Practical Pulmonary Pathology 3rd ed. Kevin O. Leslie, MD

Chapter 4. Computed Tomography of Diffuse Lung Diseases and Solitary Pulmonary Nodules

Giorgia Dalpiaz, MD

Foundations

Living With X-Rays and Working With Computed Tomography

X-Rays and Computed Tomography

Radiology is the science of studying anatomy and pathology using x-rays, or electromagnetic waves (like visible light, only with a much shorter wavelength) that can penetrate the tissues. In computed tomography (CT), the widely recognized imaging standard of reference for the assessment of most pulmonary abnormalities, a collimated fan beam of radiation is generated by an x-ray tube inside a gantry (Fig. 4.1).

The beam is quite homogeneous when it enters the body (ingoing radiation) but, point by point, inhomogeneous when it exits (outgoing radiation) because of the varying degrees of attenuation produced by the tissues. This attenuation depends heavily on the characteristics of the tissue, calcium being at the highest and air at the lowest end of a scale of soft tissue densities (e.g., organs, muscles, blood vessels, interstitium), with fat in between (Fig. 4.1).

Always point by point, the outgoing radiation activates a matrix of tiny sensing elements (detectors) during the continuous spiraling movement of the tube-detector system around the body (scan), and the information thus 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 (Fig. 4.1).

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 (grayscale), where the brightest (white) spots represent the elements with higher attenuation and the darkest (black) spots those with 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. 4.2 to 4.4). 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.

With a diffuse lung disease (DLD), the high-resolution option is used. An actual collimation of 0.5 to 2 mm and an edge-enhancing algorithm for high spatial frequency reconstruction serve to generate the final images.¹ the narrow collimation reduces the voxel size, there by minimizing the averaging of densities (attenuations) within them; this makes it possible to render subtle anatomic details (down to 0.1 to 0.2 mm in the most favorable conditions).¹ A limit is the noise of the image because of the reduced radiation penetrating such small voxels. However, at the pulmonary level, the difference in 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.

Figure 4.1 the figure summarizes conceptually the steps of a computed tomography examination, from the acquisition of the images in the gantry (1) to their display on a monitor (4). In the computer, the information about a set of volume units of body (voxels) (2) is rendered on the monitor in a scale of grays according to their average attenuation (3).

Figure 4.2 Computed tomography transverse (axial) view of the lungs at the level of the heart (sun) (case with lung pathology). In the axial images, it seems as if the patient were seen from below; consequently the right lung is to the left of the viewer. R, Right; L, left.

Terminology

In general, the structures that attenuate more are whiter (thus they are more opaque, dense, or hyperdense) than the structures that attenuate less (thus they are more transparent, lucent, or hyperlucent).

Figure 4.3 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 4.4 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.

There fore 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; in turn, however, this fat is denser than the tracheal lumen, containing air (Fig. 4.5).

In CT, the observed attenuations can also 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).

Figure 4.5 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 of 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 contrast at the lung level, allowing the recognition of small hyperlucencies (curved arrows) inside faint peripheral lung opacity.

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 (Fig. 4.5). A contrast medium is rarely used in studies performed for a suspected DLD but frequently used 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, limitations of the human eye do not permit a real-time appreciation of these details over the entire dynamic range of chest attenuations. Fortunately, because all pertinent data are available to the machine, the operator need only press a button to switch—through dedicated processing referred to as windowing and leveling—from a mediastinal window (where the details in the lung are squeezed down to absolute blackness) to a lung window (where the soft tissues are leveled out but the lung structures stand out with maximal detail) (Fig. 4.5).

Figure 4.6 Frontal view of a normal right lung, inferiorly delimited 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).

Lung Anatomy

Arteries, Veins, and Bronchi

When they are 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 (Figs. 4.2 to 4.4). 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 vs. peripheral) (Fig. 4.6). 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 transversely (Fig. 4.6). 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, in looking at a normal lung, there seems to be a general predominance of blood vessels with only sporadic visibility of bronchioles within the outer third of the lung.

The outer walls of the arteries and both the outer and inner surfaces of the bronchial walls should present a sharply defined interface with the surrounding parenchyma (Fig. 4.7). 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 different courses that become almost perpendicular at the level of the vein entrance into the mediastinum and right heart (Fig. 4.7).

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 (Fig. 4.7). When normal, lymphatics are not visible at any level, since their size is inadequate to be perceptible radiologically.

Figure 4.7 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).

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 are 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 (Figs. 4.6 and 4.7). 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. 4.8), where the hydrostatic pressure is higher and the vessels larger.

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, it means that they are thickened and hence abnormal. In general and 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 (Fig. 4.8).

Special Techniques

Increasing Visibility

Multiplanar Reformation. The high-resolution computed tomography (HRCT) technique has existed since the end of the 1970s, but it was the development of spiral multislice scanning machines in the early years of the 21st century that allowed the generation of consistent high-quality images in every spatial plane in nearly every patient (multiplanar reformation [MPR]). The first and most popular way to render the data is called averaged because, pixel by pixel, the images show the average attenuation of the tissues across the plane of section. The natural high contrast of lung tissue and thin collimation of the x-ray beam coupled with a high-frequency algorithm of reconstruction guarantee sharp details of anatomic and pathologic elements down to considerably less than 1 mm (Fig. 4.8).

Pathology that occurs in the central or peripheral regions of the lung is best studied in axial images (Fig. 4.2). Diseases that show upper or lower lung prevalence benefit from visualization in the coronal view (Fig. 4.3). Finally, disorders that prevail in the parahilar regions or the costophrenic angles are best depicted in the sagittal view (Fig. 4.4). With the volumetric approach, the planes may be varied according to the needs of the operator and targeted on the suspected disease (Box 4.1).

Figure 4.8 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).

Figure 4.9 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.

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 were lying 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. 4.9). The curved reformatted images are not real, but they are effective and easy to generate and There fore useful for practical purposes (e.g., virtual bronchoscopy).

Increasing Ambience

Maximum Intensity Projection. In 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 corrective techniques have been implemented.

The maximum intensity projection (MIP) technique renders only the voxels with higher attenuation in a thick slice (0.5 to 2 cm). The technique is suitable for rendering the vascular tree three dimensionally against a black background; moreover, with MIP, it is possible to obtain a comprehensive representation of the position of various lesions inside the lobular framework (Fig. 4.10).³ In selected cases, MIP images are useful for distinguishing between vessels and nodules and, when nodules are present, to assess their profusion.

Minimum Intensity Projection. The minimum intensity projection (minIP) technique renders only the voxels with lower attenuation in a thick slice (0.5 to 2 cm). This technique is useful for improving the visualization of hyperlucent elements (bronchi, emphysema, bullae, honeycombing) and some opacities, allowing for 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. 4.11).

Figure 4.10 the image at the left (Ave.) is an axial view of the right lung in a patient with multiple nodular lesions. The maximum intensity projection (MIP) image at the right shows a thicker axial slab at the same level and in such a way that the relationships between the lesions and the vessels are more easily appreciated, as in a tridimensional environment.

Figure 4.11 Sagittal view (minimum intensity projection 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 also be used in assessing DLD. When this is implemented, the machine renders only the structures within a specific range of attenuations and contained within a chosen volume. VR may be useful for studying a volume of lung in three dimensions from within or for inspecting its surface from outside (external VR) (Fig. 4.12). 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).

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 for 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 (Fig. 4.8), where it may simulate pathology or, alternatively, hide it. These normal densities disappear with prone positioning (Fig. 4.13); indeed, some experts recommend the routine use of prone scans when diseases under consideration characteristically involve the posterior lung (e.g., asbestosis).⁴

In normal subjects, an expiratory scan shows a uniform reduction in the size of the lungs together with a homogeneous increase in their density owing to the reduced amount of air within the alveoli. When an arterial obstructive or a bronchial stenotic disease is present, variable portions of the lung become darker than normal because of the reduced blood supply caused directly by hampered vascular filling or indirectly by hypoxemic vasoconstriction. In the expiratory CT, however, 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. 4.14). When arterial obstructive or bronchial stenotic diseases are suspected, supplementary expiratory scans should be added to complete the investigative process.

Figure 4.12 Tridimensional external lateral view of a lung in a patient with patchy hyperlucencies due to idiopathic usual interstitial pneumonia (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.

Diffuse Lung Diseases

Elementary Lesions

The radiologic appearance of each DLD depends on the elementary lesions and their distribution throughout the lung. The beginning of the radiologic process should involve verifying the existence of abnormalities, in particular of elements causing increased absorption of the x-rays (opacities) or a reduced attenuation of them (hyperlucencies). If abnormalities exist, the next step should entail identifying their prevalent aspect, which in turn depends on the underlying pathology. Another step should involve localizing the abnormalities, both in relation to the lobular architecture (when possible) and their topographic distribution throughout the lung. The lobular approach presents valuable information about the modalities of arrival/onset of the lesions and their spreading routes, and the topographic approach helps discriminate among diseases with similar presentation.

The lobular approach should be quite obvious for the pathologist, who will find it extraordinarily easy to recognize many radiologic aspects of diseases with which he or she is acquainted from gross organ inspection (a radiologic image is essentially a black-and-white representation of gross lung examined with a magnifying glass). The possibility of confirming and specifying a disease using its distribution throughout the lung may be less intuitive but will become excitingly new and beneficial with practice. After all, the two modalities are not mutually exclusive; on the contrary, they strengthen each other through the concept of pattern.

Patterns

Patterns in the practice of medicine are the ensembles of characteristic elements that give proof and name to a disease or a family of diseases.

Figure 4.13 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 the DLD universe, basic radiologic patterns play an important role at the beginning of the diagnostic assessment. According to the literature and on the basis of the personal experience, the distinction of six main radiologic patterns is suggested:

1. Septal pattern (linear pattern with preserved architecture)

2. Fibrotic pattern (linear pattern with distorted architecture)

3. Nodular pattern

4. Alveolar pattern

5. Cystic pattern

6. Dark lung pattern

Figure 4.14 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.

There are some limitations to thinking in terms of patterns. First, the same disease may present with different radiologic patterns. This may result from its variable pathologic expression in a given patient (e.g., pulmonary manifestations of progressive systemic sclerosis may show histologic usual interstitial pneumonia [UIP], nonspecific interstitial pneumonia [NSIP], organizing pneumonia [OP], and even diffuse alveolar damage patterns), from its temporal phase (e.g., a hypersensitivity pneumonitis [HP] may present in the acute, subacute, or chronic stage) or from its natural progression (e.g., an NSIP may proceed from a minimal changes pattern to end-stage lung disease). Second, the same pattern may be present in several diseases (a classical model being the systemic collagen vascular diseases [CVDs]); this is not unexpected because the lung has a limited number of reactions to different insults. These caveats are not an absolute limit to the diagnostic approach using patterns, but they underscore the necessity of a tight integration of imaging with clinical presentation and pathology in arriving at a meaningful diagnosis for the patient, as is widely recognized in the literature.⁵

Septal Pattern

Definition

A septal pattern is present when a thickening of the perilobular interstitium is appreciable, making the lobular boundaries evident. The bronchovascular bundle is also usually thickened, producing changes both at the central parahilar level and in the centrilobular core (Fig. 4.15). The final effect is that of a regular network of white lines with increased evidence of the perilobular interstitial architecture but without retraction or remodeling of pulmonary structures. For this reason, the septal pattern is also called a regular linear pattern or linear pattern with preserved architecture.

Figure 4.15 Radiology (A) and pathology (B) of septal diseases. Thickening of septal and fissurai interstitium associated with peribronchovascular cuffing is the key element of this pattern. (Pathologic image courtesy Alessandra Cancellieri, Bologna, Italy.)

Figure 4.16 Septal thickening. This sagittal view shows thickened septa in the upper lobe (curved arrows). The thickening of the interlobular septa outlines secondary pulmonary lobules of various sizes.

High-Resolution Computed Tomography Signs

A network of white lines due to thickened septal, peribronchovascular, and subpleural interstitium is the trademark of this pattern. The thickened interlobular septa appear as white lines 1 to 2 cm in length that outline the polygonal boundaries of secondary lobules (interlobular or perilobular reticulation) (Fig. 4.16). Normally these septa are not recognizable, so their presence points to an abnormality. A few lines inside the lobule may also be visible.^2,6

Centrilobular peribronchovascular thickening becomes manifest as a cuffing of the core structures of the lobule. The bronchiole, usually invisible under normal conditions, becomes evident as a white ring adjacent to a white dot of similar size (the centrilobular arteriole). It is enlarged compared with rings identifiable in adjacent portions of pulmonary parenchyma (Fig. 4.17).

Figure 4.17 the centrilobular peribronchovascular thickening manifests itself as increased visibility of the centrilobular structures (arrows).

The thickened peribronchovascular bundle at a more central level is also perceived as arteries of increased size compared with similar portions of pulmonary parenchyma and as thickening of bronchial walls (Fig. 4.18). As a rule, vessel size and bronchial wall thickness in corresponding regions of one or both lungs should be similar, and a comparative evaluation of different lung regions is helpful and makes the recognition of the abnormalities easier.²

Figure 4.18 Central peribronchovascular thickening. In this coronal image, there is a thickening of the central peribronchovascular interstitium that manifests as peribronchial cuffing of segmental bronchi (arrow) and increased size of the companion arteries (arrowhead).

The subpleural interstitial thickening should be evaluated at the edges of the lung as a white enveloping line simulating thickened pleura. This sign is often easier to identify at the fissural level, where two layers of subpleural interstitium coexist (Fig. 4.19).⁷

Pleural effusion may be an additional finding in some septal disorders. It can be small and may be seen along the costovertebral angles or fissures (Fig. 4.20), where large, significant compressive effects on the adjacent parenchyma may be present.

Subsets

Morphologic characteristics of the septal thickening pattern allow the distinction of two possible subsets of the septal pattern: smooth and nodular.

Subset Smooth

The anatomy of the three interstitial compartments (perilobular, peribronchovascular, and subpleural) is more or less regularly thickened with smooth profiles. The polygonal outlines of the lobules are visible, without focal abnormalities. Their shape is variable, depending on the CT plane (Fig. 4.21).

Inside the lobules, enlarged arteries and bronchioles with thickened walls are often visible. Smoothly thickened fissures are recognizable (Fig. 4.22), in particular with multiplanar reconstructions.⁸ Coexisting patches of faint opacities are possible owing to partial alveolar filling (ground-glass opacity [GGO]). However, these patches should not overshadow the septal aspects; otherwise an alveolar pattern should be considered.

Diseases in the septal pattern, subset smooth, are listed in Box 4.2. 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 because of minimal alveolar edema (Fig. 4.23).⁹ ttere is a tendency for the hydrostatic edema to show a symmetrical basal and posterior distribution (in supine patients) (Fig. 4.24), but patchy nongravitational distributions are not impossible.¹⁰

Figure 4.19 Subpleural interstitial thickening. The sagittal view shows thickening of subpleural interstitium, which is easily recognizable in relation to the fissures (arrowheads).

Figure 4.20 A pleural effusion is visible in this image along the costovertebral angle as a meniscus (arrows) and along the fissure (arrowhead).

Figure 4.21 Four images of the right lung in a disease presenting with septal pattern, subset smooth. A patchy distribution of thickened septa creates polygonal networks with smooth profiles.

Figure 4.22 This coronal view shows smooth thickening of a fissure (arrow), of the perilobular interstitium (curved arrow), and of the peribronchovascular interstitium (arrowhead).

Figure 4.23 This coronal view shows bilateral smooth perilobular, peribronchovascular, and subpleural thickening in a patient with hydrostatic pulmonary edema (Fig. 4.22 is a close-up of this image). Areas of faint ground-glass opacity are also present (arrows).

Heart enlargement and bilateral pleural effusion are common findings in cardiogenic pulmonary edema (Fig. 4.24); a pericardial effusion may coexist in a number of patients. When lymph flow to the systemic veins decreases, an enlargement of mediastinal lymph nodes due to fluid stagnation may occur (Fig. 4.25).¹¹

Figure 4.24 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).

Figure 4.25 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).

Figure 4.26 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.

Lymphangitic Carcinomatosis. Lymphangitic carcinomatosis (LC) may present with a fully smooth subset (Fig. 4.26),¹² but not infrequently nodular irregularities (beaded appearance of septa and fissures) and random micronodules in areas of thickening occur. Nodules result from the 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 4.27 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 4.28 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).

The lesions of LC are typically patchy, often unilateral, and not gravity-dependent (Fig. 4.27).¹² Hilar lymphadenopathy is visible in 50% of patients. Enlarged mediastinal lymph nodes can also be seen in a number of cases (25% to 50%).¹³ Dedicated CT window settings may demonstrate metastatic lesions elsewhere (Fig. 4.28).

Figure 4.29 Pulmonary venoocclusive disease in a 25-year-old man. The axial computed tomography 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.

Figure 4.30 An axial scan of the same patient as in Fig. 4.29 confirms the gravitational distribution of the lesions.

Venoocclusive Disease. The presentation of venoocclusive 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 (Fig. 4.29).^14,15

The lesions present a geographical appearance with variable localization. They are always bilateral and may have a gravitational preference (Fig. 4.30).¹⁵

A key radiologic sign is coexisting enlargement of the central pulmonary arteries compatible with arterial pulmonary hypertension (Fig. 4.31).¹⁶ the right side of the heart may also 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

Erdheim-Chester Disease. Erdheim-Chester disease (ECD) is a non-Langerhans cell systemic histiocytosis that produces smooth septal and subpleural interstitial thickening with more or less regular contours (Fig. 4.32). Multifocal areas of ground-glass attenuation, small centrilobular nodular opacities, and pleural effusion may be also present.^17,18

The septal lesions of ECD involve both lungs diffusely (Fig. 4.33), but in some cases they may predominate in the upper or lower lobes.¹⁸

Figure 4.31 A contrast-enhanced axial scan (mediastinal window) of the same patient as in Fig. 4.29 reveals a dilated central pulmonary artery (arrowhead) and a right pleural effusion (curvedarrow). Compare the size of the main pulmonary artery with the diameter of the ascending aorta (arrow) they should be the same as in a normal individual.

Figure 4.32 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.

In addition, the pleura and mediastinal structures may be involved (Fig. 4.34). The superior vena cava, along with the pulmonary trunk and main arteries, may be coated by anomalous tissue; 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 most clearly visible on images thanks to the contrast provided by the adjacent pericardial fat (Fig. 4.34).¹⁹

Subset Nodular

The interstitial compartments are thickened in nodular form, testifying to the existence of locally growing cells or extracellular deposits within the interstitial boundaries (Fig. 4.35).²⁰ Being interstitial, these nodules are dense with well-defined margins (Fig. 4.36),² embedded as they are inside thickened interlobular septa and interstitial lines with an overall beaded appearance.²¹

Figure 4.33 Widespread basal septal thickening in the same patient as in Fig. 4.32.

Figure 4.34 Axial scan (mediastinal window) of the same patient as in Fig. 4.32. An abnormal dense tissue thickens the subpleural spaces (curved arrows) and infiltrates the mediastinal fat (arrowheads).

The septal pattern, subset nodular, differs from the nodular pattern, subset lymphatic, where the nodules are more or less individually seen along appropriate routes that are not thickened. This important distinction helps the radiologist to distinguish between the two diseases (e.g., LC [septal pattern, subset nodular] from sarcoidosis [nodular pattern, subset lymphatic]).

Lymphoid interstitial pneumonia (LIP) is a multifaceted disease that may present with different patterns, including septal. However, it tends more often to show nodules along lymphatic routes, so it has been placed in the nodular pattern, subset lymphatic. Diseases in the septal pattern, subset nodular, are listed in Box 4.3.

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. 4.37).^{22,23 the} lesions of diffhse pulmonary amyloidosis show a basal and peripheral prevalence (Fig. 4.38).²⁴

Figure 4.35 Septal Pattern, subset Nodular, showing both smooth and beaded septal thickening of the peripheral interstitium (interlobular septa), in which small nodules are visible (curved arrows).

Figure 4.36 Septal Pattern, subset Nodular. The nodules inside the thickened septa and subpleural interstitium have high-density and well-defined margins (arrows).

The key to the diagnosis is the existence of subpleural, confluent, calcified consolidations (Fig. 4.39). Associated findings are lymph node enlargement and unilateral or bilateral pleural effusions.²⁵ Tracheobronchial involvement may also be present, with thickening of the tracheal and bronchial walls due to the deposition of amyloid.

Figure 4.37 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 4.38 This is a more basal scan from the same patient as in Fig. 4.37. Bull's-eye, liver; sun, heart.

Figure 4.39 Mediastinal window at the level of the great vessels (bull's-eyes) in the same patient as Fig. 4.37. The image shows patchy peripheral calcified consolidations in both lungs (arrowheads).

Fibrotic Pattern

Definition

A fibrotic pattern is present when signs of retraction and remodeling of thoracic structures are recognizable at the lobular level and/or in corresponding larger portions of the lung (Fig. 4.40).

High-Resolution Computed Tomography Signs

The signs of fibrotic disease are associated with the direct visualization of fibrotic elements or with the effects of retraction and remodeling on pulmonary structures. Direct signs of fibrosis are irregular linear opacities (irregular reticulation), vessel enlargement, traction bronchiectasis, and bronchiolectasis with bronchial wall thickening, parenchymal bands, and honeycombing. The effects of lung retraction and remodeling are identifiable as irregular displacement of fissures, crowding of vessels, and retraction of the pleural/mediastinal surfaces with interface signs. These features are all due to shrinking of the pulmonary parenchyma with volume loss.

Irregular linear opacities (irregular reticulation) are crisscrossing, nonuniform, wavering white lines that appear as though they had been traced by an unsteady hand on the lung background (Fig. 4.41). Sporadically, one could imagine that one or more of these lines might represent remnants of interlobular septa (interlobular reticulation), but as a rule interlobular septa are not seen. On the contrary, distortion due to fibrosis tends to reduce recognition of the lobular architecture.² Most of these lines crisscross spaces of lobular size, so they are also called intralobular reticulation (Fig. 4.41).

The vessels may appear enlarged, with shaggy margins (interface sign), and the bronchi are irregularly ectatic with thickened walls and a winding or corkscrew appearance (Fig. 4.42). In the periphery of the lung, the bronchioles may also be ectatic (and hence visible) with the same appearance (traction bronchiectasis and bronchiolectasis) (Fig. 4.41). Finally, parenchymal bands are long lines representing thickened connected septa at the margins of several lobules but also focal scarring or linear atelectasis.²

As a whole, the described lesions may vary in size and aspect, from a more or less coarse, obvious pattern to a subtle, hazy opacification of the lung, referred to as fibrotic GGO, that is only minimally inhomogeneous. In the latter case, ectatic bronchioles inside the GGO and superimposing irregular reticulation (indicating fibrosis) are the discriminant features (Fig. 4.42).²⁶

A peculiar feature of destructive fibrosis is honeycombing. In honeycombing, small hyperlucent areas of variable size (from 2 mm to 1 cm) and shape separated by well-defined thick walls are crowded in an area where the lung architecture is lost (Fig. 4.43).²⁷ They should be distinguished (not easy and not always possible, especially in the early cases) from roundish or elongated, windingly linear, transparencies corresponding to ectatic bronchioles (called microscopic honeycombing by Nishimura).²⁸

Signs of retraction and remodeling give further, at times striking, evidence of the existence of a fibrotic disorder. At the pulmonary interface, a pleural line with shaggy margins and connections with parenchymal irregular lines (interface signs) may be evident (Fig. 4.44). A thickening of the subpleural interstitium may also be obvious, as well as an increased thickness of extrapleural/mediastinal fat, the latter compensating for the shrinking lung (Fig. 4.44). A shaggy thickening may be also observed at the interface of the visceral pleura, which becomes angulated and displaced.

When fibrosis advances, one or more lobes and even the entire lung may become reduced in size. The signs associated with this are angulation and displacement of fissures, crowding of vessels and bronchi, and mediastinal and diaphragmatic attraction toward the affected lung (Fig. 4.45).

Figure 4.40 Radiology (A) and pathology (B) of fibrotic diseases. The signs of retraction and remodeling on the pulmonary structures are the key elements to identify this pattern. (Pathologic image courtesy Alessandra Cancellieri, Bologna, Italy.)

Figure 4.41 Irregular linear opacities (irregular reticulation) at the periphery of the lung (arrowheads) with remodeling of the lobular architecture, which is no longer recognizable. Signs of retraction are also evident on the bronchial structures with bronchiectasis and bronchiolectasis (curved arrows).

Subsets

Depending on the underlying disease, the morphologic elements and their topographic distribution may be arranged in subsets that are helpful in focusing on definite categories of fibrotic disorders and at times even on specific diseases. The main subsets of the fibrotic pattern are UIP, NSIP, tug-of-war fibrosis, and bronchocentric fibrosis.

Subset Usual Interstitial Pneumonia

The UIP subset is defined by the presence of patchy areas of irregular reticulation and gross honeycombing with prominent signs of architectural distortion (Fig. 4.46). Traction bronchiectasis and microscopic honeycombing in connection with the pathologic areas are also char- acteristic.²⁸ Some GGO is possible, but it would be less extensive than the reticulation.²⁹ Signs of retraction and remodeling of vessels, fissures, lobes, and pulmonary boundaries are common, especially in advanced cases (Fig. 4.47).

Figure 4.42 Tiny irregular lines in the anterior portion of the right lung. A long, ectatic, winding bronchus with thickened walls is clearly appreciable (arrows). The ground-glass component of the image is probably a fibrotic ground-glass opacity due to concomitant irregular reticulation and bronchiolectasis (arrowhead).

The UIP subset may be seen both in idiopathic pulmonary fibrosis (IPF) and, with identical aspects, in several CVDs or, more rarely, chronic drug toxicity. Aspects of UIP are also present in individuals who develop an acute clinical course (acute exacerbation or acceleration of IPF), where the histologic findings show superimposed features of acute lung injury; in these cases, the radiologic presentation is usually dominated by the alveolar densities of acute lung injury. This is consequently discussed under in the section Alveolar Pattern, subset Acute. Diseases in the fibrotic pattern, subset UIP, are listed in Box 4.4.

Asbestosis. The early lesions of this disease are a combination of centrilobular dotlike and branching³⁰ opacities, which are often arranged in clusters or connected by subpleural curvilinear lines (Fig. 4.48).³¹ These nodular opacities correspond to peribronchiolar nodular fibrosis, which is also responsible 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 4.43 This is an example of what is called honeycombing radiologically (arrows)—multiple air-containing hyperlucent spaces (black holes) with well-defined thick walls grouped in several layers in an area of complete loss of the lobular architecture.

Figure 4.44 Shaggy margins of pleura (arrows) and vessels (arrowheads) (interface sign) and retraction of extrapulmonary structures toward the shrunk lung (curved arrow) are also indications of an underlying pulmonary fibrosing disorder.

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. 4.49).

Diffuse parietal pleural thickening and pleural plaques with or without calcifications (Fig. 4.50; see also Figs. 4.48 and 4.49) 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 (Fig. 4.50) 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 4.45 In this advanced fibrosing disease, the volume of the lower lung is markedly reduced, as shown by high diaphragmatic domes (arrowheads) approaching lowered fissures (arrows).

Figure 4.46 Honeycombing in the posterior costophrenic lung in a sagittal view. Note the sharp demarcation of the diseased lung with the normal pulmonary parenchyma (arrows).

Chronic Hypersensitivity Pneumonitis. Fibrotic GGO and irregular reticulation with traction bronchiectasis and bronchiolectasis are the most common features of HP, 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 GGO (Fig. 4.51).³⁴

Both reticulation and honeycombing may prevail in the periphery of the lung and may show upper lung predominance (Fig. 4.52). However, a random distribution is also common. Lower lobe predominance is uncommon.³⁴

Figure 4.47 This sagittal view shows several signs of an important fibrosing pulmonary disorder: honeycombing in the anterior portions of the lung (sun), retraction of the mediastinal fat (arrow), and displacement of several ectatic bronchi (arrowheads).

Figure 4.49 Axial scan at the carinal level in the same patient as in Fig. 4.48. At this transversal level, the fibrotic involvement of the lung is only initial, and the honeycomb changes are confined into restricted areas (arrow). Bilaterally There are pleural plaques of typical aspect (arrowheads).

Figure 4.48 Axial scan at the level of the heart (sun) in a patient with asbestosis. Areas of advanced fibrosis with honeycombing (arrowhead) are seen, but also evident are more initial subpleural lines with a beaded appearance (arrow). The pattern is completed in this case by patchy areas of mosaic oligemia (curved arrows).

Figure 4.50 Calcified pleural plaques (curved arrows), subpleural lines (arrowhead), and parenchymal bands (arrows) are variably distributed in this patient with initial parenchymal asbestosis.

Figure 4.51 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).

Figure 4.52 the lesions of chronic hypersensitivity pneumonitis tend to prevail in the upper regions of the lung (arrows); this is true also for honeycombing. In this sagittal view of the left lung, the base of the lung is relatively free of lesions. This is an important element in the differential diagnosis with idiopathic usual interstitial pneumonia.

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 lungs (Fig. 4.53).³⁵

Idiopathic Usual Interstitial Pneumonia-Clinical Idiopathic Pulmonary Fibrosis. Patchy areas of dense irregular reticulation and honeycombing^28,31 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 parenchyma (Fig. 4.54).³⁶

Figure 4.53 In chronic hypersensitivity pneumonitis, interface signs and evidence of architectural derangement are usually located in shrunken upper lobes, indicated here by the upward bowing of the major fissures (arrows).

Figure 4.54 Axial scan at the level of the right liver dome (bull's-eye) and of the heart base (sun) in a patient with idiopathic usual interstitial pneumonia. 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 lung (Fig. 4.55).³⁸ Especially in advanced fibrosis, the lung becomes smaller and the indirect signs of retraction and remodeling striking.

Focal emphysematous hyperlucencies in the upper zones of the lung²⁸ but also inside the basal lesions are possible³⁹; with honeycombing, these may create diagnostic problems of differential diagnosis.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 in all fibrotic disorders.

Figure 4.55 the peripheral regions of both lungs in this frontal view of a patient with idiopathic usual interstitial pneumonia show an irregular reticulation superiorly (arrows); typical honeycombing is present at the basal level (arrowheads).

Some CVDs⁴⁴ and, more rarely, drug reactions⁴⁵ may present with aspects indistinguishable from idiopathic UIP. Consequently suspicion for the underlying disorder may be formulated only on clinical grounds, although occasionally specific signs of the original disease are also seen radiologically (Fig. 4.56).^46-48

Subset Fibrotic Nonspecific Interstitial Pneumonia

The NSIP pattern is defined by the presence of homogeneous areas of GGO associated with irregular reticulation (Fig. 4.57).⁴⁹ the percentage of each likely depends on the proportions of inflammation and fibrosis within the lung, and some authors have even attempted to identify definite subgroups based on the extent of reticulation and traction bronchiectasis.⁵⁰ Traction bronchiectasis is characteristic (Fig. 4.58). Honeycombing, on the contrary, should be absent or minimal.⁵¹

The NSIP subset may be seen both in idiopathic NSIP and in several CVD and drug reactions, but NSIP aspects may also be present in patients with acute exacerbation of NSIP (accelerated NSIP) where the histologic findings show superimposed features of acute lung injury. In the latter cases the radiologic presentation is dominated by the alveolar densities of acute lung injury. This is consequently discussed in the section Alveolar Pattern, subset Acute. Diseases in the fibrotic pattern, subset fibrotic NSIP, are listed in Box 4.5.

Idiopathic Fibrotic Nonspecific Interstitial Pneumonia. Characteristic features of disease include reticular/GGO opacities with a homogeneous aspect in the affected areas. Inside the lesions, traction bronchiectasis and bronchiolectasis are common, and their extent has been shown to be a reliable indicator of fibrosis (Fig. 4.59).⁵⁰ Dense consolidations, on the contrary, are uncommon, and their presence should raise the suspicion of another disease (such as OP, chronic eosinophilic pneumonia [CEP], or bronchioloalveolar carcinoma) or, in the appropriate clinical setting, of an acute exacerbation (see Alveolar Pattern, subsets Acute and Chronic).⁴⁹ If present, honeycombing is mild and should raise the suspicion of UIP⁵¹; however, it has been reported that, over time, a number of NSIPs originally presenting with an NSIP pattern progress to a UIP pattern.⁵²

Figure 4.56 Patchy honeycombing alternating with normal lung (usual interstitial pneumonia subset) in a patient with systemic sclerosis. In this axial scan at the subcarinal level, an enlarged esophagus with an air-fluid level is visible (arrowhead) between the intermediate bronchus at the right and the junction of the upper and lower lobe bronchi at the left (arrows).

Figure 4.57 the typical fibrotic nonspecific interstitial pneumonia subset is characterized by areas of ground-glass opacity and irregular reticulation associated with more or less evident bronchiectasis (curved arrows) but without significant honeycombing.

The disease is bilateral and symmetrical,⁴⁹ involving mainly the lower lungs in more than 90% of cases⁵¹ (Fig. 4.60); otherwise it is equally distributed. However, lesions primarily affecting the upper lobe 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 4.58 the minimum intensity projection technique is valuable in showing the size and extension of the bronchiectatic abnormalities inside the ground-glass opacity (arrowheads). Note the absence of honeycomb cysts inside the pathologic area.

Figure 4.59 This is a patient with a typical fibrotic nonspecific interstitial pneumonia subset, possibly from systemic sclerosis because the esophagus is enlarged. The periphery of both lungs is involved with a subtle reticular ground-glass opacity (arrows) without significant honeycombing. A shrunken right lower lobe (arrowhead) is more extensively involved and contains some bronchiectasis.

Figure 4.60 Frontal view of both lungs at the level of the descending aorta (sun). A basal fibrotic ground-glass opacity 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 no 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 suspicion for the underlying disorder should be formulated on clinical grounds. Occasionally specific signs of the original disease are visible radiologically (Fig. 4.61).^46-49

Subset Tug-of-War

The tug-of-war subset is defined by the presence of irregular linear opacities stretching between the mediastinum and the thoracic boundaries, bridging over variably involved bronchi, fissures, and more generally anatomic structures and even pathologic elements found on their way (Fig. 4.62). The mediastinal profiles are variably stretched outward and the thoracic pleural profiles inward, hence the proposal for the name of this fibrotic subset (Fig. 4.63). Diseases in the fibrotic pattern, subset tug-of-war, are listed in Box 4.6.

Sarcoidosis, Chronic. Fibrosis may present early in the history of the disease, when nodular elements are fairly 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 (Fig. 4.64).^55,56 Progressive fibrosis leads to a 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

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 (Fig. 4.65).^55,58

Figure 4.61 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 ground-glass opacity is gone (hence reversible) but the reticulation persists (arrows). In both images, the esophagus is enlarged (arrowheads).

Figure 4.63 Tug-of-war fibrosis, sagittal image. Straight interstitial connection lines bridge the bronchovascular bundle, entirely stretched anteriorly and superiorly (arrow), and several peripheral irregularities point inward (arrowheads).

Figure 4.62 Tug-of-war fibrosis, axial scan. Several irregular white lines extend from the hilum, which is stretched outward (arrow) at the pulmonary periphery, which in turn is irregular for the presence of several spicules directed inward (arrowheads).

Figure 4.64 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 walls (curved arrows) contribute to the feeling of a tug-of-war fibrosis. Calcified lymph nodes can be seen inside the mediastinum.

Figure 4.65 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).

Figure 4.66 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).

Mediastinal lymphadenopathy frequently coexists, often calcified. CT findings suggestive of pulmonary hypertension are possible late in the disease.² Cavitation of conglomerated masses may be seen in patients with necrotizing sarcoid granulomatosis, the entity first described by Liebow as characterized by sarcoid-like granulomas and vasculitis associated with variable degrees of necrosis (Fig. 4.66).⁵⁶

Pleuroparenchymal Fibroelastosis. Pleuroparenchymal fibroelastosis is a rare, recently described condition listed among the rare idiopathic interstitial pneumonias. It is an entity characterized by circumscribed elastotic fibrosis of the pleura and subjacent lung. Most cases are considered idiopathic, although a variety of associated conditions have been described.²⁷ Visible on HRCT is marked irregular pleural thickening as well as tags in the upper zones that merge with fibrotic coarse reticulation in the subjacent lung. Upperlobe volume loss with upper displacement of both fissures and tracheobronchial structures. Traction bronchiectasis often coexists. Irregular pleural thickening in the upper lobes is crucial for the diagnosis.²⁹

Figure 4.67 Patient with constrictive bronchiolitis posttransplantation. In this sagittal scan, there are vast areas of hyperlucent lung (dark lung) anteriorly (arrows), where vessel size and number is reduced.

Subset Bronchocentric Fibrosis

The bronchocentric subset is defined by the presence of a disease in which signs of traction and remodeling prevail at the level of the bronchial elements. The fibrosis may be focal or diffuse.

Focal fibrosis from constrictive bronchiolitis (CB) is concentrated in the bronchioli and too subtle to be appreciated radiologically. However, indirect signs of bronchial narrowing are visible, namely a patchy dark lung (Fig. 4.67). This condition is subsequently discussed in the section on dark lung pattern.

In contrast, pulmonary Langerhans cell histiocytosis (LCH), also a prominently centrilobular fibrotic process, is clearly visible in the form of thick walls around enlarged airways (Fig. 4.68) that assume early a cystic aspect.⁵⁹ Consequently its insertion in the cystic pattern has been considered more suitable. Diseases in the fibrotic pattern, subset bronchocentric fibrosis, are listed in Box 4.7.

Airway-Centered Interstitial Fibrosis. The main findings in airway-centered interstitial fibrosis are peribronchovascular interstitial thickening with traction bronchiectasis, thickened airway walls, and surrounding dense tissue with irregular margins (Fig. 4.69). 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

The lesions show a central rather than a peripheral distribution. They consistently show scarring around the airways (Fig. 4.70).⁶⁰

Figure 4.68 Patient with early pulmonary Langerhans cell histiocytosis. The several ringlike opacities visible in this image represent enlarged bronchi with thickened walls, as indicated by the tiny white dot (The companion artery) nearby (arrowheads).

Figure 4.69 At a first glance, the lesions in this patient with airway-centered interstitial fibrosis 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 Fabrizio Luppi, MD, Modena, Italy.)

Figure 4.70 Another image of the same patient as in Fig. 4.69. In the posterior left lung (curved arrows), the insistent thickening of the peripheral airways is well seen (inset). (Courtesy Fabrizio Luppi, MD, Modena, Italy.)

Nodular Pattern

Definition

A nodular pattern is defined by the presence of multiple roundish opacities ranging in diameter from 2 to 10 mm (Fig. 4.71).

High-Resolution Computed Tomography Signs

On HRCT, lung nodules appear as white, roundish lesions with variable morphology and lobular distribution depending on the route of arrival and the modality of spread.^2,7,61

Nodules that have low-density, ill-defined margins (nodular GGO) have a characteristic soft aspect, like snowflakes (Fig. 4.72). Sometimes they are very tiny and difficult to recognize.²⁰ They are commonly seen in patients with disease that primarily affects centrilobular bronchioles and the immediate area around them. The low-density CT aspect is due to minimal thickening of the peribronchiolar interstitium or partial filling of the peribronchiolar alveoli.² Both conditions are below the spatial resolution of CT; thus the common final effect is a focal low- density lesion. The ill-defined margins are due to progressive reduction of interstitial or alveolar involvement extending away from the centrilobular area to the periphery. These types of nodules may coalesce, resulting in the appearance of extensive GGO.

High-density nodules with well-defined margins are commonly seen in patients with diseases primarily affecting the interstitium; they are surrounded by aerated parenchyma and grow spherically.^2,61 Presenting with a solid aspect, like opaque beads, they obscure the edges of vessels or other structures that they touch (Fig. 4.73). They may have regular or lobulated contours, the latter aspect secondary to asymmetrical growth. The nodules may coalesce with the development of larger opacities or pseudoplaques along the costal or fissural margins.⁶²

On occasion, the nodules may have shaggy profiles, especially in diseases with a fibrotic component (Fig. 4.74). The small black areas inside these high-density nodules may be due to necrosis (Fig. 4.74) or traction bronchiolectasis. The presence of faintly increased lung attenuation around the nodules (halo sign) is most often an expression of hemorrhage (Fig. 4.74) or of inflammatory infiltrates ofany origin.^59,62 Regarding the lobular distribution, this is the result of their route of arrival and modality of spread, both underlying their distinction in subsets.

Figure 4.71 Radiology (A) and pathology (B) of a patient with nodular disease. The presence of multiple small roundish opacities scattered throughout the lung is the key element identifying this pattern. (Pathologic image courtesy Alessandra Cancellieri, Bologna, Italy.)

Figure 4.72 Nodules with low-density and ill-defined margins (nodular ground-glass opacity). Innumerable white, soft, roundish lesions are visible, with an aspect similar to snowflakes.

Subsets

The inhaled diseases show nodules close to the bronchioles in the centers of lobules (see subset Centrilobular). The diseases that grow along the lymphatics are more often seen at the periphery of the lobules and particularly along the fissures (see subset Lymphatic). The lesions that spread hematogenously are visible everywhere; There fore they may be seen in the core but also at the periphery (see subset Random), sometimes in connection with blood vessels.^61,63

Figure 4.73 Nodules with high-density well-defined margins. Several white, dense, roundish lesions are visible with an aspect similar to opaque beads.

Subset Centrilobular

On CT images, one can assume a centrilobular distribution of nodules when they stop at a certain distance from the pleural surfaces (pavid of pleura).^7,63 This feature is well demonstrated on the sagittal MIP images, where thin black lines of normal lung are seen along the fissures (Fig. 4.75).

Figure 4.74 Upper left, In this patient with sarcoidosis, the nodules present shaggy profiles related to their fibrotic component. Upper right, Nodules with shaggy profiles (arrow) are quite typical also of patients with Langerhans cell histiocytosis. Lower left, Cavitated nodule (arrowhead) in a patient with pulmonary metastatic disease. Lower right, Cavitated nodules with halo sign (curved arrow) in a patient with metastatic angiosarcoma.

Figure 4.75 Nodular pattern, subset centrilobular. The sagittal maximum intensity projection image highlights the centrilobular arrangement of the nodules that stop a certain distance from the pleural surface. As a result, they are separated from the fissures by a dark rim (arrows).

At an early stage, LCH is characterized by the presence of centrilobular nodules that, however, become cysts early.⁵⁹ Consequently, the inclusion of this disease in the cystic pattern has been considered more suitable. Diseases in the nodular pattern, subset centrilobular, are listed in Box 4.8.

Figure 4.76 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. At the periphery of the lungs, there are also branching structures with a tree-in-bud aspect (curved arrows).

Follicular Bronchiolitis. The basic features of follicular bronchiolitis consist of bilateral well- or ill-defined small centrilobular nodules (Fig. 4.76). In some patients, the centrilobular opacities may present a branching appearance, reflecting the morphology of the small airways involved, with aspects mimicking an appearance called tree-in-bud (Fig. 4.76) .^64-66

The lesions are bilateral and diffuse (Fig. 4.77), sometimes with predominant involvement of the lower zones.⁶⁴

Patchy areas of GGO are present in 75% of patients, and There is often mild bronchial wall thickening (Fig. 4.78).⁶⁶ Rare subpleural nodules may also be present (20%), and thin-walled cysts may occur due to check valve obstruction of small bronchioles by lymphoid tissue.^67,68

Subacute Hypersensitivity Pneumonitis. The HP pattern is defined by the presence of numerous centrilobular nodules usually less than 5 mm in diameter, of low density, and with ill-defined margins (nodular GGO) (Fig. 4.79).³⁵ the key to the diagnosis is the coexistence of sporadic lobular areas of air trapping appearing as patches of black lung (Fig. 4.79). These regions of lobular air trapping are caused by concomitant bronchiolar inflammation and obstruction.⁶⁹

The lesions are uniformly distributed, with possible middle to lower predominance (Fig. 4.80).^35,69

Areas of GGO often coexist. These are usually bilateral and symmetrical but can sometimes 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 called head cheese because of its resemblance to the variegated cross-sectional appearance of sausage made from parts of the head of a hog (Fig. 4.81).⁷⁰

Figure 4.77 Sagittal view of the same patient as in Fig. 4.76. This computed tomography plane highlights the visibility of the fissures (arrowheads), which are not involved with the nodules. This view also shows the craniocaudal distribution of the lesions that dominate the right upper (sun) and middle (bull's-eye) lobes.

Figure 4.78 Coronal view of the same patient as in Fig. 4.76. Bronchial wall thickening is visible in both parahilar zones (curved arrows).

Bronchiolar wall thickening may also occur, and lung cysts have occasionally been found. The latter are probably caused by partial obstruction of bronchioles (check valve mechanism).⁶⁹ 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 occasionally be present, presumably representing OP or superimposed unrelated processes such as aspiration injury or infectious pneumonia.

Figure 4.79 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 the lingula (arrowheads).

Figure 4.80 This axial scan of the same patient as in Fig. 4.79, 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.

Respiratory Bronchiolitis-Interstitial Lung Disease. The typical presentation of respiratory bronchiolitis-interstitial lung disease (RB-ILD) is that of centrilobular nodularity (Fig. 4.82), often in combination with areas of GGO and moderate centrilobular emphysema. The nodules present low-density ill-defined margins (nodular GGO); they may be tiny and difficult to recognize (Fig. 4.82).^71,72 Centrilobular nodules reflect accumulations of macrophages and inflammation in and around the respiratory bronchioles.

The nodules have an even, uniform distribution in the axial plane and predominate in the upper lobes (Fig. 4.83).⁷³ the areas of GGO involve the lung zones diffusely with a patchy distribution; this sign is thought to reflect the accumulation of macrophages in the alveoli and alveolar ducts.⁷⁴

Another common finding in RB-ILD is central and peripheral bronchial wall thickening caused by airway inflammation (90%) (Fig. 4.84). Areas of hypoattenuation are noted in 38% of patients and are most likely related to air trapping.^74,75 Sometimes signs of other smoking-related interstitial lung diseases may coexist (e.g., desquamative interstitial pneumonitis, pulmonary LCH, smoking-related pulmonary fibrosis), creating mixed patterns.⁷³

Figure 4.81 Another patient with hypersensitivity pneumonitis in the subacute phase. The image shows a patchy mixture of normal parenchyma (arrow), areas of ground-glass opacity (curved arrow), and dark lobules (arrowhead), resulting in the so-called head cheese aspect.

Figure 4.82 Respiratory bronchiolitis-interstitial lung disease 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.

Subset Lymphatic

Lymphatic nodules commonly occur along lymphatic routes. They tend to be concentrated and more visible along the costal margins and/or the fissures (avid of pleura) (Fig. 4.85).⁷ They are also visible in the perilobular interstitium as well as along vessels and bronchi.^61,63

In the lymphatic subset, however, the nodules are more or less individually seen along appropriate routes that are not intrinsically thickened. In contrast, in the septal pattern, subset nodular, the nodules appear embedded within thickened interlobular septa and subpleural lines, with an overall beaded appearance. As previously stated, this important distinction helps the radiologist distinguish between the two diseases (i.e., sarcoidosis [nodular pattern, subset lymphatic] from LC [septal pattern, subset nodular]).

Figure 4.83 Sagittal view of another patient with respiratory bronchiolitis-interstitial lung disease. Scattered small opacities of faint density (arrows) are present, predominantly in the upper lobes.

Figure 4.84 Sagittal view of the same patient as in Fig. 4.83. The findings range from barely visible micronodular ground-glass opacities to a more convincing bronchial wall thickening (arrowheads) and some centrilobular emphysema (curved arrow).

In the interstitial form of amyloidosis, the abnormalities may occur as distinct subpleural nodules, but nodular septal thickening and confluent subpleural consolidative opacities are more commonly observed (see Septal Pattern, subset Nodular). Diseases in the nodular pattern, subset lymphatic, are listed in Box 4.9.

Figure 4.85 Nodular pattern, subset lymphatic. The sagittal view beautifully shows the affinity of the nodules for the subpleural spaces—in this case, especially for the fissures (arrowheads).

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 (Fig. 4.74). The nodules are distributed along the costal margins and fissures but are also concentrated along the bronchovascular sheath (Fig. 4.86).^56,76 They may coalesce to form large nodules or pseudoplaques along the pleural margins (Fig. 4.86).⁶²

The distribution of the lesions is patchy, with a parahilar predominance (Fig. 4.86). A predilection for the upperdorsal lung zones is often present (Fig. 4.87).^56,76

Lymphadenopathy is the most common finding in sarcoidosis; it is typically hilar, bilateral, and symmetrical. In addition, mediastinal lymph node enlargement is often present, especially in the right paratracheal and subcarinal node groups (Fig. 4.88). Lymph node calcifications are visible in 25% to 50% of cases. They may be amorphous, punctate, dense, or eggshell and suggest chronic disease.⁷⁶

Occasionally, the confluence of several interstitial granulomas may result in large, irregular, masslike nodules without or with air bronchograms, resembling airspace 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.⁷⁷ 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.⁷⁸

Figure 4.86 Sarcoidosis. Several small nodules with well-defined margins and high density are distributed along the costal margins (curved arrows) and the bronchovascular bundle (arrowhead).

Figure 4.87 Sagittal view of a patient with sarcoidosis. A middle-upper predominance of the nodules is evident.

Lymphoid Interstitial Pneumonia. LIP 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, HRCT most often shows nodular aspects along lymphatic routes. The well-defined nodules range from 1 to 3 mm in diameter (Fig. 4.89). This pattern may be associated with thickening of the bronchovascular bundles, mild interlobular septal thickening, and tiny ill-defined centrilobular nodules.⁷⁹

The lesions involve mainly the lower lung zones (Fig. 4.90).⁸⁰

Figure 4.88 Contrast-enhanced frontal view through the middle of the mediastinum in a patient with sarcoidosis. Large subcarinal (arrowhead) and hilar (curved arrows) adenopathies typical of this disease are present.

Figure 4.89 This axial image in a patient with lymphoid interstitial pneumonia shows subpleural micronodules (curved arrow) and nodular thickening of interlobular septa (arrows). In this case, the lesions prevail at the right.

In Sjogren syndrome, LIP is typically associated with round or oval thin-walled cysts of variable size (Fig. 4.91). They may be seen in up to 80% of patients, are typically few in number, and measure less than 3 cm in diameter. They presumably result from air trapping due to peribronchiolar lymphoid infiltration.^81,82

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 LIP according to different series (0% to 68%).^79,81,83

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. 4.92). The high-density nodules often have well-defined margins, sometimes with calcification. Subpleural nodules have a rounded or triangular configuration; if they are confluent, they may resemble pleural plaques (pseudoplaques) (Fig. 4.92).⁸⁴

Figure 4.90 Same patient as in Fig. 4.89. The axial scan at a lower level shows some prevalence of the nodules in the lower lung.

Figure 4.91 Axial scan at the level of the heart (sun)in a patient with Sjogren syndrome. The image shows several cysts in both lungs; they appear as small, black, rounded lesions with very thin walls (arrows).

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 (Fig. 4.93).^84,85

Hilar and mediastinal lymph node enlargement may precede the appearance of parenchymal nodular lesions. Calcification of lymph nodes is common (Fig. 4.94) and may occur at the periphery of the node, producing an eggshell appearance. This so-called eggshell calcification pattern is highly suggestive of silicosis.⁸⁵

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.⁸⁶

Figure 4.92 Axial thin-section computed tomogram in a patient with silicosis. The image shows numerous small nodules in both lungs. Note also the pseudoplaques, which represent aggregates of several subpleural nodules (arrowheads).

Figure 4.93 Axial scan of a patient with silicosis. The image shows a posterior predominance of nodules and a higher profusion at the right (arrow).

Subset Random

Random nodules are visible everywhere and also touching the pleural surfaces but without a consistent relationship with them (i.e., indifferent to the pleura) (Fig. 4.95). At times, they can be seen in contact with the extremities of the vascular structures from which they seem to originate (feeding vessel sign) (Fig. 4.95).^7,63 Diseases in the nodular pattern, subset random, are listed in Box 4.10.

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. 4.96). Nodules with poorly defined margins can be identified in 16% to 30% of cases; these may reflect lepidic growth of tumor.^63,87 Nodules may also be cavitated and/or surrounded by a halo of ground-glass attenuation, which is typical of hemorrhage.^87,88

A basilar predominance is typically noted owing to preferential blood flow to the lung bases. When they are 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 common (Fig. 4.97).⁸⁷

Figure 4.94 Computed tomography scan, documented with a mediastinal window, showing tiny calcifications in the pretracheal lymph nodes (arrow).

Figure 4.95 Nodular pattern, subset random. This sagittal maximum intensity projection shows sharply defined nodules randomly distributed throughout both lungs. Some of these lie along the pleural surfaces (arrows) but without an elective affinity. Some nodules seem related to adjacent vessels (inset).

Figure 4.96 Metastatic nodules. This image shows random nodules of different sizes; one of them seems to present a feeding vessel (curved arrow). Note also the enlarged hilar (arrow) and subcarinal (arrowhead) lymph nodes.

Figure 4.97 This axial image taken through the middle lung zone shows innumerable nodules of a uniformly random distribution in this patient with metastatic disease.

Macronodules, carcinomatous lymphangitis, and enlarged lymph nodes may also be present (Fig. 4.98; see also Fig. 4.96). Occasionally intravascular tumor emboli may result in nodular or beaded enlargement of the peripheral pulmonary arteries with a tree-in-bud appearance (Fig. 4.98).⁸⁹

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. 4.99). 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.^90,91 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.^{92,93 the} nodules are distributed uniformly throughout the lungs without a cephalocaudal or central-to-peripheral preference (Fig. 4.100).⁹⁰

Figure 4.98 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).

Figure 4.99 Miliary tuberculosis. The axial image shows innumerable noncalcified nodules of miliary size scattered throughout both lungs with a random distribution. The nodules are dense and uniform in size.

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 a tree-in-bud pattern (Fig. 4.100) and lymphadenopathy.⁹⁰ Necrotic lymph nodes may be observed in 70% of seropositive and 20% of seronegative patients.⁹¹ Diffuse or localized GGO is sometimes seen; it may herald acute respiratory distress syndrome (ARDS).^92,93 Changes from previous tuberculosis are seen in 50% of the patients and 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 (Fig. 4.101).^93,94

Fungal infection may produce diffuse interstitial lung disease characterized by small nodules with a random distribution, as in military tuberculosis.⁹⁵ 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.⁹⁶ All these aspects are most commonly seen in immunocompromised patients.⁹⁷ 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 airspace consolidation.^62,98

Figure 4.100 Sagittal view of the same patient as in Fig. 4.99. 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).

Alveolar Pattern

Definition

An alveolar pattern is present when more or less broad portions of lung become more opaque than normal due to the partial or complete filling of alveoli (Fig. 4.102). The pulmonary architecture is overall preserved; if signs of interstitial involvement are present, they are not prevalent.

Figure 4.101 Coronal view of the same patient as in Fig. 4.99. Patchy areas of oligemic dark lung (arrowheads) are present in the upper lung fields.

Figure 4.102 Radiology (A) and pathology (B) of alveolar opacities. Radiologically, a portion of lung becomes whiter than normal owing to the presence of material filling the alveoli. The different intensities of white depend on the percentage of alveolar filling in different areas. (Pathologic image courtesy Alessandra Cancellieri, Bologna, Italy.)

Figure 4.103 Ground-glass opacity: hazy increase of lung attenuation with preservation of the bronchial and vascular margins (arrowheads).

Alveolar filling may be due to fluid, cells, or other material that, in most cases, radiology is not able to discriminate. Nevertheless, size and aspect of the opacities, their distribution within the lung, and a number of ancillary signs provide useful diagnostic clues in several conditions.

Pure interstitial thickening from the accumulation of cells, fluid, or other substances (including fibrosis) may simulate an alveolar pattern. However, when this occurs, associated evidence of spread along interstitial routes (see Septal Pattern) or traction/remo deling of the pulmonary structures (see Fibrotic Pattern) should be evident.

High-Resolution Computed Tomography Signs

The main signs of an alveolar disorder are GGO and consolidation. GGO appears as a hazy increase of lung attenuation with preservation of the bronchial and vascular margins (Fig. 4.103).^20,26 It may be caused by partial filling of airspaces, interstitial thickening, partial collapse of alveoli, increased capillary blood volume, or a combination of these, the common factor being the partial displacement of air.²⁰ the lobular elements and, more in general, the pulmonary architecture are not distorted (Fig. 4.103). Consolidation appears as an intense increase in pulmonary attenuation that obscures the margins of vessels and airway walls.^8,20 Consolidation is due to a complete filling of alveoli by any material (exudate, cells, or other products of disease have the same radiologic aspect), the common factor being the full displacement of air from alveoli.²⁰ However, if air persists in the lumens of the bronchi, they remain visible inside the opacity (air bronchogram) (Fig. 4.104). An area of consolidation may contain hypo- or hyperdensities, reflecting the presence of differently attenuating substances such as fat, metals, calcium, or air (Fig. 4.105). GGO and consolidation may coexist in the same patient, leading to a mixed appearance (Fig. 4.102A).

Ancillary signs are crazy paving, tree-in-bud, halo sign, reversed halo sign, and perilobular pattern. These are imaginative but effective descriptive terms that help focus attention on subset disorders of the pulmonary parenchyma and airways.

Figure 4.104 Consolidation is an increase in pulmonary attenuation that obscures the vessels and the airway walls. On the other hand, the bronchial lumen may remain visible (arrows) inside the consolidation (air bronchogram).

Figure 4.105 Upper left, the tiny dots with computed tomography attenuation inside this pulmonary lesion (arrowhead) have a fatty density. Upper right, the black dots inside this opacity (arrow) are bronchi, and the white dots are calcifications. Lower left, the black hyperlucencies inside this bronchioloalveolar carcinoma contain air (cystic BAC). Lower right, A fairly regular network of white lines is superimposed on a background of ground-glass opacity. This appearance is called crazy paving.

Figure 4.106 Upper left, Several branching linear structures in the lobular context (curved arrows) evoke the aspect of a tree-in-bud pattern. Upper right, the ground-glass opacity (GGO) surrounding central opacities is called halo sign. Lower left, A rim of denser opacity surrounding a central area of GGO is called reversed halo sign or atoll sign. Lower right, this aspect of polygonal bandlike opacities bordering elements of lobular size is known as perilobular pattern.

Crazy paving is a smooth, fairly regular network of white lines superimposed on a background of GGO, resembling shaped paving stones (Fig. 4.105).^20,99 These white lines may represent thickened intralobular/interlobular interstitium but also purely alveolar deposition of material within the airspaces at the borders of unit structures such as acini or secondary lobules.^100,101

Tree-in-bud is the name given to centrilobular dense branching linear structures originating from a single stalk and often ending in a nodular form (thus resembling a budding tree) (Fig. 4.106).^20,96 the tree reflects the existence of luminal dilatation, bronchiolar wall thickening, and impaction¹⁰² for a spectrum of endobronchiolar and peribronchiolar diseases,²⁰ the most common being infectious disorders.^96,103 the buds are micronodular opacities due to concomitant nearby filling of airway lumina¹⁰⁴ or infiltration of the centrilobular interstitium. Rarely, a tree-in-bud aspect may represent an intravascular pulmonary tumor embolism (see Hematogenous Metastases in Nodular Pattern, subset Random).^89,105

A halo sign occurs when a central area of consolidation is surrounded by a halo of GGO attenuation (Fig. 4.106).^{106 108} This sign suggests that a disease might be pathologically active, with hemorrhage, inflammation, or tumor spread at the periphery.^107,109

A reversed halo sign occurs when a ring or crescent of dense consolidation surrounds a core of GGO (Fig. 4.106). This often corresponds with patches of alveolar/septal inflammation and cellular debris surrounded by a rim of denser OP.^110,111

A perilobular pattern occurs when poorly defined bandlike opacities with an arcade-like or polygonal appearance border the interlobular septa. These opacities have greater thickness and are less sharply defined than the true interlobular thickening encountered in the septal pattern (Fig. 4.106). Indeed, they are due to the accumulation of organizing exudate in the perilobular alveoli even without septal thickening.^112,113

Figure 4.107 Diffuse, bilateral ground-glass opacities are often the modality of presentation of the acute alveolar disorders.

Subsets

The clinical presentation of the patient represents the leading and most important discriminating element that makes it possible to divide the alveolar pattern in two subsets: acute and chronic.

Subset Acute

An alveolar pattern is acute when the onset of respiratory symptoms dates back to days or weeks (1 to 14 days, according to Schwarz and King).¹¹⁴

The opacities are more often bilateral and diffuse, and they may change in appearance quite rapidly. With the exception of the presence of an underlying fibrotic disease, signs of distortion or remodeling of the pulmonary structures are not evident, at least in the early phases of disease (Fig. 4.107).

Airborne diseases can be responsible for signs of bronchial wall involvement, peribronchial consolidations, poorly defined airspace nodules of acinar aspect (4 to 10 mm) (Fig. 4.108), and even lobular hyperinflation as a consequence of the reduction in caliper of the bronchiolar lumen. Diseases in the alveolar pattern, subset acute, are listed in Box 4.11.

Acute Interstitial Pneumonia/Acute Respiratory Distress Syndrome. Areas of GGO (100%) and patchy airspace consolidation (92%)¹¹⁵ with air bronchograms¹¹⁶ are the main findings in patients with both ARDS and acute interstitial pneumonia (AIP) (Fig. 4.109).¹¹⁷ Interlobular septal thickening (89%) and intralobular reticulation (78%)¹¹⁵ with aspects of crazy paving,^110,101 thickening of the bronchovascular bundle (86%), and nodular (86%) opacities¹¹⁵ are also very frequent. Similar findings with variants have been described in acute eosinophilic pneumonia¹¹⁸¹²⁰ and acute reactions to therapeutic^{45,53,54,121,122} and illicit¹²³ drugs.

The distribution of the lesions is variable, a specific predominance either in the craniocaudal or axial directions being possible in single cases.¹¹⁵ During the progression of disease, the extent of GGO tends to increase, and more homogeneous, gravity-dependent consolidative opacities appear (Fig. 4.110).^115,117

Moving from the acute and subacute to the chronic fibrotic phase, a distortion of the interstitial and bronchovascular markings is frequent (Fig. 4.111); beyond the first week or two, a dramatic increase of subpleural cysts and bullae also occurs.¹²⁴ On the other hand, 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 AIP/ARDS are a piling up of findings from original disease, atelectasis, inflammation, and side effects of mechanical ventilation.

Figure 4.108 In an acute clinical context, peribronchial consolidations (arrow) and nodular opacities with ill-defined margins (arrowhead) may testify to the existence of an alveolar disease arriving through the airways.

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. 4.112). In patients with UIP, irregular reticulation with patchy areas of honeycombing¹²⁵’¹²⁶ is visible. In contrast, in patients with NSIP, irregular reticulation and bronchiectasis, as well as an increase of previous GGO, are present.¹²⁷

The distribution of the alveolar densities may be multifocal, diffuse (Fig. 4.113) (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.¹²⁸

The possibility of an acute exacerbation (Fig. 4.114) has been described for idiopathic UIP (clinical IPF), idiopathic NSIP, and both UIP and NSIP associated with connective tissue disorders.^128,129 the specific aspect of the two leading subsets has been described in detail under Fibrotic Pattern.

Figure 4.109 Acute respiratory distress syndrome. Bilateral patchy areas of ground-glass opacity with crazy paving aspect and an air bronchogram are visible. A bilateral pleural effusion coexists in this patient (arrowheads).

Figure 4.110 Extensive bilateral opacification of the lung in a patient with acute respiratory distress syndrome. 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.

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. 4.115) to intense consolidation.¹³⁰

The distribution of the lesions is variable and depends on both the anatomic 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 predominance (Fig. 4.116).¹³¹

Figure 4.111 Late phase of acute respiratory distress syndrome. 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.

Figure 4.112 Accelerated usual interstitial pneumonia. Areas of opacity and ground-glass opacity prevalent at 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).

Within days of an acute episode, the interlobular thickening due to hemosiderin-laden macrophages accumulating in the interstitium may give a crazy paving appearance to the opacities (Fig. 4.117). After repeated episodes, a persistent irregular reticular pattern with traction bronchiectasis, sometimes even with honeycombing, may be seen.¹³⁰

Hydrostatic Pulmonary Edema. GGOs accompanied by visible interlobular septa and a thickened peribronchovascular bundle are the most common findings (Fig. 4.118).^10,132 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 under Septal Pattern, subset Smooth.

The opacities are diffuse or patchy and bilateral if no reasons for unilaterality exist (e.g., patient’s lateral decubitus, fibrosing mediastinitis).¹³² the lesions often show gravitational or parahilar predominance related to pressure dynamics (Fig. 4.119).⁹ 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 the right middle and upper lobes is the rule in cases of myocardial infarction, papillary muscle rupture, and mitral valve insufficiency.¹⁰

Figure 4.113 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).

Figure 4.114 An extensive honeycombing (arrow) prevails at the basal level of the lung in this patient with accelerated usual interstitial pneumonia. The rest of the lung is extensively opacified, pointing to an acutely exacerbated fibrosing disorder.

Unilateral or bilateral pleural effusion and thickening of the interlobar fissures are common in hydrostatic pulmonary edema (Fig. 4.120).¹⁰ In addition, mediastinal lymphadenopathy is not rare at all in patients with left-sided heart failure.¹¹

Infectious Diseases. A mixture of lobular or diffuse GGO/ consolidation, centrilobular ill-defined nodules, and thickened interlobular septa may be seen, with 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, intraalveolar hemorrhage, and diffuse alveolar damage (Fig. 4.121).^131,133

Figure 4.115 Patient with microscopic polyangiitis. There is a diffuse granular ground- glass opacity with some discrete ill-defined nodules that seem connected to small vessels (arrows).

Figure 4.116 the alveolar opacities in this patient with alveolar hemorrhage show neat parahilar predominance.

Figure 4.117 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).

Figure 4.118 Patient with mild pulmonary edema. In this axial plane, there are patchy areas of ground-glass opacity (arrowheads) and septal lines (curved arrow), highlighting the lobular boundaries. Some pleural effusion coexists at the right (arrow).

Figure 4.119 Pulmonary edema. In this patient, a hazy ground-glass opacity from partial alveolar filling shows a noticeable central predominance (arrowheads) with sparing of the most peripheral lung.

Figure 4.120 In this patient with patchy parahilar ground-glass opacity from pulmonary edema, a pleural effusion is also visible on both sides posteriorly (arrows) and inside the fissures (arrowheads).

Figure 4.121 Patient with H1N1 influenza virus pneumonia. The pattern is dominated by dense homogeneous parahilar consolidations and peripheral nodules of hazy ground- glass opacity (arrowheads) in centrilobular position.

Figure 4.122 Patient with H1N1 influenza virus pneumonia. In this frontal view, the consolidations tend to aggregate in the parahilar areas along the bronchovascular bundles.

More than 60% of patients with Mycoplasma pneumoniae pneumonia have lower zone predominance of the lesions, whereas 50% of patients with fungi have upper zone predominance.¹³⁴ In influenza pneumonia, the opacities may show a preference for perivascular (Fig. 4.122) and subpleural areas.¹³³ Pneumocystis jirovecii presents with a striking upper lobe predominance of GGO.¹³⁵

Figure 4.123 External view of the lungs in a subject with varicella zoster virus pneumonia. The nodular lesions characteristic of this virus are clearly evident on the surface of the pulmonary parenchyma.

Nodules are frequent in patients with fungal (65%), viral (77%), and M. pneumoniae pneumonia (89%); they are much less common in patients with bacterial pneumonia (17%).¹³⁶ In varicella zoster pneumonia, well- and ill-defined nodules 1 to 10 mm in diameter are diffusely scattered throughout the lungs (Fig. 4.123); coalescence of nodules and patches of GGO are also possible.¹³³ In immunocompromised subjects, especially those infected with human immunodeficiency virus, the presence of extensive, diffuse, bilateral GGO is suggestive (although not specific) for P jirovecii pneumonia^136,137; it becomes very typical if cystic lesions are contemporarily present.¹³⁴ On the other hand, nodules are absent.¹³⁶

Subset Chronic

An alveolar pattern is chronic when the onset of respiratory symptoms dates back from months to years from the time of diagnosis.¹¹⁴

The lesions may be bilateral or unilateral (Fig. 4.124); with a few exceptions they tend to clear up slowly over time (unless they worsen and proceed to fibrosis). Often arranged in patches of conspicuous size, they have tight relationships with the large airways, but a participation of the small airways in the lobular area is also possible. The chronic lung disorders may produce more multifaceted aspects than the acute forms (Fig. 4.125). However, within the range of the alveolar signs, it is often possible to identify prevalent aspects that are useful for narrowing the diagnostic possibilities: pure GGO, mixed densities, and crazy paving and tree-in-bud signs; these are declared at the beginning of each disease presentation.

Some diseases tend to develop alveolar opacities but show prevalent aspects that make preferable their inclusion in another pattern. These are HP and RB-ILD, described in the section on nodular pattern, subset centrilobular, and the fibrosing disorders showing as GGO, discussed in the section on fibrotic pattern. Diseases in the alveolar pattern, subset chronic, are listed in Box 4.12.

Adenocarcinoma. The diffuse form of adenocarcinoma is a disease of mixed densities. Patchy areas of GGO/consolidation and/or multifocal macronodular lesions with a halo sign are the most common presentations.^138-140 A skeletal, stretched, air bronchogram is frequently seen inside the opacities (Fig. 4.126).¹⁴¹ Crazy paving aspects and collections of air within consolidations (known as cystic bronchioloalveolar carcinoma) (Fig. 4.105) are also possible.^140,142 When nodules are present at the lobular level, they assume the aspect of centrilobular ill-defined opacities or, rarely, a tree-in-bud appearance.¹³⁸

Figure 4.124 Typical presentation of an alveolar disease of chronic type (in this case, the recurrence of organizing pneumonia): unilateral patchy mixed densities (ground-glass opacity and consolidation) with air bronchogram and some remodeling of thoracic structures ( The arrows point at the mediastinum, shifted to the left).

Figure 4.125 This is an exquisite example of a chronic airborne disease with a tree-in-bud pattern (arrowhead) spreading through the airways. Here and There the bronchioli are not filled with material, so their lumens are appreciable as much as their thickened walls (arrow).

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 contralaterally (Fig. 4.127).¹⁴⁰ Bulging of fissures is possible in the presence of dense lobar consolidation (Fig. 4.128)¹⁴¹ and pleural effusion; mediastinal lymph node enlargement is also possible.¹⁴⁰

Figure 4.126 Bronchioloalveolar carcinoma. A large consolidation at the right possibly points at the origin of the disease, and elsewhere There are signs of diffuse spreading. The arrow points to a narrowed, stretched bronchus inside the main opacity.

Chronic Eosinophilic Pneumonia. CEP is a mixed-densities disease. In the early phases, bilateral homogenous airspace consolidations are the most frequent mode of presentation (65%). However, GGO may also be the predominant pattern (35%), and septal lines often coexist (72%) (Fig. 4.129).¹⁴³ In the later stages, GGO, nodules, some reticulation, and, after weeks, linear bandlike opacities parallel to the pleural surface can be seen.¹¹⁹ the opacities are characteristically arranged at the periphery of the upper lung zones in 50% of the cases,¹¹⁹ with a less frequent hinging on the bronchi appearance compared with OP lesions (Fig. 4.130).

In drug-induced eosinophilic pneumonia, areas of ground-glass attenuation, airspace consolidation, nodules, and interlobular septal thickening are common.^120,144 the clinical response to corticosteroids is usually excellent and, typically, accompanied by rapid clearing of the opacities (Fig. 4.131).¹¹⁴ Pleural effusion is possible in 10% of cases.¹¹⁹

Figure 4.127 Axial scan in a patient with multifocal bronchioloalveolar carcinoma. At the left, there is a homogeneous alveolar opacity posteriorly (arrow) and a ground-glass opacity (GGO) with crazy paving anteriorly (sun). At 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 4.128 Bronchioloalveolar carcinoma. The dense, homogeneous opacity in the right cardiophrenic angle is an entirely consolidated lobe. Note the bulging of the fissure posteriorly (arrow). Note also the black remnants of bronchi stretched inside the opacities.

Desquamative Interstitial Pneumonia. Desquamative interstitial pneumonia (DIP) is a GGO disease. Quite extensive areas of pure GGO are indeed the dominant finding (Fig. 4.132).^145,146 Centrilobular nodules are uncommon,¹⁴⁶ as are consolidative and reticular opacities.¹⁴⁵

The lesions typically start in the lower lungs and peripherally (Fig. 4.133).¹⁴⁶,¹⁴⁷

Emphysema (Fig. 4.134; see also Fig. 4.133) has been reported in about 50% of patients with DIP.¹⁴⁸ In late disease, signs of fibrosis may be superimposed, with interstitial irregular lines, interface signs, and cystic hyperlucencies inside the GGO (Fig. 4.134).^146,149

Figure 4.129 Chronic eosinophilic pneumonia. Inhomogeneous consolidation with septal lines at the right and spotty areas of ground-glass opacity bilaterally are the disease's mode of presentation in this axial scan.

Figure 4.130 the opacities of this chronic eosinophilic pneumonia are essentially peripheral, and at the right There is also a bizarre connecting trail (arrowheads) between two main foci of consolidation.

Infectious and Inflammatory Diseases. These are mixed densities and tree-in-bud entities. Single or multiple areas of consolidation/GGO alert the radiologist to the existence of an alveolar disorder.⁶⁵ 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.^64,65,68 In areas of bronchiolar involvement, expiratory air trapping is frequently evident.^65,68 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. 4.135).

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, a tree-in-bud pattern, bronchiectasis, and bronchiolectasis with a dominant symmetrical lower lobe distribution.⁶⁵ 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 (Fig. 4.136) .^150-152

Figure 4.131 Chronic eosinophilic pneumonia in the same patient as in Fig. 4.129. This is a comparable axial image of the patient after a brief period of steroid therapy; the parenchymal opacities have disappeared.

Figure 4.132 Desquamative interstitial pneumonia. Patches of ground-glass opacity are visible at the level of the lower lungs in this axial computed tomography scan. At this time, no opacities were visible at the upper levels.

Unresolving consolidative opacities with low CT attenuation values (or frankly fatty densities) point to the possibility of an exogenous lipoid pneumonia (Fig. 4.105).^153,154 In chronic mycobacterial infections, signs of retraction at the segmental or lobar level may be seen (Fig. 4.137) .¹⁵²

Mucosa-Associated Lymphoid Tissue Lymphoma. Mucosa-associated lymphoid tissue lymphoma is a mixed-densities disease. Airspace consolidations with air bronchograms from unifocal or multifocal lesions to pneumonic-like opacities of lobar size are the most common findings (Fig. 4.138).^{155 157} In the surrounding area, the spreading of disease along lymphatic routes may be responsible for a GGO with septal lines, some bronchial thickening, and micronodules with a lymphatic distribution.^155,158,159 Centrilobular nodules are also possible.¹⁵⁶

Figure 4.133 Coronal view of both lungs in a patient with desquamative interstitial pneumonia. This minimum intensity projection image allows better recognition of patchy areas of ground-glass opacity in the lower lung fields. The arrowheads point to small areas of paraseptal emphysema.

Figure 4.134 This is the same patient as in Fig. 4.132, but after several years of a poorly managed disease. Now There are several patches of ground-glass opacity (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).

The disease may be unilateral or bilateral, seemingly with no vertical or horizontal zonal predominance.¹⁵⁵ the infiltration along bronchovascular bundles may result in focal lesions typically centered on the bronchi (Fig. 4.139).^156,159

The lesions are temporally indolent¹⁵⁷ and do not tend to cavitate.¹⁵⁹ Significant hilar and mediastinal lymphadenopathies or pleural effusions are not characteristic features of the disease (Fig. 4.140).^156,159

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 (Fig. 4.141),^49,160 and honeycombing is typically absent as well.¹⁶¹

The disease is bilateral and symmetrical,¹⁶⁰ 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 (Fig. 4.142).^27,51

Figure 4.135 Disseminated tuberculosis. At the left, there is a cavitated process surrounded by bronchi with thickened walls (arrow). At the right, anteriorly, there is a triangular consolidation with air bronchogram (arrowhead). In the posterior area of the same lobe, there are tree-in-bud opacities (curved arrow), indicating bronchial spread of the process. Enlarged lymph nodes are present in the mediastinum, at the left of the aortic arch (sun).

Figure 4.136 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 of this sagittal scan.

Several CVDs⁴⁴ and chronic drug reactions¹⁶² may present with aspects indistinguishable from idiopathic NSIP. Consequently a search for a nonidiopathic underlying disorder should always be undertaken clinically, although occasionally other signs of the original disease are visible radiologically (Fig. 4.143).^46,49

Figure 4.137 Some ground-glass opacity and several ectatic bronchi with thickened walls due to a tubercular process are visible bilaterally in this axial scan. Both the mediastinum (arrowhead) and the major fissure at the left (arrow) are retracted in connection with the parenchymal process.

Figure 4.138 Pulmonary mucosa-associated lymphoid tissue lymphoma. In this case, the lesion is in the 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 raise suspicion for a different lesion.

Organizing Pneumonia. Organizing pneumonia (OP) is a mixed- densities disease. The classic presentation (60% to 80% of cases)²⁷ of 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 recognizable (Fig. 4.124).¹⁶³ Areas of GGO attenuation (60%) with septal lines (40%) may coexist.^27,143 Several variants of the classic presentation have been described for this protean disease, including multiple nodules (Fig. 4.144) 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, there by mimicking a linear septal pattern (Fig. 4.106). All are detailed in the excellent review by Oikonomou.¹⁶³

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%) (Fig. 4.145).¹⁶⁴ Cryptogenic OP often involves the lower lung zones to a greater degree than the upper.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.¹⁶⁵

Figure 4.139 Pulmonary mucosa-associated lymphoid tissue 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 clearly recognizable inside the opacity.

Figure 4.140 Mucosa-associated lymphoid tissue lymphoma in the same patient as in Fig. 4.139. 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.

The opacities of OP vary in size from a few centimeters to an entire lobe.¹⁶⁵ Most patients respond to corticosteroid therapy (Fig. 4.146) or, in cases due to drug toxicity, to cessation of therapy. On occasion, the lesions may disappear spontaneously, only to reappear elsewhere (migrating disease).¹⁶⁶

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,¹⁰¹ often in the form of sharply marginated areas with a geographical distribution (Fig. 4.147).¹⁶⁷ the extension of the pulmonary abnormalities is often feature in a number of cases (17%) (Fig. 4.145).¹⁶⁴ Cryptogenic OP often involves the lower lung zones to a greater degree than the upper.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.¹⁶⁵

Figure 4.141 the scan is an axial view at the level of the costophrenic angles in a patient with nonspecific interstitial pneumonia. The liver is evident (sun). The transparency of the basal lung is inhomogeneous because of the presence of patchy areas of pure ground-glass opacity. Some slightly ectatic bronchi are recognizable (arrows). impressive in comparison with the mild respiratory condition of the patient. This clinicoradiologic discrepancy is considered typical of this disease.¹⁶⁸

Figure 4.142 Axial scan at the level of the costophrenic angles in a subject with nonspecific interstitial pneumonia. There is quite homogeneous peripheral ground-glass opacity; however, it spares the most subpleural lung (curved arrows). The opacities are more extensive at the left.

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 possible (Fig. 4.148).¹⁶⁸

The natural course of disease is an evolution of the opacities over a period of months or years (Fig. 4.149).¹⁶⁸ Pleural effusion and cardiomegaly are absent.¹⁶⁸

Cystic Pattern

Definition

A cystic pattern is present when multiple roundish, well-defined aircontaining spaces (black holes) are variably scattered throughout the lung parenchyma (Fig. 4.150). These “holes in the lung” may be due to dilation of the bronchial structures, abnormal distention of alveolar spaces, focal destruction of lung parenchyma, or even to cavitation of solid lesions.^169,170

Figure 4.143 the pulmonary window shows nonspecific interstitial pneumonia-compatible lesions in this patient with rheumatoid arthritis, and this mediastinal window shows a chronic pleural effusion at the left (arrow). The heart (sun) is severely shifted ipsilaterally.

Figure 4.144 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 Fig. 4.124.

Figure 4.145 the consolidations of organizing pneumonia are often centered on the bronchial elements, as in the case shown (arrows).

Figure 4.146 Healed organizing pneumonia after corticosteroid therapy. Only a minimal ground-glass opacity (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.

Figure 4.147 Pulmonary alveolar proteinosis. This patient presents very typical patchy areas of ground-glass opacity with superimposed septal pattern (crazy paving).

Figure 4.148 In this case the areas of crazy paving are more or less extended throughout the lung without considerable geographical preferences.

The cystic pattern should not be confused with the dark lung pattern. In both models, the elementary lesions are hyperlucent, but in the cystic pattern these lesions are focal and not diffuse, and their density is that of pure air-containing units, as black as the ambient air outside the chest.

High-Resolution Computed Tomography Signs

The cysts appear as multiple black holes that may differ by morphologic features (walls, shape, and contents) and distribution. When present,

Figure 4.149 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.

The walls of the cysts appear as white encircling lines (Fig. 4.151) of a thickness depending on the constituent elements (e.g., cells, fibrosis) and on the phase of disease.¹⁴⁹ Cysts without walls are usually the result of local destruction of lung parenchyma (Fig. 4.152; see also Fig. 4.151).⁸

Figure 4.151 Cystic lesions. In this case, there are two associated diseases. The first is responsible for multiple focal hyperlucencies without walls (arrowheads). The second shows cysts with evident walls and also some material inside the central lucency (arrows).

Figure 4.150 Radiology (A) and pathology (B) of patients with cystic diseases. Innumerable roundish lesions are scattered throughout the lung. The cysts appear hyperlucent (black) radiologically and white pathologically. (Pathologic image courtesy Alessandra Cancellieri, Bologna, Italy.)

Figure 4.152 Typical black holes from destruction of lung parenchyma (patient with centrilobular emphysema). In the image, multiple black areas of different sizes and shapes and with no recognizable walls are visible (arrowheads). Some lesions have a tiny white dot inside them.

Figure 4.153 Cysts of a disease (lymphangioleiomyomatosis) surrounded by normal parenchyma. The lesions are roundish, homogeneously scattered throughout the lung, and more or less regularly interspersed with vascular structures of adequate size; their walls are of a uniform thickness. Compare with Fig. 4.154.

The shape of the cysts depends on the mechanism of their formation, on their relationships with each other, and on the concomitance of traction phenomena in the surrounding parenchyma.² Cysts with regular shape, for example, are usually secondary to check valve mechanisms, with localized hyperinflation occurring in the context of a normal parenchyma (Fig. 4.153). Cysts of bizarre shape, in contrast, are often due to the fusion of several single lesions and even incorporation of ectatic thick-walled bronchi, leading to fibrotic phenomena with multifocal distortion (Fig. 4.154).^2,8

Figure 4.154 Cysts of a disease (pulmonary Langerhans cell histiocytosis) characterized by the phenomena of fibrosis with distortion and remodeling. The lesions are of variable size and shape, and the thickness of their walls is irregular. It is difficult to recognize any normal lung parenchyma between them. Compare with Fig. 4.153.

Figure 4.155 Axial view of multiple hyperlucent lesions (cystic bronchiectasis) in the lower left lung, behind the heart (sun). The fluid material inside some hyperlucencies forms what is called radiologically an air-fluid level (curved arrows).

The content of the cysts should be black because, by definition, it is pure air; however, when the cysts are due to destruction or necrosis of lung parenchyma, some remnants may persist within the blackness. For example, some cystic spaces may contain a small nodular opacity representing the centrilobular artery (Fig. 4.152),¹⁷¹ and others may contain solid material due to their neoplastic nature or to a fungus ball growing inside the lumen. When infected, the cysts may contain air-fluid levels (Fig. 4.155).

Finally, the distribution of the cysts within the lungs varies with the underlying disease; this element is often useful in the diagnosis. In this regard, the usage of multiplanar reconstructions is particularly useful because it supplies a panoramic comprehensive assessment of the regional distribution of the lesions along different axes, and the use of the minIP technique can be helpful in quantifying them.³

However, some diseases partly belonging to this category develop prevalent aspects that make it preferable to include them in a different pattern. Consequently, LIP is included in the nodular pattern, subset lymphatic, and P jirovecii pneumonia is described in the section on infectious diseases, alveolar pattern, subset acute.

Honeycombing, the more distinguishing feature of some fibrosing diseases (IPF, CVD, chronic HP, asbestosis, chronic drug toxicity), is also made up of well-defined, pure airspaces separated by dense, thick walls, but here the cysts are only an aspect of an entire fibrotic environment dominating the scene. Consequently honeycombing is discussed in the section on fibrotic pattern, subset UIP. Diseases in the cystic pattern are listed in Box 4.13.

Centrilobular Emphysema

In the early stage of disease, the cysts appear as tiny roundish black holes with invisible walls surrounded by normal lung parenchyma (Fig. 4.156). The lesions are homogeneously lucent. However, sometimes a central nodular or branching opacity representing the centrilobular artery is seen. This finding may be helpful in distinguishing emphysema from other diffuse cystic diseases.¹⁷² When emphysema enlarges and involves the entire secondary lobule, remnants of vessels and septa may simulate the appearance of thin walls, usually incomplete.²

In centrilobular emphysema, the lesions typically involve mainly the upper lobes and the superior segment of both lower lobes (Fig.

4.157) .¹⁷² 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 (Fig. 4.156). 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 panlobular emphysema (Fig. 4.157).¹⁷³

Paraseptal emphysema and bullae, bronchial and tracheal abnormalities, infections, pneumothorax, and pulmonary arterial hypertension are possible associated findings (Fig. 4.158).^172,174,175 the pulmonary volume is increased owing to overinflation.

Figure 4.156 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 contain a central tiny white dot, a remnant of the centrilobular artery (curved arrows [inset]).

Figure 4.157 Frontal view of the lungs in a patient with emphysema due to cigare The smoking. The areas of emphysema are more extended cranially, especially at the right, where they involve the totality of the pulmonary lobules (arrow).

Langerhans Cell Histiocytosis

Thin- 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.⁷³ the lesions, usually less than 10 mm in diameter, are due to the coalescence of single cysts, ectatic bronchi, and surrounding paracicatricial emphysema (Fig. 4.159).^176,177 Signs of architectural distortion may be seen in the intervening lung parenchyma.⁵⁹

The distribution of the cysts may be diffuse or patchy in the axial plane, whereas in the craniocaudal directions they present a predominance in the mid- and upper lung zones with relative sparing of the lung bases (Fig. 4.160).¹⁷⁷

Figure 4.158 Sagittal view of a patient with emphysema due to cigare The 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).

Figure 4.159 Axial view of a subject with advanced Langerhans cell histiocytosis. Innumerable cystic lesions with distinct walls are variously scattered throughout both lungs. They assume various shapes and are not of 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.

In the advanced stages of disease, the cystic pattern is the only abnormality visible on CT; but in the early and intermediate stages, more or less numerous centrilobular dense, often cavitated nodules with shaggy margins are present (Fig. 4.161). In some patients, a progression from cavitated nodules to cystic lesions has been observed.¹⁷⁷ Recurrent or bilateral pneumothorax occurs in up to 25% of patients over the course of their disease.¹⁷⁸ Signs of other smoking-related interstitial lung diseases (respiratory bronchiolitis, emphysema) may coexist, creating mixed patterns.⁷⁵

Figure 4.160 Coronal view of a subject with pulmonary Langerhans cell histiocytosis. 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).

Figure 4.161 Early pulmonary Langerhans cell histiocytosis. This 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 may rarely spread along the airways, thus 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 cavitated (Fig. 4.162).¹⁷⁹ the cavitated lesions may have thin or thick walls with irregularly nodular inner walls. Air-fluid levels inside the cysts, secondary to infection, are not uncommon.

Some reports emphasize the possibility of a predominant lower lobe distribution, but involvement of the upper lobes is not uncommon (Fig. 4.163).¹⁸⁰

At the central airways level, CT shows multiple small nodules projecting into the airway lumen (Fig. 4.164) or a diffuse nodular thickening of the airway walls. Findings related to airway obstruction are infections, atelectasis, air-trapping phenomena, and bronchiectasis.¹⁷⁹ There is also a risk of malignant transformation of the pulmonary lesions.¹⁸¹

Figure 4.162 Axial scan of a patient with laryngotracheobronchial papillomatosis. In the image, a lobulated solid nodule (arrowhead) coexists with two fully cystic lesions (curved arrows).

Figure 4.163 Axial scan of the same patient as in Fig. 4.162, but at a higher level (carina). Multiple cystic lesions are also documented (curved arrows); the one at the left is bilobed.

Lymphangioleiomyomatosis

The cysts of lymphangioleiomyomatosis (LAM) are multiple and round; they are relatively uniform in size and shape and have homogeneously thin walls (Fig. 4.165).¹⁸² Typically the size of the cysts ranges from 0.5 to 2 cm in diameter and tends to increase with progression of the disease. In patients with mild disease, 25% to 80% of the lung parenchyma are replaced by cysts, characteristically surrounded by normal lung (Fig. 4.165).¹⁸³

The cysts are uniformly and symmetrically distributed throughout the lungs, equally affecting the upper/lower and central/peripheral lung parenchyma (Fig. 4.166).^182,184

In patients with advanced disease, the parenchyma are completely replaced by cysts and the pulmonary volume is increased (Fig. 4.167). Possible areas of GGO may result from edema or hemorrhage; pulmonary hemorrhage occurs in 8% to 14% of women with LAM.¹⁸⁴ the incidence of pneumothorax in LAM is high (40%) owing to the thin wall of the cysts and their proximity to the pleural surface. Pleural effusion may also be seen, and other associated abnormalities, including mediastinal or retrocrural lymph node enlargement (40%), just as often.^182,183

Figure 4.164 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.

Figure 4.165 Anatomic volume rendering of a sagittal slab in a female with lymphangioleiomyomatosis. The image shows the cystic lesions, clearly 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).

Figure 4.166 Minimum intensity projection (minIP) in a coronal view of the same patient as in Fig. 4.165. The minIP technique enhances the visibility of the lesions, which are scattered quite uniformly all through the lungs.

Figure 4.167 External volume rendering of the same patient as in Fig. 4.165. 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. 4.168).⁸⁸ However, thin-walled cysts with smooth walls may be also observed, particularly after chemotherapy.¹⁸⁵ On the other hand, metastases from angiosarcoma may have an external halo of ground-glass attenuation (30%) and an internal air-fluid level, both due to hemorrhage.^185,186

Figure 4.168 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).

Figure 4.169 Axial scan of the same patient as in Fig. 4.168, but at a lower level. The heart is indicated by the symbol of the sun (sun). One of the cystic metastases at the right (curved arrow) seems to be connected to an artery (feeding vessel sign).

The lesions occur in a random distribution, often showing a feeding vessel sign (Fig. 4.169). Most pulmonary metastases are located in the basal and peripheral zones.⁸⁸

Hemothorax and pneumomediastinum are rare associated conditions.¹⁸⁶ An uncommon complication is the occurrence of a pneumothorax due to the rupture of subpleural cavities into the pleural space. Enlarged hilar and mediastinal lymph nodes may be also present (Fig. 4.170).

Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé (BHD) syndrome¹⁸⁷ 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 and ranging widely in size (a few millimeters to several centimeters) have been reported (Fig. 4.171).^{188,189 the} cysts are not numerous; in a paper on 12 patients, the mean extent score was 13% of the whole lung.¹⁹⁰

Figure 4.170 Same patient as in Fig. 4.168. Note the enlarged, colliquated lymph nodes at the right hilar level and in the subcarinal area (arrows).

Figure 4.171 Axial scan of a patient with Birt-Hogg-Dubé syndrome. There are scattered small, thin-walled cysts of various size and shape (arrows). (Courtesy Angelo Carloni, MD, Terni, Italy.)

The cysts are variably distributed but tend to predominate in the middle and lower lung¹⁸⁸; characteristically they are located along the pleural margins in 40% of patients (Fig. 4.172).¹⁹⁰ Cysts abutting or including the proximal portion of the lower pulmonary arteries and veins have also been described.190

The lung looks normal between the cysts (Fig. 4.173). BHD syndrome can be associated with recurrent spontaneous pneumothoraces.191

Dark Lung Pattern

Definition

A dark lung pattern is present when variable portions of lung parenchyma present a reduced attenuation to the x-rays and then are darker than normal (Fig. 4.174). In a lung image, the peak of gray of the background is determined by the relative amount of air and nonair components per volume unit: the more air (i.e., from obstructive emphysema) and/or the less nonair (i.e., from hampered vascular filling or hypoxic vasoconstriction) components, the darker the background.²

Figure 4.172 Frontal view of the same patient as in Fig. 4.171. This scan nicely shows the relationship of the cysts with the pleural boundaries. The contact with them is indicated by the arrowheads. (Courtesy Angelo Carloni, MD, Terni, Italy.)

Figure 4.173 Another axial scan of the same patient as in Fig. 4.171. This image shows the cysts and the intervening parenchyma, which looks normal. (Courtesy Angelo Carloni, MD, Terni, Italy.)

Unlike the cystic pattern, the basic abnormality here is not pure black (like the ambient air outside the chest) but rather a dark gray because lung attenuates less than normal tissue. In fact, bronchi and vessels are usually recognizable within the darkness.

High-Resolution Computed Tomography Signs

Patchy or diffuse, the dark lung appears more black than normal and is associated with a simplification of the vascular tree (Fig. 4.174A); when patchy, the aspect is also called mosaic perfusion (Fig. 4.175).

In detail, the diagnostic elements to evaluate are the extent of the areas of decreased attenuation, the number and size of the vessels within them, and how the different attenuations vary in the expiratory scans. Involvement of the airways may also be present.

Figure 4.174 (A) This high-resolution computed tomography image shows a dark lung, with extensive areas of decreased attenuation (arrowheads) and reduced number and size of the pulmonary vessels. (B) Pathologically, the low-magnification images may show nearly normal-appearing lung. (Note the absence of visible bronchioles in the image.) (Pathologic image courtesy Alessandra Cancellieri, Bologna, Italy.)

Figure 4.175 Patchwork of different attenuations secondary to small airways disease (mosaic oligemia). Some areas of dark lung are of lobular size and have well-defined contours (arrowheads). In the dark regions, the vessels are smaller than in the lighter region, where they are enlarged.

The extent of the dark areas varies, from a lobule size to an entire lung, depending on the severity of disease.¹⁹² In patients with mosaic perfusion secondary to airway disease, hyperlucent areas of lobule size are common, usually with well-defined margins (Fig. 4.175). In patients with vascular disease, on the other hand, the areas of low attenuation are often larger and poorly defined.²

The vessels inside the areas of decreased attenuation are smaller and less numerous than the companion vessels in the unaffected regions where, by contrast, they may be enlarged (Fig. 4.175). The appearance of heterogeneous lung attenuation may be simulated by areas of GGO interspersed with patches of normal lung; however, in the latter case, the size of the vessels within different areas should be equal. Vessels and bronchi within the involved regions do not show distortion unless There is some pulmonary derangement.^7,193

The differentiation between vascular versus bronchial origin of a dark lung is achieved by repeating a number of CT expiratory scans. Normally, in an expiratory scan, the overall density of the lung increases homogenously. In the dark lung of vascular origin, a homogeneous increase in density occurs everywhere, so that the contrast between areas of different attenuation is maintained. On the other hand, when the dark lung is due to airway stenosis, the contrast increases (air trapping) (Fig. 4.176).¹⁹⁴

Some patients with dark lung pattern show smooth thickening of the bronchial walls (Fig. 4.177) and occasionally central and peripheral cylindrical or cystic bronchiectasis. Rarely, centrilobular branching linear densities and nodules may also be apparent.¹⁹⁴ Diseases in the dark lung pattern are listed in Box 4.14.

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 areas of low attenuation may be due to both hypoperfusion distal to occluded vessels and peripheral vascu- lopathy. The areas of increased attenuation have been related to redistribution of blood flow toward the remaining patent vascular bed¹⁹⁵; indeed, in these areas the vessels are larger and often tortuous (Fig. 4.178).

Figure 4.176 High-resolution computed tomography scans at the end of inspiration (left) and expiration (right), where several areas of dark lung are more visible. In the expiratory scan, the areas of normal lung show an increased attenuation (which is normal) (arrows), while the dark areas do not change (air trapping).

Figure 4.177 This is a sagittal image of the left lung of a patient with a dark lung pattern prevalent in the upper lobe (arrows). The image also shows thickening of the bronchial walls at the level of the central airways (arrowheads).

Figure 4.178 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).

Figure 4.179 Chronic pulmonary thromboembolism. The dark, hypoperfused areas are extensive and prevalent at the lung periphery; their margins with the normal lung (arrowheads) are ill-defined.

Scars from prior pulmonary infarctions are often found in the lower lobes, and pleural thickening from previous pleural effusion is not uncommon.¹⁹⁰

The areas of low attenuation are usually wide (larger than lobules), with ill-defined margins (Fig. 4.179).¹⁹⁵

The direct signs of chronic thromboembolism are often visible at the level of the central vessels; these signs include partial arterial obstruction with mural thrombi (Fig. 4.180), intraluminal bands and webs, calcifications within chronic thrombi, and signs of pulmonary arterial hypertension (dilation of the central pulmonary arteries secondary to the obstructed vascular lung bed, right ventricular enlargement and hypertrophy, and tortuous arteries at the pulmonary leve1) (Fig. 4.178).¹⁹⁵ In some cases, a collateral systemic blood supply may be evident, with abnormal dilation 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.¹⁹⁷ Patients with severe pulmonary hypertension may also show mild pericardial thickening or a small pericardial effusion.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia

The narrowing of the bronchiolar lumen due to the neuroendocrine cellular hyperplasia and fibrosis¹⁹⁸ is not directly visible with HRCT, but it can show up indirectly as mosaic perfusion (Fig. 4.181) with air trapping.¹⁹⁹ Small, well-defined, randomly distributed nodules less than 5 mm in diameter may also be identified in the CT images, especially when they are obtained with multislice volumetric equipment. The nodules correspond to the neuroendocrine tumorlets present histologically (Fig. 4.181).²⁰⁰

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 nodules in the lower zones (Fig. 4.182).²⁰⁰,²⁰¹

Round lesions of more than 5 mm in diameter may suggest the existence of carcinoid tumors (grade 1 neuroendocrine carcinomas) (Fig. 4.183). Some patients may also show bronchial wall thickening and cylindrical bronchiectasis.²⁰¹

Constrictive Bronchiolitis

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.

Figure 4.180 Axial contrast-enhanced computed tomography scan of a patient with chronic pulmonary thromboembolism. This axial image demonstrates an eccentric thrombus (arrowhead) appearing as a thickening of the anterior wall of the right pulmonary artery. aa, Ascending aorta; da, descending aorta; pa, main pulmonary artery.

Figure 4.181 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.

The blood vessels in the low-attenuation areas are smaller and less numerous than vessels in the areas of relatively high attenuation (Fig. 4.184).^65,67 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.¹⁹⁴

The disease is diffuse and bilateral with more common and extensive involvement of the lower lobes (Fig. 4.185).⁶⁶ Some patients with CB also show central and peripheral cylindrical bronchiectasis (Fig. 4.186). The cause of the bronchiectasis associated with bronchiolitis obliterans remains unclear, but it seems most likely due to concomitant injury of the large airways.^202,203 Rarely, centrilobular nodules or branching linear densities can also be observed.²⁰²

Figure 4.182 Maximum intensity projection (MIP) in a coronal view of the same patient as in Fig. 4.181. The MIP technique highlights the visibility of the small nodules, which are more numerous at the basal level in the area indicated by the curved arrows.

Figure 4.183 Axial view of a subject with diffuse idiopathic neuroendocrine cell hyperplasia. In the middle lobe, there is a nodule of a diameter greater than 5 mm (arrow) that could be a low-grade neuroendocrine carcinoma (carcinoid tumor).

Panlobular Emphysema

Panlobular emphysema is characterized anatomically by a uniform destruction of the pulmonary lobule; it appears radiologically as extensive areas of dark lung associated with a diffuse simplification of the pulmonary architecture (Fig. 4.187). 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 antitrypsin deficiency,¹⁷² and it may be indistinguishable from the appearance of severe CB.²⁰

Figure 4.184 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).

Figure 4.185 Axial scan of the same patient as in Fig. 4.184, but at a lower level. Extensive geographic areas of low attenuation are present (in particular at the left), interspersed with less frequent areas of relatively increased opacity. Evidence of mild bronchiectasis is present in the right lower lobe and the lingula (arrowheads).

Panlobular emphysema is generalized within the lungs, but it can be more severe in the lower lobes (Fig. 4.188).¹⁷²

In approximately 40% of patients with alpha-1 antitrypsin deficiency, bronchiectasis is present owing to destruction of the elastic lamina (Fig. 4.189).²⁰⁴ Associated paraseptal emphysema and bullae are relatively uncommon.

Swyer-James (MacLeod Syndrome)

Swyer-James syndrome is a peculiar postinfectious CB that affects the lung asymmetrically (Fig. 4.190).²⁰⁵ 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.⁶⁶

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 the rule rather than the exception.²⁰⁵ However, a predominant involvement of one lung and even of one lobe is very frequent (Fig. 4.191).²⁰⁶

Figure 4.186 Axial scan of the same patient as in Fig. 4.184, at the lung bases. Bronchiectasis is visible in the lower lobes (curved arrows) and in the basal portion of the lingula (arrowhead).

Figure 4.187 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).

Ectatic bronchi with thickened walls are often present, sometimes severely (Fig. 4.192).²⁰⁶

Imaging of the Solitary Pulmonary Nodule

Rationale for the Diagnostic Approach

The increasing availability of multidetector CT equipment is contributing to the accidental discovery of solitary pulmonary nodules (SPNs). An SPN is a round opacity of the lung less than 3 cm in diameter (if <1 cm, the term small nodule is used). Eventually, at least in the United States, most of these SPNs turn out to be benign. However, to ensure that they are not malignant, a careful assessment should be made before establishing the optimal management: follow-up, biopsy, or surgery.

Figure 4.188 Axial scan of the same patient as in Fig. 4.187 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 relatively little normal surviving parenchyma posteriorly (arrowheads).

Figure 4.189 Patients with panlobular emphysema often have minimal bronchiectasis associated with bronchial wall thickening (arrows).

The diagnostic process for SPNs develops through a decision analysis algorithm coupling the a priori probability of malignancy (risk factors) with the elements of the imaging, where CT is the standard basic imaging technique. CT has a higher sensitivity and specificity than chest radiography and gives extra information about the density of the nodule and its vascularization. Supplementary information about tumor metabolism can be further acquired by means of positron emission tomography (PET). PET uses 18F-labeled fluoro-2-deoxy-D-glucose (FDG) as a metabolic marker on the assumption that the metabolism of glucose is typically increased in malignancies. PET relies on a discriminating value of the maximum standardized uptake value (SUV_max) of FDG, expressing the highest nodular uptake, as an aid in predicting malignancy.

Figure 4.190 Patient with Swyer-James syndrome. The image shows unilaterally reduced right lung attenuation; in the dark lung, the vessels are smaller than those in the left lung. The right lung is also smaller; in fact, the mediastinum is shifted ipsilaterally (arrow).

Figure 4.191 Another patient with Swyer-James syndrome. The left lobe is extensively involved; also some portions of the right lung are relatively hyperlucent with a simplified vascular tree (arrows).

The PET technique proves reliable for solid nodules larger than 1 cm, for which it can predict a malignant tumor in 90% of cases. However, a number of malignancies—namely bronchioloalveolar carcinoma, well-differentiated adenocarcinomas, and carcinoid tumors—are often negative on PET and, conversely, infective and inflammatory nodules can present with high SUV_max uptakes. Said another way, PET (similarly to CT) should not be considered an absolute gold standard for the diagnosis of SPNs. Even when the PET scan is negative, when There is a mismatch of risk factors, clinical data, and elements of the imaging, further diagnostic procedures should be carried out.

Most of the elements summarized in the subsequent text and references have been derived from the excellent review of Truong et al.^{207 the} interested reader is encouraged to refer to the original paper for further details.

Figure 4.192 Axial scan of the same patient as in Fig. 4.190, but at a lower level. Note the cluster of cystic bronchiectasis in the azygos-esophageal recess (arrow).

Static Elements

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 detection²⁰⁸; exposure to asbestos, uranium, or radon; occurrence of symptoms²⁰⁷ (in particular hemoptysis)²⁰⁹; and a family history of lung cancer.²¹⁰ These risk factors do not enter into 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 4.15.

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 malignancy (Fig. 4.193). Unfortunately this does not mean that a well-marginated SPN with regular contours cannot be malignant; on the contrary, one of five malignancies has these characteristics.²⁰⁹ 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 close to 8 mm, the probability is approximately 10% to 20%.^211-213

Figure 4.193 Solitary pulmonary nodule (curved arrows) in a heavy smoker with chronic obstructive pulmonary disease. 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 at the left (arrow).

Computed Tomography Densitometry

Fat densities inside the nodule (Fig. 4.194) are typical of hamartoma (50%),²¹⁴ but metastases from liposarcoma and renal carcinoma may also may have fatty components.²¹⁵ Central, laminated, or popcorn calcifications inside the nodule are usually benign, but lung metastases from chondrosarcoma or osteosarcoma may present similar aspects.⁸⁸

A 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%.²¹⁶ However, when the density is mixed (solid + GGO), this percentage rises to 63%, whereas for pure GGO lesions (Fig. 4.195) the rate of malignancy is only 18%. In a large series, 20% of the lesions detected during a CT screening program represented subsolid densities.²¹⁶ 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 also be found in benign conditions (e.g., nodular OP).²⁰⁷

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.²¹⁷ It has been reported that 95% of cavitary lesions with wall thickness greater than 15 mm are malignant.²¹⁸ Up to 15% of primary lung malignancies, in particular squamous cell carcinomas, cavitate.²⁰⁷

An air bronchogram is not present in the solid lesions, but it is possible inside the nodules of GGO (Fig. 4.196). It may also be seen in bronchioloalveolar carcinoma and pulmonary lymphoma as well as in some benign lesions.

Figure 4.194 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 its fatty content.

Figure 4.195 A barely visible solitary pulmonary nodule of faint density (nodular ground-glass opacity) in the peripheral left upper lung (arrowhead). The surgical diagnosis was of a focal bronchioloalveolar carcinoma.

Dynamic Elements

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 that 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.²⁰⁷ the subsolid lesions, on the other hand, are another story. Approximately 20% of well-differentiated adenocarcinomas have a doubling time greater than 2 years,²¹⁹ and some bronchioloalveolar carcinomas may show a doubling time even greater than 3.5 years.²²⁰

Figure 4.196 Initial presentation of a diffuse bronchioloalveolar carcinoma. In this phase, the lesion has a lobular size, and the appearance is that of a mixed-densities disease with consolidative and ground-glass opacity aspects. A few small hyperlucent bronchi can be appreciated inside the opacity.

In summary, the old adage that “a nodule should be considered benign if unvaried after two years” is still acceptable now,^207,221,222 but it applies only to solid lesions. Note that the recommendations in the literature refer to the volume of a nodule. However, more often in practice, the measurements are made 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%).²²³

The timing of follow-up of a nodule incidentally discovered on CT depends on the prior probability of malignancy (risk factors), size, and density. The appropriate timing has recently been recommended in detail in a statement from the Fleischner Society.^224,225

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 and 3 cm in diameter, where the negative predictive value for malignancy of a contrast enhancement less than 15 HU is 96%.²²⁶

Figure 4.197 Same patient as in Fig. 4.194. Here a computed tomography image is shown together with the results of a positron emission tomography 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.

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. 4.197). For lung nodules, an SUV_mal cutoff of FDG of 2.5 is used as the discriminating level between benign and malignant.²²⁷ 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%.²²⁸ On the contrary, a well- differentiated adenocarcinoma that shows a GGO appearance in CT is (falsely) negative in 9 of 10 cases, and a benign nodule that shows a GGO appearance in CT is (falsely) positive in 4 of 5 cases.²²⁹

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%.²⁰⁷

Self-assessment questions and cases related to this chapter can be found online at ExpertConsult.com.

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228. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA. 2001;285(7):914-924.

229. Nomori H, Watanabe K, Ohtsuka T, et al. Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images. Lung Cancer. 2004;45(1):19-27.

Multiple Choice Questions

1. Which of the following statements regarding computed tomography of the chest is/are TRUE?

A. It is produced with collimated fan beams of radiation

B. The resulting images reflect different attenuations of internal tissues

C. Outgoing radiation activates a matrix of sensible elements in computed tomography detectors

D. The process produces a digital three-dimensional map of the scanned tissue

E. All of the above

ANSWER: E

2. Which ONE of the following statements regarding thoracic computed tomography is FALSE?

A. It is based on a matrix of voxels, as seen on a monitor

B. The highest attenuation elements in the scan are black

C. Images in transverse views are equal in quality to those in frontal views

D. For each view, a stack of images is generated

E. Computed tomography is more visually granular than plain film radiography

ANSWER: B

3. In high-resolution computed tomography of the lungs, which ONE of the following is the major factor that reduces the technical level of noise in the procedure?

A. Large voxel size

B. Broad collimation of the signals

C. Absence of a reconstruction algorithm

D. Difference of attenuation between air and lung

E. High penetrance of the radiation signal into lung

ANSWER: D

4. In assigning Hounsfield units—measures of density in computed tomography—which of the following tissues is given a value of zero?

A. Fat

B. Bone

C. Muscle

D. Water

E. Air

ANSWER: D

5. Which of the following regarding lung anatomy in computed tomograms is FALSE?

A. Bronchial walls in corresponding areas of each lung should be equal in thickness

B. Coupled bronchi and arteries should have roughly the same diameter

C. Arteries divide dichotomously and veins divide monopodially

D. Normal mediastinal pleural reflections are easily visible

E. Normal lymphatic channels are not definable

ANSWER: D

6. In computed tomograms of the lung, which ONE of the following diseases often shows a preferential involvement of the central lung fields?

A. Asbestosis

B. Idiopathic usual interstitial pneumonia

C. Alveolar proteinosis

D. Nonspecific interstitial pneumonia

E. Chronic eosinophilic pneumonia

ANSWER: C

7. Which ONE of the following radiographic techniques allows virtual bronchoscopy to be performed?

A. Curved multiplanar reformation

B. Nonaveraged data rendering

C. Voxel transformation

D. Transaxial collimation

E. None of the above

ANSWER: A

8. Which of the following computed tomographic methods is best applied to the radiographic separation of small parenchymal nodular lesions from pulmonary blood vessels?

A. Partial image extinction

B. Densitometric averaging

C. Maximum intensity projection

D. Elemental superimposition

E. Ambience diminution

ANSWER: C

9. Prone positioning of the patient for thoracic computed tomography is recommended when:

A. An endobronchial lesion is suspected

B. The patient is unusually thin

C. A central parenchymal mass is being imaged

D. Diseases of the posterior lung fields are suspected

E. All of the above

ANSWER: D

10. Expiratory computed tomograms of the chest are recommended when:

A. A peripheral parenchymal mass is being imaged

B. A bronchial-stenotic lesion is suspected

C. The patient is a child

D. Clinical congestive heart failure is present

E. None of the above

ANSWER: B

11. The basic patterns that may be seen in thoracic computed tomograms include all of the following EXCEPT:

A. Pavemented

B. Septal

C. Fibrotic

D. Cystic

E. Nodular

ANSWER: A

12. In the septal pattern of pathologic change as seen in thoracic computed tomograms, what is/are the constituent finding(s)?

A. Sickening of septal interstitium

B. Sickening of fissural interstitium

C. Accentuation of secondary pulmonary lobules

D. Peribronchovascular cuffing

E. All of the above.

ANSWER: E

13. Which of the following thoracic computed tomographic findings is/are commonly present in hydrostatic interstitial pulmonary edema?

A. Subpleural interstitial thickening

B. Patchy parenchymal ground glass opacities

C. Greatest abnormalities in the basal-posterior lung fields

D. Pleural effusion(s)

E. All of the above

ANSWER: E

14. Which ONE of the following statements concerning the thoracic computed tomographic attributes of lymphangitic carcinomatosis is FALSE?

A. Lesions are patchy

B. Disease is often unilateral

C. Regional lymphadenopathy is present in 50% of cases

D. The disease is gravity-dependent

E. Pleural effusion is seen in 50% of cases

ANSWER: D

15. Which ONE of the following is NOT a feature of usual interstitial pneumonia as seen in thoracic computed tomograms?

A. Multifocal bronchial stenosis

B. Reticulation of the subpleural parenchyma

C. Honeycomb change

D. Remodeling of pulmonary boundaries

E. Patchy intraparenchymal distribution of disease

ANSWER: A

16. Which of the following is/are potential attributes of sarcoidosis in computed thoracic tomograms?

A. Reticulonodular parenchymal densities

B. Traction bronchiectasis

C. Zigzagged and accentuated bronchovascular bundles

D. Agglomeration of central airways

E. All of the above

ANSWER: E

17. Diseases that potentially manifest with centrilobular nodules on thoracic computed tomograms include:

A. Follicular bronchitis

B. Venoocclusive disease

C. Tuberculosis

D. Bleomycin toxicity

E. All of the above

ANSWER: A

18. Which ONE of the following diseases typically presents with centrilobular nodularity, ground glass parenchymal opacities, and centrilobular emphysema on thoracic computed tomograms?

A. Langerhans cell histiocytosis (eosinophilic granuloma)

B. Nonspecific interstitial pneumonitis

C. Respiratory bronchiolitis-interstitial lung disease

D. Lymphomatoid granulomatosis

E. Granulomatosis with polyangiitis

ANSWER: C

19. Which of the following disorders presents with a random nodular pattern on thoracic computed tomograms?

A. Lymphocytic bronchiolitis

B. Miliary tuberculosis

C. Alveolar proteinosis

D. Legionella pneumonia

E. Lymphangioleiomyomatosis

ANSWER: B

20. All of the following diseases are characterized by a chronic alveolar pattern on thoracic computed tomograms EXCEPT:

A. Bronchioloalveolar carcinoma

B. Chronic eosinophilic pneumonia

C. Subacute hypersensitivity pneumonitis

D. Langerhans cell histiocytosis

E. Infectious pneumonia

ANSWER: D

Case 1

As a Distorted Fine Net

eSlide 4.1A eSlide 4.1B eSlide 4.1C eSlide 4.1D eSlide 4.1E

Short History

The patient, a 67-year-old man, was a former smoker (25 packs per year). Past medical history includes chest trauma. Current medical history: diabetes, exertional dyspnea, and Velcro sound at the lung bases.

High-Resolution Computed Tomography (eSlide 4.1A,B,C)

Retraction of right hemithorax due to an old chest wall traumatic injury. The peripheral regions of both lungs are involved by a fibrosing fine reticulation and a subpleural interface sign, mainly in the right lung. A retracted and festooned right fissure is also visible due to possible fibrosis. The lesions are prevalent at the basal level. Traction bronchio- lectasis without honeycombing are also present in the pathologic areas. The high-resolution computed tomography (HRCT) features are suggestive of fibrosing pattern, subset usual interstitial pneumonia (UIP).

Histologic Examination (eSlide 4.1D,E)

At histology, subpleural fibrosis without honeycombing is present, accounting for the interface sign on HRCT (eSlide 4.1D). Fibroblastic foci are found at the edge of the fibrosis (eSlide 4.1E). Surgical biopsy (H&E). (Images courtesy Alessandra Cancellieri, Bologna, Italy.)

Diagnosis

Multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF).

Discussion

On HRCT, a fibrotic pattern is present; signs of retraction and remodeling of the thoracic structures are visible. The final effect is an irregular network of white lines with distortion of the anatomic landmarks (see also Fibrotic Pattern in Chapter 4). The subset UIP is characterized by the existence of patchy peripheral areas of fibrosing reticulation with possible honeycombing. Bronchiectases and bronchiolectases in connection with the pathologic areas are also characteristic. Some groundglass opacity (GGO) is possible, however, often due to microscopic fibrosis. The presence of associated nonparenchymal signs may be helpful for the diagnosis of a specific disease^1,2 (Box C1.1; also see Box 4.4).

Idiopathic Pulmonary Fibrosis. The typical HRCT findings consist of peripheral areas of fibrosing reticulation, which result from a combination of intralobular lines and irregular septal thickening. Although these opacities may be diffuse throughout both lungs, in 50% to 80% of cases they predominantly or exclusively involve the lower lung zones.³ According to the international guidelines,⁴ reticular abnormalities and honeycombing must be present for a radiologic diagnosis of definite UIP pattern on HRCT. The absence of honeycombing shifts the diagnosis toward possible UIP. Dilated and distorted bronchioles (traction bronchiolectases) and bronchi (traction bronchiectases) often coexist. Rugged pleural surfaces (interface sign) are very frequent.

Collagen Vascular Diseases (CVDs) and Fibrosing Drug Toxicity. Some CVDs and, more rarely, drug reactions may present with aspects indistinguishable from idiopathic UIP. Consequently suspicion for the underlying disorder may be formulated only on clinical grounds, although occasionally associated signs of the original disease may suggest the correct diagnosis (e.g., enlarged esophagus in scleroderma).^5,6

Hypersensitivity Pneumonitis (HP), Chronic. This may present with aspects indistinguishable from idiopathic UIP. The possible association with a mixture of lobular areas of decreased attenuation due to air trapping, centrilobular nodules, may be crucial for the diagnosis.⁷

Asbestosis. The parenchymal HRCT lesions are similar to the lesions in IPF. Associated parietal pleural thickening and pleural plaques with or without calcifications are considered typical of asbestos-related disease.⁸ In conclusion, the HRCT features of our patient oriented toward a diagnosis of possible UIP with consequent surgical biopsy. Pathologic diagnosis of definite UIP pattern. Multidisciplinary diagnosis of early IPF.

References

1. Jacob J, Hansell DM. HRCT of fibrosing lung disease. Respirology. 2015;2O(6):859-872.

2. Dalpiaz G, Cancellieri A. Fibrosing pattern. In: Atlas of DLDs: A Multidisciplinary Approach. Springer; 2017. In Press.

3. Spagnolo P, Sverzellati N, Rossi G, et al. Idiopathic pulmonary fibrosis: an update. Ann Med. 2015;47(1):15-27.

4. Raghu G, Collard HR, Egan JJ, et al. ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824.

5. Karam MB, Peivareh H, Mosadegh L. Thoracic Imaging Findings of Collagen Vascular Diseases: a CT study. Tanaffos. 2014;13(1):43-47.

6. Rossi SE, Erasmus JJ, McAdams HP, et al. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 2000;20(5):1245-1259.

7. Hirschmann JV, Pipavath SN, Godwin JD. Hypersensitivity pneumonitis: a historical, clinical, and radiologic review. Radiographics. 2009;29:1921-1938.

8. Chong S, Lee KS, Chung MJ, et al. Pneumoconiosis: comparison of imaging and pathologic findings. Radiographics. 2006;26(1):59-77.

Case 2

A Strange “Galaxy”

eSlide 4.2A eSlide 4.2B eSlide 4.2C eSlide 4.2D eSlide 4.2E

Short History

Male patient, 35-year-old smoker. Chest x-ray performed for low-grade fever shows a nodule in the upper lobe. The nodule persisted for 1 month after the end of antibiotic therapy.

High-Resolution Computed Tomography (eSlide 4.2A,B,C)

In the right upper lobe, high-resolution computed tomography (HRCT) shows two contiguous solid nodules with irregular contours surrounded by multiple small satellite nodules (galaxy sign) (eSlide 4.2A,B). There are also numerous small solid nodules in middle and upper regions with a lymphatic distribution (eSlide 4.2B). Axial image with mediastinal reconstruction shows bilateral hilar lymph node enlargement (eSlide 4.2C). The HRCT features are suggestive of nodular pattern, subset lymphatic.

Histologic Examination (eSlide 4.2D,E)

Transbronchial biopsy (TBB) was performed, showing nonnecrotizing, partially coalescing granulomas, with minimal associated inflammatory infiltrate. (Images courtesy of Alessandra Cancellieri, Bologna, Italy.)

Diagnosis

Sarcoidosis.

Discussion

The galaxy sign consists of confluent nodules with multiple small peripheral nodules emanating from the margins of the central nodule. The galaxy sign results from the coalescence of granulomas, creating the appearance of a nodule. Granulomas become less concentrated at the periphery of the lesion, justifying the irregularity and micronodularity of the margins and the microsatellite nodules. It was first described as the sarcoid galaxy by Nakatsu et al. in 2002¹ in patients with sarcoidosis (also see the discussion of sarcoidosis in the section Nodular Pattern, Chapter 4). In 2005 Heo et al.² described the presence of the same sign in a series of patients with active tuberculosis (Box C2.1).

Sarcoidosis Versus Tuberculosis (TB). In both of these conditions, the galaxy sign is often located in the upper lobes. For the differential diagnosis, it is useful to consider the number of foci of galaxy sign and the presence of associated signs.^3,4 In sarcoidosis, the galaxy sign foci are often multiple, sometimes contiguous. The signs associated are perilymphatic nodules and hilar-mediastinal enlarged lymph nodes. In

TB the foci of galaxy sign are more often single. The associated signs may be excavations as an expression of necrosis and the tree-in-bud sign due to bronchiolitis.

Mimicker. The galaxy sign may simulate an expansive process, especially for the presence of irregular contours of the nodule. Careful observation, however, shows that the contours are not spiculated but irregularly micronodular. The presence of bilateral hilar and mediastinal enlarged lymph nodes, often associated with the galaxy sign, is a big help in assuming the correct diagnosis.

In conclusion, in our patient the presence of multiple galaxy signs together with micronodules with a perilymphatic distribution suggested the diagnosis of sarcoidosis. Transbronchial biopsy confirmed this hypothesis.

References

1. Nakatsu M, Hatabu H, Morikawa K, et al. Large coalescent parenchymal nodules in pulmonary sarcoidosis: “sarcoid galaxy” sign. Am J Roentgenol. 2002;178:1389-1393.

2. Heo JN, Choi YW, Jeon SC, et al. Pulmonary tuberculosis: another disease showing clusters of small nodules. AJR Am J Roentgenol. 2005;184(2):639-642.

3. Criado E, Sanchez M, Ramirez J, et al. Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation. Radiographics. 2010;30(6):1567-1586.

4. Aikins A, Kanne JP, Chung JH. Galaxy sign. J Thorac Imaging. 2012;27(6):W164.

Case 3

Bubble-like Lucencies

eSlide 4.3A eSlide 4.3B eSlide 4.3C eSlide 4.3D eSlide 4.3E

Short History

Woman, 80-year-old, diabetes mellitus since 15 years of age, and pulmonary tuberculosis at age 27. For about 2 months she had asthenia, dyspnea on exertion, joint pain, and a low-grade fever. A chest x-ray showed retraction of the left hemithorax due to an old fibrothorax and multiple bilateral consolidations. Broad-spectrum antibiotic therapy was carried out. Symptoms and chest x-ray were unmodified after 3 weeks (unresolving pneumonia).

High-Resolution Computed Tomography (eSlide 4.3A,B,C)

High-resolution computed tomography (HRCT) confirmed the volume loss in the left hemithorax due to a partially calcified fibrothorax (eSlide 4.3A). HRCT also showed an alveolar pattern appearing as bilateral patchy peripheral areas of pulmonary consolidation both in the upper and lower lobes. The opacities are not homogeneous because of several cystlike hyperlucencies of different size, some of which have a bubble-like appearance. A nodule coexists in the lower right lobe (eSlide 4.3C). Both around the nodule and the consolidations, the existence of a peripheral ground-glass opacity is particularly remarkable (halo sign) (eSlide 4.3B,C). Lymph node enlargement is not present. The HRCT features are suggestive of Alveolar Pattern, subset Chronic (neoplastic or nonneoplastic disease).

Histologic Examination (eSlide 4.3D,E)

Fiberoptic bronchoscopy was then performed. No endobronchial lesions were found. Bronchoalveolar lavage (BAL) showed a slight increase in lymphocytes and neutrophils. No tumor cells were found. Smears and cultures for M. tuberculosis were also negative. Transbronchial biopsy (TBB) was performed (eSlide 4.3D). Microscopically, TBB showed a peribronchiolar focus of well-differentiated mucinous adenocarcinoma (eSlide 4.3E). (H&E; Courtesy Alessandra Cancellieri, Bologna, Italy.)

Diagnosis

Diffuse cystic mucinous adenocarcinoma in a patient with old tubercular fibrothorax.

Discussion

A HRCT alveolar pattern presents as patchy consolidation and/or ground-glass opacity, often in association. Alveolar filling may be due to fluid, cells, or other material which, in most cases, radiology cannot discriminate. Nevertheless, characteristics of the opacities, their distribution within the lung, and a number of ancillary signs provide useful diagnostic clues in several conditions (also see Alveolar Pattern in Chapter 4).

The clinical presentation of this patient represents the leading and most important discriminating element that makes it possible to divide the alveolar pattern in two subsets: acute and chronic.¹ Our patient presents a chronic history of symptoms and unresolving pneumonia at chest x-ray. Many diseases may present a chronic alveolar pattern, but only some show bubble-like hyperlucencies within the lesions (Box C3.1).

Infectious Diseases (e.g., Tuberculosis [TB]). Infection is most often responsible for consolidations and nodules with bubble-like lucencies. In TB, the lesions are often present in the apical and posterior segments of the upper lobes and in the superior segments of the lower lobes.² There may be a tree-in-bud sign, reflecting the endobronchial spread of infection. Another hallmark is hilar/mediastinal lymphadenopathy with possible central necrosis, visible only on contrast-enhanced CT.

Pulmonary Infarct. This is often a unilateral consolidation with a basal-peripheral distribution. Cystic features are rarely present.³

Organizing Pneumonia (OP). Although cavitary infiltrates are not usually included in textbook descriptions of the disease, OP presenting with cavitating infiltrates has indeed been described, albeit rather rarely. Often There are multiple bilateral consolidations with a basal-peripheral distribution.⁴

Adenocarcinoma. Patchy areas of unresolving consolidation with possible halo sign, often with an air bronchogram or air-filled cystic spaces. Possible lower lung predominance. According to the literature, in adenocarcinoma true cavitation is rare; more often, round or oval bubble-like hyperlucencies, probably due to phenomena of bronchiolar obstruction, are responsible (pseudocavitation).⁵ Halo sign is a result of alveolar septal thickening due to lepidic growth in the alveoli adjacent to a main focus of neoplasia.

In conclusion, in our case, HRCT features could suggest a reactivation of TB in a diabetic patient but also a diffuse form of adenocarcinoma. Only transbronchial biopsy made the diagnosis of diffuse cystic mucinous adenocarcinoma.

References

1. Dalpiaz G, Cancellieri A. Atlas of DLDs: A Multidisciplinary Approach. Springer; 2017. In Press.

2. Jeong YJ, Lee KS. Pulmonary tuberculosis: up-to-date imaging and management. AJR Am J Roentgenol. 2008;191(3):834-844.

3. He H, Stein MW, Zalta B, et al. Pulmonary infarction: spectrum of findings on multidetector helical CT J Thorac Imaging. 2006;21(1):1-7.

4. Heller I, Biner S, Isakov A, et al. TB or not TB: cavitary bronchiolitis obliterans organizing pneumonia mimicking pulmonary tuberculosis. Chest. 2001;120(2):674-678.

5. Gaeta M, Caruso R, Blandino A, et al. Radiolucencies in bronchioloalveolar carcinoma: CT-pathologic correlation. Eur Radiol. 1999;9:55-59.

Case 4

A Lacy Feature

eSlide 4.4A

eSlide 4.4B

eSlide 4.4C

eSlide 4.4D

eSlide 4.4E

Short History

The patient, a 33-year-old female, was a former smoker. Her recurrent pneumothorax had been treated with talc pleurodesis. A chest x-ray shows normal lung attenuation with no signs of diffuse lung disease.

High-Resolution Computed Tomography (eSlide 4.4A,B,C)

High-resolution Computed Tomography (HRCT) images with a parenchymal setting (eSlide 4.4A,B) show multiple cysts appearing as black holes with a white encircling rim of a thickness similar to that of the fissure (thin wall). Cysts are uniform in shape, tending to give an overall homogeneous lacy appearance. HRCT sagittal reconstruction (eSlide 4.4B) shows the uniform craniocaudal distribution of the cysts without apical or basal predominance. A frontal CT image with a mediastinal window (eSlide 4.4C) shows linear high-attenuation areas in the right basal region of the pleural space. These pseudoplaques are secondary to talc on the pleural surface. The HRCT features are suggestive of Cystic Pattern, possible Lymphangioleiomyomatosis.

Pathology (eSlide 4.4D,E)

Surgical Biopsy. Random cysts with thin walls, some subpleural, are visible at low power (left, H&E). Cyst walls are irregularly thickened by smooth muscle tissue positive for smooth muscle actin (eSlide 4.4D). HMB45 and estrogen receptors (eSlide 4.4E). Surgical biopsy (H&E; eSlide 4.4D), and smooth muscle actin (eSlide 4.4E). (Courtesy Alessandra Cancellieri, Bologna, Italy.)

Diagnosis

Lymphangioleiomyomatosis (LAM).

Discussion

A cystic pattern is present when multiple roundish, well-defined aircontaining spaces (“holes”) are variably scattered throughout the pulmonary parenchyma. The holes appear black on HRCT and white on pathologic specimens (also see Cystic Pattern in Chapter 4). These “holes in the lung” may be due to dilatation of bronchial structures, abnormal distention of alveolar spaces, focal destruction of lung parenchyma, or late-stage or even cavitation of solid lesions. The cystic pattern should not be confused with the dark lung pattern. In both models, the elementary lesions are hypodense on HRCT, but in the cystic pattern they are focal and not diffuse and their density is that of pure air-containing units, as black as the ambient air outside the chest.^1,2

Many diseases may be responsible for acystic pattern (Box 4.13 in Chapter 4); There fore the thickness of the wall may be helpful in arriving at the diagnosis. Thin-walled cysts, like those observed in our patient, present a white encircling rim of a thickness similar to that of the fissure.³ These types of cysts are often secondary to check valve mechanisms in the context of a normal parenchyma. Diseases presenting with Cystic Pattern, thin-walled, are listed in Box C4.1.

Lymphangioleiomyomatosis (LAM). LAM typically occurs in young women, and the cysts are typically thin-walled and round. The most useful sign for differentiating LAM from LCH is the distribution of cysts. Unlike in LCH, cysts are diffuse throughout the lungs and may involve the juxtaphrenic recesses. The cysts are uniform in shape, tending to give an overall homogeneous lacy appearance.^4,5

Langerhans Cell Histiocytosis (LCH), End-Stage. This appears as a cystic disease with thin-walled cysts, similarly to LAM; however, they are bizarre in shape, with a predominance in the lung apices and relative sparing of the lung bases. Crucial also is the history of smoking.⁶

Lymphocytic Interstitial Pneumonia (LIP). The cysts are scattered with interspaced normal lung parenchyma. Ground-glass opacities and nodules are often associated. The disease is typically present in patients with collagen vascular disorders, in particular Sjogren syndrome.⁷

Birt-Hogg-Dubé (BHD) Disease. In BHD There are just a few scattered cysts with lower- and medial-zone predominance. The cysts are often larger than those in LAM and LCH. Subpleural lentiform cysts may involve the fissures more frequently than in other cystic diseases. BHD is a very rare condition associated with pneumothoraces, renal cell carcinomas, and skin fibrofolliculomas.⁸

In conclusion, in our case, the clinical data together with HRCT features first suggested a diagnosis of LAM. A surgical lung biopsy confirmed the hypothesis.

References

1. Gupta N, Vassallo R, Wikenheiser-Brokamp KA, et al. Diffuse cystic lung disease. Part I. Am J Respir Crit Care Med. 2015;191(12):1354-1366.

2. Gupta N, Vassallo R, Wikenheiser-Brokamp KA, et al. Diffuse cystic lung disease. Part II. Am J Respir Crit Care Med. 2015;192(1):17-29.

3. Maffessanti M, Dalpiaz G. Cystic pattern. In: Diffuse Lung Diseases: Clinical Features, Pathology HRCT. New York: Springer; 2006.

4. Abbott GF, Rosado-de-Christenson ML, Frazier AA, et al. From the archives of the AFIP: lymphangioleiomyomatosis: radiologic- pathologic correlation. Radiographics. 2005;25:803.

5. Tobino K, Johkoh T, Fujimoto K, et al. Computed tomographic features of lymphangioleiomyomatosis: evaluation in 138 patients. Eur J Radiol. 2015;84:534-541.

6. Abbott GF, Rosado-de-Christenson ML, Franks TJ, et al. From the archives of the AFIP: pulmonary Langerhans cell histiocytosis. Radiographics. 2004;24(3):821-841.

7. Silva CI, Flint JD, Levy RD, et al. Diffuse lung cysts in lymphoid interstitial pneumonia: high-resolution CT and pathologic findings. J Thorac Imaging. 2006;21:241-244.

8. Souza CA, Finley R, Müller NL, et al. Birt-Hogg-Dubé syndrome: a rare cause of pulmonary cysts. AJR Am J Roentgenol. 2005;185(5):1237-1239.

Case 5

Black and White With Air Trapping

eSlide 4.5A

eSlide 4.5B

eSlide 4.5C

eSlide 4.5D

eSlide 4.5E

eSlide 4.5F

Short History

The patient was a 60-year-old woman, an ex-smoker. Bronchial asthma from 15 years, on continuous therapy during the past 3 years. Reevaluation of clinical features for worsening cough revealed bronchiolar obstruction, nonreversible.

High-Resolution Computed Tomography (eSlide 4.5A,B,C)

Inspiratory (eSlide 4.5A) and expiratory (eSlide 4.5B) computed tomography (CT) images show patchy areas of black and white aspect with air trapping. Air trapping is seen as dark parenchymal areas that remain dark or appear even darker on end-expiration CT scans (eSlide 4.5A,B). In the dark regions, vessels are smaller than in the light regions, where they are enlarged (mosaic oligoemia/perfusion). Bronchi show minimal thickening of their walls. The features are bilateral and symmetrical without a prevalent distribution. Coronal CT image with maximum intensity projection (MIP) shows bilateral small solid nodules with a random distribution (eSlide 4.5C). The HRCT features are suggestive of dark lung pattern, possible diffuse interstitial pulmonary neuroendocrine cell hyperplasia (DIPNECH).

Histologic Examination (eSlide 4.5D,E,F)

The patient underwent a surgical lung biopsy. Centrilobular nodules (eSlide 4.5D) are composed of a proliferation of neuroendocrine cells. Besides, a neuroendocrine cell proliferation can also be observed as a linear growth within the airway walls (eSlide 4.5E). In both cases, the neuroendocrine nature can be demonstrated by the positivity with antichromogranin antiserum (insets). As a result of the secretion of fibrogenetic substances, constrictive bronchiolitis can ensue, both in the form of stenosis and complete obliteration of the lumen (eSlide 4.5F). (Images courtesy Alessandra Cancellieri, Bologna, Italy.)

Diagnosis

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH).

Discussion

A dark lung pattern (mosaic oligoemia) may be due to vascular or bronchiolar disease (Box 4.14 in Chapter 4). Air trapping is a key HRCT sign for the bronchiolar dark lung pattern. It refers to bronchiolar disease with retention of excess gas (“air”) in part of the lung, especially during expiration, mainly as a result of obstruction. Air trapping is seen as dark parenchymal areas that remain dark or appear darker on endexpiration CT scans (compare the preceding HRCT axial images). The dark lung areas may present anatomic extension (also lobular), possibly with well-defined margins.¹ Pathologic conditions with air trapping encompass relatively small number of diseases (Box C5.1).

Constrictive Bronchiolitis (CB). This is the prototype disease of the bronchiolar dark lung pattern. Often inside the dark areas, bronchi show thickening of their walls or luminal modifications, and vessels inside the white areas are enlarged.²’³

Swyer-James Syndrome (SJS). The affected lung (or a part of it) appears dark due to overdistention of the alveoli in conjunction with diminished arterial flow; often unilateral; bronchiectasis (saccular or cylindrical) may be present.⁴

Diffuse Interstitial Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH). Bilateral and symmetrical dark lung areas with air trapping are associated with small solid nodules with random distributions.^5-7

In conclusion, in our patient the HRCT features appearing as dark lung pattern with bronchiolar thickening and solid random nodules suggest the diagnosis of DIPNECH. A surgical lung biopsy confirmed the radiologic hypothesis.

References

1. Dalpiaz G, Cancellieri A. Dark lung pattern. In: Atlas of DLDs: A Multidisciplinary Approach. Springer; 2017. In Press.

2. Kang EY, Woo OH, Shin BK, et al. Bronchiolitis: classification, computed tomographic and histopathologic features, and radiologic approach. J ComputAssist Tomogr 2009;33:32-41.

3. Epler GR. Constrictive bronchiolitis obliterans: the fibrotic airw’ay disorder Expert Rev Respir Med. 2007;1:139-147.

4. Dalpiaz G, Nassetti C, Stasi G. Swyer-James syndrome: assessment of a case with high resolution and volumetric computerized tomography. Radiol Med. 1999;98(1-2):96-98.

5. Chassagnon G, Favelle O, Marchand-Adam S, et al. DIPNECH: when to suggest this diagnosis on CT. Clin Radiol. 2015;70(3):317-325.

6. Rossi G, Cavazza A, Spagnolo P, et al. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome. Eur Respir J. 2016;47(6):1829-1841.

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