobular emphysema. Multiple focal hyperlucencies with no evident walls are scattered throughout both lungs in this axial scan. Note that some of these “black holes” have a central white tiny dot, the remnant of the centrilobular artery (curved arrows [inset]).

Typically, in centrilobular emphysema, the lesions involve predominantly the upper lobes and the superior segment of both lower lobes¹⁷⁵ (Fig. 3-157). The distribution of the cysts in the affected regions is diffuse or patchy, and often the single lesions appear grouped in the centrilobular area and around the centrilobular artery (see Fig. 3-156). With more severe disease, the areas of destruction become confluent. CT documents a peripheral pruning of pulmonary vessels that are decreased in number, size, and arborization, closely mimicking the appearance of the panlobular emphysema¹⁷⁶ (see Fig. 3-157).

Figure 3-157 Frontal view of the lungs in a patient with emphysema from cigarette smoking. The areas of emphysema are more extended cranially, especially to the right where they involve the totality of the pulmonary lobules (arrow).

Paraseptal emphysema and bullae, bronchial and tracheal abnormalities, infections, pneumothorax, and pulmonary arterial hypertension are possible associated findings^175,177,178 (Fig. 3-158). The pulmonary volume is increased due to overinflation.

Figure 3-158 Sagittal view of a patient with emphysema from cigarette smoking. Several areas of centrilobular emphysema are scattered throughout the lung. Anteriorly, there also lesions from paraseptal emphysema (arrowheads) and, close to the hilum, bronchi with thickened walls are present (curved arrow).

Langerhans Cell Histiocytosis

Thin-walled and thick-walled cysts with bizarre shapes (e.g., bilobed, cloverleaf) are typically seen in the late phase of disease. The presence of a distinct wall allows their differentiation from areas of emphysema, which can be also seen in some patients.⁷⁶ The lesions, usually less than 10 mm in diameter, are due to coalescence of single cysts, ectatic bronchi, and surrounding paracicatricial emphysema^179,180 (Fig. 3-159). Signs of architectural distortion may be seen in the intervening lung parenchyma.⁵⁹

Figure 3-159 Axial view of a subject with advanced LCH. Innumerable cystic lesions with a distinct wall are variously scattered throughout both lungs. They assume various shapes and are not a uniform size. In some regions (curved arrows), there is evidence of centrilobular structures surrounded by areas of absolute hyperlucency. In this patient, the asymmetry of the chest with a noticeably smaller right hemithorax is due to a right pleural mesothelioma.

The distribution of the cysts may be diffuse or patchy in the axial plane, whereas in the craniocaudal directions they present a mid and upper lung zone predominance with relative sparing of the lung bases¹⁸⁰ (Fig. 3-160).

Figure 3-160 Coronal view of a subject with PLCH. The hyperlucent lesions extensively occupy the upper and middle zones of the lung, whereas at the lung bases there are still areas of relatively normal lung (curved arrows).

In the advanced stages of disease, the cystic pattern is the only abnormality visible in CT but in the early and intermediate stages, more or less numerous centrilobular dense, often cavitated nodules with shaggy margins are present (Fig. 3-161). In some patients, a progression from cavitated nodules to cystic lesions has been observed.¹⁸⁰ Recurrent or bilateral pneumothorax occurs in up to 25% of patients over the course of their disease.¹⁸¹ Signs of other smoking-related interstitial lung diseases (respiratory bronchiolitis, emphysema) may coexist, creating mixed patterns.⁷⁷

Figure 3-161 Early PLCH. The axial scan documents the coexistence of frankly cystic lesions (curved arrows) and nodules with shaggy margins (arrowhead). There is a hyperlucency inside the nodules, possibly centrilobular bronchioles.

Laryngotracheobronchial Papillomatosis

Laryngotracheobronchial papillomatosis is a viral infection that usually affects the upper airways but that may rarely spread along the airways disseminating to the lung parenchyma. The most common CT findings are intratracheal polypoid lesions, resulting in focal or diffuse narrowing of the trachea and pulmonary multilobulated nodules, many of which are cavitated¹⁸² (Fig. 3-162). The cavitated lesions may have thin or thick walls with irregularly nodular inner walls. Air-fluid levels inside the cysts are not uncommon, and they are secondary to infection.

Figure 3-162 Axial scan of a patient with laryngotracheobronchial papillomatosis. In the image, a lobulated solid nodule (arrowhead) coexists with two fully cystic lesions (curved arrows).

Some reports emphasize the possibility of a predominant lower lobe distribution, but the involvement of the upper lobes is not uncommon¹⁸³ (Fig. 3-163).

Figure 3-163 Axial scan of the same patient as in Figure 3-162, but at a higher level (carina). Multiple cystic lesions are documented also (curved arrows); the one to the left is bilobed.

At the central airways level, CT shows multiple small nodules projecting into the airway lumen (Fig. 3-164) or a diffuse nodular thickening of the airway walls. Findings related to the airways obstruction are infections, atelectasis, air-trapping phenomena, and bronchiectasis.¹⁸² There is also a risk of malignant transformation of the pulmonary lesions.¹⁸⁴

Figure 3-164 Four axial images from the laryngeal (upper left) to the upper tracheal level (lower right) of a patient with laryngotracheobronchial papillomatosis who has already undergone surgery (curved arrow). The lumen of the upper airways shows focal irregularities (arrowheads) at least partially related to previous surgery.

Lymphangioleiomyomatosis

The cysts of lymphangioleiomyomatosis are multiple, round, and relatively uniform in size and shape, and they have homogenously thin walls¹⁸⁵ (Fig. 3-165). Typically, the size of the cysts ranges from 0.5 to 2 cm in diameter and tends to increase with the progression of the disease. In patients with mild disease, 25% to 80% of the lung parenchyma are replaced by cysts, characteristically surrounded by normal lung¹⁸⁶ (see Fig. 3-165).

Figure 3-165 Anatomical volume rendering of a sagittal slab in a female with LAM. The image shows the cystic lesions well identified by thin regular walls. Note the regular arborization of the large vessels (arrows) and the normal position of the superior portion of the major fissure (arrowhead).

The cysts are uniformly and symmetrically distributed throughout the lungs, equally affecting the upper-lower and the central-peripheral lung parenchyma^185,187 (Fig. 3-166).

Figure 3-166 Minimum intensity projection (minIP) in a coronal view of the same patient as in Figure 3-165. The minIP technique enhances the visibility of the lesions that are scattered quite uniformly all through the lungs.

In patients with advanced disease, the parenchyma are completely replaced by cysts, and the pulmonary volume is increased (Fig. 3-167). Possible areas of GGO may result from edema or hemorrhage; pulmonary hemorrhage occurs in 8% to 14% of women with lymphangioleiomyomatosis.¹⁸⁷ The incidence of pneumothorax in lymphangioleiomyomatosis is high (40%) due to the thin wall of the cysts and their proximity with the pleural surface. Pleural effusion may also be seen, and other associated abnormalities, including mediastinal or retrocrural lymph node enlargement (40%) just as often.^185,186

Figure 3-167 External volume rendering of the same patient as in Figure 3-165. This anterior rendering shows how the lungs are hyperinflated through the abnormal touching of their anterior borders (arrows).

Cystic Metastases

Although rare (4%), pulmonary metastases may present with a cystic pattern. Most of the lesions are roundish, of variable size, and often have irregularly thickened walls with septations (Fig. 3-168).⁹⁰ However, thin-walled cysts with smooth walls may be also observed, particularly after chemotherapy.¹⁸⁸ On the contrary, metastases from angiosarcoma may have an external halo of ground glass attenuation (30%) and an internal air-fluid level, both due to hemorrhage.^188,189

Figure 3-168 Axial view at the level of the carina in a patient with multiple metastases. There is a range of lesions, from solid nodules (arrow) to fully cavitated elements (arrowhead).

The lesions occur in a random distribution, often showing a “feeding vessel” sign (Fig. 3-169). Most pulmonary metastases are located in the basal and peripheral zones.⁹⁰

Figure 3-169 Axial scan of the same patient as in Figure 3-168, but at a lower level. The heart is indicated by the symbol of the sun (sun). One of the cystic metastases to the right (curved arrow) seems connected to an artery (“feeding vessel” sign).

Hemothorax and pneumomediastinum are rare associated conditions.¹⁸⁹ An uncommon complication is the occurrence of a pneumothorax due to ruptured subpleural cavities into the pleural space. Enlarged hilar and mediastinal lymph nodes may be also present (Fig. 3-170).

Figure 3-170 Same patient as in Figure 3-168. Note the enlarged and colliquated lymph nodes at the right hilar level and in the subcarinal area (arrows).

Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé syndrome¹⁹⁰ is a rare, inheritable, multisystem disorder (autosomal dominant) characterized by skin lesions, renal tumors, and multifocal pulmonary cysts. Radiologically, multiple thin-walled cysts round to oval in shape, ranging widely in size (a few millimeters to several centimeters) have been reported^191,192 (Fig. 3-171). The cysts are not numerous; in a paper on 12 patients, the mean extent score was 13% of the whole lung.¹⁹³

Figure 3-171 Axial scan of a patient with Birt-Hogg-Dubé syndrome. There are scattered small, thin-walled cysts of various size and shape (arrows).

(Courtesy of Angelo Carloni, MD, Terni, Italy.)

The cysts are variably distributed but tend to predominate in the middle and lower lung¹⁹¹; characteristically, they are located along the pleural margins in 40% of patients¹⁹³ (Fig. 3-172). Cysts abutting or including the proximal portion of the lower pulmonary arteries and veins have been also described.¹⁹³

Figure 3-172 Frontal view of the same patient as in Figure 3-171. The scan nicely shows the relationship of the cysts with the pleural boundaries. The contact with them is indicated by the arrowheads.

(Courtesy of Angelo Carloni, MD, Terni, Italy.)

The lung looks normal in between the cysts (Fig. 3-173). Birt-Hogg-Dubé syndrome can be associated with recurrent spontaneous pneumothoraces.¹⁹⁴

Figure 3-173 Another axial scan of the same patient as in Figure 3-171. The image shows the cysts and the intervening parenchyma that looks normal.

(Courtesy of Angelo Carloni, MD, Terni, Italy.)

Chronic Pulmonary Thromboembolism

The most characteristic feature of chronic pulmonary thromboembolism is a mosaic perfusion that does not accentuate with expiratory scans (there is no air trapping). The low attenuation areas may be due both to hypoperfusion distal to occluded vessels and to peripheral vasculopathy. The areas of increased attenuation have been related to redistribution of blood flow toward the remaining patent vascular bed,¹⁹⁸ and indeed, in these areas, the vessels are larger and often tortuous (Fig. 3-178). Scars from prior pulmonary infarctions are often found in the lower lobes, and pleural thickening from previous pleural effusion is not uncommon.¹⁹⁹

Figure 3-178 Chronic pulmonary thromboembolism. Mosaic perfusion with disparity in the size of the segmental vessels, larger, and also tortuous in the areas of higher attenuation (arrowheads).

The areas of low attenuation are usually wide (larger than lobules) with ill-defined margins¹⁹⁸ (Fig. 3-179).

Figure 3-179 Chronic pulmonary thromboembolism. The dark, hypoperfused areas are extensive and prevalent in the lung periphery; their margins with the normal lung (arrowheads) are quite ill defined.

The direct signs of chronic thromboembolism are often visible at the level of the central vessels; these include partial arterial obstruction with mural thrombi (Fig. 3-180), intraluminal bands and webs, calcifications within chronic thrombi, and signs of pulmonary arterial hypertension (dilatation of the central pulmonary arteries secondary to the obstructed vascular lung bed, right ventricular enlargement and hypertrophy, tortuous arteries at the pulmonary level¹⁹⁸) (see Fig. 3-178). In some cases, a collateral systemic blood supply may be evident with abnormal dilatation and tortuosity of the bronchial, phrenic, intercostal and internal mammary arteries. Such systemic perfusion of the peripheral pulmonary arterial bed may account for the presence of focal areas of ground glass attenuation within the lung.²⁰⁰ Patients with severe pulmonary hypertension may also show a mild pericardial thickening or a small pericardial effusion.

Figure 3-180 Axial contrast-enhanced computed tomography scan of a patient with chronic pulmonary thromboembolism. This axial image demonstrates an eccentric thrombus (arrowhead) showing as a thickening of the anterior wall of the right pulmonary artery. aa, ascending aorta; da, descending aorta; pa, main pulmonary artery.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

The narrowing of the bronchiolar lumen due to the neuroendocrine cellular hyperplasia and fibrosis²⁰¹ is not directly visible with HRCT, but it can show up indirectly as mosaic perfusion (Fig. 3-181) with air trapping.²⁰² Small, well-defined, randomly distributed nodules less than 5 mm in diameter may be also identified in the CT images, especially when obtained with multislice volumetric equipment. The nodules correspond to the neuroendocrine “tumorlets” present histologically (see Fig. 3-181).²⁰³

Figure 3-181 Axial scan of a patient with chronic cough and dyspnea. The combination of a mosaic perfusion pattern with air trapping and of sporadic bilateral micronodules (arrows) suggests the diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.

Usually, both hyperlucent dark lung and nodules are randomly distributed throughout both lungs. However, at times, the coronal MIP images may show a prevalence of the nodules in the lower zones^203,204 (Fig. 3-182).

Figure 3-182 Maximum intensity projection (MIP) in a coronal view of the same patient as in Figure 3-181. The MIP technique highlights the visibility of the small nodules that are more numerous at the basal level, in the area indicated by the curved arrows.

Round lesions of more than 5 mm in diameter may suggest the existence of carcinoid tumors (grade 1 neuroendocrine carcinomas) (Fig. 3-183). Some patients may also show bronchial wall thickening and cylindrical bronchiectasis.²⁰⁴

Figure 3-183 Axial view of a subject with diffuse idiopathic neuroendocrine cell hyperplasia. In the middle lobe, there is a nodule of a diameter > 5 mm (arrow) that could be a low-grade neuroendocrine carcinoma (carcinoid tumor).

Constrictive Bronchiolitis (Bronchiolitis Obliterans)

HRCT shows patchy areas of mosaic perfusion secondary to hypoxic vasoconstriction from bronchiolar obstruction (phlogosis/fibrosis). The reason for the narrowing is not directly visible with CT, but it shows up indirectly as dark lung.

The blood vessels in the low attenuation areas are smaller and less numerous than vessels in the areas of relatively high attenuation^67,69 (Fig. 3-184). The dark lung often presents sharply defined margins and lobular or segmental extension. Air trapping on expiratory scans appears as an accentuated contrast between differently attenuating areas and may be helpful for the early detection and confirmation of the bronchial origin of the oligemia, particularly after lung transplantation.¹⁹⁷

Figure 3-184 High-resolution computed tomography of a patient with constrictive bronchiolitis. The image shows multiple patchy dark areas, especially in the right lung, associated with decreased size of pulmonary vessels (curved arrows). Note the concomitant bronchiectasis with mild bronchial wall thickening (arrowhead).

The disease is diffuse and bilateral, with more common and extensive involvement of the lower lobes⁶⁸ (Fig. 3-185). Some patients with constrictive bronchiolitis show also central and peripheral cylindrical bronchiectasis (Fig. 3-186). The cause of the bronchiectasis associated with bronchiolitis obliterans remains unclear, but it seems most likely due to concomitant injury of the large airways.^205,206 Rarely, centrilobular nodules or branching linear densities can also be observed.²⁰⁵

Figure 3-185 Axial scan of the same patient as in Figure 3-184, but at a lower level. Extensive geographic areas of low attenuation are present (in particular to the left), interspersed with less frequent areas of relatively increased opacity. Evidence of mild bronchiectasis is present in the right lower lobe and in the lingula (arrowheads).

Figure 3-186 Axial scan of the same patient as in Figure 3-184, at the lung bases. Bronchiectasis is visible in the lower lobes (curved arrows) and in the basal portion of the lingula (arrowhead).

Panlobular Emphysema

Panlobular emphysema is characterized anatomically by a uniform destruction of the pulmonary lobule, and it appears radiologically as extensive areas of dark lung associated with a diffuse “simplification” of the pulmonary architecture (Fig. 3-187). The vessels appear reduced in number and size, at times as if they were stretched and rigid inside the darkness.⁸ This is the pattern of emphysema seen in patients with alpha-1-antiprotease deficiency,¹⁷⁵ and it may be indistinguishable from the appearance of severe constrictive bronchiolitis.²⁰

Figure 3-187 Extensive areas of low attenuation with stretched vessels typical of panlobular emphysema are visible everywhere, in particular in the left lower lobe (arrow). The right lower lobe is less extensively involved (arrowhead).

Panlobular emphysema is generalized within the lungs, but it can be more severe in the lower lobes¹⁷⁵ (Fig. 3-188).

Figure 3-188 Axial scan of the same patient as in Figure 3-187 at the axial level of the heart (sun). The hyperlucent transformation of the lung is more extended and more severe at this basal level, where there is only little relatively normal surviving parenchyma posteriorly (arrowheads).

In approximately 40% of patients with alpha-1-antiprotease deficiency, bronchiectasis is present due to destruction of the elastic lamina²⁰⁷ (Fig. 3-189). Associated paraseptal emphysema and bullae are relatively uncommon.

Figure 3-189 Patients with panlobular emphysema often have minimal bronchiectasis associated with bronchial wall thickening (arrows).

Swyer-James (MacLeod Syndrome)

Swyer-James syndrome is a peculiar postinfectious constrictive bronchiolitis that affects the lung asymmetrically²⁰⁸ (Fig. 3-190). Consequently, the CT hallmark of this syndrome is a dark pattern that can be unilateral and even limited to one lobe. An associated decreased vascularity in the affected areas and air trapping during expiration are the rule.⁶⁸

Figure 3-190 Patient with Swyer-James syndrome. The image shows unilaterally reduced right lung attenuation; in the dark lung, the vessels are smaller than contralaterally. The right lung is also smaller, and in fact the mediastinum is shifted ipsilaterally (arrow).

For decades, based on chest radiographs, authorities have believed that the damage had to be unilateral, but the advent of CT has made it increasingly clear that bilateral involvement is a rule rather than an exception.²⁰⁸ However, a predominant involvement of one lung and even of one lobe is very frequent²⁰⁹ (Fig. 3-191).

Figure 3-191 Another patient with Swyer-James syndrome. The left lobe is extensively involved, but also some portions of the right lung are relatively hyperlucent with simplified vascular tree (arrows).

Ectatic bronchi with thickened walls are often present, sometimes severely²⁰⁹ (Fig. 3-192).

Figure 3-192 Axial scan of the same patient as in Figure 3-190, but at a lower level. Note the cluster of cystic bronchiectasis in the azygos-esophageal recess (arrow).

Risk Factors

A given patient’s likelihood of having a pulmonary malignancy increases with older age; current or past smoking habits; extrathoracic cancer more than 5 years before nodule detection²¹¹; exposure to asbestos, uranium, or radon; occurrence of symptoms²¹⁰ (in particular hemoptysis²¹²); and a family history of lung cancer.²¹³ These risk factors do not enter in the radiologic evaluation of the nodule per se, but they represent key elements to match with the radiologic data in the final diagnostic algorithm. The differential diagnosis of SPNs is presented in Box 3-15.

Morphologic Aspects

The risk of malignancy is increased when the nodule has ill-defined margins and lobulated or spiculated contours. In particular, spiculation with the so-called sunburst aspect (corona radiata) has a 90% predictive value of malignancy²¹⁴ (Fig. 3-193). Unfortunately, this does not mean that a well-marginated SPN with regular contours cannot be malignant, and on the contrary one of five malignancies has these characteristics.²¹² Also, size correlates with malignancy. An incidentally discovered SPN with a diameter less than 4 mm has a less than 1% chance of being a primary lung cancer, but if the diameter is in the 8-mm range, the probability is approximately 10% to 20%.^215–217

Figure 3-193 Solitary pulmonary nodule (curved arrows) in a heavy smoker with COPD. In this clinical context, the spicules that form the margins of the lesion (seen in the sunburst aspect) have a high probability of malignancy. A large bulla is responsible for the shifting of the anterior junction line to the left (arrow).

Computed Tomography Densitometry

Fat densities inside the nodule (Fig. 3-194) are typical of hamartoma (50%),²¹⁸ but metastases from liposarcoma and renal carcinoma also may have fatty components.²¹⁹ Central, laminated, or popcorn calcifications inside the nodule are usually benign, but lung metastases from chondrosarcoma or osteosarcoma may present similar aspects.⁹⁰

Figure 3-194 Solitary pulmonary nodule. The density of the nodule (curved arrows), solid in the periphery, is reduced in the center with attenuation values of −15 HU; this density might correspond to a fatty content.

An SPN may be uniformly dense (solid) or contain ground glass components (subsolid). For solid nodules, the chance of malignancy is 7%, but for subsolid nodules, this percentage rises to 34%.²²⁰ However, when the density is mixed (solid + GGO), this percentage rises to 63%, whereas for pure GGO lesions (Fig. 3-195) the rate of malignancy is “only” 18%. In a large series, 20% of the lesions detected during a CT screening program represented subsolid densities.²²⁰ A halo of GGO around a nodule (halo sign) may be due to hemorrhage, inflammation, or tumoral infiltration. This sign is not specific, and it may be found also in benign conditions (e.g., nodular OP).²¹⁰

Figure 3-195 Barely visible solitary pulmonary nodule of faint density (nodular GGO) in the peripheral left upper lung (arrowhead). The surgical diagnosis was of a focal bronchioloalveolar carcinoma.

Cavitation and Air Bronchogram

Cavitation may be benign or malignant; however, cavitation of malignant lesions tends to have more irregular and thicker walls than benign ones.²²¹ It has been reported that 95% of cavitary lesions with wall thickness greater than 15 mm are malignant.²²² Up to 15% of primary lung malignancies, in particular squamous cell carcinomas, cavitate.²¹⁰

An air bronchogram is not present in the solid lesions, but it is possible inside the nodules of GGO (Fig. 3-196). It may also be seen in bronchioloalveolar carcinoma and pulmonary lymphoma, as well as in some benign lesions.

Figure 3-196 Initial presentation of a diffuse bronchioloalveolar carcinoma. In this phase, the lesion has a lobular size, and the appearance is of a mixed densities disease with consolidative and GGO aspects. A few small hyperlucent bronchi can be appreciated inside the opacity.

Doubling Time

The doubling time is the time taken by a lesion to double its volume. The basic assumption is that, except for the infectious and inflammatory lesions, the faster the growth, the greater the chance a nodule is malignant. Indeed, the doubling time of a solid malignant nodule is in the range of 1 to 13 months, whereas that of a benign lesion tends to be shorter or longer.²¹⁰ The subsolid lesions, on the contrary, are another story. Approximately 20% of well-differentiated adenocarcinomas have a doubling time greater than 2 years,²²³ and some bronchioloalveolar carcinomas may show a doubling time even greater than 3.5 years.²²⁴

In summary, the old adage that “a nodule should be considered benign if unvaried after two years” is still acceptable now,^210,225,226 but it is suitable only for solid lesions. Note that the recommendations of the literature refer to the volume of a nodule. However, more often in practice, the measures are done on two-dimensional images using diameter so the volume should be corrected accordingly (to double its volume, a nodule should increase its diameter by about 25%).²²⁷

The timing of the follow-up of a nodule incidentally discovered on CT depends on the priori probability of malignancy (risk factors), size, and density. The appropriate timing has been recently recommended in detail in a statement from the Fleischner Society.²²⁸

Computed Tomography Contrast Enhancement

The radiologic density of a nodule increases after administration of contrast medium; this is called contrast enhancement, and it depends on the lesion’s vascularity. From the diagnostic point of view, the assumption is that the greater the contrast enhancement, the greater the probability of a nodule’s being malignant. In fact, malignancies have contrast enhancements of 20 HU or more and benign lesions less than 15 HU. Again, these data are suitable only for relatively homogeneous solid nodules measuring between 5 mm and 3 cm in diameter, where the negative predictive value for malignancy of a contrast enhancement less than 15 HU is 96%.²²⁹

Positron Emission Tomography Metabolism

Typically, the metabolism of glucose is increased in malignancies, and this peculiarity is exploited with a technique of nuclear medicine known as PET (Fig. 3-197). For lung nodules, an SUV_max cutoff of FDG of 2.5 is used as the discriminating level between benign and malignant.²³⁰ Unfortunately, PET is most efficient only for solid lesions with a diameter greater than 10 mm, where the sensitivity and specificity of the technique for detection of malignancy are about 90%.²³¹ On the contrary, a well-differentiated adenocarcinoma that shows a GGO appearance in CT is (falsely) negative in nine of ten cases, and a benign nodule that shows a GGO appearance in CT is (falsely) positive in four of five cases.²³²

Figure 3-197 Same patient as in Figure 3-194. Here a computed tomography image is shown together with the results of a PET examination where the nodule (arrowhead) does not appear to concentrate the fluoro-2-deoxy-D-glucose. The cardiac uptake is indicated by a curved arrow.

The SUV has to be considered in connection with the pretest likelihood of malignancy. For example, a negative PET reduces the likelihood of malignancy to 1% in an individual with a pretest likelihood of 20% but only to 14% in one with a pretest likelihood of 80%.²¹⁰

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