Honeycombing is characterized by the presence of cystic airspaces with thick, clearly definable fibrous walls lined by bronchiolar epithelium. It results from destruction of alveoli and loss of acinar architecture and is associated with pulmonary fibrosis. The cysts are typically layered along the pleural surface, helping to distinguish them from the nonlayered subpleural lucencies seen with paraseptal emphysema.

Honeycombing produces a characteristic appearance on CT that allows a confident diagnosis of lung fibrosis (Fig. 2-23) (21). On CT, the cystic spaces usually average 1 cm in diameter, although they can range from several millimeters to several centimeters in size. They have clearly definable walls that are 1 to 3 mm thick, they are air-filled, and they appear lucent in comparison to normal lung parenchyma. Honeycombing is usually associated with other findings of lung fibrosis, such as architectural distortion, intralobular interstitial thickening, traction bronchiectasis, and irregular linear opacities. Honeycombing on CT usually represents idiopathic pulmonary fibrosis,

collagen vascular disease, asbestosis, chronic hypersensitivity pneumonitis, or drug-related fibrosis (Table 2-1).

An interlobular septum marginates part of a secondary pulmonary lobule and contains pulmonary veins and lymphatics. These septa measure approximately 0.1 mm in thickness and are occasionally seen on normal thin-section CT scans. Abnormal thickening of interlobular septa is caused by fibrosis, edema, or infiltration by cells or other material. Within the peripheral lung, thickened septa 1 to 2 cm in length may outline part or all of a secondary pulmonary lobule, perpendicular to the pleural surface. They represent the CT counterpart of Kerley B lines seen on chest radiographs.

Interlobular septal thickening can be smooth (Fig. 2-24) or nodular (22) (Table 2-1). Smooth thickening is seen in patients with pulmonary edema or hemorrhage, lymphangitic spread of carcinoma, lymphoma, leukemia, interstitial infiltration associated with amyloidosis, and some pneumonias. Nodular or "beaded" thickening occurs in lymphangitic spread
of carcinoma (Fig. 2-25) or lymphoma, sarcoidosis, silicosis or coal worker's pneumoconiosis, lymphocytic interstitial pneumonia, and amyloidosis.

The term "cyst" is nonspecific and refers to a thin-walled (usually less than 3 mm thick), well-defined, well-circumscribed, air- or fluid-containing lesion, 1 cm or more in diameter, that has an epithelial or fibrous wall. A cystic pattern results from a heterogeneous group of diseases that have in common the presence of focal, multifocal, or diffuse parenchymal lucencies and lung destruction (Table 2-1). Pulmonary Langerhan cell histiocytosis, lymphangioleiomyomatosis, sarcoidosis, lymphocytic interstitial pneumonitis, collagen vascular diseases, Pneumocystis pneumonia, and honeycombing can manifest a cystic pattern on CT. Although they do not represent true cystic disease, centrilobular emphysema and cystic bronchiectasis mimic cystic disease on chest CT scans.

In cases of Langerhan cell histiocytosis, the cysts are often confluent, usually thin-walled, and often associated with pulmonary nodules 1 to 5 mm in diameter that may or may not be cavitary (Fig. 2-26). The intervening lung parenchyma is typically normal, without evidence of fibrosis or septal thickening. The distribution of findings is usually upper lungs, with sparing of the costophrenic sulci. The cysts are distributed diffusely throughout the lungs in lymphangioleiomyomatosis (Fig. 2-27), and nodules are not a common feature. The "cystic" spaces seen with centrilobular emphysema often contain a small nodular opacity representing the centrilobular artery (Fig. 2-28). This finding is helpful in distinguishing emphysema from lymphangioleiomyomatosis and Langerhan cell histiocytosis.

A nodular pattern refers to multiple round opacities, generally ranging in diameter from 1 mm to 1 cm, that may be very difficult to separate from one another as individual nodules on a
chest radiograph because of superimposition but which are accurately diagnosed on CT. Nodular opacities may be described as miliary (1 to 2 mm, the size of millet seeds), small, medium, or large as the diameter of the opacity increases. Nodules can be further characterized according to their margins (e.g., smooth or irregular), presence or absence of cavitation, attenuation characteristics (such as ground-glass opacity [GGO] or calcification), and distribution (e.g., centrilobular, perilymphatic, or random) (23) (Table 2-1).

Multiple small smooth or irregularly marginated nodules in a perilymphatic distribution are characteristic of sarcoidosis (Fig. 2-29). The nodules represent the coalescence of microscopic noncaseating granulomas distributed along the bronchoarterial bundles, interlobular septa, and subpleural regions. A similar appearance can be seen with silicosis or coal worker's pneumoconiosis, although with the latter, the distribution of nodules is random, with predominant upper lung zone involvement. Within affected areas, the nodules of silicosis can show a predominantly posterior distribution. As disease progresses, coalescence of the silicotic nodules leads to progressive massive fibrosis. Numerous small nodules of GGO in a centrilobular distribution are characteristic of the acute or subacute stage of extrinsic allergic alveolitis (Fig. 2-30) or respiratory bronchiolitis. The nodules are poorly defined and usually measure less than 3 mm in diameter. A random distribution of miliary nodules can be seen with hematogenous spread of tuberculosis (Fig. 2-31), fungal infection, or metastases from a variety of primary sources. When associated with irregularly shaped, thin-walled cysts, randomly distributed nodules suggest Langerhan cell histiocytosis. Multiple cavitary nodules can be seen with metastases (usually of squamous cell histology), Wegener granulomatosis, rheumatoid lung disease, septic emboli, and multifocal infection (typically of fungal or mycobacterial etiology). Multiple irregular nodules in a bronchovascular distribution are characteristic of benign lymphoproliferative disorders (Fig. 2-32), lymphoma, leukemia, and Kaposi sarcoma.

GGO is defined as “hazy increased attenuation of lung, with preservation of bronchial and vascular margins; caused by partial filling of airspaces, interstitial thickening, partial collapse of alveoli, normal expiration, or increased capillary blood volume; not to be confused with consolidation, in which bronchovascular margins are obscured; may be associated with an air bronchogram” (24). GGO is a common but nonspecific finding on CT that reflects the presence of abnormalities below the limit of CT resolution (Table 2-1). In one investigation of patients with chronic infiltrative lung disease in whom lung biopsy was performed in areas of GGO, the pattern was shown to be caused by predominantly interstitial diseases in 54% of cases, equal involvement of the interstitium and airspaces in 32%, and predominantly airspace disease in 14% (25). GGO is an important finding. In certain clinical circumstances, it can suggest a specific diagnosis, indicate a potentially treatable disease, and guide a bronchoscopist or surgeon to an appropriate area for biopsy (26).

Acute lung diseases characteristically associated with diffuse GGO include pneumonia (Fig. 2-33), pulmonary hemorrhage, and pulmonary edema. In patients with acquired immunodeficiency syndrome, the presence of focal or diffuse GGO on CT is highly suggestive of Pneumocystis pneumonia. In patients with lung transplants, GGO is very suggestive of Cytomegalovirus pneumonia or acute rejection. When diffuse GGO is seen in the first month after bone marrow transplantation, both infection and diffuse alveolar hemorrhage should be considered.

Diffuse or patchy GGO is frequently the main abnormality seen in the acute or subacute phase of extrinsic allergic alveolitis. It is also the predominant finding in patients with desquamative interstitial pneumonia, in which it reflects the presence of mild interstitial thickening and filling of the airspaces with macrophages. In pulmonary alveolar proteinosis, the areas of GGO usually have a patchy or geographic distribution. Although the abnormality consists mainly of filling of airspaces with proteinaceous material, interlobular septal thickening is frequently identified on CT in the areas of GGO, creating a "crazy paving" pattern (Fig. 2-34). Solitary small areas of GGO can signify early stage bronchioloalveolar carcinoma or atypical adenomatous hyperplasia (AAH).

Lung attenuation normally increases during exhalation. In the presence of airway obstruction and air trapping, lung remains lucent on exhalation and shows little change in cross-sectional area; this is best appreciated when patchy and compared to normal lung. Areas of air trapping are seen as relatively low in attenuation on expiratory CT scans. Areas of air trapping can be patchy and nonanatomic; can correspond to individual secondary pulmonary lobules, segments, and lobes; or may involve an entire lung. Air trapping in a lobe or lung is usually associated with large airway or generalized small airway abnormalities, whereas lobular or segmental air trapping is associated with diseases that affect small airways. Bronchiolectasis is a common associated finding. Pulmonary vessels within the low-attenuation areas of air trapping often appear small relative to vessels in the more opaque normal lung regions (27). This finding is also seen with vascular disease, such as chronic thromboembolic disease, as a result of decreased perfusion to affected areas of lung.

The presence of heterogeneous lung attenuation on inspiratory scans - the so-called mosaic pattern of lung attenuation - can result from infiltrative processes, airway obstruction and reflex vasoconstriction, mosaic perfusion resulting from vascular obstruction (e.g., chronic thromboembolic disease; Fig. 2-35), or a combination of these (Table 2-1). In patients with GGO from infiltrative processes, expiratory CT shows a proportional increase in attenuation in areas of both increased and decreased opacity. In patients with mosaic attenuation resulting from airway disease, such as obliterative bronchiolitis or asthma, attenuation differences are accentuated or seen only on expiration (Fig. 2-36). In patients with mosaic perfusion caused by vascular disease, air trapping can be seen but is not a dominant feature on expiratory CT.

The CT pattern of centrilobular nodular and branching linear opacities has been likened to the appearance of a budding tree. Many disorders can result in this pattern, the most common being infectious processes with endobronchial spread of disease (Fig. 2-37) (28,29) (Table 2-1). The common CT features of all processes producing the tree-in-bud pattern are (a) bronchiolar
dilatation and (b) impaction of bronchioles with mucus, pus, or other material. The CT findings are nonspecific, but a specific diagnosis can occasionally be suggested when the findings are correlated with patient history, clinical information, associated CT scan findings, and chronicity of disease.

The term tree-in-bud dates back to the bronchogram descriptions of normal respiratory bronchioles by Twining and Kerley (30) but has been more recently popularized by Im et al (31) to describe the CT appearance of the endobronchial spread of Mycobacterium tuberculosis.

Numerous noninfectious disorders are associated with the tree-in-bud pattern. In allergic bronchopulmonary aspergillosis, immunologic responses to the endobronchial growth of Aspergillus sp result in damage to the bronchial wall, central bronchiectasis, and the formation of mucous plugs that contain fungus and inflammatory cells. The tree-in-bud pattern is seen when the process extends to the bronchioles. In cystic fibrosis, an abnormally low water content of airway mucus is at least partially responsible for decreased mucous clearance, mucous plugging of small and large airways, and an increased incidence of bacterial airway infection. Bronchial wall inflammation progresses to bronchiectasis, and bronchiolar secretions result in a tree-in-bud pattern (Fig. 2-38). The tree-in-bud pattern can also be seen with aspiration of infected oral secretions or other irritant material (Fig. 2-39), diffuse panbronchiolitis (Fig. 2-40), obliterative bronchiolitis, and asthma.