Radiology of Diffuse Lung Disease J.Collins

Introduction

The term "diffuse" can be defined as "widely spread or scattered" (1). In the lungs, this can refer to widely scat­tered disease that is predominantly alveolar, interstitial, a combination of alveolar and interstitial, acute, chronic, symmetric, or asymmetric. Many diseases can present acutely, and become chronic, resulting in overlap between causes of acute and chronic lung disease. A single disease can present in many ways radiologically, sometimes as a focal process, and other times as a diffuse process; sometimes as an interstitial process, and other times as an alveolar process or a combination of interstitial and alveolar. It is therefore important to understand the spectrum of radiologic manifestations for different diseases. This chapter focuses on lung diseases that can present as a diffuse pattern on radio­logic imaging, discussing acute and chronic diseases separately.

Acute Diffuse lung Disease

The term "acute", as regards disease, can be defined as "brief and severe" (2). The term "brief" is nonspecific, but generally means "lasting a short time". "Severe" is also a nonspecific term, generally referring to something that

TlIbl , 18.1. Acute diffuse lung disea~e Acute alveohti~ of fibr~lng alveolilis [Klnosic allergic alveohtis Drug tOXICity

Infectious pneumonlus/bronch,us Acule radiahon pneumonitis Pulmonary hemorrhage Pulmonary edema Alveolar protelnosis

254

causes distress, or is serious, extreme, intense, or violent. The diseases listed in Table 18.1 are referred to as causes of "acute diffuse lung disease" because of their propensity to present abruptly and resolve in a short period of time, with, and sometimes without, specific treatment.

Acute Alveolitis of Fibrosing Alveolitis

Idiopathic pulmonary fibrosis (IPF), also called usual interstitial pneumonitis, or cryptogenic fibrosing alveolitis, is an inflammatory condition of the lung resulting in endstage fibrosis with honeycombing. The Hamman-Rich syndrome has been used to describe the acute, aggressive form of the disease (3). IPF is a disor­der of unknown cause. Most theories concerning patho­genesis implicate injury to alveolar endothelial and epithelial cells by circulating or inhaled agents. An immune response occurs, and activated macrophages secrete factors that activate neutrophils and stimulate fibroblasts to produce collagen. Desquamative interstitial pneumonitis is distinguished from IPF (usual interstitial pneumonitis) by extensive filling of alveoli with macrophages, a uniform histologic appearance, less interstitial component and fibrosis, a younger patient age, and a better prognosis with steroid treatment (Fig. 18.1). Some authors regard desquamative intersti­tial pneumonitis as an early phase of IPF (4). With disease progression, the active, cellular alveolitis subsides and irreversible fibrosis supervenes.

The distribution of disease in IPF is typically scattered and subpleural. High resolution computed tomography (HRCT) better defines the extent and distribution of disease than does chest radiography. Acute alveolitis can be correctly identified using HRCT by the observation of ground-glass opacity (5). Ground-glass opacity, when not associated with a predominant pattern of honeycombing or traction bronchiectasis, represents an area of reversible disease.

M. Sperber (ed.), Radiologic Diagnosis of Chest Disease© Springer-Verlag London Limited 2001

Radiology of Diffuse Lung Disease 255

a b

Figure 18.1. Desquamative interstitial pneumonitis. a Anteroposterior supine chest radiograph of a 77 year old man with acute symptoms of cough and shortness of breath shows bilateral diffuse interstitial and airspace disease. b HRCT shows bilateral ground-glass opacities and septal thickening, with a peripheral pattern of distribution on the left. Bronchial and vascular markings are still visible.

Extrinsic Allergic Alveolitis

Extrinsic allergic alveolitis (EAA), or hypersensitivity pneumonitis, results from the inhalation of antigenic organic dusts. A large number of causal antigens have been identified, including microorganisms (bacteria, fungi, thermophilic actinomycetes, amebas), animal and plant proteins, drugs, and some low molecular weight chemicals. Histologic changes are classified into acute, subacute, and chronic. The acute illness develops 4-8 h after heavy exposure to the antigen and consists of dry cough, chest tightness, dyspnea, wheeze, fever, chills, malaise, and occasionally hemoptysis. Spontaneous recov­ery follows separation from the agent, with improvement in 1 or 2 days, and complete recovery in 7-10 days.

The chest radiograph of patients with acute EAA may be normal, or show small pulmonary nodules 1-3 mm in diameter (ranging up to 8 mm), or subtle reticular inter­stitial opacities (6). These opacities may be so small and profuse that they give a ground-glass appearance. They are almost always bilateral and most commonly found in all lung zones. Patchy areas of consolidation or an inter­stitial pattern along bronchovascular bundles can develop. HRCT shows diffuse ground-glass opacities and centrilobular nodules (Fig. 18.2) (7).

Drug Toxicity

A number of commonly used drugs have been shown to affect the lungs. Prominent among these are the cytotoxic

drugs used in the treatment of cancer and hematologic malignancies. Drugs can affect the lungs by causing hypersensitivity lung disease, diffuse alveolar damage, pulmonary edema, systemic lupus erythematosus, pul­monary vasculitis, and pulmonary hemorrhage. The radi­ologic abnormalities reflect the type and acuity of the drug reaction.

In the early stages of drug toxicity, the chest radiograph may be normal. When abnormal, the radiograph shows a generalized interstitial, alveolar, or mixed process. Segmental or lobar consolidations are not a feature of diffuse toxic lung damage. On rare occasion, diffuse alveo­lar damage, caused by cytoxan, bleomycin, and methotrex­ate, can result in single or multiple pulmonary masses or nodules. Hypersensitivity reactions result in patchy areas of consolidation, often in the periphery of the lung, or a diffuse reticulonodular pattern. Edema resulting from the toxic effect of drugs is indistinguishable from cardiogenic edema. HRCT of patients with acute drug toxicity can show ground-glass opacities when the chest radiograph is normal.

Infectious Pneumonitis/Bronchiolitis

Pneumonias can be classified according to their chest radiographic appearances into bronchopneumonia, lobar pneumonia, spherical (round) pneumonia, and interstitial pneumonia. Although widely used, these terms have limited value because the same organism may produce several patterns and because patterns often overlap in individual patients. Bronchopneumonia is the most

256

a

b

common pattern, and is characterized radiologically by patchy consolidation, loss of volume, and absence of air bronchograms. In lobar pneumonia, most commonly bac­terial in etiology, the inflammatory exudate begins in the distal airspaces and spreads via the pores of Kohn across segmental boundaries, giving rise to homogeneous non­segmental consolidation. Initiation of antibiotic therapy usually prevents involvement of a whole lobe. Interstitial pneumonia refers to a radiographic pattern comprising extensive peribronchial thickening, and ill-defined reticul­nodular opacities, which may be localized or widespread. The usual causes of interstitial pneumonias are viral and Mycoplasma pneumoniae infections. Septic pulmonary

J.Collins

Figure 18.2. Extrinsic allergic alveolitis. a Posteroanterior chest radiograph of a 59 year old woman with an acute onset of fever, chills, dyspnea on exertion, headache, fatigue, minimal nonproductive cough, and hypoxemia, shows subtle bilateral, diffuse, reticular interstitial opacities. b HRCT shows bilateral ground-glass opacities and subtle centrilobu­lar nodules (arrows). The patient's symptoms resolved after hospitalization and treatment with antibiotics, but recurred after returning home. She had pet birds and her husband bred pigeons at home. Open-lung biopsy showed non caseating granulomas and lympho­cytes consistent with extrinsic allergic alveolitis from "bird fancier's lung':

emboli, usually caused by infected venous catheters, result in multiple pulmonary opacities, usually round in shape but sometimes showing the shape of a pulmonary infarct (wedge-shaped opacity based on the pleura and pointing to the hilus), of any size, often cavitating (fig. 18.3), with air bronchograms and a feeding vessel sign (8).

Aspiration pneumonia frequently causes patchy consol­idation in the dependent portions of the lungs, usually multilobar and bilateral in distribution. Consolidation with cavitation suggests bacterial or fungal disease rather than viral or Mycoplasma infection. Pneumatocele forma­tion can be difficult to distinguish from cavitation. When due to pneumonia, pneumatoceles are usually due to

Radiology of Diffuse Lung Disease

Figure 18.3. Septic emboli. HRCT of a 32 year old man with S. aureus septic emboli shows multiple rounded and irregular opacities with cavitation, and occasional air fluid levels (arrow).

infection with Staphylococcus aureus (Fig. 18.4). Diffuse miliary nodules are usually due to Mycobacterium tuber­culosis and various fungi. The nodules are even in size, usually 2-4 mm in diameter, well defined, and uniformly distributed (Fig. 18.5).

Endobronchial spread of infectious organisms can result in centrilobular nodules and linear branching opacities, best seen on HRCT, and is the most common cause of the "tree-in-bud" pattern (9). Bacterial organisms are the most common cause of a bronchiolar pattern of disease on CT, with viral, parasitic, mycobacterial, and fungal organisms less common causes. The term "tree-in-

257

Figure 18.4. Staphylococcal pneumonia. Anteroposterior supine chest radiograph of a 23 year old man with complicated staphylococcal pneumonia shows mUltiple pneumatoceles (arrows) and a large left tension pneumothorax.

bud" is commonly associated with endobronchial spread of M. tuberculosis, though this pattern is not pathogno­monic for tuberculosis. The "tree-in-bud" appearance is characteristic of active and probably contagious tuber­culosis, especially when associated with adjacent cavitary nodules in the lungs.

Most pneumonias resolve radiologically within a month, often within 10-21 days, and most of the remainder within

Figure 18.5. Miliary tuberculosis. HRCT of a 53 year old man with a history of alcohol abuse, cigarette smoking, and recent chills and night sweats shows multiple 2-3 mm nodules, randomly distributed throughout both lungs. Sputum culture was positive for acid-fast bacteria, and biopsy showed necrotizing granulomas and "red snappers':

258

2 months. Beyond 2 months, the most likely reasons for incomplete clearing are that the patient is old or has a sys­temic disease. However, a predisposing cause such as an obstructing neoplasm should always be considered in adult patients.

Radiation Pneumonitis

If any symptoms related to pulmonary irradiation occur, they are seen during the phase of acute radiation pneumon­itis or develop much later as a consequence of fibrosis and lung contraction. The usual symptoms in the acute phase are dyspnea, cough, production of tenacious sputum, and sometimes fever and night sweats. On the chest radiograph, the changes of radiation pneumonitis are generally confined to the field of irradiation. The first change is a diffuse haze in the irradiated region with obscuring of the vascular out­lines. Patchy consolidations appear, and these areas may coalesce into a nonanatomic but geometric area of pul­monary opacification. The earliest radiographic changes appear 6-8 weeks after the beginning of radiation therapy. CT is more sensitive than chest radiography in detecting postirradiation changes in the lungs, particularly in showing ground-glass opacities and shrinkage of vessels in the lung peripheral to a central field of irradiation (10).

Pulmonary Hemorrhage

A triad of features suggests diffuse pulmonary hemor­rhage (DPH): hemoptysis, anemia, and airspace opacities on the chest radiograph (11). The most common causes of DPH are antibasement membrane antibody disease (Goodpasture syndrome), connective tissue disorders, sys­temic vasculitides, idiopathic glomerulonephritis, idio­pathic pulmonary hemosiderosis, bleeding disorders, drug toxicity, and chemical lung toxicity. Less common causes include mitral stenosis, venoocclusive disease, infectious hemorrhagic necrotizing pneumonia, fat embolism, bone marrow transplantation, and hemorrhagic pulmonary edema of renal failure.

The radiographic changes of acute DPH are the same regardless of etiology and consist of airspace consolida­tion. When the bleeding is recurrent over a long period of time, interstitial changes may develop, reflecting intersti­tial fibrosis. The acute consolidation ranges from acinar shadows to patchy airspace consolidation, to widespread confluent consolidation with air bronchograms (12). The consolidation can be widespread or show a perihilar or middle to lower zone predominance and tends to be more pronounced centrally. The consolidation clears within 2-3 days, either completely or partially, leaving a linear or reticular pattern. HRCT shows consolidation or ground-

Hollins

glass opacity, which can be present when the chest radiograph is normal (13).

Pulmonary Edema

Pulmonary edema is usually due to pulmonary venous hypertension or increased permeability of the alveolar­capillary membrane. Dividing edema into conditions in which the cause is hydrostatic and those in which the cause is capillary damage makes sense, as the treatment is different for each.

Elevated pulmonary venous pressure leads to increased lymphatic drainage. Once the capacity of the pulmonary lymphatics is exceeded, pulmonary edema results. Fluid collects first in the interstitium and then spills into the air­spaces. The major causes of hydrostatic edema (also referred to as cardiogenic edema) are cardiac disease, overhydration, and fluid retention as a result of renal failure. The radiographic signs of hydrostatic pulmonary edema include interstitial septal lines, bronchial wall thickening, subpleural pulmonary edema, and airspace opacities, often with air bronchograms. Associated findings include vascular redistribution, enlargement of the cardiac silhouette and vascular pedicle, and pleural effusions. The terms "bat's wing" and "butterfly" patterns have been used to describe the appearance of perihilar airspace disease that is predominantly in the central portion of the lungs, fading out peripherally, leaving an aerated outer "cortex" of lung. A striking feature of hydro­static edema is rapid change on films taken over short intervals. Rapid clearing is particularly suggestive of the diagnosis.

Adult respiratory distress syndrome (ARDS), a form of noncardiogenic edema, is due to increased pulmonary vascular permeability in response to lung injury. The most common precipitating insults are bacterial sepsis, pneumonia, aspiration of gastric contents, circulatory shock, trauma, burns, and drug overdose. The clinical syndrome is characterized by acute, severe, progressive respiratory distress, diffuse airspace opacities on chest radiography, significant hypoxemia despite high inspired oxygen concentration, and decreased compliance of the lungs.

Radiographic features of ARDS include bilateral, wide­spread patchy, ill-defined opacities resembling car­diogenic edema, usually without cardiac enlargement, vascular redistribution, or pleural effusions. The opaci­ties progress to produce confluent opacification, usually involving all lung zones both centrally and peripherally, with prominent air bronchograms. CT scans may show that the distribution of the opacities is patchy, with preservation of normal lung regions (14). Patients with abnormal radiographs are all severely hypoxic and require assisted ventilation. During the acute phase,

Radiology of Diffuse Lung Disease

Figure 18.6. Adult respiratory distress syndrome. Anteroposterior supine chest radiograph of a 68 year old woman receiving mechanical ventilation shows bilateral diffuse airspace disease and a large left basilar pneumothorax.

many patients suffer barotrauma caused by positive­pressure ventilation with relatively noncompliant lungs. Pneumothorax, pneumomediastinum, and interstitial emphysema are common, and pneumatoceles may develop within the lungs (Fig. 18.6).

Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis represents a nonspecific response of the type II pneumocyte, the alveolar macro­phage, or both, to a variety of injuries (15). Pathologically, there is filling of the alveoli with a lipid-rich, proteina­ceous material (positive to periodic acid-Schiff stain), with normal lung interstitium. There is an association between the development of alveolar proteinosis and acute silicosis, exposure to dust or chemicals, hematologic malignancies, and immunologic abnormalities. Patients most commonly present with acute fever, weight loss, and dyspnea, and occasionally with pleuritic chest pain, hemoptysis, and pneumothorax.

The radiographic findings can be striking even when the symptoms and clinical signs are mild. The classic radiographic pattern is bilateral symmetric airspace opacity, particularly in a perihilar or hilar and basal dis­tribution (16). Less commonly, the airspace disease can be asymmetric, unilateral, or lobar. HRCT shows a retic­ular pattern superimposed on ground-glass opacities, the so-called "crazy paving sign". Resolution of radio­logic abnormalities can be spontaneous, but the majority of patients will require treatment with bronchoalveolar lavage.

259

Chronic Diffuse Lung Disease

A large number of chronic diseases may cause diffuse infiltration of the lungs. Although they are usually referred to as chronic interstitial lung diseases, the majority involve both the interstitium and the airspaces. The preferred term, therefore, is chronic infiltrative lung disease. The clinical and functional features of most of these diseases are similar. The chest radiograph may show patterns sug­gestive of a particular disease process but rarely allows a confident diagnosis. A number of studies have shown that CT can better assess the type, distribution, and severity of parenchymal abnormalities. Several chronic diffuse lung diseases have been shown to have a characteristic appear­ance on CT, even when the chest radiograph was normal or showed only nonspecific findings.

A number of signs indicate the presence of chronic infiltrative lung disease on chest radiographs and HRCT. These include abnormal interfaces, irregular linear opaci­ties, thickening of the interlobular septa, nodules, and ground-glass opacities. The differential diagnosis of chronic diffuse infiltrative lung disease is based on the type and distribution of the abnormalities. The most common patterns are summarized in Table 18.2.

Abnormal interfaces between vessels, bronchi, and visceral pleura with the surrounding parenchyma are the most common sign of chronic infiltrative lung disease

Tlbl!! 18.2. Patterns of chrOniC Infiltrative lung disease

Irregular linear panern Idiopathic pulmonary fibrosis Lymphatic spread of tumor AsbestOSIs Sarcoidosis

Thickened Inlerlobular septa Lymphatic spread of tumor SarcoidoSIS Pulmonary ed rna Idiopathic pUlmonary fibrosis

CystiC panem Lymphanglolelomyomatosls langerhan cell hlSIiOCytosis Idiopathic pulmonary fibrosis

odular pattern SIlicoSIS and coalworker's pneumoconiosis Sarcoidosis langerhan cell histiocytosis Extrinsic allergic alveoli lis

Ground-glass pattern Chronic eoSinophilic pn umonra Bronchloitlls obliterans organiZing pneumon a Extnnsic all rgic alveolitis Idiopathic pulmonary fibrosis

Airspace consolidation Bronchiolitis obliterans organizing pneumonia Chronic eosinophilic pneumonia Bronchioloalveolar cell carcinoma

260

(17). Irregular linear opacities may be seen in a number of lung diseases, and, in some cases, the pattern and distribu­tion on CT will narrow the range of diagnostic possibili­ties. For example, IPF is characterized by the presence of reticular opacities and honeycombing in the subpleural and basilar portions of lung. The fibrosis in patients with sarcoidosis is usually more severe centrally along the bronchovascular bundles (18).

Thickening of the interlobular septa is a common finding in chronic infiltrative lung diseases, and, when extensive, is seen on CT as a pattern of multiple polygonal lines. In patients with interstitial fibrosis, the thickening is irregular; in lymphangitic spread of tumor the thickening is nodular; in sarcoidosis the thickening is irregular and often associated with architectural distortion; and in pulmonary edema the thickening is smooth.

Nodules 1-10 mm in diameter can be seen with a number of chronic infiltrative lung diseases. In sarcoid­osis, the nodules are usually less than 5 mm in diameter, with smooth or irregular margins, characteristically in a perilymphatic distribution (bronchovascular bundles, subpleural regions, and interlobular septa) (19). In silico­sis, the nodules have an upper lung zone distribution.

Ground-glass opacity is defined as hazy increase in lung opacity without obscuration of underlying bronchi or blood vessels, and is commonly seen on CT with a number of acute and chronic diffuse lung diseases. In IPF, areas of ground-glass opacity correlate with active alve­olitis (in the absence of extensive honeycombing or trac­tion bronchiectasis).

Lung volumes can also provide a clue as to the etiol­ogy of chronic diffuse lung disease. Fibrotic disorders (IPF) are characterized by marked restriction and small lung volumes. On the other hand, Langerhan cell histio­cytosis and sarcoidosis, in the early stages, are usually associated with normal lung volumes, but lymphangi­oleiomyomatosis produces air-trapping with large lung volumes.

Idiopathic Pulmonary Fibrosis

IPF is characterized histologically as alveolitis and mono­nuclear cell inflammatory changes in the alveolar wall. Eventually, fibrosis develops. This end stage is referred to as honeycomb lung. These changes can be seen with collagen-vascular diseases and in response to certain drugs such as bleomycin, cyclophosphamide, or busulfan.

The characteristic radiographic findings in IPF are diffuse linear and reticular interstitial opacities obliterating normal vessels, in a subpleural and bibasilar distribution. Small, well-formed cystic spaces less than 1 cm in diameter are designated as a "honeycomb" pattern. Identification of honeycombing and severe archi­tectural distortion indicate end-stage disease. HRCT

J.Collins

Figure 18.7. Idiopathic pulmonary fibrosis. HRCT of an elderly man with chronic IPF shows extensive honeycomb lung with a subpleural and bibasilar distribution. Areas of ground glass opacity (arrows) represent fibrosis beyond the resolution of HRCT, and not reversible lung disease.

shows irregular septal thickening, irregular interfaces between lung and pleura, bronchiolectasis, honeycombing, and traction bronchiectasis, in a subpleural and basilar distribution (fig. 18.7). HRCT gives a better estimate of disease extent and shows more extensive honeycombing than does chest radiography (20).

Pulmonary Lymphatic Carcinomatosis

Pulmonary lymphangitic carcinomatosis refers to tumor growth in the lymphatics of the lung. It is seen most com­monly in carcinomas of the breast, lung, stomach, and colon. The radiographic manifestations include reticular opacities, Kerley B lines, and subpleural edema (21). The major lymph vessels are located in the bronchovascular bundles, in the interlobular septa, and in the subpleural regions of the lung. The distribution of tumor cells within these structures results in CT findings of uneven thicken­ing of bronchovascular bundles and of interlobular septa, giving them a beaded chain appearance (fig. 18.8) (22). Nodular thickening of interlobular septa helps to distin­guish lymphangitic spread of tumor from pulmonary edema on CT, which causes smooth thickening of the interlobular septa. Tumor spread, however, can also result in smooth septal thickening, and "polygonal lines" on CT.

Asbestosis

Asbestosis is defined as pulmonary interstitial fibrosis caused by asbestos exposure. The chest radiograph has limited sensitivity in detecting subtle changes of asbestosis. Considerable observer error is noted,

Radiology of Diffuse Lung Disease

particularly in patients with a normal or near-normal chest radiograph (23). When abnormal, chest radi­ographs show small linear or reticular opacities that pre­dominate in the lung bases. These may progress from a fine reticulation to a coarse linear pattern with honey­combing. The findings are similar to those seen in IPF. The presence of pleural thickening or plaques lends support to the diagnosis of asbestosis, although plaques are not invariably present.

CT is superior in characterizing and quantifying parenchymal abnormalities and in the detection of early asbestosis. Five major parenchymal abnormalities are identifiable on HRCT: (a) curvilinear subpleural lines (linear density of variable length within 1 cm and parallel to the chest wall), (b) thickened interstitial short lines (thickened interlobular septa that consists of lines 1-2 cm in length in the peripheral lung extending to the pleura), (c) subpleural dependent density (a band of increased density 2-20 mm thick bordering the dependent pleura), (d) parenchymal bands (linear densities from 2-5 cm in length coursing through the lung usually in contact with the pleura), and (e) honeycombing (24).

Silicosis and Coal Worker's Pneumoconiosis

Silicosis refers to lung disease caused primarily by inhalation of free silica. Exposed individuals usually work in quarries, drill or tunnel quartz- containing rocks, cut or polish masonry, clean boilers or castings in iron and steel foundries, or are exposed to sandblasting. The chronic form of the disease requires 20 years or more exposure to high dust concentrations before radi­ographic abnormalities are evident (25). The basic

261

Figure 18.8. Lymphangitic spread of tumor. HRCT of a 76 year old man with adenocarcinoma of the prostate shows "beaded" septal thickening (arrows), a typical appearance of Iymphangitic tumor spread in the lungs.

lesion of silicosis is a hyalinized nodule, containing silica particles.

Early in the course of disease, chest radiographs show 1-3 mm nodules, sometimes calcified, most prominent in the posterior portions of the upper two thirds of the lungs. A reticular interstitial pattern may also be seen. With time, the nodules increase in size and, number, and coalesce to form masses termed "progressive massive fibrosis". As the nodules coalesce, contraction of the upper lobes is observed and bullae form peripheral to the masses. Initially, the masses are seen in the periphery of the lung, and, with time, they migrate towards the hili, leaving emphysematous lung between the fibrotic mass and the chest wall. Similar radiographic findings are seen with coal worker's pneumoconiosis, although the two diseases are pathologically different.

HRCT can detect disease in patients with normal chest radiographs, but may be normal in the presence of pathologically proven infiltrative lung disease (26). CT findings include subpleural micronodules (similar to those seen in sarcoidosis and lymphangitic spread of cancer), diffuse nodules up to 7 mm in diameter, emphy­sema, progressive massive fibrosis, diffuse interstitial fibrosis leading to honeycombing, and lymph node enlargement and calcification (Fig. 18.9).

Lymphangioleiomyomatosis

Lymphangioleiomyomatosis is a rare disease charac­terized by progressive proliferation of smooth muscle in the walls of bronchi, bronchioles, alveolar septa, pulmonary vessels, lymphatics, and pleura (27). The process often leads to obstruction of the bronchioles with

262

a b

• .till • • 4 • , .. ,-~ .'~ ~.

Hollins

Figure 18.9. Complicated silicosis. a Posteroanterior chest radiograph of a 73 year old man employed as a foundry worker for over 20 years shows small bilateral nodules, involving predominantly the upper lung zones. b HRCT shows multiple small nodules, many of which are in a subpleural. lymphatic distribution (small arrows). central "progressive massive fibrosis'; and adjacent areas of emphysema (large arrow).

air-trapping and the development of thin-walled lung cysts that may rupture and cause pneumothorax. Obstruction of the lymphatics can occur, with subsequent development of chylous pleural effusions, and compres­sion of venules may lead to hemoptysis. The disease occurs in women of childbearing age.

Chest radiographs show diffuse reticular interstitial disease that may be associated with cysts. The lung volumes are either normal or increased. Pneumothorax is seen in about 40% of patients and chylous effusions in 60%. HRCT shows thin-walled cysts that may be dif­ficult to recognize on chest radiography. The cysts are distributed diffusely throughout the lungs. The interven­ing lung parenchyma is normal. Cystic airspaces similar to those seen in lymphangioleiomyomatosis have been described in patients with Langerhan cell histiocytosis; however, in Langerhan cell histiocytosis, a nodular component is also commonly present. Furthermore, Langerhan cell histiocytosis characteristically involves the upper two-thirds of the lungs and spares the costophrenic angles, whereas lymphangioleiomyomato­sis involves the lungs diffusely (28). Cystic airspaces are also commonly seen with pulmonary fibrosis, although IPF is characterized by the presence of a reticular pattern and honeycomb spaces with a predominant distribution in the basilar and subpleural regions, unlike the diffuse distribution seen in lymphangioleiomy­omatosis. In IPF, the honeycomb cysts are surrounded by

abnormal parenchyma, whereas most of the cysts in lymphangioleiomyomatosis are surrounded by normal lung.

Langerhan Cell Histiocytosis

Langerhans' cell histiocytosis (also referred to as histio­cytosis X and eosinophilic granuloma) is an idiopathic disease characterized by benign proliferation of mature histiocytes. Early stages of the disease are characterized by multiple granulomas composed of histiocytes, Langerhan cells, and varying numbers of eosinophils in the alveolar septa, bronchial walls, and perivascular areas. In the later stages, interstitial fibrosis and thin-walled cysts may develop. The disease occurs in young or middle­aged adults. Cigarette smoking is reported in over 90% of patients (29).

Chest radiographs show reticular, nodular, reticulo­nodular, and cystic abnormalities, often in combination (30). The disease is usually bilateral and diffuse with an upper lung zone predominance. Lung volumes are usually normal or increased. CT is superior to chest radiography in showing the morphology and distribution of lung abnor­malities (Fig. 18.10). Many lesions that appear reticular on chest radiographs are shown to represent cysts on CT. CT shows no central or peripheral predominance oflesions, but does show that many small nodules are distributed in the

Radiology of Diffuse Lung Disease 263

a b

Figure 18.10. langerhan cell histiocytosis. a Posteroanterior chest radiograph of a 32 year old man with progressive shortness of breath shows large lung volumes, bilateral reticular interstitial opacities, and thin-walled cysts. b HRG better shows the bilateral. diffuse, irregular, thin-walled cysts, and scattered small nodules (arrow). The cysts seen in patients with Iymphangioleiomyomatosis can look similar, but tend to have a smoother contour, and are not characteristically associated with parenchymal nodules.

centers of secondary pulmonary lobules around small airways. The number of nodules ranges from single to numerous, and are usually solid but can have lucent centers, presumably corresponding to small "cavities". The nodule margins are usually indistinct and often irregular, and the intervening lung parenchyma is normal (28).

Sarcoidosis

Sarcoidosis is a relatively common systemic disorder of unknown cause characterized by noncaseating granulo­mata, which may resolve spontaneously or progress to fibrosis (31). It most often occurs in young adults, with a greater prevalence in African-Americans. Pulmonary manifestations are present in 90% of patients, 20-25% of whom have permanent functional impairment (32). The diagnosis of sarcoidosis is based on the typical radiographic and clinical presentation supported by histologic evidence of sterile noncaseating granulomata in one or more organs.

The chest radiograph is abnormal in about 90% of patients and is classified according to the presence of enlarged hilar or mediastinal lymph nodes, pulmonary lesions, and fibrosis. About 60-70% of patients with sar­coidosis have a characteristic radiologic appearance con­sisting of enlarged hilar and paratracheallymph nodes with or without concomitant parenchymal changes (33). In 5-10% of patients, the radiograph is normal. When present, pulmonary lesions consist of one or a combination of fine

to coarse reticular interstitial markings, small nodules, confluent "alveolar" opacities (although, histologically, only interstitial involvement is seen), honeycombing, bullae, and architectural distortion.

Sarcoid granulomata are distributed mainly along the lymphatics in the bronchovascular sheath, and to a lesser extent, in the interlobular septa and pleura. This distrib­ution is responsible for the high rate of success in diagnosis by bronchial and transbronchial biopsies (31). The smallest lesions often are visible only on CT, with characteristic parenchymal abnormalities consisting of nodular opacities along the bronchovascular bundles, interlobular septa, major fissures, and subpleural regions (34). In the majority of cases, the nodules have irregular margins. Ground-glass opacities are commonly seen on HRCT, and probably represent active alveolitis and inter­stitial granulomas. CT is superior to chest radiography in demonstrating early fibrosis and distortion of the lung parenchyma. CT may show parenchymal abnormalities in patients with a normal chest radiograph or in patients with only hilar adenopathy apparent on the chest radi­ograph. CT, however, may be normal in patients with pul­monary involvement proved by transbronchial biopsy. The distribution of sarcoid granulomata along the lym­phatics is similar to that seen with pulmonary lymph­angitic carcinomatosis. Both may cause a beaded appearance of the bronchovascular bundles and interlob­ular septa, and the pattern may be identical on CT. In general, however, the septal thickening in sarcoidosis is usually less extensive than that seen in pulmonary

264

lymphangitic carcinomatosis, and often associated with distortion of the lobular architecture.

Extrinsic Allergic Alveolitis

This entity was discussed earlier in this chapter along with other causes of acute diffuse lung disease. EAA, however, can manifest as an acute, subacute, or chronic illness. Acutely, heavy exposure to the inciting antigen causes diffuse airspace consolidation. The consolidation resolves within a few days to reveal a fine nodular or reticulonodular pattern, characteristic of the subacute phase. The chronic stage is characterized by the presence of fibrosis, which may occur months to years after the initial exposure. CT is supe­rior to chest radiography in showing subtle centrilobular nodular opacities. HRCT is superior to conventional CT in showing areas of ground-glass opacity.

Chronic Eosinophilic Pneumonia

The term chronic eosinophilic pneumonia is used when no extrinsic causes, such as fungal hypersensitivity, drug reaction, or helminth infestation, can be identified to explain pulmonary eosinophilia. It is an idiopathic condi­tion characterized by infiltration of the lungs with eosinophils, usually associated with an increased number of eosinophils in the circulating blood. Chest radiographs characteristically show homogeneous peripheral airspace consolidation. The combination of blood eosinophilia, peripheral opacities on the chest radiograph, and rapid response to steroid therapy often obviate the need for lung biopsy (35). In many cases, however, a peripheral predom­inance of airspace opacities may not be evident on chest

a

J.Collins

radiography. In many cases, CT shows a peripheral pattern of disease when this pattern is not evident on the chest radiograph. CT, therefore, can be helpful when the clinical findings are suggestive of chronic eosinophilic pneumonia but the radiographic pattern is nonspecific.

Bronchiolitis Obliterans Organizing Pneumonia

Bronchiolitis obliterans organizing pneumonia (BOOP), also referred to as cryptogenic organizing pneumonia, is one of the most common causes of chronic diffuse lung disease, accounting for more than 20-30% of cases (36). The typical presentation is that of a 1-5 month history of low grade fever, malaise, and dry cough. Pathologically, BOOP is characterized by granulation tissue plugs in alveoli, alveolar ducts, and occasionally small airways. Pathologic changes are nonspecific, however, and similar changes are seen in a wide range of disorders. The most commonly identified disorders are infections, connective tissue disorders, and drug toxicity (37).

The chest radiograph shows patchy airspace consolida­tion that does not respond to broad-spectrum antibiotics. The consolidation on chest radiography often contains air bronchograms, and, in about half of cases, has a predomi­nantly peripheral distribution, although this is often better appreciated on CT. CT typically shows bilateral and asym­metric areas of consolidation with air bronchograms, ranging from about 1.5 cm in diameter to segmental size, often with associated ground-glass opacities (38). A pre­dominantly subpleural distribution of the consolidation is seen in about 50% of cases, and peribronchovascular distribution, similar to a bronchopneumonia, is seen in 30-50% of cases (Fig. 18.11) (39).

b

Figure 18.11. Bronchiolitis obliterans organizing pneumonia. a Posteroanterior chest radiograph of a middle-aged man with a recent upper respiratory tract infection, cough, short­ness of breath, and hypoxemia shows bilateral patchy airspace opacities. b HRCT shows airspace disease in both a peripheral and bronchovascular distribution, characteristic of BOOP.

Radiology of Diffuse Lung Disease

Bronchioloalveolar Cell Carcinoma

Bronchioloalveolar cell carcinoma is a subtype of ade­nocarcinoma, and accounts for 2-5% of lung cancers (40). The characteristic pathologic feature is a periph­eral neoplasm showing lepidic growth, with the malig­nant cells growing along the "scaffolding", or alveolar walls, of the lung. The tumor can present as a solitary pulmonary nodule or unifocal or multifocal areas of pulmonary consolidation, with the former having the best prognosis.

Bronchioloalveolar cell carcinoma can be a very slow growing tumor. It occasionally manifests on chest radi­ography as a slowly progressive airspace process, some­times present radiographically over several years, (Fig. 18.12). Because it can resemble pneumonia, it is important to document clearing of radiographic abnor­malities after treatment for presumptive pneumonia, and exclude alternative diagnoses such as slow-growing bronchioloalveolar cell cancer.

On chest radiography, the tumor appears as a solitary lobulated or spiculated pulmonary nodule, with a pro­pensity for a subpleural location, often with air bron­chograms, or as ill-defined or multiple opacities, an ill-defined opacity resembling pneumonia, patchy multi­focal areas of consolidation, or multiple ill-defined nodules. CT better shows air bronchograms, and may also show small rounded collections of air within the tumor opacities, referred to as "pseudo cavitation". Also described with these tumors is the "CT-angiogram sign", in which the vessels coursing through the tumor stand out clearly against a background of abundant low attenuation mucus within the tumor.

Figure 18.12. Bronchioloalveolar cell carcinoma. Posteroanterior chest radiograph of a middle-aged man shows bilateral diffuse airspace disease. Serial chest radiographs showed that the process was progressing over a 3 year period.

265

References

I. Steinmetz S (ed) (1993) Random House Webster's dictionary. Ballantine Books, New York, p 182.

2. Steinmetz S (ed) (1993) Random House Webster's dictionary. Ballantine Books, New York, p 8.

3. Hamman L, Rich AR (1944) Acute diffuse interstitial fibrosis of the lung. Bull Johns Hopkins Hosp 74:177-212.

4. Tubbs RR, Benjamin SP, Reich NF, et al. (1977) Desquamative inter­stitial pneumonitis - cellular phase of fibrosing alveoli tis. Chest 72:159-166.

5. Miiller NL Staples CA, Miller RR, et al. (1987) Disease activity in idiopathic pulmonary fibrosis: CT and pathologic correlation. Radiology 165:731-734.

6. Mindell HJ (1970) Roentgen findings in farmer's lung. Radiology 97:341-346.

7. Akira M, Kita N, Higashihara T, et al. (1992) Summer-type hyper­sensitivity pneumonitis: Comparison of high-resolution CT and plain radiographic findings. AJR 158:1223-1228.

8. Kuhlman JE, Fishman EK, Teigen C (1990) Pulmonary septic emboli: Diagnosis with CT. Radiology 174:211-213.

9. Aquino SL, Gamsu G, Webb WR, et al. (1996) Tree-in-bud pattern: frequency and significance on thin section CT. J Comput Assist Tomogr 20:594-599.

10. Libshitz HI, Shuman LS (1984) Radiation-induced pulmonary change: CT findings. J Comput Assist Tomogr 8:15-19.

11. Bradley JD (1982) The pulmonary hemorrhage syndromes. Clin Chest Med 3:593-605.

12. Miiller NL, Miller RR (1991) Diffuse pulmonary hemorrhage. Radiol Clin North Am 29:965-971.

13. Cheah FK, Sheppard MN, Hansell DM (1993) Computed tomogra­phy of diffuse pulmonary haemorrhage with pathological cor­relation. Clin RadioI48:89-93.

14. Maunder RJ, Shuman WP, McHugh JW, et al. (1986) Preservation of normal lung regions in the adult respiratory distress syndrome: Analysis by computed tomography. JAMA 255:2463-2465.

15. Prakash UBS, Barham SS, Carpenter HA, et al. (1987) Pulmonary alveolar phospholipoproteinosis: Experience with 34 cases and a review. Mayo Clin Proc 62:499-518.

16. Davidson JM, Mcleod WM (1969) Pulmonary alveolar protein os is. Br J Dis Chest 63:13-28.

17. Zerhouni EA, Naidich DP, Stitik FP, et al. (1985) Computed tomogra­phy of the pulmonary parenchyma. II. Interstitial disease. J Thorac Imaging 1 :54-64.

18. Miiller NL, Kullnig P, Miller RR (1989) The CT findings of pul­monary sarcoidosis: Analysis of 25 patients. AJR 152:1179-1182.

19. Lynch DA, Webb WR. Gamsu G. et al. (1989) Computed tomo­graphy in pulmonary sarcoidosis. J Comput Assist Tomogr 13:405-410.

20. Staples CA, Miiller NL. Vedal S. et al. (1987) Usual interstitial pneu­monia: Correlation of CT with clinical, functional, and radiologic findings. Radiology 162:377-381.

21. Janower ML, Blennerhaset JB (1971) Lymphangitic spread of metastatic tumor to lung. Radiology 101:267-273.

22. Stein MG. Mayo J. Miiller N. et al. (1987) Pulmonary lymphangitic spread of carcinoma: Appearance on CT scans. Radiology 162:371-375.

23. Weill H (1987) Diagnosis of asbestos-related disease. Chest 91 :802-803. 24. Aberle DR, Gamsu G. Ray CS, et al. (1988) Asbestos-related pleural

and parenchymal fibrosis: Detection with high-resolution CT. Radiology 166:729-734.

25. Ziskind M. Jones RN, Weill H (1976) Silicosis: State of the art. Am Rev Respir Dis 113:647-665.

26. Padley SPG, Hansell DM, Flower CDR, et al. (1991) Comparative accuracy of high resolution, computed tomography in the diagno­sis of chronic diffuse infiltrative lung disease. Clin Radiol 44:222-226.

266

27. Corrin B, Liebow AA, Friedman PJ (1975) Pulmonary lymphan­giomyomatosis: A review. Am J Pathol 79:348-382.

28. Moore ADA, Godwin JD, Muller NL, et al. (1989) Pulmonary histio­cytosis X: Comparison of radiographic and CT findings. Radiology 172:249-254.

29. Hance AJ, Basset F, Saumon G, et al. (1986) Smoking and interstitial lung disease: The effect of cigarette smoking on the incidence of pulmonary histiocytosis X and sarcoidosis. Ann NY Acad Sci 465:643-656.

30. Lacronique J, Roth C, Battesti JP, et al. (1982) Chest radiological features of pulmonary histiocytosis X: A report based on 50 adult cases. Thorax 37:104-109.

31. Colby TV, Carrington CB (1988) Infiltrative lung disease. In Thurlbeck WM (ed) Pathology of the lung, Thieme Medical Publishers, New York, pp 425-518.

32. Crystal RG, Bitterman PB, Rennard SI, et al. (1984) Interstitial lung diseases of unknown cause: disorders characterized by chronic inflammation of the lower respiratory tract. N Engl J Med 310:154-166.

J.Collins

33. McLoud TC, Epler GR, Gaensler EA, et al. (1982) A radiographic classification of sarcoidosis: Physiologic correlation. Invest Radiol 17:129-138.

34. Brauner MW, Grenier P, Mompoint D, et al. (1989) Pulmonary sar­coidosis: Evaluation with high-resolution CT. Radiology 172:467-471.

35. Dines DE (1978) Chronic eosinophilic pneumonia: A roentgeno­graphic diagnosis. Mayo Clin Proc 53: 129-130.

36. Adler BD, Padley SPG, Muller NL (1995) High-resolution CT in the differential diagnosis of chronic infiltrative lung disease. Appl Radiol 45-48.

37. Geddes DM (1991) BOOP & COP. Thorax 46:545-547. 38. Bouchardy LM, Kuhlman JE, Ball WC, et al. (1993) CT findings in

bronchiolitis obliterans organizing pneumonia (BOOP) with radi­ographic, clinical, and histologic correlation. J Com put Assist Tomogr 17:352-357.

39. Muller NL, Staples CA, Miller RR (1990) Bronchiolitis obliterans organizing pneumonia: CT features in 14 patients. AJR 154:983-987.

40. Auerbach 0, Garfinkel L (1991) The changing pattern of lung carcinoma. Cancer 68:1973-1977.